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SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis
Single-cell CRISPR screens are a promising biotechnology for mapping regulatory elements to target genes at genome-wide scale. However, technical factors like sequencing depth impact not only expression measurement but also perturbation detection, creating a confounding effect. We demonstrate on two...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686614/ https://www.ncbi.nlm.nih.gov/pubmed/34930414 http://dx.doi.org/10.1186/s13059-021-02545-2 |
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author | Barry, Timothy Wang, Xuran Morris, John A. Roeder, Kathryn Katsevich, Eugene |
author_facet | Barry, Timothy Wang, Xuran Morris, John A. Roeder, Kathryn Katsevich, Eugene |
author_sort | Barry, Timothy |
collection | PubMed |
description | Single-cell CRISPR screens are a promising biotechnology for mapping regulatory elements to target genes at genome-wide scale. However, technical factors like sequencing depth impact not only expression measurement but also perturbation detection, creating a confounding effect. We demonstrate on two single-cell CRISPR screens how these challenges cause calibration issues. We propose SCEPTRE: analysis of single-cell perturbation screens via conditional resampling, which infers associations between perturbations and expression by resampling the former according to a working model for perturbation detection probability in each cell. SCEPTRE demonstrates very good calibration and sensitivity on CRISPR screen data, yielding hundreds of new regulatory relationships supported by orthogonal biological evidence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s13059-021-02545-2). |
format | Online Article Text |
id | pubmed-8686614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86866142021-12-21 SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis Barry, Timothy Wang, Xuran Morris, John A. Roeder, Kathryn Katsevich, Eugene Genome Biol Method Single-cell CRISPR screens are a promising biotechnology for mapping regulatory elements to target genes at genome-wide scale. However, technical factors like sequencing depth impact not only expression measurement but also perturbation detection, creating a confounding effect. We demonstrate on two single-cell CRISPR screens how these challenges cause calibration issues. We propose SCEPTRE: analysis of single-cell perturbation screens via conditional resampling, which infers associations between perturbations and expression by resampling the former according to a working model for perturbation detection probability in each cell. SCEPTRE demonstrates very good calibration and sensitivity on CRISPR screen data, yielding hundreds of new regulatory relationships supported by orthogonal biological evidence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s13059-021-02545-2). BioMed Central 2021-12-20 /pmc/articles/PMC8686614/ /pubmed/34930414 http://dx.doi.org/10.1186/s13059-021-02545-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Method Barry, Timothy Wang, Xuran Morris, John A. Roeder, Kathryn Katsevich, Eugene SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis |
title | SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis |
title_full | SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis |
title_fullStr | SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis |
title_full_unstemmed | SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis |
title_short | SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis |
title_sort | sceptre improves calibration and sensitivity in single-cell crispr screen analysis |
topic | Method |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686614/ https://www.ncbi.nlm.nih.gov/pubmed/34930414 http://dx.doi.org/10.1186/s13059-021-02545-2 |
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