Orobas: A computational approach for scoring and analysis of quantitative chemical-genetic interactions from CRISPR-Cas9 screens

Arshia Z Hassan; Xiang Zhang; Henry N Ward; Maximilian Billmann; Salem Bajjali; Kevin R Brown; Urvi Bhojoo; Katherine Chan; Kevin Lin; Michael Costanzo; Brenda Andrews; Charles Boone; Jason Moffat; Chad L Myers

doi:10.1016/j.xpro.2026.104594

Orobas: A computational approach for scoring and analysis of quantitative chemical-genetic interactions from CRISPR-Cas9 screens

STAR Protoc. 2026 May 28;7(2):104594. doi: 10.1016/j.xpro.2026.104594. Online ahead of print.

Authors

Affiliations

¹ Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
² Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Graduate Program in Bioinformatics and Computational Biology (BICB), University of Minnesota, Minneapolis, MN 55455, USA.
³ Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Institute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
⁴ Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
⁵ Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁶ Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
⁷ Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan; Canadian Institute for Advanced Research (CIFAR), Toronto, ON M5G 1M1, Canada.
⁸ Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Institute for Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
⁹ Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Graduate Program in Bioinformatics and Computational Biology (BICB), University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: chadm@umn.edu.

PMID: 42213768
DOI: 10.1016/j.xpro.2026.104594

Abstract

We present Orobas, a computational approach for transforming raw read count data from CRISPR-Cas9 chemical-genetic screens into quantitative interaction scores. We describe steps for computing differential interaction scores with statistical tests that account for multiple CRISPR guides per gene. We then outline approaches for post-processing differential log₂-fold-change scores across multiple screens, incorporating normalization to reduce technical artifacts and correct batch effects.

Keywords: Bioinformatics; CRISPR; Computer sciences.