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Co-regulated Transcripts Associated to Cooperating eSNPs Define Bi-fan Motifs in Human Gene Networks


Previous analysis charts ubiquitous associations between the level of single transcripts and single corresponding genetic variants, eSNPs. However, most expression traits are complex, involving the cooperative action of multiple SNPs at different loci affecting multiple genes. The basic structure of variants within two source genes that affect the expression of two different target genes is compelling in terms of its potential to divulge information regarding the features of more complex interactions. We therefore devised a computational framework for the analysis of such variants, as ascertained from genomic sequencing data along with gene expression profiling of the same cohort. We focus on genetic markers that reside within interpretable regions of the genome: exon sequences, or transcription factors. Such cooperating eSNP sources are both associated with the same pair of target transcripts. We characterize such quartets through their genomic, topological and functional properties. Our findings suggest that this regulatory structure of quartets exhibits distinct characteristics and is frequent in real data, but is rarely observed in permutations.


Vyšlo v časopise: Co-regulated Transcripts Associated to Cooperating eSNPs Define Bi-fan Motifs in Human Gene Networks. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004587
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004587

Souhrn

Previous analysis charts ubiquitous associations between the level of single transcripts and single corresponding genetic variants, eSNPs. However, most expression traits are complex, involving the cooperative action of multiple SNPs at different loci affecting multiple genes. The basic structure of variants within two source genes that affect the expression of two different target genes is compelling in terms of its potential to divulge information regarding the features of more complex interactions. We therefore devised a computational framework for the analysis of such variants, as ascertained from genomic sequencing data along with gene expression profiling of the same cohort. We focus on genetic markers that reside within interpretable regions of the genome: exon sequences, or transcription factors. Such cooperating eSNP sources are both associated with the same pair of target transcripts. We characterize such quartets through their genomic, topological and functional properties. Our findings suggest that this regulatory structure of quartets exhibits distinct characteristics and is frequent in real data, but is rarely observed in permutations.


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Genetika Reprodukčná medicína

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PLOS Genetics


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