NDLI: Relating protein adduction to gene expression changes: a systems approach

Content Provider	Royal Society of Chemistry (RSC)
Author	Zhang, Bing Liebler, Daniel C. Duncan, Dexter T. Shi, Zhiao Marnett, Lawrence J. Prodduturi, Naresh
Copyright Year	2011
Abstract	Modification of proteins by reactive electrophiles such as the 4-hydroxy-2-nonenal (HNE) plays a critical role in oxidant-associated human diseases. However, little is known about protein adduction and the mechanism by which protein damage elicits adaptive effects and toxicity. We developed a systems approach for relating protein adduction to gene expression changes through the integration of protein adduction, gene expression, protein–DNA interaction, and protein–protein interaction data. Using a random walk strategy, we expanded a list of responsive transcription factors inferred from gene expression studies to upstream signaling networks, which in turn allowed overlaying protein adduction data on the network for the prediction of stress sensors and their associated regulatory mechanisms. We demonstrated the general applicability of transcription factor-based signaling network inference using 103 known pathways. Applying our workflow on gene expression and protein adduction data from HNE-treatment not only rediscovered known mechanisms of electrophile stress but also generated novel hypotheses regarding protein damage sensors. Although developed for analyzing protein adduction data, the framework can be easily adapted for phosphoproteomics and other types of protein modification data.
Starting Page	2118
Ending Page	2127
Page Count	10
File Format	HTM / HTML PDF
ISSN	1742206X
Volume Number	7
Issue Number	7
Journal	Molecular BioSystems
DOI	10.1039/c1mb05014a
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Protein\u2013protein interaction Gene Phosphoproteomics Critical Role Protein\u2013DNA interaction Random walk Anatomical terms of motion Protein Electrophile
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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