Karimzadeh, M, Jandaghi, P, Papadakis, AI et al. (11 more authors) (2018) Aberration hubs in protein interaction networks highlight actionable targets in cancer. Oncotarget, 9 (38). pp. 25166-25180. ISSN 1949-2553
Abstract
Despite efforts for extensive molecular characterization of cancer patients, such as the international cancer genome consortium (ICGC) and the cancer genome atlas (TCGA), the heterogeneous nature of cancer and our limited knowledge of the contextual function of proteins have complicated the identification of targetable genes. Here, we present Aberration Hub Analysis for Cancer (AbHAC) as a novel integrative approach to pinpoint aberration hubs, i.e. individual proteins that interact extensively with genes that show aberrant mutation or expression. Our analysis of the breast cancer data of the TCGA and the renal cancer data from the ICGC shows that aberration hubs are involved in relevant cancer pathways, including factors promoting cell cycle and DNA replication in basal-like breast tumors, and Src kinase and VEGF signaling in renal carcinoma. Moreover, our analysis uncovers novel functionally relevant and actionable targets, among which we have experimentally validated abnormal splicing of spleen tyrosine kinase as a key factor for cell proliferation in renal cancer. Thus, AbHAC provides an effective strategy to uncover novel disease factors that are only identifiable by examining mutational and expression data in the context of biological networks.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © Karimzadeh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. A copy of the licence can be found at: https://creativecommons.org/licenses/by/3.0/ |
Keywords: | cancer; genomics; computational biology; systems biology; target discovery |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 May 2018 09:42 |
Last Modified: | 25 Jun 2023 21:21 |
Status: | Published |
Publisher: | Impact Journals |
Identification Number: | 10.18632/oncotarget.25382 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:131203 |