Detection of Regulator Genes and eQTLs in Gene Networks
Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in noncoding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are “expression quantitative trait loci” or eQTLs, for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins, and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, as well as to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and software to identify eQTLs and their associated genes, to reconstruct coexpression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.
The authors’ work is supported by the BBSRC (BB/M020053/1) and Roslin Institute Strategic Grant funding from the BBSRC (BB/J004235/1).
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