Matthew Wakeling
Research Fellow
M.Wakeling@exeter.ac.uk
01392 408237
RILD Building Floor 3
University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK
Overview
Matthew graduated with a BA (and MA) in Computer Science from the University of Cambridge. Immediately following this, he worked for two years in an internet shopping startup company, before returning to the university to work for the Department of Genetics in the FlyMine group for eight years. He then studied for his engineering doctorate with the University of Surrey and the Met Office. Matthew has developed a keen interest in novel data analysis methods for short read sequencing data, particularly for extracting information (such as copy number variants, homozygosity mapping, and relatedness) from sequence reads that would otherwise be unused. He has been instrumental in the discovery of multiple gene-disease associations for monogenic diabetes and hyperinsulinism. He has been working in the monogenic diabetes group in the university medical school since 2015.
In his spare time Matthew enjoys music, gardening, DIY and mountain walking.
Qualifications
- BA, MA University of Cambridge
- EngD University of Surrey
Research
Research interests
Software engineering, data structures and algorithms, databases, data processing, performance optimisation, nonlinear minimisation, variational data assimilation.
Publications
Journal articles
De Franco E, Wakeling M, Frew R, Russ-Silsby J, Peters C, Marks S, Hattersley A, Flanagan S (In Press). A biallelic loss-of-function PDIA6 variant in a second patient with polycystic kidney disease, infancy-onset diabetes, and microcephaly. Clinical Genetics
Wakeling M, Owens NDL, Hopkinson JR, Johnson MB, Houghton JAL, Dastamani A, Flaxman CS, Wyatt RC, Hewat TI, Hopkins JJ, et al (In Press). A novel disease mechanism leading to the expression of a disallowed gene in the pancreatic beta-cell identified by non-coding, regulatory mutations controlling HK1. Nature Genetics Abstract.
Laver TW, Wakeling M, Hua JHY, Houghton J, Hussain K, Ellard S, Flanagan S (In Press). Comprehensive screening shows that mutations in the known syndromic genes are rare in infants presenting with hyperinsulinaemic hypoglycaemia. Clinical Endocrinology
Alakbarzade V, Iype T, Chioza BA, Harlalka GV, Singh R, Hardy H, Sreekantan-Nair A, Proukakis C, Kathryn J P, Clark LN, et al (In Press). Copy number variation of LINGO1 in familial dystonic tremor. Neurology Genetics
De Franco E, Caswell R, Johnson M, Wakeling M, Zung A, Dũng VC, Bích Ngọc CT, Goonetilleke R, Vivanco Jury M, El- Khateeb M, et al (In Press). De novo mutations in EIF2B1 affecting eIF2 signaling cause neonatal/early onset diabetes and transient hepatic dysfunction. Diabetes
De Franco E, Wakeling M, Flanagan S, Hattersley A (In Press). Infancy-onset diabetes caused by de-regulated AMPylation of the human endoplasmic reticulum chaperone BiP. EMBO Molecular Medicine
De Franco E, Owens N, Hattersley A, Flanagan S, Wakeling M, Johnson M, Wright C (In Press). Primate-specific ZNF808 is essential for pancreatic development in humans. Nature Genetics
Laver TW, Wakeling MN, Caswell RC, Bunce B, Yau D, Männistö JME, Houghton JAL, Hopkins JJ, Weedon MN, Saraff V, et al (2024). Chromosome 20p11.2 deletions cause congenital hyperinsulinism via the loss of FOXA2 or its regulatory elements. Eur J Hum Genet Abstract. Author URL.
Amaratunga SA, Hussein Tayeb T, Muhamad Sediq RN, Hama Salih FK, Dusatkova P, Wakeling MN, De Franco E, Pruhova S, Lebl J (2023). Paediatric diabetes subtypes in a consanguineous population: a single-centre cohort study from Kurdistan, Iraq. Diabetologia, 67(1), 113-123. Abstract.
Hopkins JJ, Wakeling MN, Johnson MB, Flanagan SE, Laver TW (2023). REVEL is Better at Predicting Pathogenicity of Loss-of-Function than Gain-of-Function Variants. Human Mutation, 2023, 1-6. Abstract.
Fasham J, Huebner AK, Liebmann L, Khalaf-Nazzal R, Maroofian R, Kryeziu N, Wortmann SB, Leslie JS, Ubeyratna N, Mancini GMS, et al (2023). SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission. Brain, 146(11), 4547-4561. Abstract. Author URL.
Russ-Silsby J, Patel KA, Laver TW, Hawkes G, Johnson MB, Wakeling MN, Patil PP, Hattersley AT, Flanagan SE, Weedon MN, et al (2023). The Role of ONECUT1 Variants in Monogenic and Type 2 Diabetes Mellitus. Diabetes, 72(11), 1729-1734. Abstract. Author URL.
Khalaf-Nazzal R, Fasham J, Inskeep KA, Blizzard LE, Leslie JS, Wakeling MN, Ubeyratna N, Mitani T, Griffith JL, Baker W, et al (2022). Bi-allelic CAMSAP1 variants cause a clinically recognizable neuronal migration disorder. Am J Hum Genet, 109(11), 2068-2079. Abstract. Author URL.
Laver TW, Wakeling MN, Knox O, Colclough K, Wright CF, Ellard S, Hattersley AT, Weedon MN, Patel KA (2022). Evaluation of Evidence for Pathogenicity Demonstrates That BLK, KLF11, and PAX4 Should Not be Included in Diagnostic Testing for MODY. Diabetes, 71(5), 1128-1136. Abstract. Author URL.
French CE, Dolling H, Mégy K, Sanchis-Juan A, Kumar A, Delon I, Wakeling M, Mallin L, Agrawal S, Austin T, et al (2022). Refinements and considerations for trio whole-genome sequence analysis when investigating Mendelian diseases presenting in early childhood. Human Genetics and Genomics Advances, 3(3). Abstract.
Laver TW, De Franco E, Johnson MB, Patel KA, Ellard S, Weedon MN, Flanagan SE, Wakeling MN (2022). SavvyCNV: Genome-wide CNV calling from off-target reads. PLOS Computational Biology, 18(3), e1009940-e1009940. Abstract.
Zhang X, Wakeling M, Ware J, Whiffin N (2021). Annotating high-impact 5'untranslated region variants with the UTRannotator. Bioinformatics, 37(8), 1171-1173. Abstract. Author URL.
Salter CG, Cai Y, Lo B, Helman G, Taylor H, McCartney A, Leslie JS, Accogli A, Zara F, Traverso M, et al (2021). Biallelic PI4KA variants cause neurological, intestinal and immunological disease. Brain, 144(12), 3597-3610. Abstract. Author URL.
Acar S, Montaser H, Patel KA, Balboa D, Ibrahim H, Lithovius V, Näätänen A, Chandra V, Demir K, Ben-Omran T, et al (2021). Loss of MANF Causes Childhood-Onset Syndromic Diabetes Due to Increased Endoplasmic Reticulum Stress. Diabetes, 70(4), 1006-1018. Abstract. Author URL.
Wakeling E, McEntagart M, Bruccoleri M, Shaw-Smith C, Stals KL, Wakeling M, Barnicoat A, Beesley C, DDD Study, Hanson-Kahn AK, et al (2021). Missense substitutions at a conserved 14-3-3 binding site in HDAC4 cause a novel intellectual disability syndrome. HGG Adv, 2(1). Abstract. Author URL.
Zhang X, Wakeling M, Ware J, Whiffin N (2020). Annotating high-impact 5’untranslated region variants with the UTRannotator. Abstract.
Wakeling MN, Laver TW, Colclough K, Parish A, Ellard S, Baple EL (2020). Misannotation of multiple-nucleotide variants risks misdiagnosis. Wellcome Open Research, 4, 145-145. Abstract.
Banerjee I, Senniappan S, Laver TW, Caswell R, Zenker M, Mohnike K, Cheetham T, Wakeling MN, Ismail D, Lennerz B, et al (2020). Refinement of the critical genomic region for congenital hyperinsulinism in the Chromosome 9p deletion syndrome. Wellcome Open Research, 4, 149-149. Abstract.
Banerjee I, Senniappan S, Laver TW, Caswell R, Zenker M, Mohnike K, Cheetham T, Wakeling MN, Ismail D, Lennerz B, et al (2020). Refinement of the critical genomic region for congenital hyperinsulinism in the Chromosome 9p deletion syndrome. Wellcome open research, 4 Abstract.
De Franco E, Lytrivi M, Ibrahim H, Montaser H, Wakeling M, Fantuzzi F, Patel K, Demarez C, Cai Y, Igoillo-Esteve M, et al (2020). YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress. Journal of Clinical Investigation, 130
Rawlins LE, Jones H, Wenger O, Aye M, Fasham J, Harlalka GV, Chioza BA, Miron A, Ellard S, Wakeling M, et al (2019). An Amish founder variant consolidates disruption of CEP55 as a cause of hydranencephaly and renal dysplasia. Eur J Hum Genet, 27(4), 657-662. Abstract. Author URL.
Wakeling MN, Laver TW, Wright CF, De Franco E, Stals KL, Patch A-M, Hattersley AT, Flanagan SE, Ellard S, DDD Study, et al (2019). Correction: Homozygosity mapping provides supporting evidence of pathogenicity in recessive Mendelian disease. Genet Med, 21(3). Abstract. Author URL.
Wakeling MN, Laver TW, Wright CF, De Franco E, Stals KL, Patch A-M, Hattersley AT, Flanagan SE, Ellard S, DDD Study, et al (2019). Homozygosity mapping provides supporting evidence of pathogenicity in recessive Mendelian disease. Genet Med, 21(4), 982-986. Abstract. Author URL.
Wakeling MN, Laver TW, Colclough K, Parish A, Ellard S, Baple EL (2019). Misannotation of multiple-nucleotide variants risks misdiagnosis. Wellcome Open Research, 4, 145-145. Abstract.
Van Bergen NJ, Guo Y, Rankin J, Paczia N, Becker-Kettern J, Kremer LS, Pyle A, Conrotte J-F, Ellaway C, Procopis P, et al (2019). NAD(P)HX dehydratase (NAXD) deficiency: a novel neurodegenerative disorder exacerbated by febrile illnesses. Brain, 142(1), 50-58. Abstract. Author URL.
Banerjee I, Senniappan S, Laver TW, Caswell R, Zenker M, Mohnike K, Cheetham T, Wakeling MN, Ismail D, Lennerz B, et al (2019). Refinement of the critical genomic region for hypoglycaemia in the Chromosome 9p deletion syndrome. Wellcome Open Research, 4, 149-149. Abstract.
Laver TW, De Franco E, Johnson MB, Patel K, Ellard S, Weedon MN, Flanagan SE, Wakeling MN (2019). SavvyCNV: genome-wide CNV calling from off-target reads. Abstract.
Johnson MBJ, De Franco E, Atma W Greeley S, Letourneau LR, Gillespie K, Wakeling MN, Ellard S, Flanagan SE, Patel K, Hattersley AT, et al (2019). Trisomy 21 is a Cause of Permanent Neonatal Diabetes that is Autoimmune but not HLA Associated. Diabetes
Yaghootkar H, Abbasi F, Ghaemi N, Rabbani A, Wakeling MN, Eshraghi P, Enayati S, Vakili S, Heidari S, Patel K, et al (2019). Type 1 diabetes genetic risk score discriminates between monogenic and Type 1 diabetes in children diagnosed at the age of <5 years in the Iranian population. Diabet Med, 36(12), 1694-1702. Abstract. Author URL.
Iacovazzo D, Flanagan S, Walker E, Quezado R, Antonio de Sousa F, Caswell R, Johnson MBJ, Wakeling M, Brandle M, Guo M, et al (2018). A MAFA missense mutation causes familial insulinomatosis and diabetes mellitus. Proceedings of the National Academy of Sciences
Laver TW, Wakeling MN, Hong Yeow Hua J, Houghton JAL, Hussain K, Ellard S, Flanagan SE (2018). Comprehensive screening shows that mutations in the known syndromic genes are rare in individuals presenting with hyperinsulinaemic hypoglycaemia. Abstract.
Stals KL, Wakeling M, Baptista J, Caswell R, Parrish A, Rankin J, Tysoe C, Jones G, Gunning AC, Lango Allen H, et al (2018). Diagnosis of lethal or prenatal-onset autosomal recessive disorders by parental exome sequencing. Prenat Diagn, 38(1), 33-43. Abstract. Author URL.
Ruark E, Holt E, Renwick A, Münz M, Wakeling M, Ellard S, Mahamdallie S, Yost S, Rahman N (2018). ICR142 Benchmarker: evaluating, optimising and benchmarking variant calling performance using the ICR142 NGS validation series. Wellcome Open Res, 3 Abstract. Author URL.
Ruark E, Holt E, Renwick A, Münz M, Wakeling M, Ellard S, Mahamdallie S, Yost S, Rahman N (2018). ICR142 Benchmarker: evaluating, optimising and benchmarking variant calling using the ICR142 NGS validation series. Wellcome Open Research, 3, 108-108. Abstract.
De Franco E, Lytrivi M, Patel K, Igoillo-Esteve M, Wakeling M, Haliloglu B, Unal E, Godbole T, Yildiz M, Ellard S, et al (2018). Mutations in YIPF5 are a novel cause of neonatal diabetes, highlighting the critical role of endoplasmic reticulum-to-Golgi trafficking in human beta cell survival. DIABETOLOGIA, 61, S106-S106. Author URL.
Low KJ, Stals K, Caswell R, Wakeling M, Clayton-Smith J, Donaldson A, Foulds N, Norman A, Splitt M, Urankar K, et al (2018). Phenotype of CNTNAP1: a study of patients demonstrating a specific severe congenital hypomyelinating neuropathy with survival beyond infancy. Eur J Hum Genet, 26(6), 796-807. Abstract. Author URL.
Laver T, Wakeling M, Knox O, De-Franco E, Flanagan S, Colclough K, Ellard S, Hattersley A, Weedon M, Patel K, et al (2018). Redefining the pathogenicity of Maturity Onset Diabetes of the Young (MODY) genes: BLK, PAX4 and KLF11 do not cause MODY. DIABETIC MEDICINE, 35, 10-10. Author URL.
Iacovazzo D, Flanagan SE, Walker E, Caswell R, Brandle M, Johnson M, Wakeling M, Guo M, Dang MN, Gabrovska P, et al (2016). A missense mutation in the islet-enriched transcription factor MAFA leads to familial insulinomatosis and diabetes. Endocrine Abstracts
Wakeling M, Eyre J, Hughes S, Roulstone I (2014). Assimilation of vertical motion from simulated cloudy satellite imagery in an idealized single column model. Quarterly Journal of the Royal Meteorological Society Abstract.
Smith RN, Aleksic J, Butano D, Carr A, Contrino S, Hu F, Lyne M, Lyne R, Kalderimis A, Rutherford K, et al (2012). InterMine: a flexible data warehouse system for the integration and analysis of heterogeneous biological data. Bioinformatics, 28(23), 3163-3165. Abstract. Author URL.
Lyne R, Smith R, Rutherford K, Wakeling M, Varley A, Guillier F, Janssens H, Ji W, Mclaren P, North P, et al (2007). FlyMine: an integrated database for Drosophila and Anopheles genomics. Genome Biol, 8(7). Abstract. Author URL.
Janssens H, Lyne R, Smith R, Guillier F, Ji W, McLaren P, Riley T, Reisinger F, Rutherford K, Wakeling M, et al (2006). Flymine:: an integrated database of <i>Drosophila</i> and anopheles genomics. JOURNAL OF NEUROGENETICS, 20(3-4), 138-139. Author URL.
Conferences
Laver T, Wakeling M, Caswell R, Bunce B, Yau D, Houghton J, Hopkins J, Weedon M, Saraff V, Kershaw M, et al (2024). Chromosome 20p11.2 deletions cause congenital hyperinsulinism via likely disruption of a FOXA2 control region. Author URL.
De Franco E, Perera LA, Harding HP, Wakeling MN, Flanagan SE, Moshina I, Raza J, Gardham A, Ron D, Hattersley AT, et al (2023). A specific homozygous variant in <i>FICD</i> is a novel cause of infancy-onset diabetes and severe neurodevelopmental delay. Author URL.
Donis R, Jeffery NM, Wakeling M, Hattersley AT, Flanagan SE, De Franco E (2023). Biallelic NARS2 variants are a novel cause of syndromic neonatal diabetes. Author URL.
Russ-Silsby JAC, Wakeling MN, Johnson MB, Flanagan SE, De Franco E (2023). Recessive PDIA6 variants cause syndromic infancy- onset diabetes with polycystic kidney disease. Author URL.
Jeffery NM, Houghton JAL, Flanagan SE, Wakeling MN, Hattersely AT, Patel K, De Franco E (2023). Recessive PDX1 variants cause neonatal diabetes with extra-pancreatic features in the majority of cases. Author URL.
Kumar R, Wakeling M, De Franco E, Self E, Flanagan SE, Patel KA, Hattersley AT (2022). 6q24 methylation defects are a novel cause of childhood/adult onset monogenic diabetes. Author URL.
Kumar R, Wakeling M, Franco ED, Self EJ, Flanagan SE, Hattersley AT, Patel KA (2022). Novel modification of monogenic diabetes gene panel test improves diagnosis of 6q24 methylation related diabetes. Author URL.
Laver TW, Wakeling MN, Knox O, Colclough K, Wright C, Ellard S, Hattersley AT, Weedon MN, Patel KA (2022). Re-evaluation of gene pathogenicity for MODY. Author URL.
Wakeling MN, Ward R, Flanagan SE, Ellard S, Hattersley AT (2022). SavvyContaminationFinder:Identifying the source of contamination inshort readsequence data. Author URL.
Kumar R, Wakeling M, De Franco E, Self E, Flanagan SE, Patel KA, Hattersley AT (2022). Simple novel modification of the existing monogenic diabetes gene panel test can improve diagnosis of diabetes due to 6q24 methylation defects. Author URL.
Van Bergen NJ, Guo Y, Rankin J, Paczia N, Becker-Kettern J, Kremer LS, Pyle A, Conrotte J, Ellaway CJ, Procopis P, et al (2019). <i>NAXD</i>mutations cause a novel neurodegenerative disorder exacerbated by febrile illnesses. Author URL.
Lytrivi M, De Franco E, Patel KA, Esteve MI, Cosentino C, Wakeling MN, Haliloglu B, Yildiz M, Godbole T, Hattersley AT, et al (2019). A Novel Genetic Syndrome of Early-Onset Diabetes, Microcephaly, and Epilepsy Due to Homozygous YIPF5 Mutations. Author URL.
Baptista J, Stals K, De Franco E, Fryer V, Wakeling M, Parrish A, Mallin L, Bussell A, Settle J, Gunning AC, et al (2019). A gene-agnostic trio exome sequencing strategy outperforms gene panel analysis. Author URL.
Baptista J, Stals K, De Franco E, Mallin L, Fryer V, Wakeling M, Parrish A, Johnson A, Settle J, Caswell R, et al (2019). A gene-agnostic trio exome strategy maximises diagnostic yield by uncovering disease-causing variants in newly discovered disease genes. Author URL.
Wakeling MN, De Franco E, Laver TW, Flanagan SE, Johnson M, Patel K, Hattersley AT, Ellard S (2019). Homozygosity mapping from small targeted NGS panels using SavvyHomozygosity - getting more from less. Author URL.
De Franco E, Wakeling MN, Johnson MB, Flanagan SE, Ellard S, Hattersley AT (2019). Integration of research within clinical care identifies 14 novel genetic causes of neonatal diabetes. Author URL.
Laver TW, Wakeling MN, Caswell R, Bunce B, Houghton JAL, Patel KA, Hussain K, Ellard S, Flanagan S (2019). Large deletions are an underappreciated cause of hyperinsulinism. Author URL.
Baptista J, Stals KL, Wakeling M, Jones G, Parrish A, Bussell A, Caswell R, Tysoe C, Baple E, Ellard S, et al (2018). High diagnostic yield through a gene-agnostic trio exome sequencing strategy that identifies mutations in new and old rare disease genes. Author URL.
