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- Title
Reconstructing the Molecular Function of Genetic Variation in Regulatory Networks.
- Authors
Wilentzik, Roni; Chun Jimmie Ye; Gat-Viks, Irit
- Abstract
Over the past decade, genetic studies have recognized hundreds of polymorphic DNA loci called response QTLs (reQTLs) as potential contributors to interindividual variation in transcriptional responses to stimulations. Such reQTLs commonly affect the transduction of signals along the regulatory network that controls gene transcription. Identifying the pathways through which reQTLs perturb the underlying network has been a major challenge. Here, we present GEVIN ("Genome-wide Embedding of Variation In Networks"), a methodology that simultaneously identifies a reQTL and the particular pathway in which the reQTL affects downstream signal transduction along the network. Using synthetic data, we show that this algorithm outperforms existing pathway identification and reQTL identification methods. We applied GEVIN to the analysis of murine and human dendritic cells in response to pathogenic components. These analyses revealed significant reQTLs together with their perturbed Toll-like receptor signaling pathways. GEVIN thus offers a powerful framework that renders a comprehensive picture of disease-related DNA loci and their molecular functions within regulatory networks.
- Subjects
GENE regulatory networks; DNA; CELLULAR signal transduction; GENE expression; DENDRITIC cells
- Publication
Genetics, 2017, Vol 207, Issue 4, p1699
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1534/genetics.117.300381