Constructing multilayer PPI networks based on homologous proteins and integrating multiple PageRank to identify essential proteins

Abstract Background Predicting and studying essential proteins not only helps to understand the fundamental requirements for cell survival and growth regulation mechanisms but also deepens our understanding of disease mechanisms and drives drug development. Existing methods for identifying essential...

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Main Authors: He Zhao, Huan Xu, Tao Wang, Guixia Liu
Format: Article
Language:English
Published: BMC 2025-03-01
Series:BMC Bioinformatics
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Online Access:https://doi.org/10.1186/s12859-025-06093-5
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author He Zhao
Huan Xu
Tao Wang
Guixia Liu
author_facet He Zhao
Huan Xu
Tao Wang
Guixia Liu
author_sort He Zhao
collection DOAJ
description Abstract Background Predicting and studying essential proteins not only helps to understand the fundamental requirements for cell survival and growth regulation mechanisms but also deepens our understanding of disease mechanisms and drives drug development. Existing methods for identifying essential proteins primarily focus on PPI networks within a single species, without fully exploiting interspecies homologous relationships. These homologous relationships connect proteins from different species, forming multilayer PPI networks. Some methods only construct interlayer edges based on homologous relationships between two species, without incorporating appropriate biological attributes to assess the biological significance of these edges. Furthermore, homologous proteins are often highly conserved across multiple species, and expanding homologous relationships to more species allows for a more accurate assessment of interlayer edge importance. Results To address these issues, we propose a novel model, MLPR, which constructs a multilayer PPI network based on homologous proteins and integrates multiple PageRank algorithms to identify essential proteins. This study combines homologous protein data from three species to construct interlayer transition matrices and assigns weights to interlayer edges by integrating the biological attributes of homologous proteins and cross-species GO annotations. The MLPR model uses multiple PageRank methods to comprehensively consider homologous relationships across species and designs three key parameters to find the optimal combination that balances random walks within layers, global jumps, interlayer biases, and interspecies homologous relationships. Conclusions Experimental results show that MLPR outperforms other state-of-the-art methods in terms of performance. Ablation experiments further validate that integrating homologous relationships across three species effectively enhances the overall performance of MLPR and demonstrates the advantages of the multiple PageRank model in identifying essential proteins.
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spelling doaj-art-a4efe44a4be4430f8023933a08eaa7812025-08-20T03:01:35ZengBMCBMC Bioinformatics1471-21052025-03-0126112710.1186/s12859-025-06093-5Constructing multilayer PPI networks based on homologous proteins and integrating multiple PageRank to identify essential proteinsHe Zhao0Huan Xu1Tao Wang2Guixia Liu3College of Computer Science and Technology, Jilin UniversityCollege of Computer Science and Technology, Jilin UniversityCollege of Computer Science and Technology, Jilin UniversityCollege of Computer Science and Technology, Jilin UniversityAbstract Background Predicting and studying essential proteins not only helps to understand the fundamental requirements for cell survival and growth regulation mechanisms but also deepens our understanding of disease mechanisms and drives drug development. Existing methods for identifying essential proteins primarily focus on PPI networks within a single species, without fully exploiting interspecies homologous relationships. These homologous relationships connect proteins from different species, forming multilayer PPI networks. Some methods only construct interlayer edges based on homologous relationships between two species, without incorporating appropriate biological attributes to assess the biological significance of these edges. Furthermore, homologous proteins are often highly conserved across multiple species, and expanding homologous relationships to more species allows for a more accurate assessment of interlayer edge importance. Results To address these issues, we propose a novel model, MLPR, which constructs a multilayer PPI network based on homologous proteins and integrates multiple PageRank algorithms to identify essential proteins. This study combines homologous protein data from three species to construct interlayer transition matrices and assigns weights to interlayer edges by integrating the biological attributes of homologous proteins and cross-species GO annotations. The MLPR model uses multiple PageRank methods to comprehensively consider homologous relationships across species and designs three key parameters to find the optimal combination that balances random walks within layers, global jumps, interlayer biases, and interspecies homologous relationships. Conclusions Experimental results show that MLPR outperforms other state-of-the-art methods in terms of performance. Ablation experiments further validate that integrating homologous relationships across three species effectively enhances the overall performance of MLPR and demonstrates the advantages of the multiple PageRank model in identifying essential proteins.https://doi.org/10.1186/s12859-025-06093-5Essential proteinsHomologous proteinsMultilayer PPI networksMultiple PageRank
spellingShingle He Zhao
Huan Xu
Tao Wang
Guixia Liu
Constructing multilayer PPI networks based on homologous proteins and integrating multiple PageRank to identify essential proteins
BMC Bioinformatics
Essential proteins
Homologous proteins
Multilayer PPI networks
Multiple PageRank
title Constructing multilayer PPI networks based on homologous proteins and integrating multiple PageRank to identify essential proteins
title_full Constructing multilayer PPI networks based on homologous proteins and integrating multiple PageRank to identify essential proteins
title_fullStr Constructing multilayer PPI networks based on homologous proteins and integrating multiple PageRank to identify essential proteins
title_full_unstemmed Constructing multilayer PPI networks based on homologous proteins and integrating multiple PageRank to identify essential proteins
title_short Constructing multilayer PPI networks based on homologous proteins and integrating multiple PageRank to identify essential proteins
title_sort constructing multilayer ppi networks based on homologous proteins and integrating multiple pagerank to identify essential proteins
topic Essential proteins
Homologous proteins
Multilayer PPI networks
Multiple PageRank
url https://doi.org/10.1186/s12859-025-06093-5
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AT taowang constructingmultilayerppinetworksbasedonhomologousproteinsandintegratingmultiplepageranktoidentifyessentialproteins
AT guixialiu constructingmultilayerppinetworksbasedonhomologousproteinsandintegratingmultiplepageranktoidentifyessentialproteins