Fig. 1
From: On predicting regulatory genes by analysis of functional networks in C. elegans
Candidate regulator prediction for natural variation in gene expression regulation using the SPF method. Genetical genomics (eQTL mapping) identifies loci involved in the regulation of gene expression. In these experiments eQTL-hotspots (trans-bands) can be identified, which indicate loci regulating the expression of many genes. a An outcome of a genetical genomics experiment is represented schematically. The genes for which the expression levels where measured in a recombinant inbred line population are shown on the Y-axis. The x-axis shows the location of the eQTL peak position (potential regulatory loci). The blue locus is an example of an eQTL-hotspot, corresponding to a position of a putative regulator of multiple genes (shown in blue). b By eQTL mapping we have obtained two types of information which can be used to identfy the regulatory gene. Firstly target genes are identified as having an eQTL at a particular genomic location. Secondly, the locus harbouring many eQTL is likely to contain a gene affecting expression of multiple targets. Therefore it is very likely that the candidate gene has a regulatory function, for example, a transcription factor or a receptor. c In many cases eQTL hotspot loci contain > 100 genes [12] and validation is important before pursuing the potential regulator. The SPF method can be used to validate eQTL hotspot by investigating if the genes mapping to the eQTL hotspot share a relationship based on hundreds of experiments categorised in WormNet [34]. A validated group of genes will have more connections in WormNet compared to a random group. Thereby the SPF method can identify false-positive eQTL hotspots, for example caused by experimental variation. D: The identification of potential regulators is laborious [29], and candidates prioritizing is imperative. A validated group of co-regulated genes can be used to predict the most likely regulator by selecting genes on the eQTL hotspot locus with the most direct connections to the target genes (dark orange circles), or indirect connections via other genes (yellow circles)