http://genomemedicine.com The latest research articles published by Genome Medicine 2013-05-14T00:00:00Z {no abstract} http://genomemedicine.com/content/5/5/41 David Gurwitz Genome Medicine 2013, null:41 2013-05-14T00:00:00Z doi:10.1186/gm445 Post-genomic expression profiling <p>David Gurwitz argues that expression profiling is currently the most promising and cost-effective tool for discovery of new prognostic, diagnostic and therapeutic biomarkers.</p> /content/figures/gm445-toc.gif Genome Medicine 1756-994X ${item.volume} 41 2013-05-14T00:00:00Z XML Protein-protein interactions (PPIs) and multi-protein complexes perform central roles in the cellular systems of all living organisms. In humans, disruptions of the normal patterns of PPIs and protein complexes can be causative or indicative of a disease state. Recent developments in the biological applications of mass spectrometry (MS)-based proteomics have expanded the horizon for the application of systematic large-scale mapping of physical interactions to probe disease mechanisms. In this review, we examine the application of MS-based approaches for the experimental analysis of PPI networks and protein complexes, focusing on the different model systems (including human cells) used to study the molecular basis of common diseases such as cancer, cardiomyopathies, diabetes, microbial infections, and genetic and neurodegenerative disorders. http://genomemedicine.com/content/5/4/37 Uros Kuzmanov Andrew Emili Genome Medicine 2013, null:37 2013-04-30T00:00:00Z doi:10.1186/gm441 Disease insights from PPI <p>Kuzmanov and Emili review recent advances in protein-protein interaction studies from various model organisms, shedding light on the mechanisms and possible treatments for human disease.</p> /content/figures/gm441-toc.gif Genome Medicine 1756-994X ${item.volume} 37 2013-04-30T00:00:00Z XML Background: A DNA methylation signature has been characterized that distinguishes rheumatoid arthritis (RA) fibroblast like synoviocytes (FLS) from osteoarthritis (OA) FLS. The presence of epigenetic changes in long term cultured cells suggest that rheumatoid FLS imprinting might contribute to pathogenic behavior. To understand how differentiallymethylated genes (DMGs) might participate in the pathogenesis of RA, we evaluated the stability of the RA signature and how DMGs are enriched in specific pathways and ontology categories. Methods: To assess the RA methylation signatures the Illumina HumanMethylation450 chip was used to compare methylation levels in RA, OA and normal (NL) FLS at passage 3, 5, and 7. Then methylation frequencies at CpGs within the signature were compared between passages. To assess the enrichment of DMGs in specific pathways, DMGs were identified as genes that possess significantly differential methylated loci within their promoter regions. These sets of DMGs were then compared to pathway and ontology databases to establish enrichment in specific categories. Results: Initial studies compared passage 3, 5 and 7 FLS from RA, OA and NL. The patterns of differential methylation of each individual FLS line were very similar regardless of passage number. Using the most robust analysis, 20 out of 272 KEGG pathways and 43 out of 34,400 GO pathways were significantly altered for RA compared with OA and NL FLS. Most interestingly, we found that the KEGG ¿Rheumatoid Arthritis¿ pathway was consistently the most significantly enriched with differentially methylated loci. Additional pathways involved with innate immunity (Complement and Coagulation, Toll-like Receptors, NOD-like Receptors, and Cytosolic DNA-sensing), cell adhesion (Focal Adhesion, Cell Adhesion Molecule), and cytokines (Cytokine-cytokine Receptor). Taken together, KEGG and GO pathway analysis demonstrates non-random epigenetic imprinting of RA FLS. Conclusions: The DNA methylation patterns include anomalies in key genes implicated in the pathogenesis of RA and are stable for multiple cell passages. Persistent epigenetic alterations could contribute to the aggressive phenotype of RA synoviocytes and identify potential therapeutic targets that could modulate the pathogenic behavior http://genomemedicine.com/content/5/4/40 John Whitaker Robert Shoemaker David Boyle Josh Hillman David Anderson Wei Wang Gary Firestein Genome Medicine 2013, null:40 2013-04-30T00:00:00Z doi:10.1186/gm444 Methylome signature in rheumatoid arthritis <p>Key genes in cultured rheumatoid arthritis cells are stably differentially methylated compared to osteoarthritis or normal cells, and are potential therapeutic targets.</p> /content/figures/gm444-toc.gif Genome Medicine 1756-994X ${item.volume} 40 2013-04-30T00:00:00Z PDF Personalized genomics will only be useful for monitoring the prognosis of patients with cancer when it becomes much more cost-effective and quicker to apply. A recent study brings this closer to reality with the development of plasma-seq, a rapid, low-cost method that sequences the circulating DNA present in the peripheral blood of patients with cancer. The power of this technique is demonstrated with the examination of tumor genomes from patients with prostate cancer.See related research article: http://genomemedicine.com/content/5/4/30 http://genomemedicine.com/content/5/4/35 Caitlin Farris Jeffrey Trimarchi Genome Medicine 2013, null:35 2013-04-29T00:00:00Z doi:10.1186/gm439 Improving prostate cancer diagnosis <p>Caitlin Farris and Jeffrey Trimarchi discuss how a new non-invasive approach for personalized diagnosis of prostate cancer shows promise for the clinic, being both time- and cost-effective.</p> /content/figures/gm439-toc.gif Genome Medicine 1756-994X ${item.volume} 35 2013-04-29T00:00:00Z XML Preterm birth (delivery at less than 37 weeks of gestation) is the leading cause of infant mortality worldwide. So far, the application of animal models to understand human birth timing has not substantially revealed mechanisms that could be used to prevent prematurity. However, with amassing data implicating an important role for genetics in the timing of the onset of human labor, the use of modern genomic approaches, such as genome-wide association studies, rare variant analyses using whole-exome or genome sequencing, and family-based designs, holds enormous potential. Although some progress has been made in the search for causative genes and variants associated with preterm birth, the major genetic determinants remain to be identified. Here, we review insights from and limitations of animal models for understanding the physiology of parturition, recent human genetic and genomic studies to identify genes involved in preterm birth, and emerging areas that are likely to be informative in future investigations. Further advances in understanding fundamental mechanisms, and the development of preventative measures, will depend upon the acquisition of greater numbers of carefully phenotyped pregnancies, large-scale informatics approaches combining genomic information with information on environmental exposures, and new conceptual models for studying the interaction between the maternal and fetal genomes to personalize therapies for mothers and infants. Information emerging from these advances will help us to identify new biomarkers for earlier detection of preterm labor, develop more effective therapeutic agents, and/or promote prophylactic measures even before conception. http://genomemedicine.com/content/5/4/34 Katherine Bezold Minna Karjalainen Mikko Hallman Kari Teramo Louis Muglia Genome Medicine 2013, null:34 2013-04-29T00:00:00Z doi:10.1186/gm438 The genomics of pre-term birth Louis Muglia and colleagues review the genetics and genomics of pre-term birth and birth timing, discussing the limitations of animal models and the progress of human studies. /content/figures/gm438-toc.gif Genome Medicine 1756-994X ${item.volume} 34 2013-04-29T00:00:00Z XML Outbreaks of infection can be devastating for individuals and societies. In this review, we examine the applications of new high-throughput sequencing approaches to the identification and characterization of outbreaks, focusing on the application of whole-genome sequencing (WGS) to outbreaks of bacterial infection. We describe traditional epidemiological analysis and show how WGS can be informative at multiple steps in outbreak investigation, as evidenced by many recent studies. We conclude that high-throughput sequencing approaches can make a significant contribution to the investigation of outbreaks of bacterial infection and that the integration of WGS with epidemiological investigation, diagnostic assays and antimicrobial susceptibility testing will precipitate radical changes in clinical microbiology and infectious disease epidemiology in the near future. However, several challenges remain before WGS can be routinely used in outbreak investigation and clinical practice. http://genomemedicine.com/content/5/4/36 Esther Robinson Timothy Walker Mark Pallen Genome Medicine 2013, null:36 2013-04-29T00:00:00Z doi:10.1186/gm440 Outbreak genomics Mark Pallen and co-authors review advances in applying high-throughput sequencing approaches for outbreak investigation (focusing on bacterial infections), and discuss the implications for clinical microbiology. /content/figures/gm440-toc.gif Genome Medicine 1756-994X ${item.volume} 36 2013-04-29T00:00:00Z XML {no abstract} http://genomemedicine.com/content/5/4/38 Bartha Knoppers Adrian Thorogood Ruth Chadwick Genome Medicine 2013, null:38 2013-04-29T00:00:00Z doi:10.1186/gm442 Mulling over HUGO ethics <p>Knoppers, Thorogood and Chadwick muse over the evolution of ethical statements and policy over the course of the human genome project and beyond, marking 10 years since its completion.</p> /content/figures/gm442-toc.gif Genome Medicine 1756-994X ${item.volume} 38 2013-04-29T00:00:00Z XML A fully automated, high-throughput method was developed to profile the fatty acids of phospholipids from human plasma samples for the application in a large epidemiological sample set (n>25,000). We report here on the data obtained for the quality control materials used with the first 860 batches, as well as the validation process. The method consists of two robotic systems combined with gas chromatography (GC), performing lipid extraction, phospholipid isolation, hydrolysis and derivatisation to fatty acid methyl esters (FAME) and on-line analysis. This is the first report showing that fatty acid profiling is an achievable strategy for metabolic phenotyping in very large epidemiological and genetic studies. http://genomemedicine.com/content/5/4/39 Laura Wang Keith Summerhill Carmen Rodriguez-Canas Ian Mather Pinal Patel Michael Eiden Stephen Young Nita Forouhi Albert Koulman Genome Medicine 2013, null:39 2013-04-25T00:00:00Z doi:10.1186/gm443 High-throughput metabolic phenotyping <p>A fully automated high-throughput method provides proof-of-concept that fatty acid profiling of human plasma is achievable for metabolic phenotyping in large epidemiological and genetic studies.</p> /content/figures/gm443-toc.gif Genome Medicine 1756-994X ${item.volume} 39 2013-04-25T00:00:00Z PDF {No abstract} http://genomemedicine.com/content/5/4/31 Martin Hibberd Genome Medicine 2013, null:31 2013-04-18T00:00:00Z doi:10.1186/gm435 Microbes in health and disease - a new series Guest Editor Martin Hibberd highlights advances in genomics, metagenomics and other high-throughput approaches for studying human-microbe interactions in health and disease, and the applications for medicine. /content/figures/gm435-toc.gif Genome Medicine 1756-994X ${item.volume} 31 2013-04-18T00:00:00Z XML {no abstract} http://genomemedicine.com/content/5/4/32 John Ioannidis Muin Khoury Genome Medicine 2013, null:32 2013-04-18T00:00:00Z doi:10.1186/gm436 Randomized trials in the genomic era <p>John Ioannidis and Muin Khoury reflect on how advances in the field of genomics are questioning the need for randomized clinical trials and revolutionizing their design.</p> /content/figures/gm436-toc.gif Genome Medicine 1756-994X ${item.volume} 32 2013-04-18T00:00:00Z XML