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Article

How Far Are We from the Completion of the Human Protein Interactome Reconstruction?

1
Laboratory of General Biology, School of Medicine, University of Patras, 26500 Patras, Greece
2
Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology Hellas (FORTH/ICE-HT), 26504 Patras, Greece
*
Author to whom correspondence should be addressed.
Academic Editors: Francisco Rodrigues Pinto and Javier De Las Rivas
Biomolecules 2022, 12(1), 140; https://doi.org/10.3390/biom12010140
Received: 8 December 2021 / Revised: 9 January 2022 / Accepted: 11 January 2022 / Published: 15 January 2022
(This article belongs to the Special Issue Computational Approaches for the Study of Biomolecular Networks)
After more than fifteen years from the first high-throughput experiments for human protein–protein interaction (PPI) detection, we are still wondering how close the completion of the genome-scale human PPI network reconstruction is, what needs to be further explored and whether the biological insights gained from the holistic investigation of the current network are valid and useful. The unique structure of PICKLE, a meta-database of the human experimentally determined direct PPI network developed by our group, presently covering ~80% of the UniProtKB/Swiss-Prot reviewed human complete proteome, enables the evaluation of the interactome expansion by comparing the successive PICKLE releases since 2013. We observe a gradual overall increase of 39%, 182%, and 67% in protein nodes, PPIs, and supporting references, respectively. Our results indicate that, in recent years, (a) the PPI addition rate has decreased, (b) the new PPIs are largely determined by high-throughput experiments and mainly concern existing protein nodes and (c), as we had predicted earlier, most of the newly added protein nodes have a low degree. These observations, combined with a largely overlapping k-core between PICKLE releases and a network density increase, imply that an almost complete picture of a structurally defined network has been reached. The comparative unsupervised application of two clustering algorithms indicated that exploring the full interactome topology can reveal the protein neighborhoods involved in closely related biological processes as transcriptional regulation, cell signaling and multiprotein complexes such as the connexon complex associated with cancers. A well-reconstructed human protein interactome is a powerful tool in network biology and medicine research forming the basis for multi-omic and dynamic analyses. View Full-Text
Keywords: protein–protein interactions; human PPI network; databases; network analysis; graph clustering protein–protein interactions; human PPI network; databases; network analysis; graph clustering
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MDPI and ACS Style

Dimitrakopoulos, G.N.; Klapa, M.I.; Moschonas, N.K. How Far Are We from the Completion of the Human Protein Interactome Reconstruction? Biomolecules 2022, 12, 140. https://doi.org/10.3390/biom12010140

AMA Style

Dimitrakopoulos GN, Klapa MI, Moschonas NK. How Far Are We from the Completion of the Human Protein Interactome Reconstruction? Biomolecules. 2022; 12(1):140. https://doi.org/10.3390/biom12010140

Chicago/Turabian Style

Dimitrakopoulos, Georgios N., Maria I. Klapa, and Nicholas K. Moschonas. 2022. "How Far Are We from the Completion of the Human Protein Interactome Reconstruction?" Biomolecules 12, no. 1: 140. https://doi.org/10.3390/biom12010140

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