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Computational
Genomics

"We live in an era of unprecedented
amounts of biological and genetic data.
Using computational methods we can
now derive insight from these datasets
to improve medical decision-making,"

- A/Prof Eleni Giannoulatou 

A/Prof Eleni Giannoulatou

head, computational genomics laboratory

Research Overview

Key Research Areas

  • Bioinformatics & Statistical Genetics
  • Analysis of high-throughput genomic datasets (whole genome/exome sequencing, RNA-seq)
  • Genetics of Cardiovascular Disease such as Congenital Heart Disease, Spontaneous Coronary Artery Dissection and Dilated Cardiomyopathy

Research Overview

High-throughput genome sequencing technologies have revolutionised our understanding of human genetic diseases. What is currently needed is new computational approaches to match these recent advances in sequencing technology. This will enable researchers to explore massive datasets more easily and translate the insights contained within to help realise a future where personalized medicine based on individual genomes is the norm.

A/Prof Giannoulatou and her team analyse large amounts of genomic data to identify genetic causes of disease and understand fundamental mechanisms in biology. The main focus of her team is to identify the genetic causes of cardiovascular disease such as congenital heart disease, spontaneous coronary artery dissection and dilated cardiomyopathy.

research projects

There are 4 key projects underway in the Computational Genomics Laboratory, led by A/Prof Eleni Giannoulatou;

1. Identification of genetic causes of Congenital Heart Disease

Congenital heart disease (CHD) defines a large set of structural and functional deficits that arise during cardiac embryogenesis affecting 8 out of 1,000 live births. The cause of 80% of the CHD cases remains unknown. We develop quantitative approaches to analyse large sequencing datasets aiming to understand the genetic mechanisms underlying CHD. This project is part of a large collaborative study with Prof Sally Dunwoodie.

2. Development of novel bioinformatics methodology to increase the current diagnostic rate of genetic diseases

We develop state-of-the-art computational methods to analyse genomic data. These include variant calling and variant prioritisation methodology, identification of splice-altering variants and robust detection of copy number variation, among others. Applications include in-house medical genomics projects such as the Congenital Heart Disease whole genome sequencing project as well as other large genomic studies.

3. Exploring the genetic architecture of Spontaneous Coronary Artery Dissection

Spontaneous coronary artery dissection (SCAD) is an emergency condition that occurs when a tear forms in one of the blood vessels in the heart. If not diagnosed and treated quickly, it can cause heart attack or sudden death. SCAD predominantly affects young healthy women with no obvious risk factors. To date no obvious cause of this acute disease has been identified. A/Prof Giannoulatou is leading the genomic analysis of a large collaborative project with Prof Bob Graham aiming to discover the genetic causes of SCAD.

4. Bioinformatics of the Australian Genomics Health Alliance Cardiovascular Flagship Data

A/Prof Giannoulatou is the co-lead of the Bioinformatics/Secondary Analysis of the genome data recruited and sequenced by the Australian Genomics Health Alliance (AGHA) Cardiovascular Flagship. Through this initiative, her team collaborates and interacts with a large multi-disciplinary group consisting of clinicians, geneticists and functional genomics experts to deliver the most accurate diagnosis to congenital heart disease and dilated cardiomyopathy patients.

laboratory members & collaborators

Laboratory Members

Mikhail Gudkov, PhD Student

Eddie Ip, PhD Student

Shannon Kwan, Master’s Student

Steven Monger, Research Assistant

Emma Rath, Postdoctoral Scientist

Anushi Shah, PhD Student

Ingrid Tarr, Research Assistant

Loïc Thibaut, Postdoctoral Scientist

Michael Troup, Research Assistant

Collaborators

Dr David Adlam, University of Leicester, UK

Nabila Bouatia-Naji, Paris Cardiovascular Research Center, France

Prof George Fountzilas, Aristotle University of Thessaloniki, Greece

A/Prof Anne Goriely, University of Oxford, UK

Prof Andrew Silver, University of London, UK

Prof David Winlaw, Heart Institute, Cardiothoracic Surgery, Cincinnati Children’s Hospital Medical Centre, Cincinnati, OH, USA

publication highlights

  1. Kalisch-Smith JI, Ved N, Szumska D, Munro J, Troup M, Harris SE, Rodriguez- Caro H, Jacquemot A, Miller JJ, Stuart EM, Wolna M, Hardman E, Prin F, Lana- Elola E, Aoidi R, Fisher EMC, Tybulewicz VLJ, Mohun TJ, Lakhal-Littleton S, De Val S, Giannoulatou E, Sparrow DB. Maternal iron deficiency perturbs embryonic cardiovascular development in mice. Nat Commun. 2021 Jun 8;12(1):3447.
  2. Ip EKK, Hadinata C, Ho JWK, Giannoulatou E, “dv-trio: a family-based variant calling pipeline using DeepVariant”, Bioinformatics, 2020, 36(11):3549-3551
  3. Wang Q, Ye J,  Fang D, Lv L, Wu W, Shi D, Li Y, Yang L, Bian X, Wu J, Jiang X, Wang K, Wang Q, Hodson MP, Thibaut LM, Ho JWK, Giannoulatou E*, Li L*, “Multi-omic profiling reveals associations between the gut mucosal microbiome, the metabolome, and host DNA methylation associated gene expression in patients with colorectal cancer”, BMC Microbiology, 2020, 20(Suppl 1):83 *Joint Corresponding Authors
  4. Chapman G, Moreau JLM, Ip E,  Szot JO, Iyer KR, Shi H, Yam MX, O’Reilly VC, Enriquez A, Greasby JA, Alankarage D, Martin EMMA, Hanna BC, Edwards M, Monger S, Blue GM, Winlaw D, Ritchie HE, Grieve SM, Giannoulatou E*, Sparrow DB*, Dunwoodie SL, “Functional genomics and gene-environment interaction highlight the complexity of Congenital Heart Disease caused by Notch pathway variants”, Human Molecular Genetics, 2019, 29(4): 566-579 *Authors contributed equally to the work
  5. Ip E, Chapman G, Winlaw D, Dunwoodie SL, Giannoulatou E, “VPOT: a customisable Variant Prioritisation Ordering Tool for annotated variants”, Genomics, Proteomics & Bioinformatics, 2019, 17(5): 540-545
  6. Monger S, Troup M, Ip E, Dunwoodie S, Giannoulatou E, “Spliceogen: An integrative, scalable tool for the discovery of splice-altering variants”, Bioinformatics, 2019, 35(21): 4405-4407
  7. Alankarage D, Ip E, Szot JO, Munro J, Blue GM, Harrison K, Cuny H, Enriquez A, Troup M, Humphreys DT, Wilson M, Harvey RP, Sholler GF, Graham RM, Ho JWK, Kirk EP, Packter N, Chapman G, Winlaw DS*, Giannoulatou E*, Dunwoodie SL*, "Identification of clinically actionable variants from genome sequencing of families with congenital heart disease”, Genetics in Medicine, 2019, (5):1111-1120 *Joint senior authors
  8. Horvat C, Johnson R, Lam L, Munro J, Mazzarotto F, Roberts AM, Herman DS, Parfenov M, Haghighi A, McDonough B, DePalma SR, Keogh AM, Macdonald PS, Hayward CS, Roberts A, Barton PJR, Felkin LE, Giannoulatou E, Cook SA, Seidman JG, Seidman CE, Fatkin D, “A Gene-Centric Strategy for Identifying Disease-Causing Rare Variants in Dilated Cardiomyopathy”, Genetics in Medicine, 2019, 21(1):133-143
  9. Adlam D, Olson T, Combaret N, Kovacic J, Iismaa S, Al-Hussaini A, O'Byrne M, Bouajila S, Georges A, Mishra K, Braund P, d'Escamard V, Huang S, Magaritis M, Nelson C, de Andrade M, Kadian-Dodov D, Welch C, Mazurkiewicz S, Jeunemaitre X, Wong C, Giannoulatou E, Sweeting M, Muller D, Wood A, McGrath-Cadell L, Fatkin D, Dunwoodie S, Harvey R, Holloway C, Empana JP, Jouven X, Olin J, Gulati R, Tweet M, Hayes S, Samani M, Graham RM, Motreff P, Bouatia-Naji N, “Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection”, Journal of the American College of Cardiology, 2019, 73(1):58-66
  10. Blue GM, Ip E, Walker W, Kirk EP, Loughran-Fowlds A, Sholler GF, Dunwoodie SL, Harvey RP, Giannoulatou E, Badawi N, Winlaw DS, “Genetic burden and associations with adverse neurodevelopment in neonates with congenital heart disease”, American Heart Journal, 2018, 201:33-39
  11. McCormick H, Young PE, Hur SJ, Booher K, Chung H, Cropley JE, Giannoulatou E*, Suter CM*, “Isogenic mice exhibit sexually-dimorphic DNA methylation patterns across multiple tissues”, BMC Genomics, 2017, 18(1):966 *Joint corresponding authors
  12. Shi H, Enriquez A, Rapadas M, Martin EMMA, Wang R, Moreau J, Lim CK, Szot JO, Ip E, Hughes J, Sugimoto K, Humphreys D, McInerney-Leo AM, Leo PJ, Maghzal GJ, Halliday J, Smith J, Colley A, Mark PR, Collins F, Sillence DO, Winlaw DS, Ho J, Guillemin GJ, Brown MA, Kikuchi K, Thomas PQ, Stocker R, Giannoulatou E, Chapman G, Duncan EL, Sparrow DB, Dunwoodie SL, “NAD Deficiency, Congenital Malformations and Niacin Supplementation”, New England Journal of Medicine, 2017, 377 (6), 544-552
  13. Giannoulatou E, Maher GJ, Ding Z, Gillis AJM, Dorssers LCJ, Hoischen A, Rajpert-De Meyts E, WGS500 Consortium , McVean G, Wilkie AOM, Looijenga LHJ, Goriely A, “Whole-genome sequencing of spermatocytic tumors provides insights into the mutational processes operating in the male germline”, PLOS ONE2017, 12(5):e0178169
  14. Lau E, Giannoulatou E, Celermajer D, Humbert M, "Epidemiology and treatment of pulmonary arterial hypertension", Nature Reviews Cardiology, 2017, 14(10):603-614
  15. Munro JE, Dunwoodie SL, Giannoulatou E, “SVPV: a structural variant prediction viewer for paired-end sequencing datasets”, Bioinformatics, 2017, 33(13):2032-2033
  16. Giannoulatou E, Park SH, Humphreys DT, Ho JWK, “Verification and validation of bioinformatics software without a gold standard: A case study of BWA and Bowtie”, BMC Bioinformatics2014, 15 (Suppl 16), S15.
  17. Armitage AE*, Stacey AR*, Giannoulatou E*, Marshall E, Sturges P, Chatha K, Pasricha SR , Prentice AM, Webster C, Pellegrino P, Williams I, Norris PJ, Drakesmith H, Borrow P, “Distinct patterns of hepcidin and iron regulation during HIV- 1, HBV and HCV infections”, Proceedings of the National Academy of Sciences of the United States of America2014, 111(33):12187-12192. *Joint first authors
  18. Giannoulatou E, McVean G, Taylor IB, McGowan SJ, Maher GJ, Iqbal Z, Pfeifer SP, Turner I, Burkitt Wright EM, Shorto J, Itani A, Turner K, Gregory L, Buck D, Rajpert-De Meyts E, Looijenga LH, Kerr B, Wilkie AO, Goriely A, “Contributions of intrinsic mutation rate and selfish selection to levels of de novo HRAS mutations in the paternal germline”, Proceedings of the National Academy of Sciences of the United States of America2013, 4:2924.
  19. International Multiple Sclerosis Genetics Consortium; Wellcome Trust Case Control Consortium 2 including Giannoulatou E, “Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis”, Nature2011476(7359):214-9.
  20. Wellcome Trust Case Control Consortium including Giannoulatou E, “Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls”, Nature2010, 464(7289):713-20.  
  21. Giannoulatou E, Yau C, Colella S, Ragoussis J, Holmes CC, “GenoSNP: a variational Bayes within-sample SNP genotyping algorithm that does not require a reference population”, Bioinformatics2008, 24(19):2209-14.