Titrating gene expression with series of systematically compromised CRISPR guide RNAs
Daniel A Santos,
Reuben A. Saunders,
Max A. Horlbeck,
John S. Hawkins,
Sonia M Scaria,
Thomas M Norman,
Jeffrey A Hussmann,
Christina R. Liem,
Carol A. Gross,
Posted 28 Jul 2019
bioRxiv DOI: 10.1101/717389 (published DOI: 10.1038/s41587-019-0387-5)
Posted 28 Jul 2019
Biological phenotypes arise from the degrees to which genes are expressed, but the lack of tools to precisely control gene expression limits our ability to evaluate the underlying expression-phenotype relationships. Here, we describe a readily implementable approach to titrate expression of human genes using series of systematically compromised sgRNAs and CRISPR interference. We empirically characterize the activities of compromised sgRNAs using large-scale measurements across multiple cell models and derive the rules governing sgRNA activity using deep learning, enabling construction of a compact sgRNA library to titrate expression of ~2,400 genes involved in central cell biology and a genome-wide in silico library. Staging cells along a continuum of gene expression levels combined with rich single-cell RNA-seq readout reveals gene-specific expression-phenotype relationships with expression level-specific responses. Our work provides a general tool to control gene expression, with applications ranging from tuning biochemical pathways to identifying suppressors for diseases of dysregulated gene expression.
- Downloaded 1,987 times
- Download rankings, all-time:
- Site-wide: 9,529
- In genomics: 949
- Year to date:
- Site-wide: 53,002
- Since beginning of last month:
- Site-wide: 40,254
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!