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Integrative COVID-19 biological network inference with probabilistic core decomposition.

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of deaths around the world. To help contribute to the understanding of crucial knowledge and to further generate new hypotheses relevant to SARS-CoV-2 and human protein interactions, we make use of the information abundant Biomine probabilistic database and extend the experimentally identified SARS-CoV-2-human protein-protein interaction (PPI) network in silico. We generate an extended network by integrating information from the Biomine database, the PPI network and other experimentally validated results. To generate novel hypotheses, we focus on the high-connectivity sub-communities that overlap most with the integrated experimentally validated results in the extended network. Therefore, we propose a new data analysis pipeline that can efficiently compute core decomposition on the extended network and identify dense subgraphs. We then evaluate the identified dense subgraph and the generated hypotheses in three contexts: literature validation for uncovered virus targeting genes and proteins, gene function enrichment analysis on subgraphs and literature support on drug repurposing for identified tissues and diseases related to COVID-19. The major types of the generated hypotheses are proteins with their encoding genes and we rank them by sorting their connections to the integrated experimentally validated nodes. In addition, we compile a comprehensive list of novel genes, and proteins potentially related to COVID-19, as well as novel diseases which might be comorbidities. Together with the generated hypotheses, our results provide novel knowledge relevant to COVID-19 for further validation.

SUBMITTER: Guo Y

PROVIDER: S-EPMC8689992 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSince the outbreak of COVID-19 in December 2019 in Wuhan, Hubei Province, China, frequent interregional contacts and the high rate of infection spread have catalyzed the formation of an epidemic network.ObjectiveThe aim of this study was to identify influential nodes and highlight the hidden structural properties of the COVID-19 epidemic network, which we believe is central to prevention and control of the epidemic.MethodsWe first constructed a network of the COVID-19 epidemic among 31 provinces in mainland China; after some basic characteristics were revealed by the degree distribution, the k-core decomposition method was employed to provide static and dynamic evidence to determine the influential nodes and hierarchical structure. We then exhibited the influence power of the above nodes and the evolution of this power.ResultsOnly a small fraction of the provinces studied showed relatively strong outward or inward epidemic transmission effects. The three provinces of Hubei, Beijing, and Guangzhou showed the highest out-degrees, and the three highest in-degrees were observed for the provinces of Beijing, Henan, and Liaoning. In terms of the hierarchical structure of the COVID-19 epidemic network over the whole period, more than half of the 31 provinces were located in the innermost core. Considering the correlation of the characteristics and coreness of each province, we identified some significant negative and positive factors. Specific to the dynamic transmission process of the COVID-19 epidemic, three provinces of Anhui, Beijing, and Guangdong always showed the highest coreness from the third to the sixth week; meanwhile, Hubei Province maintained the highest coreness until the fifth week and then suddenly dropped to the lowest in the sixth week. We also found that the out-strengths of the innermost nodes were greater than their in-strengths before January 27, 2020, at which point a reversal occurred.ConclusionsIncreasing our understanding of how epidemic networks form and function may help reduce the damaging effects of COVID-19 in China as well as in other countries and territories worldwide.

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Integrative COVID-19 biological network inference with probabilistic core decomposition.

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