Open AccesseQED: an efficient method for interpreting eQTL associations using protein networks
Author(s) -
Suthram Silpa,
Beyer Andreas,
Karp Richard M,
Eldar Yonina,
Ideker Trey
Publication year - 2008
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2008.4
Subject(s) - expression quantitative trait loci , biology , linkage disequilibrium , genetics , computational biology , quantitative trait locus , dna microarray , gene , locus (genetics) , haplotype , gene expression , genotype , single nucleotide polymorphism
Analysis of expression quantitative trait loci (eQTLs) is an emerging technique in which individuals are genotyped across a panel of genetic markers and, simultaneously, phenotyped using DNA microarrays. Because of the spacing of markers and linkage disequilibrium, each marker may be near many genes making it difficult to finely map which of these genes are the causal factors responsible for the observed changes in the downstream expression. To address this challenge, we present an efficient method for prioritizing candidate genes at a locus. This approach, called ‘eQTL electrical diagrams’ (eQED), integrates eQTLs with protein interaction networks by modeling the two data sets as a wiring diagram of current sources and resistors. eQED achieved a 79% accuracy in recovering a reference set of regulator–target pairs in yeast, which is significantly higher than the performance of three competing methods. eQED also annotates 368 protein–protein interactions with their directionality of information flow with an accuracy of approximately 75%.