Assistant Professor in Clinical Genomics of Transfusion and Transplant
Email: ng384@cam.ac.uk
Contact
Lindsay Walker, Blood transfusion Genomics Consortium Project Coordinator
BGCprojectcoordinator@medschl.cam.ac.uk
+44 (0)1223 588183 (NHSBT feature net 48183)
Description of research
I am interested in the development and application of computational and statistical methods for using large scale genomics and electronic healthcare record (EHR) data to answer research questions, which ultimately may lead to improvements in care for patients. My recent focus has been on: i) The development and accreditation of a DNA microarray based test for genotyping Erythrocyte (HEA, or blood group), Platelet (HPA) and Leukocyte (HLA) antigens in donors and patients at scale, ii) Using large scale genomics data to investigate the genetic basis of alloimmunisation and antibody production, iii) Detection of infectious disease outbreaks and other diseases using machine learning and population scale full blood count data.
Active Research Projects
The Blood transfusion Genomics Consortium (bgc.io) – An international project which aims to improve the safety and efficiency of blood and platelet transfusion by development and international accreditation of a DNA microarray-based test capable of typing HEA, HPA and HLA to diagnostic standard. As part of the project genotyping infrastructure has been successfully installed into the clinical laboratories of NHS Blood and Transplant (London, UK), The New York Blood Centre (NY, USA) and Sanquin (Amsterdam, NL) and validation of the technology is being carried out via in-triplicate genotyping of 16,000 DNA samples from blood donors submitted by seven blood services. Results from this study will be submitted to international regulators for approval to label blood cell concentrates using antigen typing results produced by the test.
HaemMatch – A project which aims to use machine learning and at scale blood genotyping data from patients and donors to improve transfusion outcomes for patients and optimise the logistics of blood delivery. The project will culminate in proof of principle study in which blood will be transfused to individuals with sickle cell disorder based on genotype data.
BloodCounts! – Machine learning based analysis of full blood count data for detection of infectious disease outbreaks at population level, in a pathogen-agnostic manner and quantitative interpretation of results at individual level for diagnostic decision support in a range of other diseases.
Genome Wide Association Studies – AIR: a case control GWAS to investigate the genetic basis of alloimmunisation against HEA antigens during pregnancy. Anti-A/B: A GWAS to investigate the genetic basis of anti-A and anti-B levels in blood donors enrolled in the INTERVAL, COMPARE and STRIDES NIHR BioResource donor health studies.
Publications
Stefanucci L, Moslemi C, Tomé AR, Virtue S, Bidault G, Gleadall NS, Watson LPE, Kwa JE, Burden F, Farrow S; DBDS Genetic Consortium; Chen J; MAGIC; Võsa U, Burling K, Walker L, Ord J, Barker P, Warner J, Frary A, Renhstrom K, Ashford SE, Piper J, Biggs G, Erber WN, Hoffman GJ, Schoenmakers N, Erikstrup C, Rieneck K, Dziegiel MH, Ullum H, Azzu V, Vacca M, Aparicio HJ, Hui Q, Cho K, Sun YV, Wilson PW, Bayraktar OA, Vidal-Puig A, Ostrowski SR, Astle WJ, Olsson ML, Storry JR, Pedersen OB, Ouwehand WH, Chatterjee K, Vuckovic D, Frontini M. SMIM1 absence is associated with reduced energy expenditure and excess weight. Med. 2024 Sep 13;5(9):1083-1095.e6. doi: 10.1016/j.medj.2024.05.015.
Hanson AL, Mulè MP, Ruffieux H, Mescia F, Bergamaschi L, Pelly VS, Turner L, Kotagiri P; Cambridge Institute of Therapeutic Immunology and Infectious Disease–National Institute for Health Research (CITIID–NIHR) COVID BioResource Collaboration; Göttgens B, Hess C, Gleadall N, Bradley JR, Nathan JA, Lyons PA, Drakesmith H, Smith KGC. Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19. Nat Immunol. 2024 Mar;25(3):471-482.
Cuenca-Guardiola J, Morena-Barrio B, Navarro-Manzano E, Stevens J, Ouwehand WH, Gleadall NS, Corral J, Fernández-Breis JT. Detection and annotation of transposable element insertions and deletions on the human genome using nanopore sequencing. iScience. 2023 Oct 14;26(11):108214.
Verdier H, Thomas P, Batista J, Kempster C, McKinney H, Gleadall NS, Danesh J, Mumford AD, Heemskerk JWM, Ouwehand WH, Downes K, Astle WJ, Turro E. A signature of platelet reactivity in CBC scattergrams reveals genetic predictors of thrombotic disease risk. Blood. 2023 Aug 30:blood.2023021100. doi: 10.1182/blood.2023021100. PMID: 37647652
Stefanucci L, Collins JH, Sims MC, Barrio-Hernandez I, Sun L, Burren O, Perfetto L, Bender I, Callahan TJ, Fleming K, Guerrero JA, Hermjakob H, Martin MJ, Stephenson JD, Paneerselvam K, Petrovski S, Porras P, Robinson PN, Wang Q, Watkins X, Frontini M, Laskowski RA, Beltrao P, Di Angelantonio E, Gomez K, Laffan M, Ouwehand WH, Mumford AD, Freson K, Carss KJ, Downes K, Gleadall NS, Megy K, Bruford E, Vuckovic D. The effects of pathogenic variants for inherited hemostasis disorders in 140,214 UK Biobank participants. Blood. 2023 Aug 30:blood.2023020118. doi: 10.1182/blood.2023020118. PMID: 37647632
Sanchis-Juan A, Megy K, Stephens J, Armirola Ricaurte C, Dewhurst E, Low K, French CE, Grozeva D, Stirrups K, Erwood M, McTague A, Penkett CJ, Shamardina O, Tuna S, Daugherty LC, Gleadall N, Duarte ST, Hedrera-Fernández A, Vogt J, Ambegaonkar G, Chitre M, Josifova D, Kurian MA, Parker A, Rankin J, Reid E, Wakeling E, Wassmer E, Woods CG; NIHR BioResource; Raymond FL, Carss KJ. Genome sequencing and comprehensive rare-variant analysis of 465 families with neurodevelopmental disorders. Am J Hum Genet. 2023 Aug 3;110(8):1343-1355. doi: 10.1016/j.ajhg.2023.07.007. PMID: 37541188
Cone Sullivan JK, Gleadall N, Lane WJ. Blood Group Genotyping. Clin Lab Med. 2022 Dec;42(4):645-668. doi: 10.1016/j.cll.2022.09.016. PMID: 36368788
Gassner C, Castilho L, Chen Q, Clausen FB, Denomme GA, Flegel WA, Gleadall N, Hellberg Å, Ji Y, Keller MA, Lane WJ, Ligthart P, Lomas-Francis C, Nogues N, Olsson ML, Peyrard T, Storry JR, Tani Y, Thornton N, van der Schoot E, Veldhuisen B, Wagner F, Weinstock C, Wendel S, Westhoff C, Yahalom V, Hyland CA. International Society of Blood Transfusion Working Party on Red Cell Immunogenetics and Blood Group Terminology Report of Basel and three virtual business meetings: Update on blood group systems. Vox Sang. 2022 Sep 19. doi: 10.1111/vox.13361. PMID: 36121188
de la Morena-Barrio B, Stephens J, de la Morena-Barrio ME, Stefanucci L, Padilla J, Miñano A, Gleadall N, García JL, López-Fernández MF, Morange PE, Puurunen M, Undas A, Vidal F, Raymond FL, Vicente V, Ouwehand WH, Corral J, Sanchis-Juan A; NIHR BioResource. Long-Read Sequencing Identifies the First Retrotransposon Insertion and Resolves Structural Variants Causing Antithrombin Deficiency. Thromb Haemost. 2022 Aug;122(8):1369-1378. doi: 10.1055/s-0042-1749345. PMID: 35764313
Downes K, Zhao X, Gleadall NS, McKinney H, Kempster C, Batista J, Thomas PL, Cooper M, Michael JV, Kreuzhuber R, Wedderburn K, Waller K, Varney B, Verdier H, Kriek N, Ashford SE, Stirrups KE, Dunster JL, McKenzie SE, Ouwehand WH, Gibbins JM, Yang J, Astle WJ, Ma P. G protein-coupled receptor kinase 5 regulates thrombin signaling in platelets via PAR-1. Blood Adv. 2022 Apr 12;6(7):2319-2330. doi: 10.1182/bloodadvances.2021005453. PMID: 34581777
Timmer T, Tanck M, Penkett C, Stirrups K, Gleadall N, de Kort W, van der Schoot E, van den Hurk K. Genetic determinants of ferritin, haemoglobin levels and haemoglobin trajectories: results from Donor InSight. Vox Sang. 2021 Aug;116(7):755-765. doi: 10.1111/vox.13066. PMID: 33491795
Thaventhiran JED, Lango Allen H, Burren OS, Rae W, Greene D, Staples E, Zhang Z, Farmery JHR, Simeoni I, Rivers E, Maimaris J, Penkett CJ, Stephens J, Deevi SVV, Sanchis-Juan A, Gleadall NS, Thomas MJ, Sargur RB, Gordins P, Baxendale HE, Brown M, Tuijnenburg P, Worth A, Hanson S, Linger RJ, Buckland MS, Rayner-Matthews PJ, Gilmour KC, Samarghitean C, Seneviratne SL, Sansom DM, Lynch AG, Megy K, Ellinghaus E, Ellinghaus D, Jorgensen SF, Karlsen TH, Stirrups KE, Cutler AJ, Kumararatne DS, Chandra A, Edgar JDM, Herwadkar A, Cooper N, Grigoriadou S, Huissoon AP, Goddard S, Jolles S, Schuetz C, Boschann F; Primary Immunodeficiency Consortium for the NIHR Bioresource, Lyons PA, Hurles ME, Savic S, Burns SO, Kuijpers TW, Turro E, Ouwehand WH, Thrasher AJ, Smith KGC. Whole-genome sequencing of a sporadic primary immunodeficiency cohort. Nature. 2020 Jul;583(7814):90-95. doi: 10.1038/s41586-020-2265-1. PMID: 32499645
Lane WJ, Gleadall NS, Aeschlimann J, Vege S, Sanchis-Juan A, Stephens J, Sullivan JC, Mah HH, Aguad M, Smeland-Wagman R, Lebo MS, Vijay Kumar PK, Kaufman RM, Green RC, Ouwehand WH, Westhoff CM. Multiple GYPB gene deletions associated with the U- phenotype in those of African ancestry. Transfusion. 2020 Jun;60(6):1294-1307. doi: 10.1111/trf.15839. PMID: 32473076
Wei W, Pagnamenta AT, Gleadall N, Sanchis-Juan A, Stephens J, Broxholme J, Tuna S, Odhams CA; Genomics England Research Consortium; NIHR BioResource, Fratter C, Turro E, Caulfield MJ, Taylor JC, Rahman S, Chinnery PF. Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans. Nat Commun. 2020 Apr 8;11(1):1740. doi: 10.1038/s41467-020-15336-3. PMID: 32269217
Bury L, Megy K, Stephens JC, Grassi L, Greene D, Gleadall N, Althaus K, Allsup D, Bariana TK, Bonduel M, Butta NV, Collins P, Curry N, Deevi SVV, Downes K, Duarte D, Elliott K, Falcinelli E, Furie B, Keeling D, Lambert MP, Linger R, Mangles S, Mapeta R, Millar CM, Penkett C, Perry DJ, Stirrups KE, Turro E, Westbury SK, Wu J, BioResource N, Gomez K, Freson K, Ouwehand WH, Gresele P, Simeoni I. Next-generation sequencing for the diagnosis of MYH9-RD: Predicting pathogenic variants. Hum Mutat. 2020 Jan;41(1):277-290. doi: 10.1002/humu.23927. PMID: 31562665
Lentaigne C, Greene D, Sivapalaratnam S, Favier R, Seyres D, Thys C, Grassi L, Mangles S, Sibson K, Stubbs M, Burden F, Bordet JC, Armari-Alla C, Erber W, Farrow S, Gleadall N, Gomez K, Megy K, Papadia S, Penkett CJ, Sims MC, Stefanucci L, Stephens JC, Read RJ, Stirrups KE, Ouwehand WH, Laffan MA; NIHR BioResource, Frontini M, Freson K, Turro E. Germline mutations in the transcription factor IKZF5 cause thrombocytopenia. Blood. 2019 Dec 5;134(23):2070-2081. doi: 10.1182/blood.2019000782. PMID: 31217188
Downes K, Megy K, Duarte D, Vries M, Gebhart J, Hofer S, Shamardina O, Deevi SVV, Stephens J, Mapeta R, Tuna S, Al Hasso N, Besser MW, Cooper N, Daugherty L, Gleadall N, Greene D, Haimel M, Martin H, Papadia S, Revel-Vilk S, Sivapalaratnam S, Symington E, Thomas W, Thys C, Tolios A, Penkett CJ; NIHR BioResource, Ouwehand WH, Abbs S, Laffan MA, Turro E, Simeoni I, Mumford AD, Henskens YMC, Pabinger I, Gomez K, Freson K. Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders. Blood. 2019 Dec 5;134(23):2082-2091. doi: 10.1182/blood.2018891192. PMID: 31064749
Sanchis-Juan A, Stephens J, French CE, Gleadall N, Mégy K, Penkett C, Shamardina O, Stirrups K, Delon I, Dewhurst E, Dolling H, Erwood M, Grozeva D, Stefanucci L, Arno G, Webster AR, Cole T, Austin T, Branco RG, Ouwehand WH, Raymond FL, Carss KJ. Complex structural variants in Mendelian disorders: identification and breakpoint resolution using short- and long-read genome sequencing. Genome Med. 2018 Dec 7;10(1):95. doi: 10.1186/s13073-018-0606-6. PMID: 30526634
Lane WJ, Westhoff CM, Gleadall NS, Aguad M, Smeland-Wagman R, Vege S, Simmons DP, Mah HH, Lebo MS, Walter K, Soranzo N, Di Angelantonio E, Danesh J, Roberts DJ, Watkins NA, Ouwehand WH, Butterworth AS, Kaufman RM, Rehm HL, Silberstein LE, Green RC; MedSeq Project. Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study. Lancet Haematol. 2018 Jun;5(6):e241-e251. doi: 10.1016/S2352-3026(18)30053-X. PMID: 29780001