POEM: Identifying joint additive effects on regulatory circuits

Maya Botzman, Aharon Nachshon, Avital Brodt, Irit Gat-Viks*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Motivation: Expression Quantitative Trait Locus (eQTL) mapping tackles the problem of identifying variation in DNA sequence that have an effect on the transcriptional regulatory network. Major computational efforts are aimed at characterizing the joint effects of several eQTLs acting in concert to govern the expression of the same genes. Yet, progress toward a comprehensive prediction of such joint effects is limited. For example, existing eQTL methods commonly discover interacting loci affecting the expression levels of a module of co-regulated genes. Such "modularization" approaches, however, are focused on epistatic relations and thus have limited utility for the case of additive (non-epistatic) effects. Results: Here we present POEM (Pairwise effect On Expression Modules), a methodology for identifying pairwise eQTL effects on gene modules. POEM is specifically designed to achieve high performance in the case of additive joint effects. We applied POEM to transcription profiles measured in bone marrow-derived dendritic cells across a population of genotyped mice. Our study reveals widespread additive, trans-acting pairwise effects on gene modules, characterizes their organizational principles, and highlights high-order interconnections between modules within the immune signaling network. These analyses elucidate the central role of additive pairwise effect in regulatory circuits, and provide computational tools for future investigations into the interplay between eQTLs.

Original languageEnglish
Article number48
JournalFrontiers in Genetics
Volume7
Issue numberAPR
DOIs
StatePublished - 19 Apr 2016

Keywords

  • Additive effects
  • EQTL
  • Gene modules
  • Immune signaling network
  • Pairwise effects

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