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

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.

SUBMITTER: Wang XW

PROVIDER: S-EPMC10033937 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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

Wang Xu-Wen XW Madeddu Lorenzo L Spirohn Kerstin K Martini Leonardo L Fazzone Adriano A Becchetti Luca L Wytock Thomas P TP Kovács István A IA Balogh Olivér M OM Benczik Bettina B Pétervári Mátyás M Ágg Bence B Ferdinandy Péter P Vulliard Loan L Menche Jörg J Colonnese Stefania S Petti Manuela M Scarano Gaetano G Cuomo Francesca F Hao Tong T Laval Florent F Willems Luc L Twizere Jean-Claude JC Vidal Marc M Calderwood Michael A MA Petrillo Enrico E Barabási Albert-László AL Silverman Edwin K EK Loscalzo Joseph J Velardi Paola P Liu Yang-Yu YY

Nature communications 20230322 1

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 ...[more]

PMID: 36949045

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Project description:Host-pathogen interactions (HPIs) are vital in numerous biological activities and are intrinsically linked to the onset and progression of infectious diseases. HPIs are pivotal in the entire lifecycle of diseases: from the onset of pathogen introduction, navigating through the mechanisms that bypass host cellular defenses, to its subsequent proliferation inside the host. At the heart of these stages lies the synergy of proteins from both the host and the pathogen. By understanding these interlinking protein dynamics, we can gain crucial insights into how diseases progress and pave the way for stronger plant defenses and the swift formulation of countermeasures. In the framework of current study, we developed a web-based R/Shiny app, Deep-HPI-pred, that uses network-driven feature learning method to predict the yet unmapped interactions between pathogen and host proteins. Leveraging citrus and CLas bacteria training datasets as case study, we spotlight the effectiveness of Deep-HPI-pred in discerning Protein-protein interaction (PPIs) between them. Deep-HPI-pred use Multilayer Perceptron (MLP) models for HPI prediction, which is based on a comprehensive evaluation of topological features and neural network architectures. When subjected to independent validation datasets, the predicted models consistently surpassed a Matthews correlation coefficient (MCC) of 0.80 in host-pathogen interactions. Remarkably, the use of Eigenvector Centrality as the leading topological feature further enhanced this performance. Further, Deep-HPI-pred also offers relevant gene ontology (GO) term information for each pathogen and host protein within the system. This protein annotation data contributes an additional layer to our understanding of the intricate dynamics within host-pathogen interactions. In the additional benchmarking studies, the Deep-HPI-pred model has proven its robustness by consistently delivering reliable results across different host-pathogen systems, including plant-pathogens (accuracy of 98.4% and 97.9%), human-virus (accuracy of 94.3%), and animal-bacteria (accuracy of 96.6%) interactomes. These results not only demonstrate the model's versatility but also pave the way for gaining comprehensive insights into the molecular underpinnings of complex host-pathogen interactions. Taken together, the Deep-HPI-pred applet offers a unified web service for both identifying and illustrating interaction networks. Deep-HPI-pred applet is freely accessible at its homepage: https://cbi.gxu.edu.cn/shiny-apps/Deep-HPI-pred/ and at github: https://github.com/tahirulqamar/Deep-HPI-pred.

Dataset Information

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

Publications

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

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