Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq
Howard Hughes Medical Institute · University of California, San Francisco · +9 more institutions
Abstract
A central goal of genetics is to define the relationships between genotypes and phenotypes. High-content phenotypic screens such as Perturb-seq (CRISPR-based screens with single-cell RNA-sequencing readouts) enable massively parallel functional genomic mapping but, to date, have been used at limited scales. Here, we perform genome-scale Perturb-seq targeting all expressed genes with CRISPR interference (CRISPRi) across >2.5 million human cells. We use transcriptional phenotypes to predict the function of poorly characterized genes, uncovering new regulators of ribosome biogenesis (including CCDC86, ZNF236, and SPATA5L1), transcription (C7orf26), and mitochondrial respiration (TMEM242). In addition to assigning…
Citation impact
- FWCI
- 49.20
- Percentile
- 100%
- References
- 77
Authors
17- JMJoseph M. Replogle
Howard Hughes Medical Institute, University of California, San Francisco, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- RAReuben A. Saunders
Howard Hughes Medical Institute, University of California, San Francisco, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- ANAngela N. Pogson
Howard Hughes Medical Institute, University of California, San Francisco, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- JAJeffrey A. Hussmann
Howard Hughes Medical Institute, University of California, San Francisco, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- ALAlexander LeNail
Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
Topics & keywords
- Biology
- Phenotype
- Genome
- Scale (ratio)
- Genetics
- Genotype
- Computational biology
- Evolutionary biology