Jan 15, 2016

A convex optimization approach for identification of human tissue-specific interactomes

BioRxiv : the Preprint Server for Biology
Shahin Mohammadi, Ananth Grama

Abstract

Analysis of organism-specific interactomes has yielded novel insights into cellular function and coordination, understanding of pathology, and identification of markers and drug targets. Genes, however, can exhibit varying levels of cell-type specificity in their expression, and their coordinated expression manifests in tissue-specific function and pathology. Tissue-specific/ selective interaction mechanisms have significant applications in drug discovery, as they are more likely to reveal drug targets. Furthermore, tissue-specific transcription factors (tsTFs) are significantly implicated in human disease, including cancers. Finally, disease genes and protein complexes have the tendency to be differentially-expressed in tissues in which defects cause pathology. These observations motivate construction of refined tissue-specific interactomes from organism-specific interactomes. We present a novel technique for constructing human tissue-specific interactomes. Using a variety of validation tests (ESEA, GO Enrichment, Disease-Gene Subnetwork Compactness), we show that our proposed approach significantly outperforms state of the art techniques. Finally, using case studies of Alzheimer's and Parkinson's diseases, we show that tissue...Continue Reading

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Mentioned in this Paper

Biological Markers
Study
Biochemical Pathway
Genes
Complex (molecular entity)
Tissue Specificity
Alzheimer's Disease
Pharmacologic Substance
Organism
Parkinson Disease

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