TY - JOUR
T1 - The OncoPPi Portal
T2 - An integrative resource to explore and prioritize protein-protein interactions for cancer target discovery
AU - Ivanov, Andrei A.
AU - Revennaugh, Brian
AU - Rusnak, Lauren
AU - Gonzalez-Pecchi, Valentina
AU - Mo, Xiulei
AU - Johns, Margaret A.
AU - Du, Yuhong
AU - Cooper, Lee Alex Donald
AU - Moreno, Carlos S.
AU - Khuri, Fadlo R.
AU - Fu, Haian
N1 - Funding Information:
The results published here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/. This research was supported in part by the National Cancer Institute of the NIH (Cancer Target Discovery and Development Network grants U01CA168449 and U01CA217875, H.F.), Emory University Research Committee grant (A.A.I.) and Winship Cancer Institute (NIH 5P30CA138292).
Publisher Copyright:
© The Author 2017. Published by Oxford University Press. All rights reserved.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Motivation As cancer genomics initiatives move toward comprehensive identification of genetic alterations in cancer, attention is now turning to understanding how interactions among these genes lead to the acquisition of tumor hallmarks. Emerging pharmacological and clinical data suggest a highly promising role of cancer-specific protein-protein interactions (PPIs) as druggable cancer targets. However, large-scale experimental identification of cancer-related PPIs remains challenging, and currently available resources to explore oncogenic PPI networks are limited. Results Recently, we have developed a PPI high-Throughput screening platform to detect PPIs between cancer-Associated proteins in the context of cancer cells. Here, we present the OncoPPi Portal, an interactive web resource that allows investigators to access, manipulate and interpret a high-quality cancer-focused network of PPIs experimentally detected in cancer cell lines. To facilitate prioritization of PPIs for further biological studies, this resource combines network connectivity analysis, mutual exclusivity analysis of genomic alterations, cellular co-localization of interacting proteins and domain-domain interactions. Estimates of PPI essentiality allow users to evaluate the functional impact of PPI disruption on cancer cell proliferation. Furthermore, connecting the OncoPPi network with the approved drugs and compounds in clinical trials enables discovery of new tumor dependencies to inform strategies to interrogate undruggable targets like tumor suppressors. The OncoPPi Portal serves as a resource for the cancer research community to facilitate discovery of cancer targets and therapeutic development. Availability and implementation The OncoPPi Portal is available at http://oncoppi.emory.edu.
AB - Motivation As cancer genomics initiatives move toward comprehensive identification of genetic alterations in cancer, attention is now turning to understanding how interactions among these genes lead to the acquisition of tumor hallmarks. Emerging pharmacological and clinical data suggest a highly promising role of cancer-specific protein-protein interactions (PPIs) as druggable cancer targets. However, large-scale experimental identification of cancer-related PPIs remains challenging, and currently available resources to explore oncogenic PPI networks are limited. Results Recently, we have developed a PPI high-Throughput screening platform to detect PPIs between cancer-Associated proteins in the context of cancer cells. Here, we present the OncoPPi Portal, an interactive web resource that allows investigators to access, manipulate and interpret a high-quality cancer-focused network of PPIs experimentally detected in cancer cell lines. To facilitate prioritization of PPIs for further biological studies, this resource combines network connectivity analysis, mutual exclusivity analysis of genomic alterations, cellular co-localization of interacting proteins and domain-domain interactions. Estimates of PPI essentiality allow users to evaluate the functional impact of PPI disruption on cancer cell proliferation. Furthermore, connecting the OncoPPi network with the approved drugs and compounds in clinical trials enables discovery of new tumor dependencies to inform strategies to interrogate undruggable targets like tumor suppressors. The OncoPPi Portal serves as a resource for the cancer research community to facilitate discovery of cancer targets and therapeutic development. Availability and implementation The OncoPPi Portal is available at http://oncoppi.emory.edu.
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U2 - 10.1093/bioinformatics/btx743
DO - 10.1093/bioinformatics/btx743
M3 - Article
C2 - 29186335
AN - SCOPUS:85045850708
SN - 1367-4803
VL - 34
SP - 1183
EP - 1191
JO - Bioinformatics
JF - Bioinformatics
IS - 7
ER -
