Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease.

"code availability analysis code together with extensive derived datasets is freely available at https://github com/mspencerchapman/clonal_selection_after_gene_therapy with some larger elements of the data available on mendeley data (10 17632/m7nz2jk8wb 1). when considering the total burden of mutations within a particular gene (fig 4e ) and the fold change of that burden (extended data fig 10e ) the confidence intervals were calculated using a custom bayesian inference algorithm (available at https://github com/mspencerchapman/gene_therapy ).; code availability analysis code together with extensive derived datasets is freely available at https://github com/mspencerchapman/clonal_selection_after_gene_therapy with some larger elements of the data available on mendeley data (10 17632/m7nz2jk8wb 1). data availability wgs data have been deposited in the european genome-phenone archive (ega) under accession no egad00001010913"

"custom r scripts used for these filtering steps are available ( https://github com/mspencerchapman/gene_therapy ).; when considering the total burden of mutations within a particular gene (fig 4e ) and the fold change of that burden (extended data fig 10e ) the confidence intervals were calculated using a custom bayesian inference algorithm (available at https://github com/mspencerchapman/gene_therapy ).; code availability analysis code together with extensive derived datasets is freely available at https://github com/mspencerchapman/clonal_selection_after_gene_therapy with some larger elements of the data available on mendeley data (10 17632/m7nz2jk8wb 1)."

"Competing interests P.J.C. is a co-founder, stockholder and consultant for FL86. M.A.F. is an employee and stockholder of AstraZeneca. D.G.K. receives laboratory funding from STRM.bio. D.A.W. serves on the following committees: Novartis steering committee, Beam Therapeutics scientific advisory board, Skyline Therapeutics (formerly Geneception) scientific advisory board and Biomarin insertion site advisor board. D.A.W. also acts as a consultant for Verve Therapeutics and Monte Rosa Therapeutics. He also has research funding from ExCellThera. E.B.E. served as a consultant for a bluebird bio steering committee. The remaining authors declare no competing interests."

"This work was supported by the Bill and Melinda Gates Foundation (INV-002189 and INV-038816, D.G.K.). M.S.C. was supported by a Wellcome Clinical PhD Fellowship. Work conducted by D.A.W. and colleagues was supported by National Institutes of Health grant R01HL (137848) and NHLBI Cure Sickle grant (OT2HL 154815). Investigators at the Sanger Institute were supported by a core grant from the Wellcome Trust. This research was funded in part by the Wellcome Trust (206194 and 108413/A/15/D). For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. J.N. is supported by a Cancer Research UK Fellowship. Work in the D.G.K. laboratory is supported by a European Research Council Starting Grant (ERC-2016-STG-715371) and a Cancer Research UK Programme Foundation Award (DCRPGF\100008). The authors thank the IT Support team of the Cancer, Ageing and Somatic mutation programme at the Sanger Institute for their support and V. Sankaran and L. Naldini for helpful discussion. The authors also thank the patients for donating the samples that have been used in this study."