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      A statistical framework for analyzing deep mutational scanning data

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          Abstract

          Deep mutational scanning is a widely used method for multiplex measurement of functional consequences of protein variants. We developed a new deep mutational scanning statistical model that generates error estimates for each measurement, capturing both sampling error and consistency between replicates. We apply our model to one novel and five published datasets comprising 243,732 variants and demonstrate its superiority in removing noisy variants and conducting hypothesis testing. Simulations show our model applies to scans based on cell growth or binding and handles common experimental errors. We implemented our model in Enrich2, software that can empower researchers analyzing deep mutational scanning data.

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          The online version of this article (doi:10.1186/s13059-017-1272-5) contains supplementary material, which is available to authorized users.

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          Introduction to Meta-Analysis

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            A general method applicable to the search for similarities in the amino acid sequence of two proteins

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              A direct approach to false discovery rates

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                Author and article information

                Contributors
                dfowler@uw.edu
                Journal
                Genome Biol
                Genome Biol
                Genome Biology
                BioMed Central (London )
                1474-7596
                1474-760X
                7 August 2017
                7 August 2017
                2017
                : 18
                : 150
                Affiliations
                [1 ]GRID grid.1042.7, Bioinformatics Division, , The Walter and Eliza Hall Institute of Medical Research, ; Parkville, VIC 3052 Australia
                [2 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Department of Medical Biology, , University of Melbourne, ; Melbourne, VIC 3010 Australia
                [3 ]ISNI 0000000403978434, GRID grid.1055.1, Bioinformatics and Cancer Genomics Laboratory, , Peter MacCallum Cancer Centre, ; Melbourne, VIC 3000 Australia
                [4 ]ISNI 0000000122986657, GRID grid.34477.33, Department of Genome Sciences, , University of Washington, ; Seattle, WA 98195 USA
                [5 ]ISNI 0000000122986657, GRID grid.34477.33, Institute for Protein Design, , University of Washington, ; Seattle, WA 98195 USA
                [6 ]ISNI 0000000122986657, GRID grid.34477.33, Department of Pathology, , University of Washington, ; Seattle, WA 98195 USA
                [7 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Sir Peter MacCallum Department of Oncology, , University of Melbourne, ; Melbourne, VIC 3010 Australia
                [8 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Department of Mathematics and Statistics, , University of Melbourne, ; Melbourne, VIC 3010 Australia
                [9 ]ISNI 0000000122986657, GRID grid.34477.33, Department of Bioengineering, , University of Washington, ; Seattle, WA 98195 USA
                Article
                1272
                10.1186/s13059-017-1272-5
                5547491
                28784151
                273dad81-44e8-475a-8dda-bd52e6e75243
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 18 April 2017
                : 6 July 2017
                Funding
                Funded by: National Institute of General Medical Sciences (US)
                Award ID: 1R01GM109110
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000057, National Institute of General Medical Sciences;
                Award ID: 5R24GM115277
                Award ID: P41GM103533
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000070, National Institute of Biomedical Imaging and Bioengineering;
                Award ID: 5R21EB020277
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1054618
                Award Recipient :
                Categories
                Method
                Custom metadata
                © The Author(s) 2017

                Genetics
                Genetics

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