A framework for integrating directed and undirected annotations to build explanatory models of cis-eQTL data

PLoS Comput Biol. 2020 Jun 9;16(6):e1007770. doi: 10.1371/journal.pcbi.1007770. eCollection 2020 Jun.

Abstract

A longstanding goal of regulatory genetics is to understand how variants in genome sequences lead to changes in gene expression. Here we present a method named Bayesian Annotation Guided eQTL Analysis (BAGEA), a variational Bayes framework to model cis-eQTLs using directed and undirected genomic annotations. We used BAGEA to integrate directed genomic annotations with eQTL summary statistics from tissues of various origins. This analysis revealed epigenetic marks that are relevant for gene expression in different tissues and cell types. We estimated the predictive power of the models that were fitted based on directed genomic annotations. This analysis showed that, depending on the underlying eQTL data used, the directed genomic annotations could predict up to 1.5% of the variance observed in the expression of genes with top nominal eQTL association p-values < 10-7. For genes with estimated effect sizes in the top 25% quantile, up to 5% of the expression variance could be predicted. Based on our results, we recommend the use of BAGEA for the analysis of cis-eQTL data to reveal annotations relevant to expression biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Bayes Theorem
  • Chromosome Mapping
  • Computational Biology / methods*
  • DNA / analysis
  • Epigenesis, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome, Human
  • Genome-Wide Association Study*
  • Genomics
  • Genotype
  • Humans
  • Molecular Sequence Annotation
  • Monocytes / metabolism
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci*
  • Software

Substances

  • DNA

Grants and funding

This research was supported by Verge Genomics, a venture funded drug discovery company (https://www.vergegenomics.com/). The funders of Verge Genomics had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.