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Multi-modal quantification of pathway activity with MAYA

Yuna Landais, View ORCID ProfileCéline Vallot
doi: https://doi.org/10.1101/2022.07.19.500633
Yuna Landais
1One Biosciences, Paris, France
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Céline Vallot
2CNRS UMR3244, Institut Curie, PSL University, Paris, France
3Translational Research Department, Institut Curie, PSL University, Paris, France
4Single Cell Initiative, Institut Curie, PSL University, Paris, France
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  • ORCID record for Céline Vallot
  • For correspondence: celine.vallot@onebiosciences.fr
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Abstract

Signaling pathways can be activated through various cascades of genes depending on cell identity and biological context. Single-cell atlases now provide the opportunity to inspect such complexity in health and disease. Yet, existing reference tools for pathway scoring resume activity of each pathway to one unique common metric across cell types. Here, we present MAYA a computational method that enables the automatic detection and scoring of the diverse modes of activation of biological pathways across cell populations. MAYA improves the granularity of pathway analysis by detecting subgroups of genes within reference pathways, each characteristic of a cell population and how it activates a pathway. Using multiple single-cell datasets, we demonstrate the biological relevance of identified modes of activation, the robustness of MAYA to noisy pathway lists and batch effect. MAYA can also predict cell types starting from lists of reference markers in a cluster-free manner. Finally, we show that MAYA reveals common modes of pathway activation in tumor cells across patients, opening the perspective to discover shared therapeutic vulnerabilities.

Competing Interest Statement

C.V. is a founder and equity holder of One Biosciences. The remaining author declares no competing interests.

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-NC-ND 4.0 International license.
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Posted July 20, 2022.
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Multi-modal quantification of pathway activity with MAYA
Yuna Landais, Céline Vallot
bioRxiv 2022.07.19.500633; doi: https://doi.org/10.1101/2022.07.19.500633
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Multi-modal quantification of pathway activity with MAYA
Yuna Landais, Céline Vallot
bioRxiv 2022.07.19.500633; doi: https://doi.org/10.1101/2022.07.19.500633

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