Mesothelioma Interactome with 367 Novel Protein-Protein Interactions

BioRxiv : the Preprint Server for Biology
Kalyani B. KarunakaranMadhavi K Ganapathiraju

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer of the thorax with a median survival of one year. We constructed an 'MPM interactome' with over 300 computationally predicted PPIs and over 1300 known PPIs of 62 literature-curated genes whose activity affects MPM. Known PPIs of the 62 MPM associated genes were derived from BioGRID and HPRD databases. Novel PPIs were predicted by applying the HiPPIP algorithm, which computes features of protein pairs such as cellular localization, molecular function, biological process membership, genomic location of the gene, gene expression in microarray experiments, protein domains and tissue membership, and classifies the pairwise features as interacting or non-interacting based on a random forest model. To our satisfaction, the interactome is significantly enriched with genes differentially expressed in MPM tumors compared with normal pleura, and with other thoracic tumors. The interactome is also significantly enriched with genes whose high expression has been correlated with unfavorable prognosis in lung cancer, and with genes differentially expressed on crocidolite exposure. 28 of the interactors of MPM proteins are targets of 147 FDA-approved drugs. By comparing differential ...Continue Reading

Related Concepts

Clinical Trials
Gene Expression
Genes
Literature
Mesothelioma
Neoplasms
Asbestos, Crocidolite
Malignant Neoplasm of Lung
Satisfaction
Proton Pump Inhibitors

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