Major Depressive Disorder Is Associated With Differential Expression of Innate Immune and Neutrophil-Related Gene Networks in Peripheral Blood: A Quantitative Review of Whole-Genome Transcriptional Data From Case-Control Studies.

BACKGROUND: Whole-genome transcription has been measured in peripheral blood samples as a candidate biomarker of inflammation associated with major depressive disorder. METHODS: We searched for all case-control studies on major depressive disorder that reported microarray or RNA sequencing measurements on whole blood or peripheral blood mononuclear cells. Primary datasets were reanalyzed, when openly accessible, to estimate case-control differences and to evaluate the functional roles of differentially expressed gene lists by technically harmonized methods. RESULTS: We found 10 eligible studies (N = 1754 depressed cases and N = 1145 healthy controls). Fifty-two genes were called significant by 2 of the primary studies (published overlap list). After harmonization of analysis across 8 accessible datasets (n = 1706 cases, n = 1098 controls), 272 genes were coincidentally listed in the top 3% most differentially expressed genes in 2 or more studies of whole blood or peripheral blood mononuclear cells with concordant direction of effect (harmonized overlap list). By meta-analysis of standardized mean difference across 4 studies of whole-blood samples (n = 1567 cases, n = 954 controls), 343 genes were found with false discovery rate <5% (standardized mean difference meta-analysis list). These 3 lists intersected significantly. Genes abnormally expressed in major depressive disorder were enriched for innate immune-related functions, coded for nonrandom protein-protein interaction networks, and coexpressed in the normative transcriptome module specialized for innate immune and neutrophil functions. CONCLUSIONS: Quantitative review of existing case-control data provided robust evidence for abnormal expression of gene networks important for the regulation and implementation of innate immune response. Further development of white blood cell transcriptional biomarkers for inflamed depression seems warranted.

The NCATS BioPlanet - An Integrated Platform for Exploring the Universe of Cellular Signaling Pathways for Toxicology, Systems Biology, and Chemical Genomics.

Chemical genomics aims to comprehensively define, and ultimately predict, the effects of small molecule compounds on biological systems. Chemical activity profiling approaches must consider chemical effects on all pathways operative in mammalian cells. To enable a strategic and maximally efficient chemical profiling of pathway space, we have created the NCATS BioPlanet, a comprehensive integrated pathway resource that incorporates the universe of 1,658 human pathways sourced from publicly available, manually curated sources, which have been subjected to thorough redundancy and consistency cross-evaluation. BioPlanet supports interactive browsing, retrieval, and analysis of pathways, exploration of pathway connections, and pathway search by gene targets, category, and availability of corresponding bioactivity assay, as well as visualization of pathways on a 3-dimensional globe, in which the distance between any two pathways is proportional to their degree of gene component overlap. Using this resource, we propose a strategy to identify a minimal set of 362 biological assays that can interrogate the universe of human pathways. The NCATS BioPlanet is a public resource, which will be continually expanded and updated, for systems biology, toxicology, and chemical genomics, available at http://tripod.nih.gov/bioplanet/.