RT Journal Article
SR Electronic
T1 Mesothelioma Interactome with 367 Novel Protein-Protein Interactions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 459065
DO 10.1101/459065
A1 Kalyani B. Karunakaran
A1 Naveena Yanamala
A1 Gregory Boyce
A1 Madhavi K. Ganapathiraju
YR 2018
UL http://biorxiv.org/content/early/2018/11/01/459065.abstract
AB 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 expression profiles induced by drug to profiles induced by MPM, potentially repurposable drugs are identified from this drug list. Development of PPIs of disease-specific set of genes is a powerful approach with high translational impact – the interactome is a vehicle to piece together an integrated view on how genes associated with MPM through various high throughput studies are functionally linked, leading to clinically translatable results such as clinical trials with repurposed drugs. The PPIs are made available on a webserver, called Wiki-Pi MPM at http://severus.dbmi.pitt.edu/wiki-MPM with advanced search capabilities.One Sentence Summary Mesothelioma Interactome with 367 novel protein-protein interactions may shed light on the mechanisms of cancer genesis and progression