Expanding the Atlas of Functional Missense Variation for Human Genes
Atina G. Cote,
Natascha van Lieshout,
Douglas M. Fowler,
Jesse D. Bloom,
David E. Hill,
Frederick P. Roth
Posted 27 Jul 2017
bioRxiv DOI: 10.1101/166595 (published DOI: 10.15252/msb.20177908)
Posted 27 Jul 2017
Although we now routinely sequence human genomes, we can confidently identify only a fraction of the sequence variants that have a functional impact. Here we developed a deep mutational scanning framework that produces exhaustive maps for human missense variants by combining random codon-mutagenesis and multiplexed functional variation assays with computational imputation and refinement. We applied this framework to four proteins corresponding to six human genes: UBE2I (encoding SUMO E2 conjugase), SUMO1 (small ubiquitin-like modifier), TPK1 (thiamin pyrophosphokinase), and CALM1/2/3 (three genes encoding the protein calmodulin). The resulting maps recapitulate known protein features, and confidently identify pathogenic variation. Assays potentially amenable to deep mutational scanning are already available for 57% of human disease genes, suggesting that DMS could ultimately map functional variation for all human disease genes.
- Downloaded 1,123 times
- Download rankings, all-time:
- Site-wide: 9,896 out of 92,645
- In molecular biology: 333 out of 3,174
- Year to date:
- Site-wide: 50,223 out of 92,645
- Since beginning of last month:
- Site-wide: 44,249 out of 92,645
Downloads over time
Distribution of downloads per paper, site-wide
- 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!