Evolink: a phylogenetic approach for rapid identification of genotype–phenotype associations in large-scale microbial multispecies data

Abstract

Motivation: The discovery of the genetic features that underly a phenotype is a fundamental task in microbial genomics. With the growing number of microbial genomes that are paired with phenotypic data, new challenges, and opportunities are arising for genotype-phenotype inference. Phylogenetic approaches are frequently used to adjust for the population structure of microbes but scaling them to trees with thousands of leaves representing heterogeneous populations is highly challenging. This greatly hinders the identification of prevalent genetic features that contribute to phenotypes that are observed in a wide diversity of species. Results: In this study, Evolink was developed as an approach to rapidly identify genotypes associated with phenotypes in large-scale multispecies microbial datasets. Compared with other similar tools, Evolink was consistently among the top-performing methods in terms of precision and sensitivity when applied to simulated and real-world flagella datasets. In addition, Evolink significantly outperformed all other approaches in terms of computation time. Application of Evolink on flagella and gram-staining datasets revealed findings that are consistent with known markers and supported by the literature. In conclusion, Evolink can rapidly detect phenotype-associated genotypes across multiple species, demonstrating its potential to be broadly utilized to identify gene families associated with traits of interest.