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- Title
Deciphering kinase–substrate relationships by analysis of domain-specific phosphorylation network.
- Authors
Damle, Nikhil Prakash; Mohanty, Debasisa
- Abstract
Motivation: In silico prediction of site-specific kinase–substrate relationships (ssKSRs) is crucial for deciphering phosphorylation networks by linking kinomes to phosphoproteomes. However, currently available predictors for ssKSRs give rise to a large number of false-positive results because they use only a short sequence stretch around phosphosite as determinants of kinase specificity and do not consider the biological context of kinase–substrate recognition.Results: Based on the analysis of domain-specific kinase–substrate relationships, we have constructed a domain-level phosphorylation network that implicitly incorporates various contextual factors. It reveals preferential phosphorylation of specific domains by certain kinases. These novel correlations have been implemented in PhosNetConstruct, an automated program for predicting target kinases for a substrate protein. PhosNetConstruct distinguishes cognate kinase–substrate pairs from a large number of non-cognate combinations. Benchmarking on independent datasets using various statistical measures demonstrates the superior performance of PhosNetConstruct over ssKSR-based predictors.Availability and implementation: PhosNetConstruct is freely available at http://www.nii.ac.in/phosnetconstruct.html.Contact: deb@nii.res.inSupplementary information: Supplementary data are available at Bioinformatics online.
- Subjects
PHOSPHORYLATION; CONTEXTUAL (Music); KINASE genetics; NETWORK performance; SEQUENCE alignment; COMPUTER network resources
- Publication
Bioinformatics, 2014, Vol 30, Issue 12, p1730
- ISSN
1367-4803
- Publication type
Article
- DOI
10.1093/bioinformatics/btu112