BMC Medical Genomics via MedWorm.com

mspecLINE: bridging knowledge of human disease with the proteome

BMC Medical Genomics — Wed, 10 Mar 2010 00:00:00 +0100

Conclusions: Although mspecLINE applies an information retrieval technique to theMEDLINE database, it is distinct from previous MEDLINE query tools inthat it combines the knowledge expressed in scientific literature withempirical proteomics data. The tool provides valuable informationabout candidate protein targets to researchers studying human diseaseand is freely available on a public web server. (Source: BMC Medical Genomics)

Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies

BMC Medical Genomics — Mon, 08 Mar 2010 00:00:00 +0100

Conclusions: This study demonstrates, for the first time, that the expression profiles of childhood leukemia are largely unique, with limited similarities to transcriptional programs active in normal hematopoietic cells, non-hematopoietic normal tissues or the most common forms of human cancer. In addition to providing important pathogenetic insights, these findings should facilitate the identification of candidate genes or transcriptional programs that can be used as unique targets in leukemia. (Source: BMC Medical Genomics)

Genome-wide methylation and expression profiling identifies promoter characteristics affecting demethylation-induced gene up-regulation in melanoma.

BMC Medical Genomics — Tue, 09 Feb 2010 00:00:00 +0100

Conclusions: Clinically, elucidating the patterns of action of decitabine could aid in predicting the likelihood of up-regulating epigenetically silenced tumor suppressor genes and others from pathways involved with tumor biology. As a first step toward an eventual translational application, we build a classifier to predict gene up-regulation based on promoter methylation and CpG content, which achieves a performance of 0.74 AUC. (Source: BMC Medical Genomics)

Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects

BMC Medical Genomics — Wed, 27 Jan 2010 00:00:00 +0100

Background: Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP) and Triglyceride (TG) (LAT) vs High ASP and TG (HAT). Subcutaneous (SC) and omental (OM) adipose tissues (n=21) were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined. Methods: LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1). ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p (Source: BMC Medical Genomics)

Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus

BMC Medical Genomics — Tue, 26 Jan 2010 00:00:00 +0100

Conclusions: Taken as a whole, the data obtained from this global gene profiling experiment have provided a detailed characterization of Graffi virus induced erythro- and megakaryoblastic leukaemias with many genes reported specific to the transcriptome of these leukaemias for the first time. (Source: BMC Medical Genomics)

Prioritizing genes for follow-up from genome wide association studies using information on gene expression in tissues relevant for type 2 diabetes mellitus

BMC Medical Genomics — Thu, 31 Dec 2009 00:00:00 +0100

Conclusions: Utilizing of gene expression profiling data from different tissues of individuals with or without T2DM or animal models thereof is a powerful tool for prioritizing SNPs from WGAS for further replication studies. (Source: BMC Medical Genomics)

Identifying significant genetic regulatory networks in the prostate cancer from microarray data based on transcription factor analysis and conditional independency

BMC Medical Genomics — Mon, 21 Dec 2009 00:00:00 +0100

Conclusions: We provide a computational framework to reconstruct the genetic regulatory network from the microarray data using biological knowledge and constraint-based inferences. Our method is helpful in verifying possible interaction relations in gene regulatory networks and filtering out incorrect relations inferred by imperfect methods. We predicted not only individual gene related to cancer but also discovered significant gene regulation networks. Our method is also validated in several enriched published papers and databases and the significant gene regulatory networks perform critical biological functions and processes including cell adhesion molecules, androgen and estrogen metabolism, smooth muscle contraction, and GO-annotated processes. Those significant gene regulations and th...

A taxonomy of epithelial human cancer and their metastases

BMC Medical Genomics — Thu, 17 Dec 2009 00:00:00 +0100

Conclusion: Our molecular taxonomy of epithelial human cancer indicates surprising correlations over tissues. This may have a significant impact on the classification of many cancer sites and may guide pathologists, both in research and daily practice. Moreover, these results based on unsupervised analysis yielded a signature predictive of clinical outcome in breast cancer. Additionally, we hypothesize that metastases from gastrointestinal origin either remember their tissue of origin or adapt to the tissue of destination. More specifically, colon metastases in the liver show strong evidence for such a bimodal tissue specific profile. (Source: BMC Medical Genomics)

A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival

BMC Medical Genomics — Tue, 15 Dec 2009 00:00:00 +0100

Conclusions: Present results provide novel evidence on the molecular basis of tumor growth inhibition mediated by mastic oil and set a rational basis for application of genomics and bioinformatic methodologies in the screening of natural compounds with potential cancer chemopreventive activities. (Source: BMC Medical Genomics)

DNA microarray profiling of genes differentially regulated by the histone deacetylase inhibitors vorinostat and LBH589 in colon cancer cell lines

BMC Medical Genomics — Mon, 30 Nov 2009 00:00:00 +0100

Conclusions: This study identified HDACi-induced alterations in critical genes involved in nucleotide metabolism, angiogenesis, mitosis and cell survival which may represent potential intervention points for novel therapeutic combinations in colon cancer. This information will assist in the identification of novel pathways and targets that are modulated by HDACi, providing much-needed information on HDACi mechanism of action and providing rationale for novel drug combination partners. We identified a core signature of 11 genes which were modulated by both vorinostat and LBH589 in a similar manner in both cell lines. These core genes will assist in the development and validation of a common gene set which may represent a molecular signature of HDAC inhibition in colon cancer. (Source: BMC ...

A metadata approach for clinical data management in translational genomics studies in breast cancer

BMC Medical Genomics — Mon, 30 Nov 2009 00:00:00 +0100

Conclusions: We describe a metadata approach for managing similarities and differences in clinical datasets in a standardized way that uses Common Data Elements (CDEs). We apply and evaluate the approach by integrating the five different clinical datasets of METABRIC. (Source: BMC Medical Genomics)

Accurate molecular classification of cancer using simple rules

BMC Medical Genomics — Fri, 30 Oct 2009 00:00:00 +0100

Conclusions: In cancerous gene expression datasets, a small number of genes, even one or two if selected correctly, is capable of achieving an ideal cancer classification effect. This finding also means that very simple rules may perform well for cancerous class prediction. (Source: BMC Medical Genomics)

Exon expression in lymphoblastoid cell lines from subjects with schizophrenia before and after glucose deprivation

BMC Medical Genomics — Mon, 21 Sep 2009 23:00:00 +0100

Conclusion: Experimental manipulation of cells lines from subjects with schizophrenia may be a useful approach to explore stress related gene expression alterations in schizophrenia and to identify SNP variants associated with gene expression. (Source: BMC Medical Genomics)

Transcriptional profiling differences for articular cartilage and repair tissue in equine joint surface lesions

BMC Medical Genomics — Sun, 13 Sep 2009 23:00:00 +0100

Conclusions: The magnitude of divergence in transcriptional profiles between normal chondrocytes and the cells that populate repair tissue reveal substantial functional differences between these two cell populations. At the four-month postoperative time point, the relative deficiency within repair tissue of gene transcripts which typically define articular cartilage indicate that while cells occupying the lesion might be of mesenchymal origin, they have not recapitulated differentiation to the chondrogenic phenotype of normal articular chondrocytes. (Source: BMC Medical Genomics)

Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells.

BMC Medical Genomics — Wed, 09 Sep 2009 23:00:00 +0100

Conclusions: Human trabecular meshwork cells in culture express all known GRalpha and GRbeta translational isoforms, and GCs with similar potency but subtly different chemical structure are capable of regulating common and unique gene subsets and presumably biologic responses in these cells. These GC structure-dependent effects appear to be TM cell-lineage dependent. (Source: BMC Medical Genomics)

Evaluation of a new high-dimensional miRNA profiling platform

BMC Medical Genomics — Wed, 26 Aug 2009 23:00:00 +0100

Conclusions: These results indicate that very small amounts of starting material are sufficient to allow sensitive miRNA profiling using the Illumina miRNA high-dimensional platform. Nonlinear biases were observed between replicates, indicating the need for abundance-dependent normalization. Overall, the performance characteristics of the Illumina miRNA profiling system were excellent. (Source: BMC Medical Genomics)

Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke.

BMC Medical Genomics — Thu, 20 Aug 2009 23:00:00 +0100

Conclusion: Global transcriptional analysis identified a set of genes responding to MTS exposure in mouse lung. These genes returned to basal levels following smoking cessation, providing evidence to support the benefits of smoking cessation. Detailed analyses were undertaken for IL-6 and its associated pathways. Our results provide further insight into the role of these pathways in lung injury and inflammation induced by MTS. (Source: BMC Medical Genomics)

Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells

BMC Medical Genomics — Wed, 19 Aug 2009 23:00:00 +0100

Conclusions: Our results suggest that inhibitors of MAO-A, already in clinical use to treat depression, may have potential application as therapeutic PCa drugs by inhibiting oncogenic pathway activity and promoting differentiation. (Source: BMC Medical Genomics)

MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes

BMC Medical Genomics — Mon, 17 Aug 2009 23:00:00 +0100

Background: MicroRNAs (miRNAs) are non-coding RNA molecules involved in post-transcriptional control of gene expression of a wide number of genes, including those involved in glucose homeostasis. Type 2 diabetes (T2D) is characterized by hyperglycaemia and defects in insulin secretion and action at target tissues. We sought to establish differences in global miRNA expression in two insulin-target tissues from inbred rats of spontaneously diabetic and normoglycaemic strains. Methods: We used a miRNA microarray platform to measure global miRNA expression in two insulin-target tissues: liver and adipose tissue from inbred rats of spontaneously diabetic (Goto-Kakizaki [GK]) and normoglycaemic (Brown-Norway [BN]) strains which are extensively used in genetic studies of T2D. MiRNA data were inte...

A gene expression profile for detection of sufficient tumour cells in breast tumour tissue: microarray diagnosis eligibility

BMC Medical Genomics — Tue, 11 Aug 2009 23:00:00 +0100

Conclusion: The developed 13-gene profile provides an objective tool for assessment whether a breast cancer sample contains sufficient tumour cells for microarray diagnostics. It will improve the efficiency and throughput for diagnostic gene expression profiling as it no longer requires histopathological analysis for initial tumour percentage scoring. Such profile will also be very use useful for assessment of tumour cell percentage in biopsies where conventional histopathology is difficult, such as fine needle aspirates. (Source: BMC Medical Genomics)

Integrated microarray and multiplex cytokine analyses of Kaposi's Sarcoma Associated Herpesvirus viral FLICE Inhibitory Protein K13 affected genes and cytokines in human blood vascular endothelial cells

BMC Medical Genomics — Wed, 05 Aug 2009 23:00:00 +0100

Conclusions: While K13 may account for change in the expression of a majority of genes observed following KSHV infection, it is not sufficient for inducing lymphatic reprogramming of blood vascular endothelial cells. (Source: BMC Medical Genomics)

Identification and Validation of Suitable Endogenous Reference Genes for Gene Expression Studies in Human Peripheral Blood

BMC Medical Genomics — Tue, 04 Aug 2009 23:00:00 +0100

Conclusion: The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease. (Source: BMC Medical Genomics)

Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data

BMC Medical Genomics — Mon, 03 Aug 2009 23:00:00 +0100

Conclusion: The results of this study suggest that prostate tumor progression is associated with the suppression of integrin-based cell adhesion. Suppression of integrin expression driven by integrin-mediated cell death may lead to increased cell proliferation and motility and increase tumor malignancy. (Source: BMC Medical Genomics)

Host sequence motifs shared by HIV predict response to antiretroviral therapy

BMC Medical Genomics — Wed, 22 Jul 2009 23:00:00 +0100

Conclusions: HIV sequence mutates in a way that preserves peptide sequence motifs that are also found in the human proteome. The presence and absence of such motifs at specific regions of the HIV sequence is highly predictive of response to therapy. These motifs are well established in bioinformatics databases and do not require identification via in-vitro mutation experiments. (Source: BMC Medical Genomics)

An assessment of the portability of ancestry informative markers between human populations

BMC Medical Genomics — Sun, 19 Jul 2009 23:00:00 +0100

Conclusion: We find that BritAIMs are generally not useful to distinguish between continental groups or within continental groups distantly related to Britain. Moreover, our analyses suggest that the portability of AIMs across geographical scales (e.g. between Europe and Britain) can be limited and should therefore be taken into consideration in the design and interpretation of genetic association studies. (Source: BMC Medical Genomics)

Novel transcriptional profile in wrist muscles from cerebral palsy patients

BMC Medical Genomics — Mon, 13 Jul 2009 23:00:00 +0100

Conclusions: This is the first transcriptional profile performed on spastic muscle of CP patients and these adaptations were not characteristic of those observed in other disease states such as Duchenne muscular dystrophy and immobilization-induced muscle atrophy. Further research is required to understand the mechanism of muscle adaptation to this upper motor neuron lesion that could lead to the development of innovative therapies. (Source: BMC Medical Genomics)

Finding exclusively deleted or amplified genomic areas in lung adenocarcinomas using a novel chromosomal pattern analysis

BMC Medical Genomics — Mon, 13 Jul 2009 23:00:00 +0100

Conclusion: Analyzing jointly deletions and amplifications through our latent class model analysis allows highlighting specific genomic areas with exclusively amplified or deleted recurrent CNAs which are good candidate for harboring oncogenes or tumor suppressor genes. (Source: BMC Medical Genomics)

Genomic profiling distinguishes familial multiple and sporadic multiple meningiomas

BMC Medical Genomics — Wed, 08 Jul 2009 23:00:00 +0100

Conclusions: Genomic profiling can provide an unbiased adjunct to traditional meningioma classification and provides a basis for exploring the different genetic underpinnings of tumor initiation and progression. Most importantly, the striking difference observed between sporadic and familial multiple meningiomas indicates that genomic profiling can provide valuable information for differential diagnosis of subjects with multiple meningiomas and for considering the risk for tumor occurrence in their family members. (Source: BMC Medical Genomics)

Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitus

BMC Medical Genomics — Wed, 08 Jul 2009 23:00:00 +0100

Conclusions: Combining transcriptomics in animal models and comparative genomics provides important information to improve functional annotations of disease susceptibility loci in humans and experimental support for testing candidate genes in human genetics. (Source: BMC Medical Genomics)

The Gene expression Grade Index: a potential predictor of relapse for endocrine-treated breast cancer patients in the BIG 1-98 trial

BMC Medical Genomics — Wed, 01 Jul 2009 23:00:00 +0100

Conclusions: This analysis supports the GGI as a good predictor of relapse for ER-positive patients, even among patients who receive L. Validation of these results, in a larger series from BIG 1-98, is planned using the simplified GGI represented by a smaller set of genes and tested by qRT-PCR on paraffin-embedded tissues. (Source: BMC Medical Genomics)

NMD inhibition fails to identify tumour suppressor genes in microsatellite stable gastric cancer cell lines

BMC Medical Genomics — Sun, 28 Jun 2009 23:00:00 +0100

Conclusions: Although UPF1 was substantially repressed, thus resulting in the inhibition of the NMD system, we did not find genes inactivated by nonsense mutations. Our results show that the GINI strategy leads to a high number of false positives. (Source: BMC Medical Genomics)

A Gene Signature for Post-Infectious Chronic Fatigue Syndrome

BMC Medical Genomics — Wed, 24 Jun 2009 23:00:00 +0100

Conclusions: Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for differential diagnosis and treatment. (Source: BMC Medical Genomics)

Gene expression profiling identifies activated growth factor signaling in poor prognosis (Luminal-B) estrogen receptor positive breast cancer

BMC Medical Genomics — Tue, 23 Jun 2009 23:00:00 +0100

Conclusions: These data demonstrate that activation of GF signaling pathways, independent of HER2 over-expression, could be contributing to the poor prognosis of the luminal-B ER+ BC subtype. (Source: BMC Medical Genomics)

MLL rearrangements in pediatric acute lymphoblastic and myeloblastic leukemias: MLL specific and lineage specific signatures

BMC Medical Genomics — Mon, 22 Jun 2009 23:00:00 +0100

Conclusions: Our study demonstrated that a small subset of genes identifies MLL-specific rearrangements and clearly separates acute leukemia samples according to lineage origin. The subset included well-known genes and newly discovered markers that identified ALL and AML subgroups, with and without MLL rearrangements. (Source: BMC Medical Genomics)

Identification and analysis of miRNAs in human breast cancer and teratoma samples using deep sequencing

BMC Medical Genomics — Tue, 09 Jun 2009 04:00:00 +0100

Conclusions: Pyrosequencing of small RNAs, together with a computational pipeline, can be used to identify miRNAs in tumor and other tissues. Measures of miRNA end variability may in the future be incorporated into the discovery pipeline as a discriminatory feature. Breast cancer samples show a distinct miRNA expression profile compared to normal adjacent breast. (Source: BMC Medical Genomics)

Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer

BMC Medical Genomics — Mon, 08 Jun 2009 04:00:00 +0100

Conclusions: Selective epigenetic disruption of distinct biological pathways was observed during development of platinum resistance in ovarian cancer. Integrated analysis of DNA methylation and gene expression may allow for the identification of new therapeutic targets and/or biomarkers prognostic of disease response. Finally, our results suggest that epigenetic therapies may facilitate the prevention or reversal of transcriptional repression responsible for chemoresistance and the restoration of sensitivity to platinum-based chemotherapeutics. (Source: BMC Medical Genomics)

A longitudinal study of gene expression in healthy individuals

BMC Medical Genomics — Sun, 07 Jun 2009 04:00:00 +0100

Conclusions: This study defines the range and variability of gene expression in healthy men and women over a six-month period. These parameters can be used to estimate the number of subjects needed to observe significant differences from normal gene expression in clinical studies. A set of genes that varied by gender was also identified as were a set of genes with elevated expression in a subject with iron deficiency anemia and another subject being treated for lung cancer. (Source: BMC Medical Genomics)

Genomic profiling identifies common HPV-associated chromosomal alterations in squamous cell carcinomas of cervix and head and neck

BMC Medical Genomics — Mon, 01 Jun 2009 04:00:00 +0100

Conclusions: In this study hrHPV-specific, organ-specific, and pan-SCC chromosomal alterations were identified. The existence of hrHPV-specific alterations in SCCs of different anatomical origin suggests that these alterations are crucial for hrHPV-mediated carcinogenesis. (Source: BMC Medical Genomics)

Identification of gene co-regulatory modules and associated cis-elements involved in degenerative heart disease

BMC Medical Genomics — Thu, 28 May 2009 04:00:00 +0100

Conclusion: We identified patterns comprised of putative cis-regulatory motifs enriched in the upstream promoter sequence of genes that undergo similar changes in expression secondary to cardiomyopathies of various etiologies. Our analysis is a first step towards understanding transcription factor networks that are active in regulating gene expression during degenerative heart disease. (Source: BMC Medical Genomics)

Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer

BMC Medical Genomics — Wed, 27 May 2009 04:00:00 +0100

Conclusion: Our results demonstrate that hypermethylation rather than hypomethylation of 3.3-kb repeats is the predominant event in HPV-associated cervical cancer and provide new insight into the epigenetic changes of repetitive DNA elements in carcinogenesis. (Source: BMC Medical Genomics)

The A's, G's, C's, and T's of Health Disparities

BMC Medical Genomics — Fri, 22 May 2009 04:00:00 +0100

In order to eliminate health disparities in the United States, more efforts are needed to address the breadth of social issues directly contributing to the healthy divide observed across racial and ethnic groups. Socioeconomic status, education, and, very generally, the environment are intimately linked to health outcomes. However, with the tremendous advances in technology and increased investigation into human genetic variation, genomics is poised to play a valuable role in bolstering efforts to find new treatments and preventions for chronic conditions and diseases that disparately affect certain groups. Promising studies focused on understanding the genetic underpinnings of diseases such as prostate cancer or beta-blocker treatments for heart failure are illustrative of the positive co...

Prediction of HIV-1 virus-host protein interactions using virus and host sequence motifs

BMC Medical Genomics — Mon, 18 May 2009 04:00:00 +0100

Conclusions: A list of host proteins highly enriched with those targeted by HIV-1 proteins can be obtained by searching for host protein motifs along virus protein sequences. The resulting set of host proteins predicted to be targeted by virus proteins will become more accurate with better annotations of motifs and domains. Nevertheless, our study validates the role of linear binding motifs shared by virus and host proteins as an important part of the crosstalk between virus and host. (Source: BMC Medical Genomics)

Similar gene expression profiles of sporadic, PGL2-, and SDHD-linked paragangliomas suggest a common pathway to tumorigenesis

BMC Medical Genomics — Mon, 11 May 2009 04:00:00 +0100

Conclusions: The similarity in gene-expression profiles suggests that PGL2, like SDHD, is involved in the functionality of the SDH complex, and that tumor formation in these subgroups involves the same pathways as in SDH linked paragangliomas. We were not able to clarify the exact identity of PGL2 on 11q13. The lack of differential gene-expression of chromosome 11 genes might indicate that chromosome 11 loss, as demonstrated in SDHD-linked paragangliomas, is an important feature in the formation of paragangliomas regardless of their genetic background. (Source: BMC Medical Genomics)

Data integration from two microarray platforms identifies bi-allelic genetic inactivation of RIC8A in a breast cancer cell line

BMC Medical Genomics — Mon, 11 May 2009 04:00:00 +0100

Conclusions: We demonstrate a data integration strategy leading to the identification of RIC8A as a gene undergoing a classical double-hit genetic inactivation in a breast cancer cell line, as well as in vivo evidence of loss of RIC8A expression in a subgroup of aggressive TP53 mutant breast cancers. (Source: BMC Medical Genomics)

Identification of microbial DNA in human cancer

BMC Medical Genomics — Fri, 08 May 2009 04:00:00 +0100

Conclusions: DK-MICROBE can identify previously unknown infectious agents in human tumors, and is now available for further applications for the identification of pathogen DNA in human cancer and other diseases. (Source: BMC Medical Genomics)

High-resolution analysis of copy number alterations and associated expression changes in ovarian tumors

BMC Medical Genomics — Wed, 06 May 2009 04:00:00 +0100

Conclusions: These analyses provide detailed views of ovarian cancer genomic changes and highlight the benefits of using multiple reference sample types for the evaluation of CNA-specific expression changes. (Source: BMC Medical Genomics)

Development of a fingerprinting panel using medically relevant polymorphisms

BMC Medical Genomics — Mon, 20 Apr 2009 04:00:00 +0100

Conclusions: The polymorphisms in this panel are currently represented on a number of common genotyping platforms making QA/QC flexible enough to accommodate a large number of studies. In addition, this panel can serve as a resource for investigators who are interested in the effects of disease in a population, particularly for common diseases. (Source: BMC Medical Genomics)

Complexity in the Genetic Architecture of Leukoaraiosis in Hypertensive Sibships from the GENOA Study

BMC Medical Genomics — Tue, 07 Apr 2009 04:00:00 +0100

Conclusions: These results indicate that the genetic architecture of leukoaraiosis is complex, yet predictive, when the contributions of SNP main effects are considered in combination with effects of SNP interactions with other genes and covariates. (Source: BMC Medical Genomics)

Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis

BMC Medical Genomics — Wed, 25 Mar 2009 04:00:00 +0100

Conclusions: Target prediction programs and expression profiling techniques do not yet adequately represent the complexity of miRNA-mediated gene repression, and new methods may be required to better elucidate these pathways. Our data suggest the physiologic impact of miRNAs on cellular transcription results from a multifaceted network of miRNA and mRNA relationships, working together in an interconnected system and in context of hundreds of RNA species. The methods described here for comparative analysis of cellular miRNA and mRNA will be useful for understanding genome wide regulatory responsiveness and refining miRNA predictive algorithms. (Source: BMC Medical Genomics)

Distinct gene subsets in pterygia formation and recurrence: dissecting complex biological phenomenon using genome wide expression data

BMC Medical Genomics — Tue, 10 Mar 2009 04:00:00 +0100

Conclusions: Aberrant wound healing is therefore a key process in this disease, and strategies in wound remodeling may be appropriate in halting pterygium or its recurrence. For patients demonstrating a profile of 'recurrence', it may be necessary to manage as a poorer prognostic case and perhaps, more adjunctive treatment after resection of the primary lesion. (Source: BMC Medical Genomics)

Impact of sample acquisition and linear amplification on gene expression profiling of lung adenocarcinoma: laser capture micro-dissection cell-sampling versus bulk tissue-sampling

BMC Medical Genomics — Mon, 09 Mar 2009 04:00:00 +0100

Conclusions: LCM-coupled microarray expression profiling was shown to uniquely identify a large number of differentially expressed probesets not otherwise found using bulk tissue sampling. The information gain realized from the LCM sampling was limited to differential analysis, as the absolute expression values obtained for some probesets using this study's protocol were biased during the second round of amplification. Consequently, LCM may enable investigators to obtain additional information in microarray studies not easily found using bulk tissue samples, but it is of critical importance that potential amplification biases are controlled for. (Source: BMC Medical Genomics)

Impaired immune function in Gulf War Illness.

BMC Medical Genomics — Thu, 05 Mar 2009 05:00:00 +0100

Conclusions: GWI patients demonstrated impaired immune function as demonstrated by decreased NK cytotoxicity and altered gene expression associated with NK cell function. Pro-inflammatory cytokines, T-cell ratios, and dysregulated mediators of the stress response (including salivary cortisol) were also altered in GWI cases compared to control subjects. An interesting and potentially important observation was that the exercise challenge augments these differences, with the most significant effects observed immediately after the stressor, possibly implicating some block in the NK and CD8 T-cells ability to respond to "stress-mediated activation". This has positive implications for the development of laboratory diagnostic tests for this syndrome and provides a paradigm for exploration of the ...

Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour

BMC Medical Genomics — Tue, 03 Mar 2009 05:00:00 +0100

Conclusion: The findings highlight the usefulness of combining gene expression patterns and epigenetic data to identify tumour biomarkers, and suggest that NDRG2 silencing might bear influence on tumour invasiveness, being associated with a more advanced stage. (Source: BMC Medical Genomics)

Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment

BMC Medical Genomics — Mon, 23 Feb 2009 05:00:00 +0100

Conclusion: Genome-level transcriptional profiling from childhood onset rheumatic diseases suggested complex interactions in two arms of the immune system in both diseases. The disease associated networks showed scale-free network patterns similar to those reported in normal physiology. We postulate that these features have important implications for therapy as such networks are relatively resistant to perturbation. (Source: BMC Medical Genomics)

Disease-Associated Pathophysiologic Structures in Pediatric Rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment

BMC Medical Genomics — Mon, 23 Feb 2009 05:00:00 +0100

Conclusions: Genome-level transcriptional profiling from childhood onset rheumatic diseases suggested complex interactions in two arms of the immune system in both diseases. The disease associated networks showed scale-free network patterns similar to those reported in normal physiology. We postulate that these features have important implications for therapy as such networks are relatively resistant to perturbation. (Source: BMC Medical Genomics)

High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays

BMC Medical Genomics — Thu, 19 Feb 2009 05:00:00 +0100

Conclusions: MIP technology can be used to generate high quality CN and genotype data in FFPE as well as fresh frozen samples. (Source: BMC Medical Genomics)

Diurnal variation of the human adipose transcriptome and the link to metabolic disease

BMC Medical Genomics — Mon, 09 Feb 2009 05:00:00 +0100

Conclusion: Diurnal rhythm plays an important role in the physiology and regulation of energy metabolism in the adipose tissue and should be considered in the selection of novel targets for the treatment of obesity and other metabolic disorders. (Source: BMC Medical Genomics)

Muscle Research and Gene Ontology: New standards for improved data integration.

BMC Medical Genomics — Thu, 29 Jan 2009 05:00:00 +0100

Conclusions: The revised GO structure should improve the interpretation of data from high-throughput (e.g. microarray and proteomic) experiments in the area of muscle science and muscle disease. We actively encourage community feedback on, and gene product annotation with these new terms. Please visit the Muscle Community Annotation Wiki (http://wiki.geneontology.org/index.php/Muscle_Biology). (Source: BMC Medical Genomics)

Validation of previously identified serum biomarkers for breast cancer with SELDI-TOF MS: a case control study

BMC Medical Genomics — Mon, 19 Jan 2009 05:00:00 +0100

This study's aim is to validate three proteins previously reported to be discriminative between breast cancer cases and healthy controls. These proteins had been identified as a fragment of inter-alpha trypsin inhibitor H4 (4.3 kDa), C-terminal-truncated form of C3a des arginine anaphylatoxin (8.1 kDa) and C3a des arginine anaphylatoxin (8.9 kDa). Methods: Serum protein profiles of 48 breast cancer patients and 48 healthy controls were analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Differences in protein intensity between breast cancer cases and controls were measured with the Mann-Whitney U test and adjusted for confounding in a multivariate logistic regression model. Results: Four peaks, with mass-to-charge ratio (m/z) 4276, 4...

Iron behaving badly: inappropriate Iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

BMC Medical Genomics — Thu, 08 Jan 2009 05:00:00 +0100

Conclusions: Overall we argue, by synthesising a widely dispersed literature, that the role of poorly liganded iron has been rather underappreciated in the past, and that in combination with peroxide and superoxide its activity underpins the behaviour of a great many physiological processes that degrade over time. Understanding these requires an integrative, systems-level approach. (Source: BMC Medical Genomics)

Genomic selection of reference genes for real-time PCR in human myocardium

BMC Medical Genomics — Mon, 29 Dec 2008 05:00:00 +0100

Conclusions: This study used publicly available gene array data to identify a strategy for normalization involving two reference genes in combination that may have broad application for accurate and reliable normalization of RT-qPCR data in failed and non-failed human myocardium. (Source: BMC Medical Genomics)

Biological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes

BMC Medical Genomics — Thu, 18 Dec 2008 05:00:00 +0100

Conclusions: This study proposes that cell communication and cell death are major biological processes perturbed in risk of breast cancer conferred by low-penetrance variants, and defines the common omic properties, molecular interactions and possible functional effects of candidate genes and proteins. (Source: BMC Medical Genomics)

Searching for molecular markers in head and neck squamous cell carcinomas (HNSCC) by statistical and bioinformatic analysis of larynx-derived SAGE libraries

BMC Medical Genomics — Tue, 11 Nov 2008 05:00:00 +0100

Conclusions: To the best of our knowledge, this is the first study reporting SAGE data in head and neck squamous cell tumors. Statistical analysis was effective in identifying differentially expressed genes reportedly involved in cancer development. The differential expression of a subset of genes was confirmed in additional larynx carcinoma samples and in carcinomas from a distinct head and neck subsite. This result suggests the existence of potential common biomarkers for prognosis and targeted-therapy development in this heterogeneous type of tumor. (Source: BMC Medical Genomics)

Pathways affected by asbestos exposure in normal and tumour tissue of lung cancer patients

BMC Medical Genomics — Tue, 11 Nov 2008 05:00:00 +0100

Conclusions: Our results indicate alterations in protein ubiquitination related both to cancer type and asbestos. We present for the first time pathway analysis results on asbestos-associated lung cancer, providing important insight into the most relevant targets for future research. (Source: BMC Medical Genomics)

The ventro-medial prefrontal cortex: a major link between the autonomic nervous system, regulation of emotion, and stress reactivity?