Multi-omic integration using interpretable machine learning reveals genetic mechanisms of trait variation and phenotypic plasticity in switchgrass

Abstract

Uncovering the genetic architecture of quantitative traits is challenging because polygenic control yields small individual gene effects and because gene-gene and genotype-by-environment interactions add further complexity. To understand the genetic basis of polygenic traits and their plasticity across environments, we integrated genome-wide SNPs and RNA-seq transcript data with interpretable statistical and machine learning models in a switchgrass (Panicum virgatum) diversity panel grown at contrasting field sites in Michigan and Texas. Notably, in addition to single environments, our trait prediction models were able to predict phenotypic differences, across environments i.e., plasticity. By interpreting trait prediction models with explainable machine learning methods, we identified genes that are the most predictive of flowering time and annual biomass production across environments, based on their associated gene expression levels and nearby SNPs. This approach recovered canonical flowering regulators and revealed novel, environment-specific candidate flowering genes. Further, transcriptome models consistently recovered more switchgrass genes homologous to experimentally validated genes in Arabidopsis and rice than SNP-based models. Feature interaction scores from the models also allow the identification of trait and environment-dependent gene-gene interactions, where flowering time showed stronger and more abundant interactions than biomass. While some of the interactions identified are consistent with the link between flowering time and yield, most are novel predictors that need to be further evaluated. These findings provide insight into the genetic basis of trait variation and plasticity across environments and help prioritize candidate genes for functional validation and cultivar improvement.