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

Abstract

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. RAISING outperformed Phylogenetic Generalized Least Squares (PGLS), ridge regression and DeepGenomeScan, with significantly higher true positive rates (TPR) in detecting genetic adaptation. It reduced computational time by 60-fold and increased TPR by up to 28% compared to DeepGenomeScan on published data. In more complex demographic simulations, RAISING showed lower false discoveries and significantly higher TPR, up to 17-fold, compared to other methods. RAISING demonstrated robustness with least sensitivity to demographic history, selection gradient and their interactions. We developed a sliding window method for genome-wide implementation of RAISING to overcome the computational challenges of high-dimensional genomic data. Applied to African, European, South Asian and East Asian populations, we identified multiple genomic regions undergoing polygenic selection. Notably, ∼70% of the regions identified in Africans are unique, with broad patterns distinguishing them from non-Africans, corroborating the Out of Africa dispersal model.