Assessment of community efforts to advance network-based prediction of protein–protein interactions

Xu-Wen Wang, Lorenzo Madeddu, Kerstin Spirohn, Leonardo Martini, Adriano Fazzone, Luca Becchetti, Thomas P. Wytock, István A. Kovács, Olivér M. Balogh, Bettina Benczik, Mátyás Pétervári, Bence Ágg, Péter Ferdinandy, Loan Vulliard, Jörg Menche, Stefania Colonnese, Manuela Petti, Gaetano Scarano, Francesca Cuomo, Tong Hao, Florent Laval, Luc Willems, Jean-Claude Twizere, Marc Vidal, Michael A. Calderwood, Enrico Petrillo, Albert-László Barabási, Edwin K. Silverman, Joseph Loscalzo, Paola Velardi () and Yang-Yu Liu ()
Additional contact information
Xu-Wen Wang: Brigham and Women’s Hospital and Harvard Medical School
Lorenzo Madeddu: Translational and Precision Medicine Department Sapienza University of Rome
Kerstin Spirohn: Dana-Farber Cancer Institute
Leonardo Martini: Sapienza University of Rome
Adriano Fazzone: CENTAI Institute
Luca Becchetti: Sapienza University of Rome
Thomas P. Wytock: Northwestern University
István A. Kovács: Northwestern University
Olivér M. Balogh: Semmelweis University
Bettina Benczik: Semmelweis University
Mátyás Pétervári: Semmelweis University
Bence Ágg: Semmelweis University
Péter Ferdinandy: Semmelweis University
Loan Vulliard: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Jörg Menche: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Stefania Colonnese: University of Rome “Sapienza”
Manuela Petti: Sapienza University of Rome
Gaetano Scarano: University of Rome “Sapienza”
Francesca Cuomo: University of Rome “Sapienza”
Tong Hao: Dana-Farber Cancer Institute
Florent Laval: Dana-Farber Cancer Institute
Luc Willems: University of Liège
Jean-Claude Twizere: University of Liège
Marc Vidal: Dana-Farber Cancer Institute
Michael A. Calderwood: Dana-Farber Cancer Institute
Enrico Petrillo: Brigham and Women’s Hospital and Harvard Medical School
Albert-László Barabási: Brigham and Women’s Hospital and Harvard Medical School
Edwin K. Silverman: Brigham and Women’s Hospital and Harvard Medical School
Joseph Loscalzo: Brigham and Women’s Hospital and Harvard Medical School
Paola Velardi: Translational and Precision Medicine Department Sapienza University of Rome
Yang-Yu Liu: Brigham and Women’s Hospital and Harvard Medical School

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Comprehensive understanding of the human protein-protein interaction (PPI) network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Despite the remarkable experimental efforts undertaken to date to determine the structure of the human interactome, many PPIs remain unmapped. Computational approaches, especially network-based methods, can facilitate the identification of previously uncharacterized PPIs. Many such methods have been proposed. Yet, a systematic evaluation of existing network-based methods in predicting PPIs is still lacking. Here, we report community efforts initiated by the International Network Medicine Consortium to benchmark the ability of 26 representative network-based methods to predict PPIs across six different interactomes of four different organisms: A. thaliana, C. elegans, S. cerevisiae, and H. sapiens. Through extensive computational and experimental validations, we found that advanced similarity-based methods, which leverage the underlying network characteristics of PPIs, show superior performance over other general link prediction methods in the interactomes we considered.

Date: 2023
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DOI: 10.1038/s41467-023-37079-7

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