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PLOS Studies Examine Genes Co-Expressed in Depression, More

In PLOS Genetics, members of the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium explore networks of co-expressed genes behind that common, polygenic, psychiatric condition. Using a newly developed analytical framework known as eMAGMA — which relies on summary statistics from genome-wide association studies, in combination with tissue-specific expression quantitative trait locus insights from tissues such as brain or blood — the researchers narrowed in on 58 new candidate risk genes and dozens of genes implicated in the gene in the past. "Major depression risk genes were enriched in gene co-expression modules in multiple brain tissues," they report, noting that "the implicated gene modules contained genes involved in synaptic signaling, neuronal development, and cell transport pathways."

A University of Chicago team compares three-dimensional chromatin interactions and related gene regulatory effects in induced pluripotent stem cells from humans and chimpanzees for another PLOS Genetics paper. The investigators used Hi-C and RNA sequencing to profile chromatin interactions and gene expression, respectively, in four human and chimp iPSCs. Their results pointed to conservation when it came to 'lower-order,' pairwise three-dimensional interactions. When it came to higher order, large-scale genome architecture, including topologically associating domain patterns, that conservation broke down, contributing to more than 9,600 Hi-C distinct contact events and related gene expression differences in the human and chimp iPSCs.

Chinese researchers reporting in PLOS One take a look at the role of conserved minichromosome maintenance (MCM) family gene levels in lung adenocarcinoma. The team turned to RNA sequence data from the Cancer Genome Atlas database to assess MCM gene expression patterns in 535 lung adenocarcinoma tumors and 59 matched normal samples from 515 individuals. The analysis highlighted MCM genes implicated in everything from cell cycle progression to DNA damage response, the authors note, including a handful of MCM genes that appeared to coincide with survival in the lung cancer patients with available clinical data. They report that "MCM4, MCM5, and MCM8 may be considered as potential prognostic biomarkers in patients with [lung adenocarcinoma]," but caution that the clinical significance of these genes and potential mechanisms of action will need further experimental and clinical trial validation.