Petrovski Laboratory: Computational Genomics

Research Overview

The Petrovski group focuses its research efforts on the design, development and application of computational methodologies to better understand the relationship between an individual’s genome variation and their risk of developing a genetic disorder.

Our goals are to convert genomics data into information, the information into knowledge and ultimately that knowledge into improved clinical management. We seek to improve Precision Diagnostics by providing concepts and workflows with clinical application in mind; thus, facilitating Precision Medicine.

Current laboratory interests include leveraging human standing variation (population genetic) data to identify the typical and indirectly the atypical patterns of genetic variation in individual genomes. We work to develop and apply appropriate methods for the interpretation of individual case or large genomic studies. We are also engaged in projects that use patient- and general population-ascertained genomic data to further improve our biological understanding of human genes, proteins, complexes and networks. Finally, we are engaged in studies to facilitate the transition from discovery to translational genetics.

Staff

  • Slavé Petrovski, Senior Research Fellow (Group Leader)
  • Alison Anderson, Postdoctoral Fellow, Bioinformatician (2016 - Current)
  • Michael Silk, PhD Student (2017 - Current)
  • Dana Jazayeri, co-supervision PhD Student (2014 - Current)
  • Benedict Nathaniel, Masters Student (2017 - Current)
  • Kerry Mullan, Honours Student (2017 - Current)
  • Joshua Traynelis (Visiting student 2016)

Collaborators

International:

  • Professor Andrew S. Allen, Department of Biostatistics and Bioinformatics, Duke University
  • Professor David B. Goldstein, Institute for Genomic Medicine (IGM), Columbia University
  • Professor Mike Johnson, Centre for Clinical Translation at the Division of Brain Sciences, Imperial College London
  • Professor Stephen Traynelis, Department of Pharmacology, Emory University; http://functionalvariants.emory.edu/index.html
  • Mr Quanli Wang, Staff Bioinformatics Engineer, Becton & Dickinson Genomics

Local: 

  • Dr. David Ascher, Ascher laboratory: Structural Biology and Bioinformatics, University of Melbourne
  • Professor David Balding, Centre for Systems Genomics, School of Mathematics and Statistics, University of Melbourne
  • Professor Samuel F. Berkovic, Department of Medicine, Austin Health, University of Melbourne
  • Professor Jozef Gecz, Neurogenetics Research Program, The University of Adelaide
  • Professor Terence J O'Brien, Department of Medicine, Royal Melbourne Hospital, University of Melbourne
  • Professor Steven Petrou, Florey Institute
  • Professor Ingird Scheffer, Department of Medicine, Austin Health, University of Melbourne

Funding

Current:

  • NHMRC Career Development Fellowship: INTEGRATING POPULATION GENETICS, IN SILICO AND FUNCTIONAL DATA TO ENABLE PRECISION MEDICINE IN THE EPILEPSIES (2017 - 2021; APP1126877; CIA)
  • NHMRC Project Grant: DETECTION OF SOMATIC MUTATIONS IN SPORADIC EPILEPSIES (2017 - 2020; APP1129054; CIC)
  • NHMRC Project Grant: GENOMICS OF ANTIEPILEPTIC DRUG-INDUCED STEVENS JOHNSON SYNDROME (2016 - 2019; APP1103979; CIB)
  • NHMRC Project Grant: PHARMACOGENOMICS OF AED ASSOCIATED BIRTH DEFECTS (2014 - 2017; APP1059858; CIA)

Past:

  • NHMRC Early Career Fellowship: IDENTIFYING GENETIC DETERMINANTS OF EPILEPSY, AND EPILEPSY TREATMENT OUTCOME, USING WHOLE-GENOME SEQUENCE DATA (2012 - 2016; APP1035130; CIA)
  • Melbourne Early Career Research Grant: PREDICTIVE ANALYTICS TO IMPROVE EPILEPSY TREATMENT AND DISEASE OUTCOMES (2012-2013; 110804; CIA)
  • Royal Melbourne Hospital Project Grant: GENOME-WIDE MULTIGENIC PHARMACOGENOMIC CLASSIFIERS FOR NEWLY TREATED EPILEPSY (2010 - 2013; CIA)

Research Opportunities

This research project is available to PhD students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

2017

  • Petrovski S, Todd JL, Durheim MT, Wang Q, et al. An Exome Sequencing Study to Assess the Role of Rare Genetic Variation in Pulmonary Fibrosis. Am J Respir Crit Care Med 2017
  • Ogden KK, Chen W, Swanger SA, McDaniel MJ, ..., Petrovski S, Cohen AE, Aizenman E, Traynelis SF, Yuan H. Molecular Mechanism of Disease-Associated Mutations in the Pre-M1 Helix of NMDA Receptors and Potential Rescue Pharmacology. PLOS Genetics 2017
  • Epi4K Consortium & Epilepsy Phenome/Genome Project. Ultra-rare genetic variation in the common epilepsies: a case-control sequencing study. Lancet Neurology 2017

2016

  • Swanger SA, Chen W, Wells G, Burger PB, …, Petrovski S, Traynelis SF, Yuan H. Mechanistic insight into NMDA receptor dysregulation by rare variants in the GluN2A and GluN2B agonist binding domains. American Journal of Human Genetics 2016, Volume 99, Issue 6, pp 1261–1280.
  • Need AC, Shashi V, Schoch K, Petrovski S, Goldstein DB. The Importance of Dynamic Reanalysis In Diagnostic Whole Exome Sequencing. J Med Genet 2016.
  • Petrovski S and Goldstein DB. Unequal representation of genetic variation across ancestry groups creates healthcare inequality in the application of precision medicine. Genome Biology 2016; 17:157.
  • Epi4K Consortium. De novo mutations in SLC1A2 and CACNA1A are important causes of epileptic encephalopathies. American Journal of Human Genetics 2016; 99(2), 287–298.
  • Petrovski S, Küry S, Myers CT, Anyane-Yeboa K, et al. Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia and seizures. American Journal of Human Genetics 2016; 98 (5), 1001-1010.
  • Petrovski S, Parrott RE, Roberts JL, Huang H, et al. Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature. Journal of Clinical Immunology 2016.
  • Gussow AB, Petrovski S, Wang Q, Allen AS, Goldstein DB. The intolerance to functional genetic variation of protein domains predicts the localization of pathogenic mutations within genes. Genome Biology 2016

2015

  • Halvorsen M, Petrovski S, Shellhaas R, Tang Y, Crandall L, Goldstein DB, Devinsky O. Mosaic mutations in early-onset genetic diseases. Genetics in Medicine 2015.
  • Bagnall RD, Crompton DE, Petrovski S, Lam L, et al. Exome‐based analysis of cardiac arrhythmia, respiratory control and epilepsy genes in sudden unexpected death in epilepsy. Annals of Neurology  2015.
  • Petrovski S, Gussow AB, Wang Q, Halvoersen M, Han Y, Weir WH, Allen AS, Goldstein DB. The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity. PLoS Genetics 2015 (Sep 2;11(9):e1005492).
  • Petrovski S, Shashi V, Schoch K, Petrou S, et al. Exome sequencing results in successful riboflavin treatment of a rapidly progressive neurological condition. Molecular Case Studies 2015 (doi:10.1101/mcs.a000257).
  • Shashi V, Petrovski S, Schoch K, Crimian R, et al. Sustained Therapeutic Response to Riboflavin in a Child with a Progressive Neurological Condition, Diagnosed by Whole Exome Sequencing. Molecular Case Studies  2015 (doi: 10.1101/mcs.a000265).
  • Williams C, Jiang YH, Shashi V, Crimian R, Schoch K, McHale D, Goldstein DB, Petrovski S. Additional Evidence that PGAP1 Complete Loss of Function Causes Autosomal Recessive Global Developmental Delay and Encephalopathy. Clinical Genetics  2015 (doi: 10.1111/cge.12581).
  • Cirulli ET, Lasseigne BN, Petrovski S, Sapp PC, et al. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science 2015 Vol. 347 no. 6229 pp. 1436-1441
  • Zhu X, Petrovski S, Xie P, Ruzzo EK, et al. Whole exome sequencing in undiagnosed genetic diseases: Interpreting 119 trios. Genetics in Medicine (2015) 17,774–781.

2014

  • EuroEPINOMICS-RES Consortium, Epilepsy Phenome Genome Project, and Epi4K Consortium. De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies. American Journal of Human Genetics. 2014 Oct 2;95(4):360-70.
  • Petrovski S, Goldstein DB. Phenomics and the interpretation of personal genomics. Sci Transl Med. 2014 Sep 17;6(254):254fs35.
  • International League Against Epilepsy Consortium on Complex Epilepsies. Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies. Lancet Neurology 2014 Sep;13(9):893-903.
  • Zhu X, Need AC, Petrovski S, Goldstein DB. One gene, many neuropsychiatric diseases: lessons from Mendelian diseases. Nature Neuroscience. 2014 Jun;17(6):773-781
  • Speed D, Hoggart C, Petrovski S, Tachmazidou I, et al. Genetic determinants for remission of seizures in newly treated epilepsy: a prospective cohort genome-wide association study. Hum Mol Genet. 2014 Jan 1;23(1):247-258.

2013

  • Petrovski S, Wang Q, Heinzen, EL, Allen AS, Goldstein DB. Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes. PLOS Genetics 2013; 9(8): e1003709.
  • Epi4K Consortium & Epilepsy Phenome/Genome Project. De novo mutations in epileptic encephalopathies. Nature. 2013; Sep 12;501(7466):217-221.
  • Goldstein DB, Allen A, Keebler J, Margulies E, Petrou S, Petrovski S, Sunyaev S. Sequencing studies in human genetics: design and interpretation. Nature Review Genetics 2013 14,460–470.

Find Slavé Petrovski on PubMed and Google Scholar!

Research Projects

This Research Group doesn't currently have any projects



Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience & Psychiatry



Key Contact

For further information about this research, please contact Dr Slavé Petrovski

Department / Centre

Medicine and Radiology