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

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 insigh...

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Autores principales: Dimitrakopoulos, Georgios N., Klapa, Maria I., Moschonas, Nicholas K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774112/
https://www.ncbi.nlm.nih.gov/pubmed/35053288
http://dx.doi.org/10.3390/biom12010140
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author Dimitrakopoulos, Georgios N.
Klapa, Maria I.
Moschonas, Nicholas K.
author_facet Dimitrakopoulos, Georgios N.
Klapa, Maria I.
Moschonas, Nicholas K.
author_sort Dimitrakopoulos, Georgios N.
collection PubMed
description 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.
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spelling pubmed-87741122022-01-21 How Far Are We from the Completion of the Human Protein Interactome Reconstruction? Dimitrakopoulos, Georgios N. Klapa, Maria I. Moschonas, Nicholas K. Biomolecules Article 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. MDPI 2022-01-15 /pmc/articles/PMC8774112/ /pubmed/35053288 http://dx.doi.org/10.3390/biom12010140 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dimitrakopoulos, Georgios N.
Klapa, Maria I.
Moschonas, Nicholas K.
How Far Are We from the Completion of the Human Protein Interactome Reconstruction?
title How Far Are We from the Completion of the Human Protein Interactome Reconstruction?
title_full How Far Are We from the Completion of the Human Protein Interactome Reconstruction?
title_fullStr How Far Are We from the Completion of the Human Protein Interactome Reconstruction?
title_full_unstemmed How Far Are We from the Completion of the Human Protein Interactome Reconstruction?
title_short How Far Are We from the Completion of the Human Protein Interactome Reconstruction?
title_sort how far are we from the completion of the human protein interactome reconstruction?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774112/
https://www.ncbi.nlm.nih.gov/pubmed/35053288
http://dx.doi.org/10.3390/biom12010140
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