UK Infrastructure for Large-scale Clinical Genomics Research

英国大规模临床基因组学研究基础设施

• 批准号: MC_PC_14089
• 负责人: Mark Caulfield
• 金额: $ 764.17万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_PC_14089
• 关键词: UK; Infrastructure; Large; scale; Clinical

This proposal to the MRC will establish a shared, secure, high performance data and compute infrastructure as a platform for large-scale clinical genomics research based on the data flows of the UK 100,000 Genomes project.Samples and data from patients with cancer and rare, inherited disorders will be provided by NHS England, working in collaboration with Cancer Research UK and programmes funded by the NIHR and the MRC. Genomics England, a company wholly owned by the Department of Health, will pay for the generation of whole genome sequence data.Genomics England will pay also for the generation of summary reports, based upon clinical annotations of this data, and will return these to the NHS to support patient care. Genomics England will make anonymised, redacted versions of the data available for industrial research strictly within a secure, managed environment.The proposed infrastructure will provide a similar environment for academic research, with a more comprehensive collection of genomic and patient data, including the read-level data used for the generation of variant calls and summary reports. The infrastructure will include software tools to support the production of 'research-ready' data sets, the effective management of patient and genomic data, and the delivery of collaborative clinical research.The project partners have experience in infrastructure development and clinical genomics research, and will be able to reuse designs, procedures, and software developed and tested within existing programmes and organisations, including UKBiobank and the European Bioinformatics Institute.A formal mechanism will be established for engagement with public, charitable, and philanthropic funders, and with the clinical research projects that they fund. Subject to capacity constraints, projects that add appropriate value to the Genomics England programme will be provided with access to the compute infrastructure at no charge.

这份提交给MRC的提案将建立一个共享的、安全的、高性能的数据和计算基础设施，作为基于英国100,000基因组项目数据流的大规模临床基因组研究的平台。来自癌症和罕见遗传性疾病患者的样本和数据将由英国国家医疗服务体系（NHS）与英国癌症研究中心（cancer Research UK）以及英国国家卫生研究院（NIHR）和英国医学研究委员会（MRC）资助的项目合作提供。英国卫生部（Department of Health）全资拥有的英国基因组学公司（Genomics England）将为全基因组序列数据的生成支付费用。英国基因组学公司还将根据这些数据的临床注释支付生成总结报告的费用，并将这些报告返还给NHS，以支持患者护理。英国基因组学公司将严格在一个安全、可控的环境中为工业研究提供匿名、编辑版本的数据。拟议的基础设施将为学术研究提供类似的环境，具有更全面的基因组和患者数据收集，包括用于生成变体调用和摘要报告的读取级数据。该基础设施将包括软件工具，以支持“研究就绪”数据集的生产，患者和基因组数据的有效管理，以及协作临床研究的交付。项目合作伙伴具有基础设施开发和临床基因组学研究的经验，并且能够在现有项目和组织（包括UKBiobank和欧洲生物信息学研究所）中重用开发和测试的设计、程序和软件。将建立一个正式机制，与公众、慈善机构和慈善资助者以及他们资助的临床研究项目进行接触。在能力有限的情况下，为基因组学英国计划增加适当价值的项目将免费提供使用计算基础设施的机会。

项目成果

Uncovering the burden of hidden ciliopathies in the 100 000 Genomes Project: a reverse phenotyping approach.

• DOI: 10.1136/jmedgenet-2022-108476
• 发表时间: 2022-12
• 期刊: Journal of medical genetics
• 影响因子: 4

100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report.

• DOI: 10.1056/nejmoa2035790
• 发表时间: 2021-11-11
• 期刊: The New England journal of medicine
• 作者: 100,000 Genomes Project Pilot Investigators;Smedley D;Smith KR;Martin A;Thomas EA;McDonagh EM;Cipriani V;Ellingford JM;Arno G;Tucci A;Vandrovcova J;Chan G;Williams HJ;Ratnaike T;Wei W;Stirrups K;Ibanez K;Moutsianas L;Wielscher M;Need A;Barnes MR;Vestito L;Buchanan J;Wordsworth S;Ashford S;Rehmström K;Li E;Fuller G;Twiss P;Spasic-Boskovic O;Halsall S;Floto RA;Poole K;Wagner A;Mehta SG;Gurnell M;Burrows N;James R;Penkett C;Dewhurst E;Gräf S;Mapeta R;Kasanicki M;Haworth A;Savage H;Babcock M;Reese MG;Bale M;Baple E;Boustred C;Brittain H;de Burca A;Bleda M;Devereau A;Halai D;Haraldsdottir E;Hyder Z;Kasperaviciute D;Patch C;Polychronopoulos D;Matchan A;Sultana R;Ryten M;Tavares ALT;Tregidgo C;Turnbull C;Welland M;Wood S;Snow C;Williams E;Leigh S;Foulger RE;Daugherty LC;Niblock O;Leong IUS;Wright CF;Davies J;Crichton C;Welch J;Woods K;Abulhoul L;Aurora P;Bockenhauer D;Broomfield A;Cleary MA;Lam T;Dattani M;Footitt E;Ganesan V;Grunewald S;Compeyrot-Lacassagne S;Muntoni F;Pilkington C;Quinlivan R;Thapar N;Wallis C;Wedderburn LR;Worth A;Bueser T;Compton C;Deshpande C;Fassihi H;Haque E;Izatt L;Josifova D;Mohammed S;Robert L;Rose S;Ruddy D;Sarkany R;Say G;Shaw AC;Wolejko A;Habib B;Burns G;Hunter S;Grocock RJ;Humphray SJ;Robinson PN;Haendel M;Simpson MA;Banka S;Clayton-Smith J;Douzgou S;Hall G;Thomas HB;O'Keefe RT;Michaelides M;Moore AT;Malka S;Pontikos N;Browning AC;Straub V;Gorman GS;Horvath R;Quinton R;Schaefer AM;Yu-Wai-Man P;Turnbull DM;McFarland R;Taylor RW;O'Connor E;Yip J;Newland K;Morris HR;Polke J;Wood NW;Campbell C;Camps C;Gibson K;Koelling N;Lester T;Németh AH;Palles C;Patel S;Roy NBA;Sen A;Taylor J;Cacheiro P;Jacobsen JO;Seaby EG;Davison V;Chitty L;Douglas A;Naresh K;McMullan D;Ellard S;Temple IK;Mumford AD;Wilson G;Beales P;Bitner-Glindzicz M;Black G;Bradley JR;Brennan P;Burn J;Chinnery PF;Elliott P;Flinter F;Houlden H;Irving M;Newman W;Rahman S;Sayer JA;Taylor JC;Webster AR;Wilkie AOM;Ouwehand WH;Raymond FL;Chisholm J;Hill S;Bentley D;Scott RH;Fowler T;Rendon A;Caulfield M
• 通讯作者: Caulfield M

Identification and validation of a novel pathogenic variant in GDF2 (BMP9) responsible for hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations.

• DOI: 10.1002/ajmg.a.62584
• 发表时间: 2022-03
• 期刊: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
• 影响因子: 2
• 作者: Balachandar, Srimmitha;Graves, Tamara J.;Shimonty, Anika;Kerr, Katie;Kilner, Jill;Xiao, Sihao;Slade, Richard;Sroya, Manveer;Alikian, Mary;Curetean, Emanuel;Thomas, Ellen;McConnell, Vivienne P. M.;McKee, Shane;Boardman-Pretty, Freya;Devereau, Andrew;Fowler, Tom A.;Caulfield, Mark J.;Alton, Eric W.;Ferguson, Teena;Redhead, Julian;McKnight, Amy J.;Thomas, Geraldine A.;Aldred, Micheala A.;Shovlin, Claire L.
• 通讯作者: Shovlin, Claire L.

SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile.

• DOI: 10.1016/j.gim.2022.02.013
• 发表时间: 2022-06
• 期刊: GENETICS IN MEDICINE
• 影响因子: 8.8
• 作者: Al-Jawahiri, Reem;Foroutan, Aidin;Kerkhof, Jennifer;McConkey, Haley;Levy, Michael;Haghshenas, Sadegheh;Rooney, Kathleen;Turner, Jasmin;Shears, Debbie;Holder, Muriel;Lefroy, Henrietta;Castle, Bruce;Reis, Linda M.;Semina, V. Elena;Lachlan, Katherine;Chandler, Kate;Wright, Thomas;Clayton-Smith, Jill;Hug, Franziska Phan;Pitteloud, Nelly;Bartoloni, Lucia;Hoffjan, Sabine;Park, Soo-Mi;Thankamony, Ajay;Lees, Melissa;Wakeling, Emma;Naik, Swati;Hanker, Britta;Girisha, Katta M.;Agolini, Emanuele;Giuseppe, Zampino;Alban, Ziegler;Tessarech, Marine;Keren, Ziegler Boris;Afenjar, Alexandra;Zweier, Christiane;Reis, Andre;Smol, Thomas;Tsurusaki, Yoshinori;Nobuhiko, Okamoto;Sekiguchi, Futoshi;Tsuchida, Naomi;Matsumoto, Naomichi;Kou, Ikuyo;Yonezawa, Yoshiro;Ikegawa, Shiro;Callewaert, Bert;Freeth, Megan;Kleinendorst, Lotte;Donaldson, Alan;Alders, Marielle;De Paepe, Anne;Sadikovic, Bekim;McNeill, Alisdair
• 通讯作者: McNeill, Alisdair

Diverse ancestry whole-genome sequencing association study identifies TBX5 and PTK7 as susceptibility genes for posterior urethral valves.

• DOI: 10.7554/elife.74777
• 发表时间: 2022-09-20
• 期刊: eLife
• 影响因子: 7.7
• 作者: Chan MMY;Sadeghi-Alavijeh O;Lopes FM;Hilger AC;Stanescu HC;Voinescu CD;Beaman GM;Newman WG;Zaniew M;Weber S;Ho YM;Connolly JO;Wood D;Maj C;Stuckey A;Kousathanas A;Genomics England Research Consortium;Kleta R;Woolf AS;Bockenhauer D;Levine AP;Gale DP
• 通讯作者: Gale DP