MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'NHGRI Active Grants' source. Thu, 04 Nov 2010 17:53:01 +0100 http://www.medworm.com/index.php?rid=3941234&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR43HG05807%26cr_yr DESCRIPTION (provided by applicant): Greater availability of personalized genetic information regarding the efficacy or toxicity of medications could lead to improved patient care and save consumers, insurers and medical institutions billions of dollars per year. Although the field of pharmacogenomics has had some success in discovering relationships between genetic variants and drug response, a great deal of genetic variation in drug response remains unexplained. Our broad, long term research aim is to identify novel pharmacogenetic associations using web-based phenotyping of efficacy and toxicity for several major drug classes. With that goal in mind, our short term aim is to determine whether web-based collection of phenotype data along with genome-wide data for thousands of 23andMe cus... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941234 Mon, 06 Sep 2010 17:00:00 +0100 3941234 http://www.medworm.com/index.php?rid=3941242&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05915%26cr_yr DESCRIPTION (provided by applicant): Base-selective heavy atom labels for electron microscopy-based DNA sequencing Project Summary/Abstract The development of inexpensive and rapid DNA sequencing technology remains a major challenge of broad scientific interest. Preliminary work at Halcyon Molecular has shown that transmission electron microscopy (TEM) can be used to obtain ultra-fast ultra-low-cost DNA sequences. Since efficient electron scattering to a detector is highly dependent on atomic number (Z), it is possible to label single stranded DNA (ssDNA) with heavy atoms. To test the limits of this trend, we propose a multipronged approach to selectively prepared metal-DNA base pair complexes. Our effort will be synergistic, taking advantage of the experience of the Toste group in organom... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941242 Wed, 01 Sep 2010 17:00:00 +0100 3941242 http://www.medworm.com/index.php?rid=3941241&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05871%26cr_yr DESCRIPTION (provided by applicant): Our group has laid the groundwork in developing a unique, nanopore based method for DNA sequencing by nanopore induced photon emission (SNIPE), which utilizes optical detection rather than the more ubiquitous electrical detection. Our approach is superior to other nanopore approaches as the readout does not involve enzymes, parallelization is straightforward, and the readout is non-destructive. In this grant we propose three distinct aims (developed in parallel), which when brought together, will enable DNA sequencing at an unprecedented scale in terms of speed (>2 10^6 bases/s,) and extremely low cost. Our first aim is to dramatically increase the throughput, speed and accuracy of SNIPE. In order to achieve this, we will concentrate our efforts on para... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941241 Wed, 01 Sep 2010 17:00:00 +0100 3941241 http://www.medworm.com/index.php?rid=3941240&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR13HG05940%26cr_yr DESCRIPTION (provided by applicant): This proposal requests support for a Keystone Symposia meeting entitled Functional Consequences of Structural Variation in the Genomes, organized by Evan E. Eichler and Matthew Hurles, which will be held in Steamboat Springs, Colorado from January 7 - 12, 2011. Sequencing of genomes has led to the discovery of a spectrum of both small-scale and large-scale genetic variation among individuals. Changes in copy-number and genome structural variation are common in most mammalian species and affect a wide range of phenotypic traits. The goal of this meeting will be to explore the relative impact of structural variation on common and rare human genetic diseases; to discuss our understanding of normal patterns of structural variation as revealed by sequencing ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941240 Wed, 01 Sep 2010 17:00:00 +0100 3941240 http://www.medworm.com/index.php?rid=3941239&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05925%26cr_yr DESCRIPTION (provided by applicant): Clefts of the lip and/or palate (CLP) are common birth defects of complex etiology. About 70% of individuals are born with an isolated cleft and no other structural or cognitive abnormalities. Clefts affect 1 in 700 births and require surgical, nutritional, dental, speech, and behavioral interventions. They impose substantial economic burdens with an expense per person in excess of $200,000 lifetime. In addition to their impact in early life, CLP is associated with a lifetime increase in death from all causes as well as an increased risk for mental health disorders and cancer. It is now practical to identify common variants associated with the etiology of complex traits by using a combination of family collections, careful phenotyping, and genome wide a... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941239 Wed, 01 Sep 2010 17:00:00 +0100 3941239 http://www.medworm.com/index.php?rid=3941238&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05851%26cr_yr DESCRIPTION (provided by applicant): We have discovered that distinct tunneling signals can be generated for all four nucleosides (and 5-methyldeoxycytidine) using one pair of tunneling electrodes functionalized with a simple reagent containing a hydrogen-bond donor and a hydrogen bond acceptor. The goals of this proposal are to extend the measurements to nucleotides in aqueous electrolyte, and then to small oligomers. We will quantify the fraction of single-molecule reads and determine the factors that control this fraction with the goal of eliminating signals that come from more than one nucleotide in the gap at a time. We will explore the factors that control the width of the distribution of current signals for all four bases (and 5-methyl C) with the goal of improving the discriminatio... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941238 Wed, 01 Sep 2010 17:00:00 +0100 3941238 http://www.medworm.com/index.php?rid=3941237&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05096%26cr_yr DESCRIPTION (provided by applicant): We propose to develop a method for direct real-time sequencing of single DNA molecules from genomic DNA at the speed and accuracy of the natural DNA polymerases using native nucleotides. We will harness the power of the true nano-machines used in DNA replication, the natural DNA polymerases. Unlike the difficult to engineer man-made nanostructures of nanopore sequencing used to distinguish the 4 base types in close proximity and constant fluctuation, DNA polymerases have precise atomic-resolution 3D structures and can synthesize very long DNA molecules with high fidelity and velocity. The error rate of a DNA polymerase with proof-reading function could be as low as one in a million bases and a processive polymerase such as phi29 DNA polymerase can synth... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941237 Wed, 01 Sep 2010 17:00:00 +0100 3941237 http://www.medworm.com/index.php?rid=3941236&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR43HG05865%26cr_yr DESCRIPTION (provided by applicant): The feasibility of a label-free technology, Millikan Sequencing, will be evaluated for de novo sequencing of mammalian genomes for under $1,000. This novel sequencing-by-synthesis approach measures the increased charge as nucleotides are added to DNA templates attached to a tethered bead. Opposing electrical, hydrodynamic and entropic forces will be used to measure the bead displacement, which is a function of the length of DNA attached to the bead. Simultaneous detection of an array of millions of beads undergoing chain elongation will allow high-throughput sequencing. Model calculations and preliminary results indicate that this method should enable accurate, long read length and label-free DNA sequencing. The lack of labels leads to negligible reagen... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941236 Wed, 01 Sep 2010 17:00:00 +0100 3941236 http://www.medworm.com/index.php?rid=3941235&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05852%26cr_yr DESCRIPTION (provided by applicant): We propose to further develop and utilize ultra-high throughput polony genome sequencing with the primary goal of generating raw data to re-sequence the human genome in about one week (including library prep and sequencing) for less than $1,000. Currently, the technology is well advanced, but further progress is needed to meet our goals. As the critical quantitative milestone of the project, we will report the sequence for a human genome with a target sequence quality equivalent to or better than that of the mouse assembly published in December 2002 (Nature 420:520, 2002). The project is divided into four specific aims, which are to (1) increase the polony sequencing read length using a cyclic ligation strategy that involves enzymatic cleavage, (2) impr... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941235 Wed, 01 Sep 2010 17:00:00 +0100 3941235 http://www.medworm.com/index.php?rid=3941243&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05262%26cr_yr DESCRIPTION (provided by applicant): The requirement for splicing in humans is nearly ubiquitous. Human genes contain eight introns on average and greater than 93% of human genes undergo alternative splicing. These alternatively spliced forms are thought to contribute to the complexity of the human proteome. Further, alternative splicing is known to permit regulation of gene expression, such as during development and in response to environmental stimuli. Additionally, at least 15% of human diseases result from errors in splicing. Thus, to interpret the function of the human genome and to investigate human disease, we must describe qualitatively and quantitatively how the human transcriptome is spliced under a variety of conditions, the long-term goal of this project. Despite the developmen... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941243 Tue, 31 Aug 2010 17:00:00 +0100 3941243 http://www.medworm.com/index.php?rid=3941246&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05701%26cr_yr DESCRIPTION (provided by applicant): One of the most fundamental problems in genetics is the problem of identifying genetic variants that are shared identical by descent (IBD) from a recent common ancestor. Usually the concept of IBD is applied to data from families, but it can be applied to unrelated individuals because such individuals are related, even if only very distantly. This project will develop methods to detect and utilize IBD information from genome- wide data in related and unrelated individuals. These methods will make it possible to detect additional genes and variants that are involved in human disease, including common, complex diseases such as heart disease and diabetes The detected IBD information will be useful for determining regions where affected individuals in a ped... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941246 Wed, 25 Aug 2010 17:00:00 +0100 3941246 http://www.medworm.com/index.php?rid=3941245&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05848%26cr_yr DESCRIPTION (provided by applicant): This 4-year qualitative, ethnographic project addresses a Grand Challenge for the future of genomic research and a NHGRI ELSI Research Program priority area: the analysis of the impact of genomics on concepts of race, ethnicity, and individual and group identity. The goals of the project are: (a) to describe how race and ethnicity are conceptualized by genetic epidemiologists in gene-environment interaction (GEI) studies of complex diseases; (b) to examine how those conceptions specifically and concretely impact GEI study design and actual, implemented study procedures, and (c) to analyze the consequences of the uses of race and ethnicity in GEI studies for societal understandings of race and ethnicity and individual and group differences. The controver... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941245 Wed, 25 Aug 2010 17:00:00 +0100 3941245 http://www.medworm.com/index.php?rid=3941244&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05084%26cr_yr DESCRIPTION (provided by applicant): Recent studies suggest that many diseases, particularly those that commonly afflict our population, result from interactions among multiple alleles. In an attempt to understand these complex phenotypes, recent experimental efforts in model organisms have focused on measuring such interactions by engineering combinatorial genetic perturbations. Due to the enormous space of possible mutants, brute-force experimental investigation is simply not feasible, and thus, there is a critical need for computational strategies for intelligent exploration of genetic interaction networks. The specific objective of this application is to develop a computational framework for leveraging the existing genomic or proteomic data to enable intelligent direction of combinator... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941244 Wed, 25 Aug 2010 17:00:00 +0100 3941244 http://www.medworm.com/index.php?rid=3941247&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05725%26cr_yr DESCRIPTION (provided by applicant): The 1000 Genomes Project is an initiative to sequence the complete genomes of over 1000 individuals and create a reference set of common and uncommon genetic variation among various ethnic populations. This project aims to more comprehensively identify all types of genetic variation, including Single nucleotide polymorphisms (SNPs) and Structural genome variants (SVs) which include regions that have been duplicated, deleted, inverted, or translocated through the course of human evolution. Some of these structural variants have been correlated with many different disease phenotypes and thus play a major role in human health. In the course of the pilot phase of this project, numerous diverse, yet complementary, analytical methods have been developed to de... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941247 Wed, 18 Aug 2010 17:00:00 +0100 3941247 http://www.medworm.com/index.php?rid=3941249&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05840%26cr_yr DESCRIPTION (provided by applicant): Biobanks that collect and store participants' clinical and genetic information have become important tools in genomic research, disseminating data to a large number of investigators conducting genome-wide association studies and other genomic research. The ubiquity of these biobanks in research and the fact that many of their uses will be undetermined at the time a participant consents pose a host of ethical challenges related to privacy rights, participant consent, and data sharing. Moreover, in an atmosphere where the promise of genetic medicine is high, considerable discussion has arisen about whether, how, and when biobanks should return individual research results to participants who want such data. A number of recommendations have been published t... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941249 Mon, 16 Aug 2010 17:00:00 +0100 3941249 http://www.medworm.com/index.php?rid=3941248&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR03HG05908%26cr_yr DESCRIPTION (provided by applicant): Common diseases, such as bipolar disorder, asthma, heart disease, cancer, etc. are caused by a complex interplay among multiple genetic and environmental risk factors. Both common and rare genetic variants are expected to influence risk to these traits. Thus far, most research in nding disease susceptibility variants has focused, out of necessity, on the discovery of common susceptibility variants (i.e. variants with a population frequency of at least 5%). Genome-wide association studies have been very successful at nding common variants robustly associated with many complex traits. However, taken together, these variants only explain a small fraction of the estimated trait heritability. Recent advances in sequencing technologies have brought along subs... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941248 Mon, 16 Aug 2010 17:00:00 +0100 3941248 http://www.medworm.com/index.php?rid=3941252&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR43HG05949%26cr_yr DESCRIPTION (provided by applicant): Sequencing is very powerful for identifying differences in genomic DNA that may regulate cell function and diseases, pre-dispose persons to certain diseases, or warn of adverse drug metabolism. It provides a basis for identifying differences in gene expression, though such applications have been limited and are problematic because each expressed gene can vary from a single copy per cell to 10's of thousands of copies. Further, its application to formalin fixed paraffin-embedded tissue (FFPE) is quite challenging. Millions of such samples, along with the corresponding treatment modalities and known clinical outcomes, are archived at clinical centers and hospitals. Millions of such samples have also been archived from in vivo studies of safety, metabolism... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941252 Fri, 13 Aug 2010 17:00:00 +0100 3941252 http://www.medworm.com/index.php?rid=3941251&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR43HG05288%26cr_yr DESCRIPTION (provided by applicant): This Small Business Innovative Research Phase 1 project will research and develop an enabling manufacturing platform based on lithographic production of plastic fiber microarray plates. These plates will have important advantages over existing glass-fiber microarray plates: the platform of choice for gene sequencing, biochips, microtiter plates, micro and picowell plates, microfluidic arrays and microcapillary arrays. The glass fiber plates have been extensively used to perform optical readout of fluorescence signals indicative of specific biochemical reactions. In Phase 1, the proposed monomer materials will be studied and optimized. The selected materials will be polymerized into the structural form of a fiber optic microarray plate. The mechanical an... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941251 Fri, 13 Aug 2010 17:00:00 +0100 3941251 http://www.medworm.com/index.php?rid=3941250&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR15HG05913%26cr_yr DESCRIPTION (provided by applicant): Multi-species alignments at a genome-wide level have been valuable resources for annotating the human genome. The current alignment programs are geared toward identifying substitutions and insertions/deletions, but fail to find short inversions. The core computational models in most aligners explicitly account for substitutions and insertions/deletions that are as small as one base. However, an inversion needs to form a strong alignment to be included in the final results. An in-space inversion is a genomic rearrangement where a sequence interval is replaced by its reverse complement. Small in-space inversions can easily confuse aligners and cause misalignment. This type of misalignment becomes more serious when there are more species to be aligned, sin... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941250 Fri, 13 Aug 2010 17:00:00 +0100 3941250 http://www.medworm.com/index.php?rid=3941253&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05220%26cr_yr DESCRIPTION (provided by applicant): Second-generation sequencing (sec-gen) technology is poised to radically change how genomic data is obtained and used. Capable of sequencing millions of short strands of DNA in parallel, this technology can be used to assemble complex genomes for a small fraction of the price and time of previous technologies. In fact, a recently formed international consortium, the 1000 Genomes Project, plans to sequence the genomes of approximately 1,200 people. The possibility of comparative analysis at the sequence level of a large number of samples across multiple populations may be achievable within the next five years. These datasets also present unprecedented challenges in statistical analysis and data management. For example, a central goal of the 1000 Genomes ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941253 Wed, 11 Aug 2010 17:00:00 +0100 3941253 http://www.medworm.com/index.php?rid=3941254&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05824%26cr_yr DESCRIPTION (provided by applicant): The majority of gut microbes remain uncultivatable, and this significant obstacle must be overcome to understand the role of the microbiome in human health. The goal of this project is to develop a high-throughput method to grow previously uncultivatable bacteria. Our previous work with uncultivatable microorganisms from the external environment has lead to a number of advances: (1) it is possible to cultivate a substantial number of otherwise uncultivatable bacteria by growing them in situ. When microorganisms are placed into a diffusion chamber which is then returned to their natural environment, a substantial proportion of otherwise uncultivatable microorganisms will grow; (2) reinoculation from chamber to chamber produces domesticated variants that ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941254 Sun, 01 Aug 2010 17:00:00 +0100 3941254 http://www.medworm.com/index.php?rid=3819993&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05820%26cr_yr DESCRIPTION (provided by applicant): The human microbiome represents a largely undefined consortium of organisms that may play a role in human health and disease. New technologies are needed to isolate and sequence individual reference genomes for a better understanding of the complex microbial ecology of the human host. Specific Aims: 1) To test a mechanism for isolating and amplifying polymerase colonies (polonies) from the whole genome of single cells using solid phase PCR in a polyacrylamide hydrogel; and 2) to explore UV-photocatalysis as a method of selectively weakening microbial cell walls, thereby rendering the genome accessible to DNA polymerase. Research Design: A whole genome amplification method that is sensitive to one genome equivalent (1-5 fg) of DNA was developed in this l... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3819993 Sun, 01 Aug 2010 17:00:00 +0100 3819993 http://www.medworm.com/index.php?rid=3819992&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05826%26cr_yr DESCRIPTION (provided by applicant): Understanding the human microbiome is critical in maintaining human health and preventing disease, but it has been unclear how specific microbes affect health and disease because the majority of microbes cannot be cultivated using traditional methods. Technologies are needed that can both increase the success rate for cultivating microbes and target cultivation efforts towards microbes of high biomedical interest. This project will use microfluidic confinement to overcome the limitations of traditional cultivation and targeting methods by developing single cell confinement technology. Stochastic confinement of single cells in droplets of small volumes (picoliters to nanoliters) will isolate microbial species and, potentially, enable cultivation of new m... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3819992 Sun, 01 Aug 2010 17:00:00 +0100 3819992 http://www.medworm.com/index.php?rid=3819991&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR43HG06022%26cr_yr DESCRIPTION (provided by applicant): Next-generation sequencing (NGS) platforms are fundamentally altering genetic and genomic research by providing massive amounts of data in a low-cost, high-throughput format. The main drawback of existing technologies is the short sequence read lengths they produce. As a result, de novo assembly of daunting genomes is still impossible and resequencing and assembly of human genomes is a significant challenge when analyzing complex genomic regions. New tools that bridge the gap between massively parallel short read sequencing technologies (35-500 bases) and the need for large scaffolds to assemble a genome (100,000 bases) are clearly needed. The SBIR Phase I grant proposal New Strategies for De Novo Sequencing of Daunting Genomes proposes to develop a new... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3819991 Sun, 01 Aug 2010 17:00:00 +0100 3819991 http://www.medworm.com/index.php?rid=3819990&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05811%26cr_yr DESCRIPTION (provided by applicant): Background. Human health is intimately connected with the presence and activities of a wide range of microbial species that live on and within us (the microbiota). Characterization of these microbes will help us to understand how they influence human health. The Human Microbiome Project (HMP) aims to sequence the genomes from a large number of the thousands of bacterial species to be found within our microbiota for this purpose. When considering our gut microbiota, a major difficulty encountered is that the majority (~75%) of the many hundreds of bacterial species that reside there are as-yet uncultured, severely restricting the amount of research that can be done to characterize them fully in terms of their contributions to health. There is thus an urg... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3819990 Sun, 01 Aug 2010 17:00:00 +0100 3819990 http://www.medworm.com/index.php?rid=3819989&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05816%26cr_yr DESCRIPTION (provided by applicant): The microbiota of the human vagina can profoundly affect the health of women and neonates. For instance, women with the condition bacterial vaginosis (BV) have increased risks of acquiring sexually transmitted infections such as HIV, and pregnant women with BV have increased risk of preterm birth. Our understanding of BV is hampered by the failure to cultivate many of the bacteria associated with this condition. PCR methods have demonstrated that novel and uncultivated bacterial species are common in women with BV and some uncultivated bacteria are associated with important adverse outcomes such as antibiotic failure and ascending infection. Microbial genome sequencing efforts hold the promise of providing new insights regarding the metabolic interactio... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3819989 Sun, 01 Aug 2010 17:00:00 +0100 3819989 http://www.medworm.com/index.php?rid=3819988&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05065%26cr_yr DESCRIPTION (provided by applicant): The complex and dynamic communities of microbes that are present on and within the human body (the human microbiota) are thought to profoundly influence human health in a variety of ways, through effects on human physiology, nutrition, immunity, and development. Studies on humans and vertebrate animal models have generated evidence that this is the case for some specific diseases and suggest that further studies in this area may be vital for the understanding, prevention, and treatment of many human diseases, as well as the maintenance of homeostasis. It is currently a challenge to even identify comprehensively the components of the human microbiota, although genomic approaches have greatly improved the feasibility of doing so. The study of the collecti... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3819988 Sun, 01 Aug 2010 17:00:00 +0100 3819988 http://www.medworm.com/index.php?rid=3819994&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR13HG05790%26cr_yr DESCRIPTION (provided by applicant): This proposal requests partial support for a Gordon Research Conference (GRC) on The Biology of Post- Transcriptional Gene Regulation, to be held at Salve Regina University in Newport, Rhode Island, from July 18th to July 23rd, 2010. This GRC is the fourth of a series that has been held every other year since 2004. The broad and long-term goal of the Conference is to improve our current understanding of fundamental mechanisms and regulation of RNA biogenesis in normal and disease states. The emphasis is on post- transcriptional transactions involving the generation and metabolism of mRNA, but this extends to transcriptional coupling, and to factors involved in translation and its control, including tRNA and non-coding (e.g., micro) RNAs. The Specific Ai... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3819994 Fri, 09 Jul 2010 17:00:00 +0100 3819994 http://www.medworm.com/index.php?rid=3941255&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DF32HG05944%26cr_yr DESCRIPTION (provided by applicant): Population genetics is a crucial tool for facilitating medical genetics and disease gene mapping studies. This proposal outlines two novel population genetic techniques that each facilitate disease gene mapping in different ways. First, it describes a probabilistic technique for detecting the proportion of homozygosity an individual is likely to have based on SNP array data. This is useful for prioritizing disease case sample individuals for whole genome sequencing and subsequent homozygosity mapping to identify recessive disease genes. Such a tool is useful for large outbred populations such as European Americans for which homozygous regions are likely to be short and therefore cannot be unambiguously detected using existing techniques for SNP array da... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3941255 Thu, 01 Jul 2010 17:00:00 +0100 3941255 http://www.medworm.com/index.php?rid=3819995&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05232%26cr_yr DESCRIPTION (provided by applicant): Technologies for the measurement of mRNA quantities within cells are key components of a biomedical researcher (Source: NHGRI Active Grants) NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3819995 Thu, 01 Jul 2010 17:00:00 +0100 3819995 http://www.medworm.com/index.php?rid=3728949&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05773%26cr_yr DESCRIPTION (provided by applicant): Our primary goals in developing a program for the analysis of sequence data from the 1000 Genomes Project (TGF) are to address fundamental issues in human biology, including how best to identify rare variants affecting complex human phenotypes, what proportion of the heritability for complex traits is attributable to rare vs. common variants, and how to predict which genes are most likely to harbor rare variants associated with complex traits.. To achieve these goals we have assembled a multi-disciplinary team with access to a variety of unique resources. Our specific aims are: 1) We will develop and apply a variety of approaches for characterizing rare variants that affect complex human phenotypes. While this aim will focus on development of methods to... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3728949 Thu, 01 Jul 2010 17:00:00 +0100 3728949 http://www.medworm.com/index.php?rid=3728948&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR43HG05282%26cr_yr DESCRIPTION (provided by applicant): The immediate objective of our research is to generate a method that will enable researchers to multiplex Chromatin ImmunoPreciptation-Sequencing (ChIP-Seq) analysis in a single Next generation DNA sequencing run. In the to-be-developed method: i) a set of antibodies directed against specific DNA-binding proteins are uniquely bar-coded with a DNA 'ZipCode;' ii) covalent cross-links between DNA-binding proteins and chromosomal DNA are formed by treating cells with formaldehyde; iii) the set of DNA-barcoded antibodies specific to the proteins of interest are used to selectively coimmunoprecipitate the protein-bound DNA fragments that were covalently cross-linked; iv) excess antibodies and chromosomal DNAs are removed by washing; v) the enriched protein-bo... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3728948 Thu, 01 Jul 2010 17:00:00 +0100 3728948 http://www.medworm.com/index.php?rid=3728947&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05747%26cr_yr DESCRIPTION (provided by applicant): Results from several genome-wide association (GWA) studies have recently emerged showcasing the discovery of specific genetic variations found to be associated with several common, complex diseases. Leveraging these findings and fueled by the rapidly decreasing costs of performing genome-wide single nucleotide polymorphism (SNP) scans, a small number of companies have begun offering tests that aim to calculate an individual's risk for these common diseases using this genome-wide technology, direct-to-consumer (DTC) over the internet. While the offering of these tests - both at this stage of scientific discovery and directly to the consumer - has been the subject of much intense controversy, it is nevertheless the case that many individual consumers are ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3728947 Thu, 01 Jul 2010 17:00:00 +0100 3728947 http://www.medworm.com/index.php?rid=3728946&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR03HG05774%26cr_yr DESCRIPTION (provided by applicant): This Investigator-Initiated Small Grant (R03) application proposes a novel physical approach to achieve desired random fragmentation of genomic DNA for preparation of a DNA fragment library suitable for next-generation sequencing. In contrast to existing apparatuses which mechanically break DNA, the proposed method uses an essentially different principle. Electromagnetic energy is applied on the molecules to fragment the DNA. The amount of energy delivered can be precisely tuned, is uniformly distributed within a large compartment enabling multiple samples to be processed simultaneously, and readily penetrates through the container into the enclosed solution. The aim is to prove the suitability of the method for preparation of libraries for multiple nex... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3728946 Thu, 01 Jul 2010 17:00:00 +0100 3728946 http://www.medworm.com/index.php?rid=3728945&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05238%26cr_yr DESCRIPTION (provided by applicant): DNA methylation plays a critical role in regulating lineage specification and restriction of potency during mammalian development; aberrant patterns of DNA methylation are generally observed in cancers. Second-generation sequencing of bisulfite treated DNA is enabling DNA methylation to be examined in greater detail, and recently demonstrated array-based capture technique allow ultra-deep bisulfite sequencing in selected genomic regions. This project develops algorithmic and statistical methods required to formulate and test specific hypotheses about DNA methylation based on data from these novel experimental technologies. A family of statistical models will be designed to characterize features of DNA methylation in a cell or sample, and algorithms will... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3728945 Thu, 01 Jul 2010 17:00:00 +0100 3728945 http://www.medworm.com/index.php?rid=3728950&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05719%26cr_yr DESCRIPTION (provided by applicant): The study of repetitive DNA, microsatellites, a class of genomic variation which exhibits a 10,000 fold higher mutability than single nucleotide polymorphisms has been hampered by the lack of data at microsatellite- containing loci. That is, until now, with the emergence of data from the 1000 Genomes Project. We hypothesize that these hypervariable loci, once analyzed in depth will yield a new appreciation for their value and role in the genome as new biomarkers and functional elements. Baseline measurements of the variability at these loci in the substantial 1000 Genomes Project cohort will provide important information required to exploit these loci, both computationally and in the laboratory. The primary goal of the proposed research is to complete a... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3728950 Sat, 26 Jun 2010 17:00:00 +0100 3728950 http://www.medworm.com/index.php?rid=3728951&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC3HG05812%26cr_yr DESCRIPTION (provided by applicant): In this program, we will enable direct sequencing from RNA templates by adapting Pacific Biosciences' high throughput Single-Molecule Real-Time (SMRT) DNA sequencing to an RNA-dependent polymerase so SMRT RNA sequencing can be performed on the same instrument. SMRT sequencing provides long reads (currently 3kb and expected to increase to 10kb by the end of the program). This will have important implications to analysis of transcriptomes, crucial to all areas of medical biology. For example it will avoid cDNA conversion and its associated biases and provide the ability to examine alternative splice forms in their entirely rather than by imputed structure as with current methods. Pacific Biosciences is uniquely positioned to develop this technology becaus... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3728951 Tue, 15 Jun 2010 17:00:00 +0100 3728951 http://www.medworm.com/index.php?rid=3728952&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR13HG05791%26cr_yr DESCRIPTION (provided by applicant): This is an application for support of a conference sponsored by the Genetics Society of America (GSA) entitled Genetics 2010: Model Organisms to Human Biology, to be held in Boston, MA on June 12-15, 2010. The GSA believes that in this age it is important to convene a meeting that brings together investigators who study model organisms with investigators who study human biology and disease. This combination promotes a dynamic forum for the exchange of results and ideas between scientists who do not normally interact. Research on model organisms has provided the foundation for our modern-day understanding of human biology, ranging from elucidating the mechanisms for transcriptional regulation to the discoveries that provided the basis for genome-wide ass... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3728952 Fri, 11 Jun 2010 17:00:00 +0100 3728952 http://www.medworm.com/index.php?rid=3728953&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR44HG05279%26cr_yr DESCRIPTION (provided by applicant): Tremendous advances in genomics during the past two decades hold great potential for the development of new health innovations. For this potential to be realized in the form of advances in biomedical research and novel prevention, diagnosis, treatment and disease management strategies, we must overcome one technological barrier, namely the ability to perform reliable molecular profiling analyses of low quantity cells/nucleic acid material. Current technologies are not suitable for most low-quantity nucleic applications, and require multiple nucleic acid manipulation and amplification steps that are known to introduce biases and artifacts that confound downstream analyses and reduce/eliminate quantitative power. This grant application proposes various st... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3728953 Wed, 09 Jun 2010 17:00:00 +0100 3728953 http://www.medworm.com/index.php?rid=3728954&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05948%26cr_yr DESCRIPTION (provided by applicant): Activation of eukaryotic gene transcription involves the coordination of a multitude of transcription factors and cofactors on regulatory DNA sequences such as promoters and enhancers and on the chromatin structure containing these elements. Therefore, identification of these regulatory DNA elements is of utmost importance for understanding gene regulation in both healthy and diseased cells. Previous studies have demonstrated many characteristic epigenetic modifications occur at regulatory DNA elements, e.g., high levels of histone acetylation at gene promoters and at many enhancers. In addition, it is known that many regulatory elements carry these epigenetic modifications only in specific cell/tissue types or according to environmental conditions. In ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3728954 Tue, 01 Jun 2010 17:00:00 +0100 3728954 http://www.medworm.com/index.php?rid=3643707&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DP20HG05535%26cr_yr DESCRIPTION (provided by applicant): Research on the genetics of Psychiatric, Neurologic, and Behavioral (PNB) phenotypes reveals a panorama of complexity that creates several challenges: 1) the data are difficult for clinicians to assimilate and integrate into their practices, and even more so for patients and other members of society to understand and use; 2) because the traits investigated by PNB geneticists often have significance for our self-perceptions, new data can challenge our self-images in fundamental ways. In response to these challenges, with the objective of helping clinicians, patients and their families, and the general public better use evolving knowledge, we propose to develop the framework for a Center of Excellence in ELSI Research (CEER) on PNB Genetics. Over a 3-year... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643707 Tue, 01 Jun 2010 17:00:00 +0100 3643707 http://www.medworm.com/index.php?rid=3643706&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR43HG04027%26cr_yr DESCRIPTION (provided by applicant): The overall goal of our research is to develop and extend powerful exact statistical tools for testing genetic association, and to incorporate these methods into two existing, widely used software packages (Cytel Studio, SAS) that will serve the needs of data analysts in pharmaceuticals, genetic epidemiology and public health, and other fields which require a greater understanding of the genetic determinants of complex disease. The demand for these analytic tools is rising dramatically, as rapid progress in genotyping technology is making it easier and less costly to measure sampled subjects for ever larger numbers of genetic markers. Genetic association represents an observed correlation between an investigative genetic marker and some physical trait, ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643706 Tue, 01 Jun 2010 17:00:00 +0100 3643706 http://www.medworm.com/index.php?rid=3643705&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05692%26cr_yr DESCRIPTION (provided by applicant): Next-generation sequencing technologies are capable of producing tens of millions of sequence reads during each instrument run, and are quickly being applied in diverse types of experiments (e.g. RNA-Seq, miRNA-Seq, ChIP-Seq, BS-seq, CNV-Seq) to address biomedical questions by cost-effectively generating genome-wide datasets. While sequencing has been promoted as overcoming longstanding limitations of microarray-based studies, its data files are much larger than for microarrays, and its diverse data types raise similar as well as novel statistical and computational challenges. There is a pressing need for statistical and computational tools to address what leaders in the field have stated are the largest problems: data analysis and data integration. We ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643705 Tue, 01 Jun 2010 17:00:00 +0100 3643705 http://www.medworm.com/index.php?rid=3643712&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05086%26cr_yr This study pursues this goal by addressing the current gap in empirical research of the perspectives and practices of two key stakeholders: consumers and industry leaders. Using qualitative methods, the proposed study will focus on the products and services offered by DTC personal genome company, 23andMe, Inc., to discover the social networks created through the sharing of personal genomic information, the perspectives of individuals within these networks on the meaning of personal genomic information, and the potential impact of social networks on the landscape of large scale genomic research of human traits and disease, in particular, the potential blurring of the boundary between consumer and research participant. To achieve these goals, this study will engage in network ethnography (Ho... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643712 Fri, 28 May 2010 17:00:00 +0100 3643712 http://www.medworm.com/index.php?rid=3643711&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05728%26cr_yr DESCRIPTION (provided by applicant): The international 1000 Genomes Project is designed to generate a new dataset of high resolution variation in the human genome to support various studies on human biology, including human population genetics, association studies and studies of human diseases. The genomes of more than 1000 anonymized individuals from 10 populations will be sequenced using state of the art sequencing technologies. This project is in response to a RFA (RFA-HG-09-002) for analyzing the dataset. It will focus on the area of estimating mutational parameter, characterizing linkage disequilibrium and detecting natural selection on various locations of the human genome. The primary aim is to develop new/or improve existing statistical methods based mostly on coalescent theory tak... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643711 Fri, 28 May 2010 17:00:00 +0100 3643711 http://www.medworm.com/index.php?rid=3643710&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05087%26cr_yr DESCRIPTION (provided by applicant): Researchers and institutions are ethically and legally obligated to safeguard research participants' privacy and the confidentiality of their data. Indeed, the success of the research enterprise depends on the public's confidence that private information will be vigorously protected. Certificates of Confidentiality, authorized by federal law, are an important tool for meeting this expectation. By shielding researchers and institutions from forced disclosure of identifying data in any legal proceeding, Certificates are intended to facilitate participation by reassuring prospective participants about the security of their information and thus allow research to proceed on sensitive topics critical to the public's health. In fact, Certificates are commonly ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643710 Fri, 28 May 2010 17:00:00 +0100 3643710 http://www.medworm.com/index.php?rid=3643709&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR03HG05776%26cr_yr DESCRIPTION (provided by applicant): A significant number of NIH-funded projects are under the jurisdiction of an explicit data release policy. Such projects include: any project with direct costs of more than $500,00 per year, any genome-wide association study, and most community resource projects. (Community resource projects are large, costly projects designed from the outset to produce data and materials that will be of use to the broader scientific community, in contrast to hypothesis driven research.) Data release policies have generated controversy and confusion among scientists, particularly when the data in question come from human beings. Policies that favor public data release may be contravened by promises of privacy and confidentiality made to human research participants durin... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643709 Fri, 28 May 2010 17:00:00 +0100 3643709 http://www.medworm.com/index.php?rid=3643708&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05226%26cr_yr This study will help determine to what extent behavioral observations and morphological measurements are predictive of genomic patterns of variation, and what role natural selection plays in shaping fine-scale patterns of genetic variability. This information will also serve as a model for the population genetics of human variation. Moreover, it is essential for elucidating the factors that have affected genetic variation in species that serve as major biomedical models for humans. Establishing baseline levels of neutral polymorphism and linkage disequilibrium in these species will facilitate the proper design and analysis of both candidate gene studies and genome-wide association studies to identify the genetic determinants of complex traits. PUBLIC HEALTH RELEVANCE: This research on larg... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643708 Fri, 28 May 2010 17:00:00 +0100 3643708 http://www.medworm.com/index.php?rid=3643713&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05700%26cr_yr DESCRIPTION (provided by applicant): The human genome encodes hundreds of proteins that contain RNA-binding domains, most of which are poorly-characterized, and genomic analyses indicate widespread use of post- transcriptional gene regulation: there is high sequence conservation in 5' and 3' untranslated regions (UTRs), alternative splicing is prevalent, and there are many individual examples of subcellular transcript localization, differential regulation of translation, and regulation of transcript decay, often in a disease-relevant context. A key aspect of understanding human gene regulation will be to map post-transcriptional regulatory networks, and an essential step in mapping these networks is to obtain an accurate description of the RNA-binding activity of all of the RNA-binding pro... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643713 Wed, 26 May 2010 17:00:00 +0100 3643713 http://www.medworm.com/index.php?rid=3643714&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05753%26cr_yr DESCRIPTION (provided by applicant): Conceptually, pseudo-complementary DNA (pcDNA) is a structure-free polymer composed of base analogs that don't interact with each other but are able to Watson-Crick pair to regular bases in a complementary probe. Base pairs in the resulting hybrids are composed of unique combinations of modified and natural nucleotides. The ability to convert native DNA or RNA into structure-free pcDNA would significantly improve the reliability and efficiency of short probes by eliminating interference from secondary structure in the target. The exquisite ability of such probes to discriminate against mismatches favors their use in the direct detection of single nucleotide polymorphisms. pcDNA targets would also facilitate the practical use of universal oligonucleotide... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643714 Fri, 14 May 2010 17:00:00 +0100 3643714 http://www.medworm.com/index.php?rid=3643715&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DP20HG05551%26cr_yr DESCRIPTION (provided by applicant): One of the intended goals of the ELSI CEER program is to provide guidance on policy issues that arise from novel genetic and genomic science and applications. This focus, however, misses epigenetic processes. Epigenetics involves the point at which nature and nurture intersect via discrete environmentally imposed modifications to the genome. These modifications include DNA methylation, and their distribution across the genome creates cell-specific epigenomes that control cell-specific expression patterns. Unlike the DNA sequence of the genome, which is relatively static throughout life, the epigenome is dynamic during fetal and childhood development. This dynamic aspect of the epigenome creates opportunities, such as novel cancer therapies, but it also ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643715 Tue, 11 May 2010 17:00:00 +0100 3643715 http://www.medworm.com/index.php?rid=3643716&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05745%26cr_yr DESCRIPTION (provided by applicant): Alternative splicing of messenger RNA is a common event in humans. A variety of processes contribute to alternative splicing, including use of alternative 5' untranslated regions and initiation codons, polyadenylation signals, cryptic splice sites, overlapping exons, and cassette exons that may or may not be included in a message. In combination, these variations can produce an enormous number of different signals. Understanding the complexity of this transcriptome is a necessary step beyond the Human Genome Project and is the first item in the NHGRI's Grand Challenge. Current tools to identify and quantify splice variants are inadequate. This research project will develop and refine a method for identifying all known splice variants in a genome. This a... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3643716 Wed, 28 Apr 2010 17:00:00 +0100 3643716 http://www.medworm.com/index.php?rid=3537016&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05785%26cr_yr DESCRIPTION (provided by applicant): Recent high-throughput proteomic studies that identify protein complexes and/or binary interactions have not only produced a wealth of information, but have underscored the ubiquitous and fundamental role protein-protein interactions (PPIs) play in cell biology. In part as a consequence of these studies, PPIs are rapidly gaining acceptance as promising drug targets with tremendous therapeutic potential, however very little is known about the structural features that render a PPI druggable, or the chemical characteristics that constitute an effective inhibitor of a PPI. With the exception of a small number of success stories, target-based screening strategies have done poorly at identifying PPI inhibitors. This proposal describes a novel approach to deve... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3537016 Wed, 28 Apr 2010 17:00:00 +0100 3537016 http://www.medworm.com/index.php?rid=3537017&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG04524%26cr_yr DESCRIPTION (provided by applicant): Pre-mRNA splicing is a critical and regulated processing event where introns are precisely excised from nascent RNA transcripts. PTB is one of the major regulators of alternate splicing. However our understanding of how PTB and many other RNA binding proteins achieve specificity is incomplete. The goal of this research proposal is to develop efficient methods to identify the sequence elements that govern splicing in the genome and to understand how these elements work together. While this method is broadly applicable, this proposal focuses exclusively on PTB binding pre-mRNA by building on preliminary data obtained from a pilot study. There are two complementary parts to this project. The first aim describes a means for the experimental validation of th... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3537017 Mon, 26 Apr 2010 17:00:00 +0100 3537017 http://www.medworm.com/index.php?rid=3537019&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05763%26cr_yr DESCRIPTION (provided by applicant): While NextGen sequencing of small RNAs will provide important insights into a variety of biological processes the sequencing process is inherently biased, either by library construction or by RNA chemistry, leading to large misrepresentations of RNA abundance. To alleviate the biases inherent in cloning RNA populations, we propose to carry out the directed evolution of T4 RNA ligase. We will use a novel emulsion method to evolve ligases that are sequence and structure non-specific. We will also expand conventional cloning methods to try to identify particular sub-populations of small RNAs, such as those that contain 5'-triphosphates. We will determine the relative efficacy of both our normalization attempts and our new cloning strategies through NextGen... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3537019 Thu, 15 Apr 2010 17:00:00 +0100 3537019 http://www.medworm.com/index.php?rid=3537018&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR03HG05732%26cr_yr DESCRIPTION (provided by applicant): Gene expression is a fundamental determinant of phenotypic variation in humans and model organisms. Regulation of gene expression is known to have a substantial heritable component, and is believed to underly much of the genetic contribution to disease risk and other phenotypic variation. Thus, in order to understand how genetic variation affects phenotypic variation, it is important to understand how genetic variation affects gene expression levels. Although previous studies have identified individual regulatory variants, the overall genetic architecture of gene expression regulation is poorly understood. Genetic control of gene expression may include individual cis variants, individual trans variants, as well as epistatic interactions between networks... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3537018 Thu, 15 Apr 2010 17:00:00 +0100 3537018 http://www.medworm.com/index.php?rid=3537020&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05756%26cr_yr This study will determine how much these sorts of interests matter to people, and how such interests should be accommodated by biobank policies. (Source: NHGRI Active Grants) NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3537020 Thu, 08 Apr 2010 17:00:00 +0100 3537020 http://www.medworm.com/index.php?rid=3514311&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05230%26cr_yr DESCRIPTION (provided by applicant): Methods for in-depth characterization of transcriptomes and quantification of transcript levels have emerged as valuable tools for understanding cellular physiology and human disease biology, and have begun to be utilized in various clinical diagnostic applications. Current methods, however, typically require RNA to be converted to cDNA prior to measurements. This step has been shown to introduce many biases and artifacts. In order to best characterize the true transcriptome, we propose the application of single molecule, true Direct RNA Sequencing (tDRS) in which RNA is sequenced without prior conversion to cDNA. The benefits of tDRS include the ability to use minute quantities (e.g. on the order of picograms) of RNA with minimal/no sample manipulation... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3514311 Thu, 01 Apr 2010 17:00:00 +0100 3514311 http://www.medworm.com/index.php?rid=3514312&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05252%26cr_yr DESCRIPTION (provided by applicant): The goal of this project is to develop platform technology that measures how the epigenome influences transcription factor binding and gene activation at a controlled promoter sequence as the chromosome location is varied. This platform is built around the idea that the value of the existing yeast deletion libraries (Yeast Knock Outs, YKO) can be used for position-effect experiments to measure epigenetic regulation on a genome- wide scale. The availability of thousands of isogenic strains, each of which differs only in the position of a single gene cassette at a distinct chromosomal locus, provides a controlled genetic marker that can be assayed to understand how epigenetic features at different positions influence transcription. YKO libraries will be u... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3514312 Mon, 01 Feb 2010 17:00:00 +0100 3514312 http://www.medworm.com/index.php?rid=3234654&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05216%26cr_yr The objective of this particular application is to engineer nanopost arrays for sep- arating long DNA. To accomplish this goal, Brownian dynamics simulations will be used to design the devices, single-molecule videomicroscopy will be used to validate the simulations, and analytical separation experiments will be used to evaluate the device performance. Preliminary results, based on this approach, contradict the con- ventional wisdom that the posts need to be closely spaced or randomly distributed to ensure frequent collisions with the DNA. Rather, these preliminary data indicate that sparse ordered arrays have the potential to greatly increase the separation power of nanopost separation media. Based upon this insight, the research is plan is divided into four specific aims: Specific Aim 1:... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3234654 Mon, 01 Feb 2010 17:00:00 +0100 3234654 http://www.medworm.com/index.php?rid=3234655&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05254%26cr_yr DESCRIPTION (provided by applicant): Linkage mapping of Quantitative Trait Loci (QTL) in inbred line crosses of animal (mouse) models of human diseases and association mapping of QTL in human populations for genome- wide gene expression traits and disease phenotypes (and other 'omics', e.g. metabolomics, traits) are very powerful approaches to the identification of genes, pathways and regulatory networks underlying complex human diseases. Most of these systems genetics analyses are performed in multiple steps, with QTL mapping on all variables of interest (e.g., gene expression profiles, disease related phenotypes) being a very critical first step. For this first step, methods for standard QTL mapping have been used, i.e. methods for QTL mapping on a small number of traits, and even more r... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3234655 Thu, 28 Jan 2010 17:00:00 +0100 3234655 http://www.medworm.com/index.php?rid=3234656&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR03HG05225%26cr_yr DESCRIPTION (provided by applicant): Gene therapy research has involved children and adults as research subjects, but not fetuses. It is anticipated that with further advances in knowledge, research into fetal gene therapy will become feasible and worth pursuing. This project explores whether the current regulations for protecting research subjects will provide adequate protections and guidance for future research involving human prenatal gene therapy. It seeks to determine whether additions or other revisions to the regulations are needed to deal with the ethical issues that will be raised in protecting human subjects in such research. Examples of issues that will need to be addressed include the following: 1) The current regulations do not specify how risks and benefits should be balance... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3234656 Tue, 26 Jan 2010 17:00:00 +0100 3234656 http://www.medworm.com/index.php?rid=3234657&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DF32HG05308%26cr_yr DESCRIPTION (provided by applicant): Despite many association studies of single nucleotide polymorphisms (SNPs) and disease, the genetic basis of most common disease is poorly understood. One possible reason for this is that disease-causing SNPs are evolutionarily disadvantageous, and as a result, a large number of individually rare mutations cause disease. It is difficult to study the relationship between rare genetic variants and common disease using current laboratory and statistical techniques. In order to design optimal studies of rare variants, additional population genetic models, which provide predictions of the correlation, or linkage disequilibrium (LD), between rare and common SNPs are required. Previously developed population genetic models of deleterious variation do not satis... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3234657 Fri, 01 Jan 2010 17:00:00 +0100 3234657 http://www.medworm.com/index.php?rid=3234658&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DF32HG05197%26cr_yr DESCRIPTION (provided by applicant): Whole genome sequences and high-resolution tools have revealed that mammalian genomes have a complex and highly variable physical structure. We now recognize that structural variation (SV), defined as differences in the copy number, orientation or location of genomic segments larger than Ikb, are prevalent in mammals. At least ~1,000 SVs distinguish the genomes of two humans, these affect an abundance of genes, and SVs are increasingly found to underlie normal and disease phenotypes. SV is of special relevance to our understanding of evolution and disease because single mutational events can affect large phenotypic changes, and because structural mutation rates vary dramatically between hotspots and coldspots. We are only in the very early stages of und... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=3234658 Thu, 31 Dec 2009 17:00:00 +0100 3234658 http://www.medworm.com/index.php?rid=2950039&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05693%26cr_yr DESCRIPTION (provided by applicant): This application proposes a systematic effort to collect and analyze multi-factorial Pharmaco-Response Signatures (PRSs) for 15 therapeutic small molecules across a bank of 80 cancer cells lines for which genomic data is becoming available. The signatures will be used to elucidate response mechanisms, identify specific determinants of drug sensitivity or resistance at the cellular level, and create new response classifiers. PRSs will be based on high dimensionality measurements of phenotypes in single cells collected using high content microscopy supplemented by biochemical and plate-based assays, all performed at multiple times following exposure to drug at multiple doses (for a total of ca. 5 x105 unique measurements). The data will be analyzed using ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2950039 Wed, 30 Sep 2009 17:00:00 +0100 2950039 http://www.medworm.com/index.php?rid=2950038&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DF32HG05292%26cr_yr DESCRIPTION (provided by applicant): Understanding the genetic and environmental factors influencing phenotypes is central to improving human health. However, most studies of genetic architecture involve populations living in the United States, Europe and Asia. Though large, these population samples capture only a tiny subset of the standing genetic and phenotypic variation in humans. Africa on the other hand contains tremendous phenotypic, cultural, linguistic, genetic and environmental diversity and is the source of the worldwide range expansion of all modern humans in the past 100,000 years. In fact, African populations show levels of genetic diversity and substructure equivalent to that seen at the global level. Some of these observed differences are thought to reflect local adaptation... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2950038 Wed, 30 Sep 2009 17:00:00 +0100 2950038 http://www.medworm.com/index.php?rid=2850204&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR43HG05046%26cr_yr DESCRIPTION (provided by applicant): New Resources for e-Patients addresses the unmet medical needs of consumers who search for health and healthcare information online, currently a population of more than 160 million people in the U.S. It will fill gaps and address deficiencies in currently available online health information resources. It will maximize the value of public domain health information from U.S. Government sources. Textual consumer health information will be collected from NIH, FDA and other government sources. This information will be subjected to automated topic analysis and classification using methods of natural language processing and statistical text-mining to discover and extract topics on i) diseases and conditions; ii) treatments, benefits and risks; and iii) genomic... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850204 Wed, 30 Sep 2009 17:00:00 +0100 2850204 http://www.medworm.com/index.php?rid=2850203&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05331%26cr_yr DESCRIPTION (provided by the applicant): Abstract: This application addresses broad Challenge Area (10): Information Technology for Processing Health Care Data, and specific Challenge Topic, 10-HG-101: New information technology and resources for disease prevention and personalized medicine. Background: The long established wisdom of including family health history as a key part of an individual's medical record has been invigorated by the new emphasis on personalized medicine. While in the past, family health history was used to understand an individual's disease risk and to focus disease prevention efforts, in 21st century medicine, family health history's importance will increase as it will be essential to put detailed personal genetic information into a clinical context, namely the con... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850203 Wed, 30 Sep 2009 17:00:00 +0100 2850203 http://www.medworm.com/index.php?rid=2850202&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05639%26cr_yr DESCRIPTION (provided by applicant): The aims of the ENCODE (Encyclopedia of DNA Elements) and modENCODE (model organism ENCODE) projects are to apply high-throughput, cost-efficient approaches to generate a catalog of functional elements in the human, worm, and fly genomes, which will serve as the basis for biomedical research advances. By their smaller genome size, powerful genetics, and ease of experimentation, D. melanogaster and C. elegans can help guide the study of functional elements in the human genome, reveal new insights into global gene regulation and embryo development, and enable experimental studies of gene function and regulation which are not accessible in mammalian systems. This proposal aims to enhance the value of these datasets by creating a Data Analysis Center (DAC) ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850202 Wed, 30 Sep 2009 17:00:00 +0100 2850202 http://www.medworm.com/index.php?rid=2850201&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05094%26cr_yr DESCRIPTION (provided by applicant): We propose to develop a novel disposable semiconductor sensor and system able to directly and rapidly read gigabases of de novo sequence. The system is comprehensive, and includes simplified and robust sample preparation technology, and produces data fully compatible with current standards. A new type of semiconductor sensor - an Ion Torrent Chip -has been designed and developed to directly detect polymerization of DNA without the need for ANY intermediate enzymatic reactions, chemiluminescence, fluorescence, optics, optical imaging, or other constraints of having to detect light or use unnatural reagents. The system consisting of disposable Ion Torrent Chips, an integrated chip reader and fluidics, and can be produced at extremely low costs and generat... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850201 Wed, 30 Sep 2009 17:00:00 +0100 2850201 http://www.medworm.com/index.php?rid=2850200&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05618%26cr_yr DESCRIPTION (provided by applicant): In this program, we will enable direct DNA methylation profiling during real-time DNA sequencing, without bisulfite conversion. We will accomplish this by tailoring Pacific Biosciences' high throughput Single-Molecule Real-Time (SMRT) DNA sequencing technology for the detection of altered DNA polymerase kinetics due to the presence of 5-methylcytosine (5mC) in the DNA template. In addition, we will develop five-base SMRT sequencing, in which the 5th base indicates the presence of 5mC in the original sample. Our proposed technologies offer several advantages over current methylation profiling techniques. For example, direct methylation sequencing without bisulfite conversion and DNA amplification will reduce the time and effort required for sample prepar... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850200 Wed, 30 Sep 2009 17:00:00 +0100 2850200 http://www.medworm.com/index.php?rid=2850199&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05619%26cr_yr DESCRIPTION (provided by applicant): Abstract Current estimates place the number of personal variants at approximately 4 million per genome. Given the rapid advances in genome sequencing technologies and the future democratization of human genome sequencing, small groups and even individual scientists will soon be performing their own human genome projects. We believe that the ability to automatically annotate the millions of variants that these projects will produce, to combine data from multiple projects, and to recover subsets of annotated variants for diverse downstream analyses will become a critical analysis bottleneck. Despite the need, there are no publically available tools that automate these procedures. In response to the NHGRI's RFA Development and Application of Statistical an... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850199 Wed, 30 Sep 2009 17:00:00 +0100 2850199 http://www.medworm.com/index.php?rid=2850198&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05625%26cr_yr DESCRIPTION (provided by applicant): Nanopore sequencing offers the possibility of rapid single molecule sequencing with long reads, almost no sample preparation, and direct electronic readout from a small, computer-chip-like device. Nanopores are orifices that are so small that electrophoretic translocation of DNA through them necessarily occurs one base at a time. All nanopores require some means of localizing DNA with atomic precision as well as controlling its speed of translocation through the pore. Here, we introduce an entirely new type of nanopore for the DNA translocation, the single walled carbon nanotube (SWCNT). SWCNTs are relatively homogeneous on an atomic scale, easy to manufacture with no special nanofabrication, and can form excellent electrodes, simplifying tunneling read... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850198 Wed, 30 Sep 2009 17:00:00 +0100 2850198 http://www.medworm.com/index.php?rid=2850197&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05668%26cr_yr DESCRIPTION (provided by applicant): Increasingly large and diverse data sets are being generated by publically funded screening centers using various high- and low-throughput screening technologies. Much of this data is accessible. The largest public repository of small molecule screening results is PubChem, currently covering over 1,500 assays for 370,000 compounds. The number of publically available assays is expected to grow more than 10 fold during the next five years. The utility of this invaluable resource is currently limited, because the knowledge contained in complex and diverse bioassay data sets is not formalized and therefore cannot be accessed for comprehensive computational analysis or integration with other data sources. This proposal is to attack this limitation. For the p... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850197 Wed, 30 Sep 2009 17:00:00 +0100 2850197 http://www.medworm.com/index.php?rid=2850196&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05679%26cr_yr DESCRIPTION (provided by applicant): We propose to use bacterial artificial chromosome (BAC) recombineering to epitope tag 40 transcription factors per year for chromatin immunoprecipitation (ChIP) followed by sequencing to map binding sites genome wide. A major hurdle for the ENCODE project is the availability of ChIP-grade antibodies for each factor to be analyzed. Epitope tagging of chromatin-associated proteins presents an alternative approach for ChIP, using the same epitope-specific antibody for each factor. Expressing epitope tagged factors from BACs ensures that the factors are expressed at near-physiological levels due to the presence of endogenous regulatory sequences that drive each tagged factor from its native local genomic context. We propose to analyze a diversity of transcr... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850196 Wed, 30 Sep 2009 17:00:00 +0100 2850196 http://www.medworm.com/index.php?rid=2850195&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05680%26cr_yr Enter the text here that is the new abstrRecent advances in large-scale DNA sequencing have the potential for rapid advances in correlating disease phenotypes with genotypes. Infectious disease research has long focused on the pathogen's role in infection but less so on the impact of the host genotype. The current epidemic of Methicillin Resistant Staphylococcus aureus (MRSA) infection is a Grand Opportunity to apply new genetic methods to understanding this disease. There are multiple outcomes from MRSA infection, ranging from curable localized infection to devastating invasive infection. The project will study 500 subjects with MRSA infections by applying high throughput DNA sequencing to candidate genes involved in immune and other host responses to infection to correlate the outcome of... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850195 Wed, 30 Sep 2009 17:00:00 +0100 2850195 http://www.medworm.com/index.php?rid=2850194&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05697%26cr_yr DESCRIPTION (provided by applicant): This proposal responds to the GO Program ARRA Medical Sequencing Discovery Projects to establish next-generation technologies for medical resequencing in smaller academic laboratories compared to larger facilities like the Genomic Sequencing Centers. In this application, we propose to use next-generation sequencing for medical resequencing of genes that have shown highly significant associations with gout and serum uric acid levels in genome-wide association studies (GWAS) in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). Resequencing will characterize the overall genetic architecture by identification of both common functional variants that underlie GWAS statistical associations, as well as rare variants with larger phenotyp... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850194 Wed, 30 Sep 2009 17:00:00 +0100 2850194 http://www.medworm.com/index.php?rid=2850193&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05624%26cr_yr DESCRIPTION (provided by applicant): Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy, with an incidence of about 1 in 8,000 adults. The most common form of the disease, DM1, is caused by an expanded CTG repeat in the 3' UTR of the DMPK gene, and CUG repeat RNAs from this gene fold into hairpins that accumulate in nuclear foci, resulting in effective depletion of the alternative splicing factor Muscleblind (MBNL1) and hyperactivation of the splicing factor CUG Binding Protein 1 (CUGBP1). Misregulation of splicing by these factors is central in the disease. Thus, characterization of the spectrum of changes in the transcriptomes of DM patients is central to understanding disease pathogenesis. This project seeks to understand the molecular basis of DM and to i... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850193 Wed, 30 Sep 2009 17:00:00 +0100 2850193 http://www.medworm.com/index.php?rid=2850192&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05354%26cr_yr DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06) Enabling Technologies and Specific Challenge Topic 06-HG-102: Technologies for obtaining genomic, proteomic, and metabolomic data from individual viable cells in complex tissues. Perhaps the greatest challenge in the area of proteomics is to develop methods that can report on the abundances and post-translational modification states of many different proteins in a single cell or cell type obtained with high spatial and temporal resolution from complex, living tissue. There are two fundamental issues that need to be addressed in order to meet this challenge. First, new and innovative sample collection methods are needed to enable the fast and efficient recovery of material from single cells embedded in... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850192 Wed, 30 Sep 2009 17:00:00 +0100 2850192 http://www.medworm.com/index.php?rid=2850191&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05556%26cr_yr DESCRIPTION (provided by applicant): The mitochondrion is the center stage for energy metabolism, apoptosis, signaling, and ion homeostasis. Much of what we know about this organelle comes from studying mitochondrial respiratory chain disease (RCD). This devastating disease is due to genetic defects in the mtDNA or the nuclear DNA that give rise to a malfunctioning mitochondrial respiratory chain. Virtually all organ systems can be affected. RCD affects an estimated 1:5000 live births and is devastating - it is extremely difficult to diagnose, requiring consultation by multiple physicians and invasive biopsies, and at present no effective therapies are available. A small fraction of these disorders are maternally, but the vast majority of these disorders are due to mutations in nuclear gen... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850191 Wed, 30 Sep 2009 17:00:00 +0100 2850191 http://www.medworm.com/index.php?rid=2850190&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05581%26cr_yr DESCRIPTION (provided by applicant): This application responds to NHGRI's call for Medical Sequencing Discovery Projects that will use next-generation sequencing technology to tackle high-impact challenges in medical genetics. We propose to build on our successes in the study of blood lipid levels and other complex traits in a Sardinian population cohort by generating draft whole genome sequences for 1,000 individuals using whole genome shotgun approaches, as pioneered by the 1,000 Genomes Project. The proposed experimental plan poses many logistical, computational and statistical challenges, which we are uniquely poised to address - as evidenced by our track record in the organization and phenotyping of the population cohort from a highly inter-related town-dwelling subgroup of the founde... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850190 Wed, 30 Sep 2009 17:00:00 +0100 2850190 http://www.medworm.com/index.php?rid=2850189&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05592%26cr_yr DESCRIPTION (provided by applicant): We aim to provide a comprehensive foundation for development of an ultra-low-cost, ultra-fast nucleic acid polymer sequencing technology based on single-atom resolution transmission electron microscopy (TEM) of heavy atom-labeled nucleic acid polymers. Our particular approach is based on TEM imaging of ultra-dense (3 nm strand-to-strand spacing) parallel arrays of high molecular weight ssDNA molecules labeled base- selectively with heavy atoms. This will allow read lengths of at least ~150 kb and potentially as much as 2-4 Mb or more, with no special difficulties posed by highly repetitive DNA. With appropriate optimization, automation, and scaling, and with further funding beyond the scope of this proposal, this technology (TEM sequencing) will potenti... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850189 Wed, 30 Sep 2009 17:00:00 +0100 2850189 http://www.medworm.com/index.php?rid=2850188&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05596%26cr_yr DESCRIPTION (provided by applicant): DNA sequencing is currently in the midst of disruptive technological shifts, with 454, Illumina, and Solid providing us with enormous throughput increases and large reductions in cost per base. Massively parallel technologies deliver a few Gbp of sequence per week as short fragments, or reads. New applications of sequencing only recently considered impractical are enabled: personal genome sequencing, metagenomics analysis of 'soups' containing several, to hundreds of unique organisms, and finally, de novo sequencing of novel genomes of complex organisms. No matter how the sequencing is done, reads must be assembled computationally, if they are to be useful. Given the read length and read quality limitations of new instruments and the massive volume of d... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850188 Wed, 30 Sep 2009 17:00:00 +0100 2850188 http://www.medworm.com/index.php?rid=2850187&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05597%26cr_yr Increasing amounts of sequence data are being generated in multiple biomedical research disciplines, particularly through the application of next-generation sequencing technologies to the genomic analysis of humans and their associated microbiome. However, the bioinformatic infrastructure necessary for sequence processing, requiring demanding software installations and access to powerful CPUs, currently presents a dramatic bottleneck for the further expansion of research in this field. Our proposal aims to address this problem through the generation of a portable, stand-alone Virtual Machine (VM) software package that combines all essential tools to perform basic Metagenomic, Viral and Eukaryotic sequence analysis. This VM will allow researchers to easily implement entire software pipeline... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850187 Wed, 30 Sep 2009 17:00:00 +0100 2850187 http://www.medworm.com/index.php?rid=2850186&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05602%26cr_yr DESCRIPTION (provided by applicant): Large-scale efforts are underway to systematically map transcription factors binding sites throughout the human genome. The ENCODE project has focused its initial attention on two cell lines, 1) K562 cells, a myeloid precursor cell line and 2) GM12878, a lymphoblastoid cell line, and our laboratory has mapped the binding sites of a large number of transcription factor expressed in these cells. To study their conservation and help provide functional information into these binding sites and to determine if these sites are occupied in vivo, we propose two types of studies. First, we will map the binding sites of at least 30 transcription factor orthologs that have been analyzed in the human ENCODE project in mouse MEL and CH12 cells which are analogous to ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850186 Wed, 30 Sep 2009 17:00:00 +0100 2850186 http://www.medworm.com/index.php?rid=2850185&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05605%26cr_yr Statistical Methods for Next-Generation Sequencing in Disease Association Studies Through this project we propose to develop statistical approaches and software for genotype calling andassociation testing in next-generation sequence data. The field is driven by molecular advances that allow foraffordable, massively parallel sequencing. The rapid development of statistical methods for next-generationsequence data in disease studies is necessary to keep pace with the advancing molecular technology. Next-generation sequencing is based on random, short-read technology; thus the coverage of any nucleotide ishighly variable and subject to error. Distinguishing random error from truly variable sites is required for SNP-calling. One step beyond this is identifying the individual's actual genotype ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850185 Wed, 30 Sep 2009 17:00:00 +0100 2850185 http://www.medworm.com/index.php?rid=2850184&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05608%26cr_yr DESCRIPTION (provided by applicant): This application addresses NHGRI RFA-OD-09-004 for Medical Sequencing Discovery Projects. The ultimate goal of this proposal is to scale a new approach to identify the candidate genes and mutations that underlie rare Mendelian diseases in humans by exome resequencing. For decades, linkage analysis has been the mainstay of human genetics. However, for rare Mendelian diseases where family collection is difficult or pedigrees are small, this approach is less useful. Although the molecular bases of more than 2,600 Mendelian diseases have been determined by linkage mapping or a candidate gene approach, a nearly equal number remain to be solved (OMIM). We have assembled a collection of rare pediatric and adult Mendelian diseases that are representative of thi... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850184 Wed, 30 Sep 2009 17:00:00 +0100 2850184 http://www.medworm.com/index.php?rid=2850183&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05546%26cr_yr DESCRIPTION (provided by applicant): Next-gen sequencing technologies are generating an incredible amount of data in a very short time span. While the raw sequence data is submitted to NCBI, at present there is no standard pipeline at NIH that can process this vast amount of data in a uniform, robust, fast and accurate manner to produce the variant calls needed for further biological research. For large collaborative projects, such as 1000 genomes or TCGA, it is critical to the quality of the results that all data for the project be processed consistently, through a single, validated analysis pipeline. The pipelines must be able to validate the data. recalibrate error rates, merge data for each sample across multiple sources and technologies, align to reference, and call SNP's and structur... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850183 Wed, 30 Sep 2009 17:00:00 +0100 2850183 http://www.medworm.com/index.php?rid=2850182&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05428%26cr_yr We present here a technique to quantify expression of up to 100 genes in 1-10 cells residing in intact tissue in an animal. This powerful approach is broadly applicable to the study of a wide variety of biological processes. Specifically, we propose that these techniques can distinguish gene expression patterns in a selected cell type in gross tissue samples and allow the recognition of regulatory pathways and metabolic processes that are fundamental to stem cell and cancer cell behaviors. (Source: NHGRI Active Grants) NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850182 Wed, 30 Sep 2009 17:00:00 +0100 2850182 http://www.medworm.com/index.php?rid=2850181&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05338%26cr_yr DESCRIPTION (provided by applicant): This proposal on Nanodiagnostics and Nanotherapeutics:Building Research Ethics and Oversight responds to RFA-OD-009-0003, addressing Challenge Area 02: Bioethics and Challenge Topic Unique Ethical Issues Posed by Emerging Technologies, as set forth in 02-OD (OSP)-101. The ability to manipulate atoms and molecules at the nanoscale has catalyzed the emerging field of nanomedicine. While many biological phenomena occur at the nanoscale, nanomedicine denotes material fabricated at the scale of 1-100 nanometers (nm) to take advantage of novel properties (biological, optical, thermal, chemical, and mechanical) that manifest at the nanoscale. A focal area of development is nanodiagnostics and nanotherapeutics. These fields use nanotechnology to develop nanosca... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850181 Wed, 30 Sep 2009 17:00:00 +0100 2850181 http://www.medworm.com/index.php?rid=2850180&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR43HG05186%26cr_yr DESCRIPTION (provided by applicant): Miniaturized DNA Sequencer for Identification of Microbial Pathogens Abstract. The goal of this project is develop a compact and inexpensive DNA sequencer based on the implementation of sequencing-by-synthesis chemistry on a droplet-based digital microfluidic cartridge. The proposed device would be capable of sequencing 10's to 100's of base pairs using an inexpensive disposable cartridge and a compact and simple piece of equipment. The cartridge will also integrate sample preparation capability, including DNA amplification, to enable widespread use by non-specialists and provide rapid and reliable results at low cost. The initial application for this technology will be microbial pathogen identification. The rationale for this is that even a few tens of... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850180 Wed, 30 Sep 2009 17:00:00 +0100 2850180 http://www.medworm.com/index.php?rid=2850179&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG04838%26cr_yr DESCRIPTION (provided by applicant): Our proposal is to develop an ontology of qualities (i.e. distinguishing characteristics such as: long, short, increased, decreased, red, blue, and so on) and use it, in conjunction with ontologies of particular anatomies and biological processes, to describe phenotypic data from zebrafish, fruit fly, mouse, and human rigorously. This work will provide one of the integral components necessary for integrating phenotypic descriptions semantically with other aspects of biomedical knowledge. Currently these descriptions are recorded either as free text or using a terminology that is idiosyncratic to a single organism or research project. We have chosen these particular data sets because of the preliminary work that has already been carried out on these data... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850179 Wed, 30 Sep 2009 17:00:00 +0100 2850179 http://www.medworm.com/index.php?rid=2850178&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG04836%26cr_yr DESCRIPTION (provided by applicant): Today, ontologies are critical instruments for biomedical investigators, especially in those areas, such as cancer research, that require the command of a vast amount of information and a systemic approach to the design and interpretation of experiments. In fact, ontologies are proliferating in all areas of biomedical research, offering both challenges and opportunities. One of the principal challenges to the full realization of their potential stems from the fact that ontologies are developed in isolation, rendering it impossible to move, for instance, from genes to organisms, to diseases, to drugs. The National Center for Biomedical Ontology (NCBO) represents a fundamental endeavor in the collection, coordination and distribution of biomedical ontolog... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850178 Wed, 30 Sep 2009 17:00:00 +0100 2850178 http://www.medworm.com/index.php?rid=2850177&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05117%26cr_yr DESCRIPTION (provided by applicant): Primary care physicians have almost no training in genetics, nor in the ethical, legal and social implications (ELSI) of genetic testing, diagnosis and therapy. Further, mere provision of curricular content fails to impact physician behavior. However, programs with elements that are based on established educational and adult learning principles have been shown to effective in affecting behavioral change. We propose to evaluate whether participation in a web-based curriculum focusing on the ethical legal and social issues in primary care genetics will improve primary care physicians' approach to genetic issues. Specifically, we will assess whether participation will improve physician knowledge, attitudes, and practice-behaviors. We will recruit 120 PCPs ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850177 Wed, 30 Sep 2009 17:00:00 +0100 2850177 http://www.medworm.com/index.php?rid=2850176&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05137%26cr_yr DESCRIPTION (provided by applicant): This proposal represents a response to NIH RFA-HG-08-004 Genome-Wide Association (GWA) Studies of Treatment Response in Randomized Clinical Trials. We propose that we perform a GWA study using DNA samples from the Success A breast cancer trial of adjuvant chemotherapy. Breast cancer, the most common cancer, and the second-leading cause of cancer death in women, is of major public health importance. Most women with breast cancer are treated with, and benefit significantly from combination chemotherapy. However, patients with breast cancer display large individual variation in efficacy and the occurrence of drug-related adverse events in response to chemotherapy. The SUCCESS A trial enrolled 3754 breast cancer patients and had two arms. One arm involved t... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850176 Wed, 30 Sep 2009 17:00:00 +0100 2850176 http://www.medworm.com/index.php?rid=2850209&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05654%26cr_yr DESCRIPTION (provided by applicant): The goal of this project is to produce comprehensive, high-definition maps of mouse regulatory DNA marked by DNaseI hypersensitive sites to parallel the human catalogue currently under production by the ENCODE Project. Digital DNaseI technology enables efficient genome-wide mapping of accessible chromatin and DNaseI hypersensitive sites. The core regions of DNaseI hypersensitive sites are constitutively populated by regulatory factor binding sites, the nucleotide-resolution footprints of which may be systematically exposed on a genome-wide scale by ultra-deep sequencing. DNaseI hypersensitive sites exhibit marked cell-type variability; accordingly, production of a comprehensive catalog will require surveying a wide range of cell types. Cell types target... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850209 Tue, 29 Sep 2009 17:00:00 +0100 2850209 http://www.medworm.com/index.php?rid=2850208&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05604%26cr_yr DESCRIPTION (provided by applicant): PROJECT SUMMARY: The Connectivity Map 100k project aims to forge a path toward a comprehensive 'functional look-up table' that that links disease biology, genome function and small-molecule action. Such a Connectivity Map would enable researchers worldwide to generate testable hypotheses that might otherwise remain undiscovered. By using genomic signatures as a common language with which to describe different cellular states, a broad range of research applications would be enabled. We propose here an ambitious plan to generate 100,000 Connectivity Map profiles of genetic and pharmacologic perturbation that will serve two important purposes. First, it will generate an expanded Connectivity Map database that will further support biological discovery. Seco... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850208 Tue, 29 Sep 2009 17:00:00 +0100 2850208 http://www.medworm.com/index.php?rid=2850207&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05058%26cr_yr DESCRIPTION (provided by applicant): Zebrafish with its growing arsenal of tools that allow the generation of transgenics, gene knockdowns and knockouts, and mutant resources coupled with its high-throughput and cost efficiency is quickly becoming the major animal model for drug screens and gene related studies. However, as with other vertebrate genomes, the majority of the zebrafish genome (97%) is made up of non-genic sequences whose functional necessity remains largely unknown. One vital function that is clearly embedded in these regions is gene regulation, instructing genes when and where to turn on or off. However, unlike genes where we know their genomic location, their code, and the consequences of nucleotide changes within them, in gene regulatory sequences we don't have that knowl... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850207 Tue, 29 Sep 2009 17:00:00 +0100 2850207 http://www.medworm.com/index.php?rid=2850206&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05445%26cr_yr DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (12): Science, Technology, Engineering, and Mathematics Education (STEM) and specific Challenge Topic, 12-OD-104: Innovative approaches to STEM education. Title of project: Promoting genetic literacy in students and teachers: The effectiveness of non-classroom instructional strategies and settings Rapid advancements in genetic technology, the popularity and coverage of genetics by the press, and the increased understanding of the role genetics plays in our health necessitates a basic understanding of the science for everyone. In spite of this increased exposure to genetics, a study by Bowling (2008) indicated that the public's genetics literacy remains relatively low. Studies looking specifically at the ge... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850206 Tue, 29 Sep 2009 17:00:00 +0100 2850206 http://www.medworm.com/index.php?rid=2850205&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05160%26cr_yr DESCRIPTION: (provided by applicant): More than 750,000 Americans suffer stroke each year. Of these, nearly 160,000 die and hundreds of thousands are disabled. The burden on the public health is even greater given that 11 million subclinical strokes per year contribute to cognitive decline and dementia. Ischemic stroke accounts for 85% of all strokes. Established stroke risk factors play major roles in defining stroke risk at a population level, but prediction of individual risk remains unrealized. Identification of factors that place individuals at risk for ischemic stroke is central to the development of therapeutic preventative strategies. The Vitamin Intervention for Stroke Prevention (VISP) trial, an NIH-funded, multicenter, double-blind, randomized, controlled clinical trial, was des... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850205 Tue, 29 Sep 2009 17:00:00 +0100 2850205 http://www.medworm.com/index.php?rid=2850211&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DF32HG05192%26cr_yr DESCRIPTION (provided by applicant): Instructions for building tissues and organs are encoded into the genome and at each Step of embryonic development a series of transcriptional regulatory events are required for their accurate execution. Understanding the regulatory programs that pattern genes during embryogenesis is a key step in understanding developmental diseases and the mechanisms behind the formation and repair of healthy tissues and organs. The mechanisms that pattern tissues and organs are strikingly similar across species. Therefore model organisms, like the fruit fly, provide convenient experimental systems to explore the basic principles that guide tissue morphogenesis. Despite the availability of numerous genomes and techniques to physically map transcription factor binding ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850211 Mon, 28 Sep 2009 17:00:00 +0100 2850211 http://www.medworm.com/index.php?rid=2850210&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05157%26cr_yr DESCRIPTION (provided by applicant): The Department of Biostatistics at the University of Washington proposes to establish a Coordinating Center for a series of genome-wide association studies of treatment response in randomized clinical trials. The Coordinating Center will be administered within the Center for Biomedical Statistics of the Department of Biostatistics and it will take advantage of the experience gained by departmental activities as Coordinating Center for the Geneva project. Geneva is a series of 14 genome-wide association studies within the Gene-Environment Initiative. The new RTC-WGA Coordinating Center will be co-directed by Bruce Weir, Chair of the Department of Biostatistics and PI of the Geneva Coordinating Center, and by Patrick Heagerty, Director of the Center for B... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850210 Mon, 28 Sep 2009 17:00:00 +0100 2850210 http://www.medworm.com/index.php?rid=2850217&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05439%26cr_yr DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (02) Bioethics and specific Challenge Topic, 02-HG-101: Informed consent and data access policies. The ethical, legal, and social issues (ELSI) underlying the development and implementation of state-sponsored birth cohort studies and their accompanying biobanks are complex and potentially volatile. Michigan and other states, such as Connecticut and California, are in the midst of investigating and deliberating on how to set up biobanks, and there is a pressing need for practical ELSI research and guidelines for these historic initiatives. Consequently, to facilitate the development of state-sponsored population birth cohort databases for a wide range of studies, including genetics, research is urgently nee... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850217 Sat, 26 Sep 2009 17:00:00 +0100 2850217 http://www.medworm.com/index.php?rid=2850216&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05491%26cr_yr This study will be important as genetic research moves towards participants truely realizing the benefits of the research they are a part of. (Source: NHGRI Active Grants) NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850216 Sat, 26 Sep 2009 17:00:00 +0100 2850216 http://www.medworm.com/index.php?rid=2850215&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05591%26cr_yr DESCRIPTION (provided by applicant): The first human genome sequence was published in 2001, yet as of now, eight years later, major questions remain, such as how many genes are encoded by the genome, and of those genes, how many functional products are encoded due to phenomena like alternative splicing. The Encyclopedia of DNA Elements (ENCODE) project has been coordinated by National Human Genome Research Institute (NHGRI) to answer these questions by comprehensively classifying functional elements on the human genome. The pilot phase of the project studied 1% of the genome in detail, revealing extensive transcription well beyond that predicted by classical gene models. The biological function of a significant portion of the discovered transcripts is unclear. The ENCODE project is now sca... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850215 Sat, 26 Sep 2009 17:00:00 +0100 2850215 http://www.medworm.com/index.php?rid=2850214&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05573%26cr_yr DESCRIPTION (provided by applicant): Our goal is to discover and use relationships between mouse and human regulatory genomes to advance the ENCODE Project in its effort to map all functional elements in the human genome. Our comparative approach aims to uncover principles and solve problems that are proving difficult by studying the human genome alone. ENCODE is vigorously mapping hundreds of function-associated biochemical markers in selected cell lines, resulting already in tens of millions of reproducible biochemical features. Some observed protein:DNA interactions find and refine known transcriptional enhancers, promoters, silencers, together with associated chromatin structure, as was anticipated. But substantial questions arise as to how many of the myriad biochemical events are fun... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850214 Sat, 26 Sep 2009 17:00:00 +0100 2850214 http://www.medworm.com/index.php?rid=2850213&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05471%26cr_yr DESCRIPTION (provided by applicant): This application addresses the broad Research Area: 06, Enabling Technologies And Challenge Topic: 06-HG-102* Technologies for obtaining genomic, proteomic, and metabolomic data from individual viable cells in complex tissues. Methods will be developed to analyze gene expression from single cancer cells enabling studies at an unprecedented level of sensitivity. We propose techniques to measure RNA transcription from individual circulating tumor cells (CTCs) isolated from the blood of cancer patients. By accessing confirmed cancer cells, separated from the large background of normal cells, it will be possible to gain unexplored knowledge about the disease process and its spread through the body by metastasis. Recent advances in several key technologies h... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850213 Sat, 26 Sep 2009 17:00:00 +0100 2850213 http://www.medworm.com/index.php?rid=2850212&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG04900%26cr_yr DESCRIPTION (provided by applicant): It is recognized that research on the human microbiome is important for its potential scientific and medical impact. The complexity of microbiome research, however, could change the way that genetics is studied and understood because it calls for a more complex, nuanced framework for defining and demonstrating causality. The understanding of the human microbiome could also disrupt traditional assumptions about definitions of species, self, disease and normality. It is also recognized that microbiome research can raise ethical, legal, and social issues. The mandate to study the ELSI issues of human microbiome research at this stage implicitly embraces the concept of preventive or prophylactic bioethics. While useful, such an approach can be less effectiv... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850212 Sat, 26 Sep 2009 17:00:00 +0100 2850212 http://www.medworm.com/index.php?rid=2850226&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05152%26cr_yr DESCRIPTION (provided by applicant): The results of the early-terminated WHI hormone trials (WHI-HT) led to a dramatic 50% reduction in hormone use by post-menopausal women in the ensuing 5 years since the trial was terminated. Yet, controversy persists, and several important clinical and scientific questions remain unresolved. Individuals are known to vary considerably in response to drug therapy and other interventions, both in magnitude of treatment effect and in risk of adverse events. Much of this variation in drug response has been hypothesized to have a genetic basis. Based on previous data from animal models, observational human studies, and accruing candidate gene and plasma biomarker and proteomic data from WHI-HT, estrogen and progesterone have multi-factorial effects on atheros... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850226 Fri, 25 Sep 2009 17:00:00 +0100 2850226 http://www.medworm.com/index.php?rid=2850225&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05542%26cr_yr DESCRIPTION (provided by applicant): Project Summary Wide availability of next-generation sequencing (NGS) instruments has enabled any investigator, for a modest cost, to produce enormous amounts of DNA sequence data. However, working with these raw sequences presents significant problems for individual investigators, small labs, or core facilities. For an experimental group with no computational expertise, simply running a data analysis program is a barrier, let alone building a compute and data storage infrastructure capable of dealing with NGS data. Fortunately, a computational model - Cloud computing - has recently emerged and is ideally suited to the analysis of large- scale sequence data. In this model, computation and storage exist as virtual resources, which can be dynamically allo... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850225 Fri, 25 Sep 2009 17:00:00 +0100 2850225 http://www.medworm.com/index.php?rid=2850224&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05598%26cr_yr DESCRIPTION (provided by applicant): DNA sequencing technology has improved dramatically over recent years with orders of magnitude improvements in the yield of sequence data having resulted from applying massively parallel approaches. Helicos has taken next generation sequencing even further with its single molecule technology, allowing simpler sample prep, lower sample quantities, and lower costs than competing platforms. However, this cost is still not low enough to make whole genome sequencing routinely available for medical or other applications. For sequencing whole genomes to become widespread, it will be necessary to further lower the cost to $1000 or less. With the improvements that can be accomplished via this grant over the next two years, this goal could be realized. Sequencing... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850224 Fri, 25 Sep 2009 17:00:00 +0100 2850224 http://www.medworm.com/index.php?rid=2850223&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG04938%26cr_yr The objective of this project is to develop a powerful new method for mammalian cell genetics for use in the identification of undiscovered genetic networks in cancer and other diseases. The specific aims are: 1. To generate a new platform for loss-of-function genetics. We will use a cell line haploid for all but one human chromosome and efficient gene-trap mutagenesis as an alternative methodology for phenotype-based, recessive genetic screens. 2. To use gene-trap screens in haploid cells to identify cancer relevant genes. We will employ this unique technology to discover novel genetic networks operative in cancer cell biology; our initial efforts aim to elucidate unknown genetic components of death-receptor induced apoptosis and therapeutic response to Gleevec. PUBLIC HEALTH RELEVANCE: U... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850223 Fri, 25 Sep 2009 17:00:00 +0100 2850223 http://www.medworm.com/index.php?rid=2850222&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05110%26cr_yr DESCRIPTION (provided by applicant): The technologies that make sequencing DNA fast, cheap and widely available have the potential to revolutionize bio-medical research and herald the era of personalized medicine. Being able to sequence human genomes for $1000 will enable comparative studies of variations between individuals in both sickness and health. Ultimately it can improve the quality of medical care by identifying patients who will gain the greatest benefit from a particular medicine, and those who are most at risk of adverse reactions. Nanopore-based sequencing technologies attempt to thread a long DNA molecule through a few nanometer wide nanopore and use physical differences between the four base types to read the sequence of bases in DNA. The two major potential benefits of nano... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850222 Fri, 25 Sep 2009 17:00:00 +0100 2850222 http://www.medworm.com/index.php?rid=2850221&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05570%26cr_yr DESCRIPTION (provided by applicant): The overall goal of this proposal is to develop a strategy towards clinical resequencing of the human genome which we define as the application of human genome resequencing to large clinical populations for disease gene discovery research as well as a clinical application that has diagnostic potential. Our strategy relies on third generation single molecule DNA sequencing as utilized by the Pacific Biosciences platform. We anticipate that single molecule DNA sequencing technology will ultimately be the sequencer of choice given these systems' rapid collection of massive amounts of DNA sequences from patient samples with clinical outcome annotation, and cost-effective operation at a fraction of the current costs of other sequencing technologies. This fir... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850221 Fri, 25 Sep 2009 17:00:00 +0100 2850221 http://www.medworm.com/index.php?rid=2850220&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05118%26cr_yr DESCRIPTION (provided by applicant): The proposed research is to synthesize a 2-D array of proteins with various peptide sequences on a solid substrate on demand, using a nozzleless, directional droplet-ejector array and MEMS (microelectromechanical systems) technology. The proposed research is to lay down the underlying technologies for a portable and affordable system for synthesis of protein probe arrays on a solid substrate. The synthesis system for protein probe array is to make protein chip technology available to individual laboratories so that the laboratories may be able to immobilize thousands of peptides on a solid substrate for bioassay and screening, and have far greater flexibility in chip design and faster turnaround in fabricating new chips. The envisioned portable protein ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850220 Fri, 25 Sep 2009 17:00:00 +0100 2850220 http://www.medworm.com/index.php?rid=2850219&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DP41HG04693%26cr_yr DESCRIPTION (provided by applicant): The goal of the proposed project is to address a well-documented lack of genetics education among health professionals, which is a rate-limiting step in the integration of genetics and genomics into mainstream health care. The five-year project will create, disseminate, and evaluate a set of educational resources for health professionals who are not trained in genetics. Those resources will acquaint health professionals with the application of genetics and genomics to prevention, diagnosis, and treatment of disease and will raise awareness of the ethical, legal, and social implications of genetically based health care. All resources will be available free of charge. The specific aims are: 1. Create, disseminate, and evaluate genetics-education resources... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850219 Fri, 25 Sep 2009 17:00:00 +0100 2850219 http://www.medworm.com/index.php?rid=2850218&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05111%26cr_yr This study aims to systematically annotate the RNA transcripts and chromatin domains in the zebrafish genome by an integrated experimental and computational strategy. Previous studies in mouse and human have demonstrated that the combination of tiling microarrays, RNA expression profiling, chromatin immunoprecipitation, gene set enrichment analysis and gene module analysis can identify and annotate large numbers of novel genomic elements. We will apply these approaches to experimentally annotate the zebrafish genome for functional genomic elements (Aim 1) and generate a publicly available atlas of coding and non-coding genes and their functional relationships (Aim 2). Taken together, this project will provide a comprehensive and dynamic map of genomic elements in zebrafish. PUBLIC HEALTH R... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850218 Fri, 25 Sep 2009 17:00:00 +0100 2850218 http://www.medworm.com/index.php?rid=2850227&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG04856%26cr_yr DESCRIPTION (provided by applicant): Learning more about the human microbiome is likely to change the way medicine is practiced. It may also have implications for our society and our legal system and important implications for how we conceive and address the ethics of medicine and biomedical research. The goal of our project will, therefore, be identifying the ethical, social, and legal implication raised by the study of the human microbiome so as to provide insight and guidance for scientists who will be engaged in the work and members of our society who will be asked to cooperate in the studies and to live with the consequences. Our project will bring together an interdisciplinary team of 27 health professionals, scientists, and scholars from the humanities and social sciences to explore... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850227 Thu, 24 Sep 2009 17:00:00 +0100 2850227 http://www.medworm.com/index.php?rid=2850228&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05115%26cr_yr The objective of this project is to engineer a new protein pore, MspA, for nanopore DNA sequencing. MspA's short and narrow constriction, its extreme stability against denaturation and its tolerance to mutations make this protein an ideal, inexpensive and novel nanopore sequencing development platform. We have obtained exciting results that demonstrate the feasibility of our proposal. We designed and made MspA mutants that pass DNA. Importantly, mutated MspA can already nearly resolve single nucleotides using co-passing current alone. Molecular dynamics simulation of MspA agrees excellently with experiment. A prototype fast, low-noise current amplifier was built specifically for nanopore sequencing experiments. Our specific aims are to (i) rationally design, produce and test MspA mutants t... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850228 Wed, 23 Sep 2009 17:00:00 +0100 2850228 http://www.medworm.com/index.php?rid=2850237&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05359%26cr_yr DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic 06-HG-103: Methods to sequence highly variable, repeat-rich regions of complex genomes. A remarkable 45% of our genome consists of repetitive elements - more than 40-fold the mass contribution of protein-coding sequences. Retrotransposons termed long interspersed elements (LINEs) are among the most predominant and dynamic of these. More than 500,000 LINEs, both intact 6kb elements and fragments, comprise 17% of the human genome. Their presence is intriguing because LINEs are major forces in the evolution of mammalian genomes, with the potential to significantly alter neighboring gene expression levels and mRNA structure. The youngest LINEs, known as T... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850237 Tue, 22 Sep 2009 17:00:00 +0100 2850237 http://www.medworm.com/index.php?rid=2850236&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05468%26cr_yr DESCRIPTION (provided by applicant): This application addresses broad challenge area (01) Bioethics, and specific Challenge Topic, 02-HG-101: Informed Consent and Data Access Policies. Our project title is The Impact of Data Access Policies on Biobank Participation. The NIH data access policy for genetic research provides enormous opportunities for genetic investigators but also raises a number of challenges for educating and recruiting participants into large-scale genetic research studies. The NIH released a final data access and sharing policy for genome-wide association studies (GWAS) in August, 2007. The policy requires specific phenotypic and genetic data from GWAS be deposited into a government controlled, limited access database. The goal of this study is to examine how NIH data ac... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850236 Tue, 22 Sep 2009 17:00:00 +0100 2850236 http://www.medworm.com/index.php?rid=2850235&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05552%26cr_yr DESCRIPTION (provided by applicant): Project Summary / Abstract Rapid technological advances mean that sequencing technologies can now be deployed on a genomic scale to further our understanding of human traits and diseases. Massive-throughput genotyping technologies have provided a tool for large-scale assessment of the contribution of common genetic variants (particularly SNPs) to complex traits. It is expected that next-generation sequencing technologies will substantially broaden the scope of genetic variants to include rarer SNP variants, as well as short insertion and deletion polymorphisms, copy number polymorphisms and other large structural variants. Extracting the full benefits of these new sequencing technologies will require new analytical tools and data processing pipelines, b... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850235 Tue, 22 Sep 2009 17:00:00 +0100 2850235 http://www.medworm.com/index.php?rid=2850234&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05613%26cr_yr DESCRIPTION (provided by applicant): The economical sequencing of a number of individual human genomes has been made possible by next-generation sequencing (NGS) methods. These same sequencing methods are now being applied to gene expression profiling. However, next-generation methods, when applied to mRNA sequencing, rely on PCR, which introduces bias, distorts the overall mRNA distribution, and cannot generally be applied to individual cells. Capitalizing on our group's recent work on single-molecule DNA sequencing by synthesis with fluorogenic dNTP substrates, we propose a novel method for multiplex sequencing of individual mRNA molecules using a reserve transcriptase that employs fluorogenic nucleotide substrates to sequence mRNA directly during the synthesis of cDNA. Upon incorporatio... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850234 Tue, 22 Sep 2009 17:00:00 +0100 2850234 http://www.medworm.com/index.php?rid=2850233&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC2HG05553%26cr_yr DESCRIPTION (provided by applicant): The potential use of nanopores for DNA sequencing has gained significant momentum. This is partly due to innovative solid state techniques, but more so due to breakthroughs using biological pores. One promise of nanopore sequencing has been very long read lengths, however we and others have performed most of our experiments using short synthetic DNA oligomers. In this proposal, we present experiments designed to test how efficiently nanopores can control and process long DNA templates (up to 2500 nt in length) as they are catalytically modified by DNA polymerases. Our work will focus on T7 DNA polymerase (T7 DNApol) and the Klenow fragment of DNA polymerase I (KF), coupled to the alpha hemolysin biopore (1-HL). There are three aims: Aim 1. Limit DNA rep... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850233 Tue, 22 Sep 2009 17:00:00 +0100 2850233 http://www.medworm.com/index.php?rid=2850232&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05482%26cr_yr DESCRIPTION (provided by applicant): This application addresses board Challenge Area (08) Genomics and specific challenge topic, 08-DA-102 Improved Bioinformatics Analysis for Deep Sequencing. The number of human samples undergoing whole-genome sequencing is expected to increase dramatically in the next few years, as advances in next-generation sequencing technologies continue to lower the cost of sequencing. In addition to detection of sequence variation, these data can be used to estimate DNA copy number variation and subsequently to examine correlation between copy number and phenotype. In this proposal, we aim to develop a series of computational steps and integrated analysis pipeline for accurate estimation of copy number from next-generation sequencing data. This involves efficient p... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850232 Tue, 22 Sep 2009 17:00:00 +0100 2850232 http://www.medworm.com/index.php?rid=2850231&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05369%26cr_yr DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (02) Bioethics and specific Challenge Topic, 02-HG-102 Direct to Consumer (DTC) Personal Genomics-Ethical, Legal and Social Implications Research. Completing the Human Genome and the Human HapMap Projects has enabled studies associating genetic variation with complex diseases such as various cancers, coronary artery disease, and diabetes. This has led to the emergence of direct-to-consumer testing companies offering genomic profiling to inform individuals about their risk for dozens of diseases and traits. Such testing is being offered with the assumption that identification of an increased risk could lead to preventative measures to reduce a person's risk for developing disease or to improve disease outco... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850231 Tue, 22 Sep 2009 17:00:00 +0100 2850231 http://www.medworm.com/index.php?rid=2850230&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05334%26cr_yr DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (08) Genomics, and specific Challenge Topic, 08-OD-101, Computational approaches for epigenomic analysis. While the primary DNA sequence of the human genome is ultimately responsible for the encoding and functioning of each cell, a plethora of chromatin and DNA modifications have been described in recent years that can modulate the interpretation of this primary sequence. These epigenetic modifications lead to the diversity of function across different human cell types, and play key roles in the establishment and maintenance of cellular identity during development, and also in health and disease. The human ENCODE project, the NIH Epigenome Roadmap, and several other large-scale experimental efforts are cur... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850230 Tue, 22 Sep 2009 17:00:00 +0100 2850230 http://www.medworm.com/index.php?rid=2850229&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DRC1HG05332%26cr_yr DESCRIPTION (provided by applicant): This Application addresses broad Challenge Area (08), Genomics, and Specific Challenge Topic 08-HG-101 Technology and resources for high throughput functional analysis of functional elements in genomic sequences. A two year project is proposed to expand, to exploit, to extend, and to apply on a demonstration basis a completely novel approach to high throughput cis-regulatory analysis. We have very recently developed the initial component of this new technology as a tool for rapid validation of sea urchin embryo gene regulatory network models, and demonstrated its efficacy in facilitating the discovery and in measuring the quantitative activity of previously unknown cis-regulatory modules with a throughput of up to 100x that of traditional methods. The e... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850229 Tue, 22 Sep 2009 17:00:00 +0100 2850229 http://www.medworm.com/index.php?rid=2850238&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05211%26cr_yr DESCRIPTION (provided by applicant): We propose to develop, implement and streamline an informatics pipeline to fill the gap between production and analysis for gene-region specific high coverage data from the full-scale 1000 Genomes Project. The developed pipeline aims to process data generated from exomes using direct capture technologies and next-generation sequencing as a major part of the 1000 Genomes Project, to identify and catalog SNPs and indels that enable a detailed understanding of the genetic variants distribution within coding regions among the human population. We will develop and improve several software packages for read mapping, variant discovering, and data quality assurance in terms of statistical rigor and software engineer aspects so they will be suitable for general ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850238 Fri, 18 Sep 2009 17:00:00 +0100 2850238 http://www.medworm.com/index.php?rid=2850241&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05209%26cr_yr DESCRIPTION: (provided by applicant): The 1000 Genomes Project is an initiative to sequence the complete genomes of over 1000 individuals and create a reference set of common and uncommon genetic variation among various ethnic populations. This project aims to more comprehensively identify all types of genetic variation, including Single nucleotide polymorphisms (SNPs) and Structural genome variants (SVs) which include regions that have been duplicated, deleted, inverted, or translocated through the course of human evolution. Some of these structural variants have been correlated with many different disease phenotypes and thus play a major role in human health. In the course of the pilot phase of this project, numerous diverse, yet complementary, analytical methods have been developed to d... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850241 Wed, 16 Sep 2009 17:00:00 +0100 2850241 http://www.medworm.com/index.php?rid=2850240&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05208%26cr_yr DESCRIPTION: (provided by applicant): The 1000 Genomes Project is developing data resources and analytical methods required for the next stage of human genetics research: (a) discovering millions of novel polymorphisms with frequencies 0.5%-10%, which can then be tested for association to disease via imputation and direct genotyping in patients, and (b) bringing together genome centers, technology companies and population geneticists in a collaborative framework to develop data formats, analytical methods and standards for sensitive, accurate genome-wide resequencing for rare variants. The Project's goals are aggressive as detection of rare variants requires unprecedented accuracy, multiplied by the inclusion of multiple rapidly-evolving next generation sequencing platforms. Key tasks for ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850240 Wed, 16 Sep 2009 17:00:00 +0100 2850240 http://www.medworm.com/index.php?rid=2850239&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DF31HG05201%26cr_yr This study will assess the implications of new genetic technology for its potential positive and negative effects on this important immigration policy. PUBLIC HEALTH RELEVANCE: My ultimate career goal is to become an academic researcher focusing on the ethical, legal and social implications of genetic technologies in society. My particular research goal in this proposal, supported by my experiences as an immigrant, is to explore the intersection of law and policy with genetic science in the development of immigration policy. The proposed research will consider the use of genetic testing immigration procedures for family re-unification, and will explore the potential impact of genetic testing in the context of immigrant perspectives on how families are defined and family ties constructed. T... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850239 Wed, 16 Sep 2009 17:00:00 +0100 2850239 http://www.medworm.com/index.php?rid=2850242&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05155%26cr_yr DESCRIPTION: (provided by applicant): The National Human Genome Research Institute (NHGRI) has launched a series of research training activities in Genomics and Ethical, Legal, and Social Issues (ELSI), comprising the Research Training Consortium (RTC), with a focus on increasing the successful participation of individuals from Under Represented Minorities (URM). While the various grantees are involved in evaluating and tracking progress towards their goals for their own programs, this has not been done systematically, making it difficult to compare and pool data across programs. The major goal of RFA-HG-08-006 is to establish a Data Analysis and Coordinating Center (DACC) to facilitate and streamline the evaluation and tracking component for the entire MAP initiative. An interdisciplinary... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850242 Tue, 15 Sep 2009 17:00:00 +0100 2850242 http://www.medworm.com/index.php?rid=2850245&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05214%26cr_yr DESCRIPTION: (provided by applicant): The 1000 Genomes Project aims to achieve a nearly complete catalog of common human genetic variants by generating high-quality sequence data surveying the genomes of >1000 individuals. This catalog will include SNPs, copy number variants, and short insertion and deletion polymorphisms. By cataloging and describing the relationships between these variants, the Project will provide important benefits to genetic association studies of complex disease. Specifically, availability of very complete lists of candidate functional variants will: (a) accelerate fine-mapping efforts in gene regions indentified through genome-wide association studies or candidate gene studies; (b) improve the power of future genetic association studies by enabling design of next ge... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850245 Fri, 11 Sep 2009 17:00:00 +0100 2850245 http://www.medworm.com/index.php?rid=2850244&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DU01HG05210%26cr_yr DESCRIPTION: (provided by applicant): The International 1000 Genomes Project (1000 Genomes) aims to leverage the emergence of next generation sequencing technologies to catalogue common human genetic variability. The ambitious goals and timeline of 1000 Genomes will require highly coordinated collaboration by multiple research groups. While aspects of our development efforts will involve all three platforms, a major proportion of our proposal will focus on optimal integration of SOLID data into the 100 Genomes data production pipeline. Our goal is to insure that the unique capabilities of the platform are maximized during data processing, while adhering to common data and analytical standards established across the 1000 Genomes. In Aim 1, we will develop tools for monitoring data quality, ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850244 Fri, 11 Sep 2009 17:00:00 +0100 2850244 http://www.medworm.com/index.php?rid=2850243&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DP01HG05062%26cr_yr DESCRIPTION: (provided by applicant): The genomics research community is facing a time of tremendous opportunity and challenge as it deals with the increasing amounts of data produced by ever improving technology platforms. The vast amounts of data of diverse types (sequence, expression, epigenetic, RNAi screens, etc.) offer the prospect of integrating different views of biological states, and the promise of a deeper mechanistic understanding. However, such integration is out of reach for most biologists. The increasing need to use multiple sophisticated computational methods and tools to gain insights from the wealth of available data poses a major barrier. The number of computational tools and methods has also grown quickly over the past few years increasing the difficulty of finding the... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850243 Fri, 11 Sep 2009 17:00:00 +0100 2850243 http://www.medworm.com/index.php?rid=2850246&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05171%26cr_yr DESCRIPTION (provided by applicant): Federal Regulation of Probiotics: An Analysis of the Existing Regulatory Framework and Recommendations for Alternative Frameworks. This proposal requests funding to support an evaluation of existing regulatory frameworks and their appropriateness for the regulation of new probiotic products that are available in the market or will be available in the near future. The project will include a literature review, review of existing relevant statutes and regulations, and three day-long meetings that will each bring together 15-20 invited participants from the regulatory, scientific, biotechnology, government and academic communities to discuss whether the existing regulatory framework of foods, dietary supplements, and drugs is sufficient to ensure the safety... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850246 Fri, 04 Sep 2009 17:00:00 +0100 2850246 http://www.medworm.com/index.php?rid=2850254&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05066%26cr_yr DESCRIPTION (provided by applicant): Flow cytometry (FCM) is a versatile multicolor technology for multi-parameter analysis which is unparalleled in its facility and capacity for bioassay multiplexing, the performance of multiple assays in a single sample volume. By increasing multi-sample throughput 20-fold, recently developed HyperCyt technology has overcome historic barriers to application of this and other powerful features of FCM in the high throughput screening (HTS) drug and probe discovery enterprise. Specific aims here address the long term goal of a robust FCM platform capable of extended, fully automated operation in the HTS environment. In Aim 1 the HyperCyt platform will be modified to process four 384-well quadrants of a 1536-well plate in parallel, using four sampling probes... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850254 Tue, 01 Sep 2009 17:00:00 +0100 2850254 http://www.medworm.com/index.php?rid=2850253&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05109%26cr_yr DESCRIPTION (provided by applicant): The ability to sequence a human genome with high accuracy and speed, and at low cost, is critical to the emerging field of personalized medicine. In response to this demand, our research team developed the novel method of DNA sequencing-by-synthesis (SBS) on a solid surface, which has been recognized as a successful new paradigm for deciphering DNA sequences. In this grant application, we will use molecular engineering approaches to take our successful SBS strategy to the next level by adapting it for single molecule sequencing using fluorescent reversible terminators. Template DNA molecules will be attached to a glass surface modified by covalent attachment of PEG-primers under conditions where as many as 1 billion clearly separated single molecules ar... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850253 Tue, 01 Sep 2009 17:00:00 +0100 2850253 http://www.medworm.com/index.php?rid=2850252&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05090%26cr_yr DESCRIPTION (provided by applicant): There are extensive ongoing efforts to develop high-throughput low-cost DNA sequencing with the eventual goal of $1000 for an individual genome. Some approaches use physical properties to identify the bases, but most methods use fluorescent probes as extrinsic labels. Such extrinsic probes are needed because of the low quantum yield of the DNA bases. We propose to develop metallic nanostructures which will increase the brightness of intrinsic nucleotide emission, decrease the background, and efficiently direct the emission toward a detector. Additionally, these structures will provide spectral separation for base calling. These effects are possible due to through-space near-field interactions of the bases with electron clouds in the metal, which are cal... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850252 Tue, 01 Sep 2009 17:00:00 +0100 2850252 http://www.medworm.com/index.php?rid=2850251&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05095%26cr_yr DESCRIPTION (provided by applicant): Our aim is to develop a DNA sequencing device based upon the blockade of ionic current in the transmembrane protein pore a-hemolysin (aHL). Compared to other proposed nanopore-based approaches, the protein pore current blockade (PPCB) method is arguably the simplest, both conceptually and technologically, but recently has been passed over in favor of more complex methods. Recent electronic readout and bilayer lipid membrane advances by the proposers have greatly alleviated prior signal-to-noise ratio and robustness issues. New experimental data and an accurate Stochastic Model for DNA Motion (SMDM) within a-HL now indicate threshold feasibility for sequencing by the PPCB method. Inspection of calculated SMDM responses to known input DNA sequences shows ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850251 Tue, 01 Sep 2009 17:00:00 +0100 2850251 http://www.medworm.com/index.php?rid=2850250&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05149%26cr_yr DESCRIPTION (provided by applicant): Sequence-specific transcription factors (TFs) regulate gene expression through their interactions with DNA sequences in the genome. These interactions control critical steps in development and responses to environmental stimuli, and their dysfunction can contribute to the progression of various diseases. In this project, as our model system we will examine primary human skeletal muscle myoblasts differentiating into myotubes. In metazoans, regulatory motifs tend to co-occur within stretches of noncoding sequence referred to as cis regulatory modules (CRMs) that regulate expression of the nearby gene(s). In this project, we will assess the physical and functional interactions of CRMs according to their interactions with their immediately adjacent target ... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850250 Tue, 01 Sep 2009 17:00:00 +0100 2850250 http://www.medworm.com/index.php?rid=2850249&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DF32HG05176%26cr_yr DESCRIPTION (provided by applicant): What is the genomic architecture of a quantitative trait? Despite substantial effort to answer this question in humans and model organisms, we remain far from understanding how many genes, gene-gene interactions, and gene-environment interactions underlie most polygenic traits, such as human disease. Global gene expression studies, which treat each transcript in the genome as a quantitative trait, have provided crucial insights into the genetic basis of trait differences between individuals. In particular, a cross of the BY lab strain and the RM wine strain of the budding yeast Saccharomyces cerevisiae that was done by the lab of Leonid Kruglyak, where I am presently a postdoctoral fellow, has illuminated the genetic complexity underlying expression dif... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850249 Tue, 01 Sep 2009 17:00:00 +0100 2850249 http://www.medworm.com/index.php?rid=2850248&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG05097%26cr_yr DESCRIPTION (provided by applicant): Capitalizing on our group's experience on single molecule enzymology, we propose a novel method for multiplex sequencing of individual nucleic acid molecules using a sequencing-by-synthesis approach that employs fluorogenic nucleotide substrates. Upon incorporation of a non-fluorescent, terminal phosphate-labeled nucleotide substrate by a polymerase, a fluorogenic polyphosphate molecule is released, and subject to fast enzymatic digestion, yielding a single fluorophore, the color of which is dependent on the identity of the incorporated nucleotide. To facilitate single molecule fluorescence detection, an individual nucleic acid molecule is confined in a sealed sub-femtoliter nanoreactor, in which the sequencing reaction takes place continuously. Using c... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850248 Tue, 01 Sep 2009 17:00:00 +0100 2850248 http://www.medworm.com/index.php?rid=2850247&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05100%26cr_yr DESCRIPTION (provided by applicant): The goal of this project is to test the feasibility of a new single-molecule DNA sequencing strategy that combines solid-state nanopores with mass spectrometry. The idea is to sequentially cleave each nucleotide or base from a DNA molecule as it transits a nanopore, then identify each one by determining its mass-to-charge ratio in a mass spectrometer. Identifying the bases of a translocating DNA molecule by mass spectrometry is appealing because: 1) It is an extremely sensitive technique that can easily distinguish the four DNA bases from their significantly different masses; 2) Modern ion detectors can detect the impact of single ions with a quantum efficiency approaching unity; 3) Those same ion detectors register ions as ~ 20 ns electrical pulses, of... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850247 Tue, 01 Sep 2009 17:00:00 +0100 2850247 http://www.medworm.com/index.php?rid=2850255&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG05107%26cr_yr DESCRIPTION (provided by applicant): Culture-independent metagenomic studies are essential for understanding our relationship with the organisms comprising the human microbiome, defining optimal microbial composition to maintain health, and devising selective treatment strategies to eliminate pathogens without harming beneficial species. To use metagenomic data effectively, raw DNA sequence data (reads) must be processed computationally (assembled) to obtain longer sequences (contigs). Existing software packages for this purpose are quite inefficient when presented with large, taxonomically diverse samples, resulting in considerable wastage of reads that cannot be assembled. Efforts to maximize assembly efficiency by relaxing stringency can lead to inappropriate joining of sequences from u... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850255 Mon, 24 Aug 2009 17:00:00 +0100 2850255 http://www.medworm.com/index.php?rid=2850261&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR03HG05121%26cr_yr DESCRIPTION (provided by applicant): MLPA (multiplex ligation-dependent probe amplification) and MS-MLPA (methylation- specific MLPA) have rapidly evolved as promising methods for copy number variation and DNA methylation studies. The goal of this proposal is to continue the development of software for genomic and methylation-specific MLPA probe design. We have developed H-MAPD, a web based probe design tool that automates the generation and selection of probes for human genomic MLPA. We propose to expand the software in two ways: 1) To extend H-MAPD to support mouse and rat genomic MLPA probe design. 2) To develop a separate tool to handle MS-MLPA probe design. One major obstacle for MLPA and MS-MLPA is the difficulty in probe design. By automating the tedious probe design process, our so... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850261 Mon, 17 Aug 2009 17:00:00 +0100 2850261 http://www.medworm.com/index.php?rid=2850260&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG04842%26cr_yr DESCRIPTION (provided by applicant): A number of applications of nanometer scale pores have emerged recently in biotechnology inspired partly by their function in the biological context. This proposal relates to an exploratory method for sequencing DNA and other linear polyelectrolytes of biological significance by driving them through a single nanopore using an electric field. Analogous field mediated transfer across nanopores is believed to be part of the normal molecular level machinery of eukaryotic cells. A fair amount of experimental data has accumulated since the landmark 1996 paper by Kasianowicz, Brandin, Branton and Deamer [Proc. Natl. Acad. Sci. 93, 13770 - 13773 (1996)]. demonstrating the possibility of detecting the passage of individual molecules through a nanopore by observi... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850260 Mon, 17 Aug 2009 17:00:00 +0100 2850260 http://www.medworm.com/index.php?rid=2850259&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR01HG04852%26cr_yr DESCRIPTION (provided by applicant): Metagenomics is a new scientific discipline that has developed in the last several years. It is both a set of research techniques, comprising many related approaches and methods, and a research field. As a scientific field, metagenomics attempts to resolve four tiers of questions: 1) what micro-organisms are present in a particular complex microbiome, such as human gut? 2) in what proportions? 3) what they are doing? and 4) how will they react to environmental changes, such as a change in diet? Currently, the approach to answer these questions has been one of brute force shotgun sequencing and 16S sequence surveys. However these technologies can only hint as to which kinds of bacteria are present, and the information provided tends to be biased to the c... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850259 Mon, 17 Aug 2009 17:00:00 +0100 2850259 http://www.medworm.com/index.php?rid=2850258&cid=s_37143_50_f&fid=37143&url=http%3A%2F%2Fwww.genome.gov%2Fpage.cfm%3FpageID%3D17015407%26display_abstract%3Don%26query_grantid%3DR21HG04895%26cr_yr DESCRIPTION (provided by applicant): Microbial communities play a significant role in maintaining human health. However, understanding the complex relationship between a human host and its resident microbial flora presents a considerable challenge. For example, the total number of microbial cells residing in an individual is estimated to far outnumber the individual's somatic cells. Unfortunately, the identity, distribution, and functional significance of the majority of these microorganisms are unknown. The situation is further complicated by the inability to culture many of these organisms in the laboratory. Here, we propose the development of a microfabricated device that enables the parallel culturing and characterization of individual members of a microbial community. Single cells wil... NHGRI Active Grants funding http://www.medworm.com/rss/comments.php?id=2850258 Mon, 17 Aug 2009 17:00:00 +0100 2850258