A New Era in Functional Genomics Screens

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2021 Sep 21

PMID 34545248

Citations 83

Authors

Laralynne Przybyla

Luke A Gilbert

Affiliations

Soon will be listed here.

Abstract

The past 25 years of genomics research first revealed which genes are encoded by the human genome and then a detailed catalogue of human genome variation associated with many diseases. Despite this, the function of many genes and gene regulatory elements remains poorly characterized, which limits our ability to apply these insights to human disease. The advent of new CRISPR functional genomics tools allows for scalable and multiplexable characterization of genes and gene regulatory elements encoded by the human genome. These approaches promise to reveal mechanisms of gene function and regulation, and to enable exploration of how genes work together to modulate complex phenotypes.

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References

Doudna J, Charpentier E . Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science. 2014; 346(6213):1258096. DOI: 10.1126/science.1258096. View

Nakamura M, Gao Y, Dominguez A, Qi L . CRISPR technologies for precise epigenome editing. Nat Cell Biol. 2021; 23(1):11-22. DOI: 10.1038/s41556-020-00620-7. View

Holtzman L, Gersbach C . Editing the Epigenome: Reshaping the Genomic Landscape. Annu Rev Genomics Hum Genet. 2018; 19:43-71. DOI: 10.1146/annurev-genom-083117-021632. View

Shalem O, Sanjana N, Zhang F . High-throughput functional genomics using CRISPR-Cas9. Nat Rev Genet. 2015; 16(5):299-311. PMC: 4503232. DOI: 10.1038/nrg3899. View

Doench J . Am I ready for CRISPR? A user's guide to genetic screens. Nat Rev Genet. 2017; 19(2):67-80. DOI: 10.1038/nrg.2017.97. View

Hanna R, Doench J . Design and analysis of CRISPR-Cas experiments. Nat Biotechnol. 2020; 38(7):813-823. DOI: 10.1038/s41587-020-0490-7. View

Knott G, Doudna J . CRISPR-Cas guides the future of genetic engineering. Science. 2018; 361(6405):866-869. PMC: 6455913. DOI: 10.1126/science.aat5011. View

Wang H, La Russa M, Qi L . CRISPR/Cas9 in Genome Editing and Beyond. Annu Rev Biochem. 2016; 85:227-64. DOI: 10.1146/annurev-biochem-060815-014607. View

Pickar-Oliver A, Gersbach C . The next generation of CRISPR-Cas technologies and applications. Nat Rev Mol Cell Biol. 2019; 20(8):490-507. PMC: 7079207. DOI: 10.1038/s41580-019-0131-5. View

10.

Dixit A, Parnas O, Li B, Chen J, Fulco C, Jerby-Arnon L . Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens. Cell. 2016; 167(7):1853-1866.e17. PMC: 5181115. DOI: 10.1016/j.cell.2016.11.038. View

11.

Adamson B, Norman T, Jost M, Cho M, Nunez J, Chen Y . A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response. Cell. 2016; 167(7):1867-1882.e21. PMC: 5315571. DOI: 10.1016/j.cell.2016.11.048. View

12.

Jaitin D, Weiner A, Yofe I, Lara-Astiaso D, Keren-Shaul H, David E . Dissecting Immune Circuits by Linking CRISPR-Pooled Screens with Single-Cell RNA-Seq. Cell. 2016; 167(7):1883-1896.e15. DOI: 10.1016/j.cell.2016.11.039. View

13.

Warren H, Evangelou E, Cabrera C, Gao H, Ren M, Mifsud B . Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nat Genet. 2017; 49(3):403-415. PMC: 5972004. DOI: 10.1038/ng.3768. View

14.

Lambert J, Ibrahim-Verbaas C, Harold D, Naj A, Sims R, Bellenguez C . Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat Genet. 2013; 45(12):1452-8. PMC: 3896259. DOI: 10.1038/ng.2802. View

15.

Horlbeck M, Xu A, Wang M, Bennett N, Park C, Bogdanoff D . Mapping the Genetic Landscape of Human Cells. Cell. 2018; 174(4):953-967.e22. PMC: 6426455. DOI: 10.1016/j.cell.2018.06.010. View

16.

Norman T, Horlbeck M, Replogle J, Ge A, Xu A, Jost M . Exploring genetic interaction manifolds constructed from rich single-cell phenotypes. Science. 2019; 365(6455):786-793. PMC: 6746554. DOI: 10.1126/science.aax4438. View

17.

Costanzo M, Kuzmin E, van Leeuwen J, Mair B, Moffat J, Boone C . Global Genetic Networks and the Genotype-to-Phenotype Relationship. Cell. 2019; 177(1):85-100. PMC: 6817365. DOI: 10.1016/j.cell.2019.01.033. View

18.

Domingo J, Baeza-Centurion P, Lehner B . The Causes and Consequences of Genetic Interactions (Epistasis). Annu Rev Genomics Hum Genet. 2019; 20:433-460. DOI: 10.1146/annurev-genom-083118-014857. View

19.

Tian R, Gachechiladze M, Ludwig C, Laurie M, Hong J, Nathaniel D . CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons. Neuron. 2019; 104(2):239-255.e12. PMC: 6813890. DOI: 10.1016/j.neuron.2019.07.014. View

20.

Chow R, Chen S . Cancer CRISPR Screens In Vivo. Trends Cancer. 2018; 4(5):349-358. PMC: 5935117. DOI: 10.1016/j.trecan.2018.03.002. View