Validation and refinement of gene-regulatory pathways on a network of physical interactions.
As genome-scale measurements lead to increasingly complex models of gene regulation, systematic approaches are needed to validate and refine these models. Towards this goal, we describe an automated procedure for prioritizing genetic perturbations in order to discriminate optimally between alternative models of a gene-regulatory network. Using this procedure, we evaluate 38 candidate regulatory networks in yeast and perform four high-priority gene knockout experiments. The refined networks support previously unknown regulatory mechanisms downstream of SOK2 and SWI4.
Center for Biomolecular Science and Engineering, Baskin School of Engineering, University of California, Santa Cruz, CA 95064, USA. chyeang@soe.ucsc.edu
Chen-Hsiang
CH
Yeang
H Craig
HC
Mak
Scott
S
McCuine
Christopher
C
Workman
Tommi
T
Jaakkola
Trey
T
Ideker
D019295:Computational Biology / Q000379:methods; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D023281:Genomics; D048088:Informatics; D008957:Models, Genetic; D009415:Nerve Net; D012333:RNA, Messenger / Q000235:genetics; D015203:Reproducibility of Results
D012333:RNA, Messenger