Research Projects and Themes

Research at the KCCG is focused on improving the value, interpretation and translation of genomic information for patient care.

KCCG: Realising the clinical value of the genome

From 2017, the Kinghorn Centre for Clinical Genomics will be focused on realising the clinical value of the genome. With the launch of Genome.One, the first of KCCG’s missions was achieved in the context of rare and inherited disease diagnosis. This launch also resulted in a transition of all clinical, production and directly commercialisable activities into Genome.One.

With the major shift in focus for KCCG, in parallel with rapid developments across the clinical genomics landscape, we have redefined KCCG’s mission in line with the advances in clinical genomics and the current healthcare, research and political environment.

In its next phase, KCCG will focus on the following areas: identifying new medically-significant genetic variants by mining population-scale genomic data and associated health records; expanding the clinical utility of whole genome sequencing particularly searching for disease-related variants in noncoding regions of the genome; accessing, implementing and evaluating the most advanced and efficient genomic technologies; establishing genomic tests for cancer diagnosis, prognosis, and risk prediction; and developing targeted educational programs and resources for health professionals, patients and communities.

We are already working on projects that integrate the skills and knowledge of team members across all programs to ensure that we are not siloed and make the most of our diverse expertise.

The following research themes will become part of our new programs. This page will be updated in the coming weeks.

Kidney disease


Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic kidney disorder. ADPKD commonly leads to End Stage Renal Disease (ESRD), where patients will require dialysis treatments or kidney transplants. This project is being undertaken in collaboration with Dr Tim Furlong (St Vincent’s Hospital) and Professor John Shine (Garvan Institute of Medical Research).

Led by KCCG’s Dr Mark Cowley, whole genome sequencing is being used to identify disease-causing variants in genes that had traditionally been difficult to sequence. With this research we hope to be able to design a more cost-effective and accurate molecular diagnostic test for ADPKD, and in the process improve diagnostic yield.

Cancer of the pituitary, head, neck and skullbase

Tumours of the pituitary, head and neck represent a diverse group of malignancies that share common and significant clinical challenges. These include being frequently locally advanced when detected, cause significant morbidity and long term quality of life and due to their anatomical location are difficult to cure.

The aim of this project is to utilise a custom targeted sequencing gene panel or whole genome sequencing to screen multiple genes simultaneously to genetically characterise these four tumour types in ~500 patients. Proposed outcomes include an improved understanding of tumour biology, identifying robust prognostic markers, improving treatment algorithms and driving new therapeutic developments. This is a multidisciplinary project with diverse clinical and analytic expertise including Dr Ann McCormack, Dr Richard Harvey, Professor Sandra O’Toole, Dr Ruta Gupta, Dr Mark Cowley, Dr Mark McCabe and Associate Professor Marcel Dinger. We anticipate that the application of next generation sequencing will enable rapid translation into clinical practice, leading to a cost-effective improvement in the diagnosis and care of this patient group. 


KCCG projects - heart

Dilated cardiomyopathy (DCM) is a myocardial disorder defined by dilation and contractile dysfunction of the left and right ventricles and has a significant hereditary component. Truncating mutations in the giant sarcomeric protein titin are predicted to cause a significant proportion of DCM cases. This project is a collaboration between Professor Diane Fatkin at the Victor Chang Cardiac Research Institute and KCCG's Dr Andre Minoche and Dr Mark Cowley.

The aim is to determine whether truncating titin mutations are sufficient to cause DCM and constitute the most common genetic risk factor for DCM. We propose that early identification of individuals at risk of developing DCM due to the presence of titin mutations will facilitate preventative interventions. Whole genome sequencing makes it possible to efficiently sequence the very large titin gene, as well as the many other genes implicated in DCM, in patient families.

Transplantation Genomics

Nearly 30,000 organ transplants are performed in the United States every year. They routinely extend lives, but the success of these procedures continues to be limited by problems that arise when the recipient’s immune system rejects their new organ and other complications.

Now, a large international team of transplant surgeons and scientists (International Genetics & Translational Research in Transplantation Network (iGeneTRAiN): see video) has come together to investigate the genetic factors behind transplant successes and failures. As part of iGeneTRAiN, KCCG (represented by Associate Professor Marcel Dinger, provide high-throughput genomics capability to sequence and analyse the genomes of organ donors and recipients with the ultimate goals of: discovering genetic variants that lead or contribute to rejection and other complications of transplantations; expanding the biomarkers found in urine and blood samples that may predict rejection weeks or months before patients show symptoms; and individualized patient treatments.

Tumour evolution

It has been hypothesised that cancer progresses following an evolutionary process (Nowell, 1976). That is, the sequential acquisition of genetic and epigenetic alterations leads to the development of tumour sub-clones with differing fitness, which react to selective pressure in different microenvironments, ultimately resulting in highly metastatic tumours. This has been observed in a number of cancer types, and has substantial implications for how to determine the comprehensive genetic makeup of a patient’s tumour, and how to best treat each tumour.

This project, led by Dr Mark Cowley, involves the development of methods based to characterise the extent of tumour heterogeneity, across multiple timepoints. These methods are based on combinations of deep whole genome sequencing, and targeted panel or exome sequencing. Together with Drs Padron and Yoder from Moffit Cancer Centre (Florida), we used deep WGS to investigate the impact of treatment upon the tumour evolution of a patient with Chronic Myelomonocytic Leukemia (CMML) (Merlevede et al, Nature Communications, in press). Dr Velimir Gayevskiy and Dr Mark Cowley are collaborating with Prof Neil Watkins to investigate the tumour evolution of patients with lung cancer.

WGS-based precision medicine for cancer patients

The goal of this project is to develop WGS-based methods for precision medicine, and improve patient management and treatment. Dr Mark Cowley and Dr Mark Pinese are developing fast turn around methods for comprehensively characterising, and summarising the clinically actionable genetic variants present in a tumour, linked to potential treatments and/or clinical trials.

Mitochondrial disease KCCG projects - mitochondrion

Mitochondrial disease (MD) is the most common type of inherited metabolic disease in Australia (1:500 live births), affecting both children and adults of all ages. MD can present with a wide spectrum of symptoms ranging from mild chronic disease to acute severe episodes or fatal illness. Due to its clinical variability and complexity, MD is often difficult to diagnose and usually requires a complex array of clinical investigations, metabolic screening and muscle (or liver) biopsy.

Early diagnosis is critical to early intervention and introduction of preventative lifestyle changes that may limit disease severity. In this cross-disciplinary collaborative project, involving clinical experts Professor John Christodoulou, Professor Carolyn Sue and Dr Kishore Kumar, we will apply state-of-the-art whole genome sequencing (WGS) and bioinformatic analyses to identify disease-causing genetic mutations in our large cohorts of mitochondrial disease patients with the overall aim to radically simplify the way we diagnose MD. 

Craniofacial and cleft palate

Cleft lip/palate is one of the most common malformations and the aetiology is largely unknown. Our Rare Disease Genomics team, led by Dr Tony Roscioli, is investigating the largest international cohort of 300 people from multi-affected families with cleft palate with genomic studies to identify causative genes. This international collaboration involves researchers and clinicians from Australia, North America and Europe including Professors Andrew Lidral, Jeff Murray, Timothy Cox, Hans van Bokhoven and Huiqing Zhou. Novel genes that have been identified in this project include a novel pathway with multiple interacting genes represented. A number of these are being modelled through CRISPR animal mutagenesis to recapitulate the phenotype.  Active investigations of those families with craniosynostosis syndromes without a known aetiology are also in progress.


Although rare, immunodeficiencies are a significant component of health budgets. Many of these conditions are due to mutations in single genes and are amenable to diagnosis and gene identification through genomic testing. The KCCG’s Rare Disease Genomics team is in active collaboration with a consortium of clinical immunologists in NSW, ACT and Victoria and has access to detailed functional analyses through collaboration with the Tangye Lab at the Garvan Institute.

Professor Chris Goodnow, Dr Paul Gray and Dr Tony Roscioli have initiated a pilot study of 60 whole genome sequences is being undertaken in patients from the Sydney Children’s Hospital and it is anticipated that a number of novel disease genes will be identified through this work. Professor Chris Goodnow and Professor Robert Brink from the Garvan Institute will lead the production of mouse animal models to confirm novel immune disease gene findings. Dr Tony Roscioli leads a department of health grant to sequence 140 people with immunodeficiencies to identify novel aetiologies.

Intellectual disability

Intellectual Disability (ID) is among the most important unmet challenges in healthcare due to its prevalence, lifelong nature and frequency of recurrence. Genomic analysis is being applied for both clinical diagnostics and research gene identification

in people with intellectual disability. Led by KCCG’s Dr Tony Roscioli, the project is an active collaboration with the Genetics of Learning Disability (GoLD) consortium, led by Dr Mike Field, and clinical genetics units around Australasia to maximise genomic outcomes for these families. A Centre for Research Excellence in the Genetics of Learning Disability (CRE-GOLD) is being assessed to facilitate the discovery of new Intellectual Disability genes and disease mechanisms, and to improve diagnosis and clinical care of patients with ID.  Professor Deborah Schofield joins with Dr Tony Roscioli and Dr Mike Field to investigate the health economic and psychosocial impacts of ID through an NHMRC Partnership grant.  These families will in addition to those ascertained at Liverpool hospital through philanthropic support from the Garvan Foundation will be studied by this group. IN 2016, a clinical geneticist from Liverpool Hospital has initiated a master's degree in the genomics of intellectual disability as part of these studies. Families with Early Onset Epilepsy will also be investigated with WGS through a second NSW Department of Health grant led by Dr Tony Roscioli. Families with neuromuscular disorders are another focus of activity for gene identification in association with Dr Michelle Farrar, particularly those affected with motorneurone disease and spinal muscular atrophy where the aetiology is unknown.

Parkinsons and movement disorders


The term ‘movement disorder’ describes a group of genetic disorders in which there is an excess of movement or a paucity of movement. Many relatively common disorders can fall into this category, including Parkinson disease, dystonia, and hereditary spastic paraplegia. Movement disorders are frequently disabling and can disrupt a person’s working life. Gene discovery has been critical to improving our understanding of the underlying disease mechanisms, but routine diagnosis remains expensive and time consuming due to the diversity of genes involved. Dr Kishore Kumar, in collaboration with Professor Carolyn Sue, is evaluating the cost, practicalities, efficiency and effectiveness of whole genome sequencing as a diagnostic tool. In the process, they will investigate the regions outside of the protein-coding genes (the non-coding regions) of the genome. This study will enable gene discovery and drive further laboratory-based research into the biological mechanisms causing movement disorders, potentially leading to new treatments.

Mendelian Disorders

Next generation sequencing is highly applicable to the diagnosis of Mendelian disorders as many are due to single gene mutations. The KCCG has an active program, led by Dr Tony Roscioli, to diagnose the aetiology of Mendelian disorders with clinical laboratory accreditation planned achieved in 2016. A number of clinical researchers including Dr Lisa Ewans, a member of the genomic analysis team, are actively involved in research degrees to define novel Mendelian genes in this cohort.  A new project supported by a third Department of Health Grant led by Dr Tony Roscioli will investigate those families with Mendelian disorders who have not been diagnosed by whole exome sequencing with WGS.  This study will look in detail at Copy Number Variation and non-coding variants.

The Rare Disease and Translational Genomics teams at the KCCG are collaborating with Dr Aaron Quinlan’s laboratory at the Centre for Public Health Genomics at the University of Utah to create a dynamic interface to facilitate the rapid interpretation of genomic data for clinical and research use. 

Seave - KCCG's variant filtration platform

Making sense of the millions of genetic variants present in a genome is extremely challenging. To address this challenge, the KCCG has developed a researcher- and clinician-friendly, web-based platform for filtering variants. It allows variants from WGS, exomes or targeted sequencing to be annotated, and filtered according to inheritance models, pathogenicity, rarity, and implication in known disease. By making it straightforward to curate gene lists, users can restrict their search to genetic variants to only those genes associated with the patient phenotype. Seave is well suited for filtering genetic variants in families with Mendelian disorders, but is also being adapted for filtering cancer datasets. Dr Velimir Gayevskiy is the main developer of Seave, who is working closely with Dr Mark Cowley and Dr Tony Roscioli to continue to develop Seave to solve the needs of both rare disease, and cancer research. Access to Seave is on a collaborative basis - please contact Mark Cowley for more information.


KCCG projects - measured man Phenomics is the study of the collective physical and biochemical characteristics (phenotypes) of an organism. Phenomics plays a crucial role in the interpretation of genomic data and diagnosis of disease. Our research program in phenomics, led by Dr Tudor Groza, covers the entire phenotype analytics spectrum, from representation to acquisition (from publications or clinical reports) and spans cross-species integration and decision making (e.g. disorder prediction or patient matchmaking). Current projects include:

  • a phenotype concept recognition pipeline;
  • a phenotype-centric patient archive;
  • a community-driven knowledge curation platform for Orphanet rare disorders knowledge; and a crowdsourcing platform for curating phenotype-disorder associations from scientific publications.

More information on current projects can be found on the phenomics team page.

The tight integration of phenomics and genomics is important not only for advancing the understanding of the information encoded in the genome, but also is critical for the effective implementation of genomics in the clinic. These projects proceed as critical collaborations with Professor Andreas Zankl, Dr Gareth Baynam and Professor Hugh Dawkins.

Health economics of genomics

Beyond the impact on patients affected by heritable disease, clinical genomics has the potential to significantly impact upon the health and welfare system through various indirect effects, including early diagnosis, treatment optimisation and population-level screening. The adoption of genomic medicine in routine healthcare will require detailed economic analyses to understand and model these impacts. Professor Deborah Schofield is an internationally renowned health economist who through her position at the Garvan Institute is developing health economic models to define the costs and benefits to our health system through genomic testing. She is working in close collaboration with Professor John Mattick,  A/Prof Marcel DingerDr Tony Roscioli, Dr Mark Cowley, Prof Michael Buckley, A/Prof Nadine Kaparian, A/Prof Kristine Barlow-Stewart, Dr Michael Field, and Dr Rupendra Shrestha to refine the knowledge in this area and to provide guidance for future development of health policies. 

Copy number and structural variantschromosomes

It is anticipated that whole genome sequencing will be the single test that defines mutations at all levels of the genome. The ultimate success of this methodology will mean that other test such as karyotypes and chromosome microarrays will no longer be needed in the future. A dedicated team (Dr Mark CowleyDr Andre MinocheDr Tony Roscioli, Dr Mike Field, Associate Professor Michael Buckley and Associate Professor Marcel Dinger) are investigating the sensitivity of whole genome sequencing to determine whether it can replace chromosome microarrays as a diagnostic methodology.

Education and engagement

If the benefits of genomic technologies are to be realised, there needs to be a strengthening of formal and healthcare education and effective public engagement. KCCG’s education and communication team, led by Bronwyn Terrill collaborates with educators, health and ethics researchers and social scientists to develop strategies for effective education across a range of audiences. Current projects include explorations of:

  • Australian public attitudes to and expectations of personal genomics, funded by the Australian Research Council. This collaboration involves an interdisciplinary research and practical from Sydney, Melbourne, the UK and Canada. This project will survey and interview members of the Australian public to assess their attitudes and understanding of and current engagement with personal genomics, and look at the ethical implications of this emerging science;
  • Gaps and opportunities in clinical, diagnostic and informatics education, training and workforce, as part of the Australian Genomics Health Alliance Program 4 (funded by the National Health and Medical Research Council; CI Bronwyn Terrill);
  • Australian stakeholders’ views of the impact of genomics on genetic counselling (conducted by University of Sydney Master of Genetic Counselling student Kirsten Boggs  and Tanya Dwarte);
  • Educational needs of NSW-based medical specialists around genomics (in collaboration with the NSW Health Centre for Genetics Education);
  • Views of healthy people – including health professionals – who have undergone personal genome screening, focusing on how best to inform and prepare individuals for this process (in collaboration with the University of Sydney);
  • Opportunities to incorporate genome science literacy into schools education, aligned with the F-10 Australian Curriculum (Master’s student project through Monash University);
  • Developing schools-focused education resources for Year 10 teachers and students (with the NSW Health Centre for Genetics Education and teacher advisors).

Comprehensive characterisation of the entire genome

The comprehensive characterisation of genetic variation present in a patient’s genome is essential to improve diagnostic rates. This requires the identification of single nucleotide variants, short insertions and deletions, structural and copy number variants, regions of homozygosity, repeat-length typing, phasing and haplotyping, retroviral insertions and transposon jumping, mitochondrial genetic variation and assessment of heteroplasmy, and an assessment of the impact of both coding, and noncoding genetic variation. The Translational Genomics and Production and Clinical Informatics teams are working on improved methods for comprehensive genome characterisation. The Information Architecture team is working on solving the infrastructure challenge of storing and analysing tens to hundreds of thousands of genomes.

Image credits: Dr David Furness, Wellcome Images; Early Spring/Shutterstock; Gordon Museum, Wellcome Images; Mark Lythgoe & Chloe Hutton, Wellcome Images; NHGRI; Sebastian Kaulitzki/Shutterstock; University of Edinburgh, Wellcome Images.