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 -
