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Case-control analysis of single-cell RNA-seq studies

Viktor Petukhov, Anna Igolkina, Rasmus Rydbirk, Shenglin Mei, Lars Christoffersen, Konstantin Khodosevich, Peter V. Kharchenko
doi: https://doi.org/10.1101/2022.03.15.484475
Viktor Petukhov
1Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
2Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, 02115, USA
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Anna Igolkina
3Gregor Mendel Institute, Vienna, 1030, Austria
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Rasmus Rydbirk
1Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
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Shenglin Mei
2Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, 02115, USA
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Lars Christoffersen
1Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
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Konstantin Khodosevich
1Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
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  • For correspondence: peter_kharchenko@post.harvard.edu konstantin.khodosevich@bric.ku.dk
Peter V. Kharchenko
2Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, 02115, USA
4Harvard Stem Cell Institute, Cambridge, MA, 02138 USA
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  • For correspondence: peter_kharchenko@post.harvard.edu konstantin.khodosevich@bric.ku.dk
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Summary

Single-cell RNA-seq (scRNA-seq) assays are being increasingly utilized to investigate specific hypotheses in both basic biology and clinically-applied studies. The design of most such studies can be often reduced to a comparison between two or more groups of samples, such as disease cases and healthy controls, or treatment and placebo. Comparative analysis between groups of scRNA-seq samples brings additional statistical considerations, and currently there is a lack of tools to address this common scenario. Based on our experience with comparative designs, here we present a computational suite (Cacoa – case-control analysis) to carry out statistical tests, exploration, and visualization of scRNA-seq sample cohorts. Using multiple example datasets, we demonstrate how application of these techniques can provide additional insights, and avoid issues stemming from inter-individual variability, limited sample size, and high dimensionality of the data.

Competing Interest Statement

P.V.K. serves on the Scientific Advisory Board to Celsius Therapeutics Inc. and Biomage Inc.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 18, 2022.
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Case-control analysis of single-cell RNA-seq studies
Viktor Petukhov, Anna Igolkina, Rasmus Rydbirk, Shenglin Mei, Lars Christoffersen, Konstantin Khodosevich, Peter V. Kharchenko
bioRxiv 2022.03.15.484475; doi: https://doi.org/10.1101/2022.03.15.484475
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Case-control analysis of single-cell RNA-seq studies
Viktor Petukhov, Anna Igolkina, Rasmus Rydbirk, Shenglin Mei, Lars Christoffersen, Konstantin Khodosevich, Peter V. Kharchenko
bioRxiv 2022.03.15.484475; doi: https://doi.org/10.1101/2022.03.15.484475

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