Relevance Rank Platform (RRP) for Functional Filtering of High Content Protein-Protein Interaction Data

TY - JOUR

T1 - Relevance Rank Platform (RRP) for Functional Filtering of High Content Protein-Protein Interaction Data

AU - Pokharel, Yuba Raj

AU - Saarela, Jani

AU - Szwajda, Agnieszka

AU - Rupp, Christian

AU - Rokka, Anne

AU - Lal Kumar Karna, Shibendra

AU - Teittinen, Kaisa

AU - Corthals, Garry

AU - Kallioniemi, Olli

AU - Wennerberg, Krister

AU - Aittokallio, Tero

AU - Westermarck, Jukka

N1 - © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2015/12

Y1 - 2015/12

N2 - High content protein interaction screens have revolutionized our understanding of protein complex assembly. However, one of the major challenges in translation of high content protein interaction data is identification of those interactions that are functionally relevant for a particular biological question. To address this challenge, we developed a relevance ranking platform (RRP), which consist of modular functional and bioinformatic filters to provide relevance rank among the interactome proteins. We demonstrate the versatility of RRP to enable a systematic prioritization of the most relevant interaction partners from high content data, highlighted by the analysis of cancer relevant protein interactions for oncoproteins Pin1 and PME-1. We validated the importance of selected interactions by demonstration of PTOV1 and CSKN2B as novel regulators of Pin1 target c-Jun phosphorylation and reveal previously unknown interacting proteins that may mediate PME-1 effects via PP2A-inhibition. The RRP framework is modular and can be modified to answer versatile research problems depending on the nature of the biological question under study. Based on comparison of RRP to other existing filtering tools, the presented data indicate that RRP offers added value especially for the analysis of interacting proteins for which there is no sufficient prior knowledge available. Finally, we encourage the use of RRP in combination with either SAINT or CRAPome computational tools for selecting the candidate interactors that fulfill the both important requirements, functional relevance, and high confidence interaction detection.

AB - High content protein interaction screens have revolutionized our understanding of protein complex assembly. However, one of the major challenges in translation of high content protein interaction data is identification of those interactions that are functionally relevant for a particular biological question. To address this challenge, we developed a relevance ranking platform (RRP), which consist of modular functional and bioinformatic filters to provide relevance rank among the interactome proteins. We demonstrate the versatility of RRP to enable a systematic prioritization of the most relevant interaction partners from high content data, highlighted by the analysis of cancer relevant protein interactions for oncoproteins Pin1 and PME-1. We validated the importance of selected interactions by demonstration of PTOV1 and CSKN2B as novel regulators of Pin1 target c-Jun phosphorylation and reveal previously unknown interacting proteins that may mediate PME-1 effects via PP2A-inhibition. The RRP framework is modular and can be modified to answer versatile research problems depending on the nature of the biological question under study. Based on comparison of RRP to other existing filtering tools, the presented data indicate that RRP offers added value especially for the analysis of interacting proteins for which there is no sufficient prior knowledge available. Finally, we encourage the use of RRP in combination with either SAINT or CRAPome computational tools for selecting the candidate interactors that fulfill the both important requirements, functional relevance, and high confidence interaction detection.

KW - Algorithms

KW - Biomarkers, Tumor/metabolism

KW - Carboxylic Ester Hydrolases/metabolism

KW - Cell Line, Tumor

KW - Computational Biology/methods

KW - Humans

KW - NIMA-Interacting Peptidylprolyl Isomerase

KW - Neoplasm Proteins/metabolism

KW - Peptidylprolyl Isomerase/metabolism

KW - Phosphorylation

KW - Protein Interaction Mapping/methods

KW - Protein Phosphatase 2/metabolism

KW - Proteins/metabolism

U2 - 10.1074/mcp.m115.050773

DO - 10.1074/mcp.m115.050773

M3 - Journal article

C2 - 26499835

SN - 1535-9476

VL - 14

SP - 3274

EP - 3283

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

IS - 12

ER -