An integrative approach for causal gene identification and gene regulatory pathway inference

Zhidong Tu, Li Wang, Michelle N. Arbeitman, Ting Chen, Fengzhu Sun

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Motivation: Gene expression variation can often be linked to certain chromosomal regions and are tightly associated with phenotypic variation such as disease conditions. Inferring the causal genes for the expression variation is of great importance but rather challenging as the linked region generally contains multiple genes. Even when a single candidate gene is proposed, the underlying biological mechanism by which the regulation is enforced remains unknown. Novel approaches are needed to both infer the causal genes and generate hypothesis on the underlying regulatory mechanisms. Results: We propose a new approach which aims at achieving the above objectives by integrating genotype information, gene expression, protein-protein interaction, protein phosphorylation, and transcription factor (TF)-DNA binding information. A network based stochastic algorithm is designed to infer the causal genes and identify the underlying regulatory pathways. We first quantitatively verified our method by a test using data generated by yeast knock-out experiments. Over 40% of inferred causal genes are correct, which is significantly better than 10% by random guess. We then applied our method to a recent genome-wide expression variation study in yeast. We show that our method can correctly identify the causal genes and effectively output experimentally verified pathways. New potential gene regulatory pathways are generated and presented as a global network.

Original languageEnglish
Pages (from-to)e489-e496
JournalBioinformatics
Volume22
Issue number14
DOIs
StatePublished - 15 Jul 2006
Externally publishedYes

Fingerprint

Dive into the research topics of 'An integrative approach for causal gene identification and gene regulatory pathway inference'. Together they form a unique fingerprint.

Cite this