A Multi-Method Approach for Proteomic Network Inference in 11 Human Cancers.

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Serval ID
serval:BIB_143EFDA31CDA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A Multi-Method Approach for Proteomic Network Inference in 11 Human Cancers.
Journal
Plos Computational Biology
Author(s)
Şenbabaoğlu Y., Sümer S.O., Sánchez-Vega F., Bemis D., Ciriello G., Schultz N., Sander C.
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
12
Number
2
Pages
e1004765
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural Publication Status: epublish
Abstract
Protein expression and post-translational modification levels are tightly regulated in neoplastic cells to maintain cellular processes known as 'cancer hallmarks'. The first Pan-Cancer initiative of The Cancer Genome Atlas (TCGA) Research Network has aggregated protein expression profiles for 3,467 patient samples from 11 tumor types using the antibody based reverse phase protein array (RPPA) technology. The resultant proteomic data can be utilized to computationally infer protein-protein interaction (PPI) networks and to study the commonalities and differences across tumor types. In this study, we compare the performance of 13 established network inference methods in their capacity to retrieve the curated Pathway Commons interactions from RPPA data. We observe that no single method has the best performance in all tumor types, but a group of six methods, including diverse techniques such as correlation, mutual information, and regression, consistently rank highly among the tested methods. We utilize the high performing methods to obtain a consensus network; and identify four robust and densely connected modules that reveal biological processes as well as suggest antibody-related technical biases. Mapping the consensus network interactions to Reactome gene lists confirms the pan-cancer importance of signal transduction pathways, innate and adaptive immune signaling, cell cycle, metabolism, and DNA repair; and also suggests several biological processes that may be specific to a subset of tumor types. Our results illustrate the utility of the RPPA platform as a tool to study proteomic networks in cancer.
Keywords
Cluster Analysis, Databases, Protein, Gene Expression Profiling, Humans, Neoplasm Proteins/analysis, Neoplasm Proteins/genetics, Neoplasms/genetics, Neoplasms/metabolism, Principal Component Analysis, Protein Interaction Maps/physiology, Proteomics/methods, Software
Pubmed
Open Access
Yes
Create date
26/06/2016 15:23
Last modification date
20/08/2019 12:42
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