Deep learning insights into distinct patterns of polygenic adaptation across human populations.

Response to spatiotemporal variation in selection gradients resulted in signatures of polygenic adaptation in human genomes. We introduce RAISING, a two-stage deep learning framework that optimizes neural network architecture through hyperparameter tuning before performing feature selection and prediction tasks. We tested RAISING on published and newly designed simulations that incorporate the complex interplay between demographic history and selection gradients.

Evidence for a sex-dependent effect modification in the association between IFN-λ DNA polymorphisms and expression of IFN-λ and interferon-stimulated genes in human PBMCs.

Human interferon (IFN) lambda (IFNL, IFN-L or IFN-λ) locus has several functional genetic variants but their role in regulating in vivo gene expression, and whether they associate with antiviral states in healthy individuals, is not clear. In this study, we recruited ∼550 healthy individuals belonging to both sexes, genotyped them for several IFNL genetic variants and measured, by qPCR, the expression of IFNL2/3, IFNL4 and four IFN-stimulated genes (ISGs) (MX1, OAS1, ISG15 and RSAD2) from their peripheral blood mononuclear cells (PBMC) both before and after stimulation with a viral mimic, poly I: C. We also measured secreted levels of several cytokines including IFN-λ1 and IFN-λ3 in poly I:C stimulated PBMCs.

Post-GWAS functional analyses of suggests its role in glaucomatous neurodegeneration.

Primary angle closure glaucoma (PACG) affects more than 20 million people worldwide, with an increased prevalence in south-east Asia. In a prior haplotype-based GWAS, we identified a novel genic region, significantly associated with PACG. In the current study, we have extended our perception of involvement in glaucomatous neurodegeneration in a zebrafish model, through investigating phenotypic consequences pertinent to retinal degeneration upon knockdown of cntnap5 by translation-blocking morpholinos.

Multivariate genetic architecture reveals testosterone-driven sexual antagonism in contemporary humans.

Sex difference (SD) is ubiquitous in humans despite shared genetic architecture (SGA) between the sexes. A univariate approach, i.e.

Small molecules that disrupt RAD54-BLM interaction hamper tumor proliferation in colon cancer chemoresistance models.

RAD54 and BLM helicase play pivotal roles during homologous recombination repair (HRR) to ensure genome maintenance. BLM amino acids (aa 181-212) interact with RAD54 and enhance its chromatin remodeling activity. Functionally, this interaction heightens HRR, leading to a decrease in residual DNA damage in colon cancer cells.