Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions

<p>Abstract</p> <p>Background</p> <p>High-throughput methods for detecting protein-protein interactions enable us to obtain large interaction networks, and also allow us to computationally identify the associations of proteins as protein complexes. Although there are me...

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Main Authors: Kashima Hisashi, Fujimori Shigeo, Saito Rintaro, Ozawa Yosuke, Ishizaka Masamichi, Yanagawa Hiroshi, Miyamoto-Sato Etsuko, Tomita Masaru
Format: Article
Language:English
Published: BMC 2010-06-01
Series:BMC Bioinformatics
Online Access:http://www.biomedcentral.com/1471-2105/11/350
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author Kashima Hisashi
Fujimori Shigeo
Saito Rintaro
Ozawa Yosuke
Ishizaka Masamichi
Yanagawa Hiroshi
Miyamoto-Sato Etsuko
Tomita Masaru
author_facet Kashima Hisashi
Fujimori Shigeo
Saito Rintaro
Ozawa Yosuke
Ishizaka Masamichi
Yanagawa Hiroshi
Miyamoto-Sato Etsuko
Tomita Masaru
author_sort Kashima Hisashi
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>High-throughput methods for detecting protein-protein interactions enable us to obtain large interaction networks, and also allow us to computationally identify the associations of proteins as protein complexes. Although there are methods to extract protein complexes as sets of proteins from interaction networks, the extracted complexes may include false positives because they do not account for the structural limitations of the proteins and thus do not check that the proteins in the extracted complex can simultaneously bind to each other. In addition, there have been few searches for deeper insights into the protein complexes, such as of the topology of the protein-protein interactions or into the domain-domain interactions that mediate the protein interactions.</p> <p>Results</p> <p>Here, we introduce a combinatorial approach for prediction of protein complexes focusing not only on determining member proteins in complexes but also on the DDI/PPI organization of the complexes. Our method analyzes complex candidates predicted by the existing methods. It searches for optimal combinations of domain-domain interactions in the candidates based on an assumption that the proteins in a candidate can form a true protein complex if each of the domains is used by a single protein interaction. This optimization problem was mathematically formulated and solved using binary integer linear programming. By using publicly available sets of yeast protein-protein interactions and domain-domain interactions, we succeeded in extracting protein complex candidates with an accuracy that is twice the average accuracy of the existing methods, MCL, MCODE, or clustering coefficient. Although the configuring parameters for each algorithm resulted in slightly improved precisions, our method always showed better precision for most values of the parameters.</p> <p>Conclusions</p> <p>Our combinatorial approach can provide better accuracy for prediction of protein complexes and also enables to identify both direct PPIs and DDIs that mediate them in complexes.</p>
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spelling doaj.art-d40ed492de404aaf9eb285e97e0ae40c2022-12-22T00:57:14ZengBMCBMC Bioinformatics1471-21052010-06-0111135010.1186/1471-2105-11-350Protein complex prediction via verifying and reconstructing the topology of domain-domain interactionsKashima HisashiFujimori ShigeoSaito RintaroOzawa YosukeIshizaka MasamichiYanagawa HiroshiMiyamoto-Sato EtsukoTomita Masaru<p>Abstract</p> <p>Background</p> <p>High-throughput methods for detecting protein-protein interactions enable us to obtain large interaction networks, and also allow us to computationally identify the associations of proteins as protein complexes. Although there are methods to extract protein complexes as sets of proteins from interaction networks, the extracted complexes may include false positives because they do not account for the structural limitations of the proteins and thus do not check that the proteins in the extracted complex can simultaneously bind to each other. In addition, there have been few searches for deeper insights into the protein complexes, such as of the topology of the protein-protein interactions or into the domain-domain interactions that mediate the protein interactions.</p> <p>Results</p> <p>Here, we introduce a combinatorial approach for prediction of protein complexes focusing not only on determining member proteins in complexes but also on the DDI/PPI organization of the complexes. Our method analyzes complex candidates predicted by the existing methods. It searches for optimal combinations of domain-domain interactions in the candidates based on an assumption that the proteins in a candidate can form a true protein complex if each of the domains is used by a single protein interaction. This optimization problem was mathematically formulated and solved using binary integer linear programming. By using publicly available sets of yeast protein-protein interactions and domain-domain interactions, we succeeded in extracting protein complex candidates with an accuracy that is twice the average accuracy of the existing methods, MCL, MCODE, or clustering coefficient. Although the configuring parameters for each algorithm resulted in slightly improved precisions, our method always showed better precision for most values of the parameters.</p> <p>Conclusions</p> <p>Our combinatorial approach can provide better accuracy for prediction of protein complexes and also enables to identify both direct PPIs and DDIs that mediate them in complexes.</p>http://www.biomedcentral.com/1471-2105/11/350
spellingShingle Kashima Hisashi
Fujimori Shigeo
Saito Rintaro
Ozawa Yosuke
Ishizaka Masamichi
Yanagawa Hiroshi
Miyamoto-Sato Etsuko
Tomita Masaru
Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions
BMC Bioinformatics
title Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions
title_full Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions
title_fullStr Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions
title_full_unstemmed Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions
title_short Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions
title_sort protein complex prediction via verifying and reconstructing the topology of domain domain interactions
url http://www.biomedcentral.com/1471-2105/11/350
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