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Enrichment analysis on regulatory subspaces: a novel direction for the superior description of cellular responses to SARS-CoV-2

Pedro Rodrigues, Rafael S. Costa, View ORCID ProfileRui Henriques
doi: https://doi.org/10.1101/2021.12.15.472466
Pedro Rodrigues
aIDMEC, Instituto Superior Tecnico, Universidade de Lisboa, Lisbon, Portugal
bINESC-ID and Instituto Superior Tecnico, Universidade de Lisboa, Lisbon, Portugal
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Rafael S. Costa
aIDMEC, Instituto Superior Tecnico, Universidade de Lisboa, Lisbon, Portugal
cLAQV-REQUIMTE, DQ, NOVA School of Science and Technology, Caparica, Portugal
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Rui Henriques
bINESC-ID and Instituto Superior Tecnico, Universidade de Lisboa, Lisbon, Portugal
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  • ORCID record for Rui Henriques
  • For correspondence: rmch@tecnico.ulisboa.pt
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Abstract

Statement The enrichment analysis of discriminative cell transcriptional responses to SARS-CoV-2 infection using biclustering produces a broader set of superiorly enriched GO terms and KEGG pathways against alternative state-of-the-art machine learning approaches, unraveling novel knowledge.

Motivation and methods The comprehensive understanding of the impacts of the SARS-CoV-2 virus on infected cells is still incomplete. This work identifies and analyses the main cell regulatory processes affected and induced by SARS-CoV-2, using transcriptomic data from several infectable cell lines available in public databases and in vivo samples. We propose a new class of statistical models to handle three major challenges, namely the scarcity of observations, the high dimensionality of the data, and the complexity of the interactions between genes. Additionally, we analyse the function of these genes and their interactions within cells to compare them to ones affected by IAV (H1N1), RSV and HPIV3 in the target cell lines.

Results Gathered results show that, although clustering and predictive algorithms aid classic functional enrichment analysis, recent pattern-based biclustering algorithms significantly improve the number and quality of the detected biological processes. Additionally, a comparative analysis of these processes is performed to identify potential pathophysiological characteristics of COVID-19. These are further compared to those identified by other authors for the same virus as well as related ones such as SARS-CoV-1. This approach is particularly relevant due to a lack of other works utilizing more complex machine learning tools within this context.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 16, 2021.
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Enrichment analysis on regulatory subspaces: a novel direction for the superior description of cellular responses to SARS-CoV-2
Pedro Rodrigues, Rafael S. Costa, Rui Henriques
bioRxiv 2021.12.15.472466; doi: https://doi.org/10.1101/2021.12.15.472466
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Enrichment analysis on regulatory subspaces: a novel direction for the superior description of cellular responses to SARS-CoV-2
Pedro Rodrigues, Rafael S. Costa, Rui Henriques
bioRxiv 2021.12.15.472466; doi: https://doi.org/10.1101/2021.12.15.472466

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