Claudia Cabrera, Ph.D

Development and application of bioinformatics tools and methodologies for a better understanding of complex traits and diseases. Areas of research include genetical genomics data analysis of hypertension and cardiovascular diseases, response to trauma (injury), and paediatric endocrinology among others.

Analysis and annotation of high-throughput data :

• Whole genome sequencing
• Exome sequencing
• RNA-Seq
• Genome-wide association studies
• Microarray analysis

Software development: genomicper (CRAN)

https://CRAN.R-project.org/package=genomicper

Circular genomic permutation approach uses GWAS results to establish the significance of pathway/gene-set associations whilst accounting for genomic structure. All SNPs in the GWAS are placed in a 'circular genome' according to their location. Then the complete set of SNP association p-values are permuted by rotation with respect to the SNPs' genomic locations. Two testing frameworks are available: permutations at the gene level, and permutations at the SNP level. The permutation at the gene level uses fisher's combination test to calculate a single gene p-value, followed by the hypergeometric test. The SNP count methodology maps each SNP to pathways/gene-sets and calculates the proportion of SNPs for the real and the permutated datasets above a pre-defined threshold. Genomicper requires a matrix of GWAS association p-values. The SNPs annotation and pathways annotations can be performed within the package or provided by the user.

Funding:

NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK

Calabrese C, Pyle A, Griffin H, Coxhead J, Hussain R, Braund PS, et al. Heteroplasmic mitochondrial DNA variants in cardiovascular diseases. PLoS genetics. 2022;18:e1010068.

Chen J, Spracklen CN, Marenne G, Varshney A, Corbin LJ, Luan Ja, et al. The trans-ancestral genomic architecture of glycemic traits. Nature genetics. 2021;53:840-60.

Olczak KJ, Taylor‐Bateman V, Nicholls HL, Traylor M, Cabrera CP, Munroe PB. Hypertension genetics past, present and future applications. Journal of internal medicine. 2021;290:1130-52.

Argentesi G, Zhou J, Azizan E, Cabrera CP, Cottrell E, Wu X, et al. Aldosterone-producing adenomas with dual mutations of GNA11/Q and CTNNB1 lead to hypertension in puberty, pregnancy or menopause, and complete cure by adrenalectomy.  Journal of Human Hypertension 2021.

Saengkaew T, Ruiz-Babot G, David A, Mancini A, Mariniello K, Cabrera CP, et al. Whole exome sequencing identifies deleterious rare variants in CCDC141 in familial self-limited delayed puberty. NPJ Genom Med. 2021;6:107.

Zhou J, Azizan EAB, Cabrera CP, Fernandes-Rosa FL, Boulkroun S, Argentesi G, et al. Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause. Nature genetics. 2021;53:1360-72.

Magavern EF, Warren HR, Ng FL, Cabrera CP, Munroe PB, Caulfield MJ. An Academic Clinician's Road Map to Hypertension Genomics: Recent Advances and Future Directions MMXX. Hypertension 2021;77:284-95.

Nicholls HL, John CR, Watson DS, Munroe PB, Barnes MR, Cabrera CP. Reaching the End-Game for GWAS: Machine Learning Approaches for the Prioritization of Complex Disease Loci. Front Genet. 2020;11:350.

Mancini A, Howard SR, Marelli F, Cabrera CP, Barnes MR, Sternberg MJE, et al. LGR4 deficiency results in delayed puberty through impaired Wnt/β-catenin signaling. JCI Insight. 2020;5.

Aarum J, Cabrera CP, Jones TA, Rajendran S, Adiutori R, Giovannoni G, et al. Enzymatic degradation of RNA causes widespread protein aggregation in cell and tissue lysates. EMBO reports. 2020:e49585.

Surendran P, Feofanova EV, Lahrouchi N, Ntalla I, Karthikeyan S, Cook J, et al. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals. Nature genetics. 2020.

Cottrell E, Cabrera CP, Ishida M, Chatterjee S, Greening J, Wright N, et al. Rare CNVs provide novel insights into the molecular basis of GH and IGF-1 insensitivity. European journal of endocrinology. 2020;183:581-95.

Wu X, Garg S, Cabrera CP, Azizan E, Zhou J, Mein C, et al. OR34-02 Somatic Transmembrane Domain Mutations of a Cell Adhesion Molecule, CADM1, Cause Primary Aldosteronism by Preventing Gap Junction Communication Between Adrenocortical Cells. J Endocr Soc. 2020;4:OR34-02.

de las Fuentes L, Sung YJ, Noordam R, Winkler T, Feitosa MF, Schwander K, et al. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. Molecular Psychiatry. 2020.

Mancini A, Howard SR, Cabrera CP, Barnes MR, David A, Wehkalampi K, Heger S, Lomniczi A, Guasti L, Ojeda SR, Dunkel L. EAP1 regulation of GnRH promoter activity is important for human pubertal timing. Human molecular genetics. 2019. Epub 2019/01/05. doi: 10.1093/hmg/ddy451. PubMed PMID: 30608578.

Giri A, Hellwege JN, Keaton JM, Park J, Qiu C, Warren HR, Torstenson ES, Kovesdy CP, Sun YV, Wilson OD, Robinson-Cohen C, Roumie CL, Chung CP, Birdwell KA, et al. Trans-ethnic association study of blood pressure determinants in over 750,000 individuals. Nature genetics. 2019;51(1):51-62. Epub 2018/12/24. doi: 10.1038/s41588-018-0303-9. PubMed PMID: 30578418; PubMed Central PMCID: PMCPMC6365102.

Bastiaenen R, Nolte IM, Munroe PB, Riese H, Nelson C, O'Connor H, Gang Y, Warren HR, Cabrera C, Reinhard W, Hengstenberg C, Rijsdijk FV, Spector T, Snieder H, et al. The narrow-sense and common single nucleotide polymorphism heritability of early repolarization. International journal of cardiology. 2019;279:135-40. Epub 2018/10/10. doi: 10.1016/j.ijcard.2018.09.119. PubMed PMID: 30297186.

Evangelou E, Warren HR, Mosen-Ansorena D, Mifsud B, Pazoki R, Gao H, Ntritsos G, Dimou N, Cabrera CP, Karaman I, Ng FL, Evangelou M, Witkowska K, Tzanis E, et al. Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nature genetics. 2018;50(10):1412-25. Epub 2018/09/19. doi: 10.1038/s41588-018-0205-x. PubMed PMID: 30224653; PubMed Central PMCID: PMCPMC6284793.

Howard SR, Oleari R, Poliandri A, Chantzara V, Fantin A, Ruiz-Babot G, Metherell LA, Cabrera CP, Barnes MR, Wehkalampi K, Guasti L, Ruhrberg C, Cariboni A, Dunkel L. HS6ST1 Insufficiency Causes Self-Limited Delayed Puberty in Contrast With Other GnRH Deficiency Genes. The Journal of clinical endocrinology and metabolism. 2018;103(9):3420-9. Epub 2018/06/23. doi: 10.1210/jc.2018-00646. PubMed PMID: 29931354; PubMed Central PMCID: PMCPMC6126894.

Sung YJ, Winkler TW, de Las Fuentes L, Bentley AR, Brown MR, Kraja AT, Schwander K, Ntalla I, Guo X, Franceschini N, Lu Y, Cheng CY, Sim X, Vojinovic D, et al. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure. American journal of human genetics. 2018;102(3):375-400. Epub 2018/02/20. doi: 10.1016/j.ajhg.2018.01.015. PubMed PMID: 29455858; PubMed Central PMCID: PMCPMC5985266.

Howard SR, Guasti L, Poliandri A, David A, Cabrera CP, Barnes MR, Wehkalampi K, O'Rahilly S, Aiken CE, Coll AP, Ma M, Rimmington D, Yeo GSH, Dunkel L. Contributions of Function-Altering Variants in Genes Implicated in Pubertal Timing and Body Mass for Self-Limited Delayed Puberty. The Journal of clinical endocrinology and metabolism. 2018;103(2):649-59. Epub 2017/11/22. doi: 10.1210/jc.2017-02147. PubMed PMID: 29161441; PubMed Central PMCID: PMCPMC5800831.

Ren M, Ng FL, Warren HR, Witkowska K, Baron M, Jia Z, Cabrera C, Zhang R, Mifsud B, Munroe PB, Xiao Q, Townsend-Nicholson A, Hobbs AJ, Ye S, et al. The biological impact of blood pressure-associated genetic variants in the natriuretic peptide receptor C gene on human vascular smooth muscle. Human molecular genetics. 2018;27(1):199-210. Epub 2017/10/19. doi: 10.1093/hmg/ddx375. PubMed PMID: 29040610; PubMed Central PMCID: PMCPMC5886068.

Dibenedetto S, Niklison-Chirou M, Cabrera CP, Ellis M, Robson LG, Knopp P, Tedesco FS, Ragazzi M, Di Foggia V, Barnes MR, Radunovic A, Marino S. Enhanced Energetic State and Protection from Oxidative Stress in Human Myoblasts Overexpressing BMI1. Stem cell reports. 2017;9(2):528-42. Epub 2017/07/25. doi: 10.1016/j.stemcr.2017.06.009. PubMed PMID: 28735850; PubMed Central PMCID: PMCPMC5549966.

Cabrera CP, Manson J, Shepherd JM, Torrance HD, Watson D, Longhi MP, Hoti M, Patel MB, O'Dwyer M, Nourshargh S, Pennington DJ, Barnes MR, Brohi K. Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study. PLoS medicine. 2017;14(7):e1002352. Epub 2017/07/18. doi: 10.1371/journal.pmed.1002352. PubMed PMID: 28715416; PubMed Central PMCID: PMCPMC5513400.

van den Berg ME, Warren HR, Cabrera CP, Verweij N, Mifsud B, Haessler J, Bihlmeyer NA, Fu YP, Weiss S, Lin HJ, Grarup N, Li-Gao R, Pistis G, Shah N, et al. Discovery of novel heart rate-associated loci using the Exome Chip. Human molecular genetics. 2017;26(12):2346-63. Epub 2017/04/06. doi: 10.1093/hmg/ddx113. PubMed PMID: 28379579; PubMed Central PMCID: PMCPMC5458336.

Warren HR*, Evangelou E*, Cabrera CP*, Gao H, Ren M, Mifsud B, Ntalla I, Surendran P, Liu C, Cook JP, Kraja AT, Drenos F, Loh M, Verweij N, et al. Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nature genetics. 2017;49(3):403-15. Epub 2017/01/31. doi: 10.1038/ng.3768. PubMed PMID: 28135244; PubMed Central PMCID: PMCPMC5972004.

Sordi R, Nandra KK, Chiazza F, Johnson FL, Cabrera CP, Torrance HD, Yamada N, Patel NS, Barnes MR, Brohi K, Collino M, Thiemermann C. Artesunate Protects Against the Organ Injury and Dysfunction Induced by Severe Hemorrhage and Resuscitation. Annals of surgery. 2017;265(2):408-17. Epub 2017/01/07. doi: 10.1097/sla.0000000000001664. PubMed PMID: 28059970.

Kraja AT, Cook JP, Warren HR, Surendran P, Liu C, Evangelou E, Manning AK, Grarup N, Drenos F, Sim X, Smith AV, Amin N, Blakemore AIF, Bork-Jensen J, et al. New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals. Circulation Cardiovascular genetics. 2017;10(5). Epub 2017/10/17. doi: 10.1161/circgenetics.117.001778. PubMed PMID: 29030403; PubMed Central PMCID: PMCPMC5776077.

Sofer T, Wong Q, Hartwig FP, Taylor K, Warren HR, Evangelou E, Cabrera CP, Levy D, Kramer H, Lange LA, Horta BL, Kerr KF, Reiner AP, Franceschini N. Genome-Wide Association Study of Blood Pressure Traits by Hispanic/Latino Background: the Hispanic Community Health Study/Study of Latinos. Scientific reports. 2017;7(1):10348. Epub 2017/09/06. doi: 10.1038/s41598-017-09019-1. PubMed PMID: 28871152; PubMed Central PMCID: PMCPMC5583292.

Wain LV, Vaez A, Jansen R, Joehanes R, van der Most PJ, Erzurumluoglu AM, O'Reilly PF, Cabrera CP, Warren HR, Rose LM, Verwoert GC, Hottenga JJ, Strawbridge RJ, Esko T, et al. Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney. Hypertension (Dallas, Tex : 1979). 2017. Epub 2017/07/26. doi: 10.1161/hypertensionaha.117.09438. PubMed PMID: 28739976; PubMed Central PMCID: PMCPMC5783787.

Howard SR, Guasti L, Ruiz-Babot G, Mancini A, David A, Storr HL, Metherell LA, Sternberg MJ, Cabrera CP, Warren HR, Barnes MR, Quinton R, de Roux N, Young J, et al. IGSF10 mutations dysregulate gonadotropin-releasing hormone neuronal migration resulting in delayed puberty. EMBO molecular medicine. 2016;8(6):626-42. Epub 2016/05/04. doi: 10.15252/emmm.201606250. PubMed PMID: 27137492; PubMed Central PMCID: PMCPMC4888853.

Ehret GB, Ferreira T, Chasman DI, Jackson AU, Schmidt EM, Johnson T, Thorleifsson G, Luan J, Donnelly LA, Kanoni S, Petersen AK, Pihur V, Strawbridge RJ, Shungin D, et al. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nature genetics. 2016;48(10):1171-84. Epub 2016/09/13. doi: 10.1038/ng.3667. PubMed PMID: 27618452; PubMed Central PMCID: PMCPMC5042863.

Cabrera CP*, Ng FL*, Warren HR*, Barnes MR, Munroe PB, Caulfield MJ. Exploring hypertension genome-wide association studies findings and impact on pathophysiology, pathways, and pharmacogenetics. Wiley interdisciplinary reviews Systems biology and medicine. 2015;7(2):73-90. Epub 2015/02/07. doi: 10.1002/wsbm.1290. PubMed PMID: 25655479.

Huffman JE, Albrecht E, Teumer A, Mangino M, Kapur K, Johnson T, Kutalik Z, Pirastu N, Pistis G, Lopez LM, Haller T, Salo P, Goel A, Li M, et al. Modulation of genetic associations with serum urate levels by body-mass-index in humans. PLoS One. 2015;10(3):e0119752. Epub 2015/03/27. doi: 10.1371/journal.pone.0119752. PubMed PMID: 25811787; PubMed Central PMCID: PMCPMC4374966.

Kokkinopoulos I, Ishida H, Saba R, Ruchaya P, Cabrera C, Struebig M, Barnes M, Terry A, Kaneko M, Shintani Y, Coppen S, Shiratori H, Ameen T, Mein C, et al. Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo. PLoS One. 2015;10(10):e0140831. Epub 2015/10/16. doi: 10.1371/journal.pone.0140831. PubMed PMID: 26469858; PubMed Central PMCID: PMCPMC4607431.

Cabrera CP, Dunn IC, Fell M, Wilson PW, Burt DW, Waddington D, Talbot R, Hocking PM, Law A, Knott S, Haley CS, de Koning DJ. Complex traits analysis of chicken growth using targeted genetical genomics. Animal genetics. 2012;43(2):163-71. Epub 2012/03/13. doi: 10.1111/j.1365-2052.2011.02223.x. PubMed PMID: 22404352.

Wei WH, Hemani G, Gyenesei A, Vitart V, Navarro P, Hayward C, Cabrera CP, Huffman JE, Knott SA, Hicks AA, Rudan I, Pramstaller PP, Wild SH, Wilson JF, et al. Genome-wide analysis of epistasis in body mass index using multiple human populations. European journal of human genetics : EJHG. 2012;20(8):857-62. Epub 2012/02/16. doi: 10.1038/ejhg.2012.17. PubMed PMID: 22333899; PubMed Central PMCID: PMCPMC3400731.

Cabrera CP, Navarro P, Huffman JE, Wright AF, Hayward C, Campbell H, Wilson JF, Rudan I, Hastie ND, Vitart V, Haley CS. Uncovering networks from genome-wide association studies via circular genomic permutation. G3 (Bethesda, Md). 2012;2(9):1067-75. Epub 2012/09/14. doi: 10.1534/g3.112.002618. PubMed PMID: 22973544; PubMed Central PMCID: PMCPMC3429921.

Wei W, Hemani G, Hicks AA, Vitart V, Cabrera-Cardenas C, Navarro P, Huffman J, Hayward C, Knott SA, Rudan I, Pramstaller PP, Wild SH, Wilson JF, Campbell H, et al. Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates. PLOS ONE. 2011;6(8):e23836. doi: 10.1371/journal.pone.0023836.

de Koning DJ, Cabrera CP, Haley CS. Genetical genomics: combining gene expression with marker genotypes in poultry. Poultry science. 2007;86(7):1501-9. Epub 2007/06/19. doi: 10.1093/ps/86.7.1501. PubMed PMID: 17575201