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Updated: Jul 4, 2026
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Competitive Genomic Screens of Barcoded Yeast Libraries
Published on: August 11, 2011
A one-week automated genome-wide optical pooled screen using OttoSeq.
Bryce Kirby1, Matteo Di Bernardo2,3, Iain M Cheeseman2,4
1Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA.
Genome Biology
|July 3, 2026
Summary
We developed OttoSeq, an automated platform for optical pooled screens (OPS), significantly reducing labor and time. This innovation enables rapid, large-scale genetic perturbation analysis for biological discovery.
Area of Science:
- Genomics
- Cell Biology
- Bioinformatics
Background:
- Optical pooled screens (OPS) are powerful for large-scale genetic screens.
- Current OPS methods are hindered by labor-intensive sequencing and analysis.
- A need exists for automated, high-throughput OPS solutions.
Purpose of the Study:
- To introduce OttoSeq, an automated platform for optical pooled screens (OPS).
- To demonstrate the efficiency and scalability of OttoSeq for genome-wide screening.
- To streamline the process of genetic perturbation analysis.
Main Methods:
- Integration of the Otto2 fluid handling system with the Brieflow analysis pipeline.
- Development of an automated workflow for in situ sequencing and data interpretation.
- Implementation of a genome-wide cell painting screen.
Main Results:
- OttoSeq completed a genome-wide screen in eight days.
- The platform processed 5,198,240 high-quality cells across 21,732 gene knockouts.
- Analysis identified 320 functional gene clusters, demonstrating robust interpretation capabilities.
Conclusions:
- OttoSeq significantly accelerates OPS by automating key processes.
- The platform enables efficient, large-scale genetic perturbation studies.
- Automated OPS platforms like OttoSeq are crucial for advancing biological research.
