Translational Genome Informatics Team

A/Prof Sarah Kummerfeld Dr Alexander Drew Dr Andre Minoche  
Dr Kishore Kumar Dr Lisa Ewans John Reeves
(with Clinical Translation
and Education)

Mission statement

To expand the clinical utility of whole-genome sequencing by developing algorithms to annotate pathogenic loci in noncoding regions of the genome, applied to a range of rare monogenic disorders of substantial unmet need.


Rare diseases are highly complex, often life-threatening and chronically debilitating. While these conditions are individually rare, they cumulatively affect around 1 in 12 Australians. Today, using whole genome sequencing and focussing our interpretation on the 2% of the genome that is protein-coding, we have improved the diagnostic rates for rare diseases to 60% on average. This still leaves a substantial fraction of patients that remain undiagnosed. One of the major challenges lies in understanding the link between rare diseases, and noncoding genetic variation, i.e. variation in the 98% of the genome that we currently ignore.

This team led by Dr Sarah Kummerfeld, are developing new tools and algorithms to interrogate the non-protein-coding genome and make new discoveries that can be translated to the clinic. This includes understanding the role of non-protein-coding regions in disease, especially splice and regulatory regions, as well as developing improved approaches to identify all sizes and types of genomic variation from the nuclear and mitochondrial genomes, and improved tools to annotated an understand this information ( Their research is a combination of bioinformatic method development, applied to a number of rare conditions, including renal, cardiac, mitochondrial, epilepsy and movement disorders. 

Disease-focused research activities

The Translational Genomics Informatics Team conducts research in the following disease-focused areas:

Bioinformatic tools and resources 

Comprehensive characterisation of the 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 Genome Informatics team is working on improved methods for comprehensive genome characterisation.

Copy number and structural variants - ClinSV

Whole Genome Sequencing has the potential to comprehensively identify genetic variants of all sizes across the genome, from single base changes to entire chromosome changes.

Dr André Minoche leads the development of ClinSV, a dedicated Structural Variant and Copy Number Variant analysis pipeline. ClinSV has high sensitivity (>95%), reproducibility (>95%) and low false positive rate (<5%) to identify CNV and SV from short read WGS. It does this through careful integration of supporting evidence from multiple variant callers, and from cases vs 500 controls, with a visualisation framework. 

Ben Lundie, Dr Mike Field, Dr Michael Buckley, Prof Leslie Burnett, Prof Andreas Zankl, and Dr Greg Peters.

KCCG’s variant filtration platform - Seave

Making sense of the millions of genetic variants present in a genome is extremely challenging. To address this challenge, Dr Vel Gayevskiy has led the development of Seave (, 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. Importantly, it stores short variants alongside CNV and SV, allowing integrated variant queries to be performed. Seave is being widely used for diagnosing patients with Mendelian disorders, rare disease gene discovery, genomics education, inherited cancer risk assessment, and somatic cancer genomics.

Dr Velimir Gayevskiy was the main developer of Seave, who is working closely with Dr Mark Cowley and clinical geneticists, medical specialists and genetic pathologists continue to develop Seave to solve the needs of both rare disease, and cancer research. Access to Seave is on a collaborative basis.

Regions of homozygosity - ROHmer

Consanguineous individuals have higher rates of genetic disorders, due to the inheritance of large, identical blocks of the genome. Ms Clare Puttick developed ROHmer to identify regions of homozygosity, also known as long contiguous stretches of homozygosity (LCSH), to both restrict the clinical analyses to regions more likely to be relevant to disease, and to estimate to extent of consanguinity in a genome. This research was undertaken with Dr Mark Cowley, Dr Tony Roscioli, Dr Kishore Kumar, and Ben Lundie.

Mitochondrial heteroplasmy - mity

Mitochondria are the energy producing organelles in cells, and they have their own small, circular, 16Kb genome. Each cell has multiple mitochondria, and each mitochondrion has multiple copies of the genome, giving rise to mitochondrial heteroplasmy, where a variant can be present in 0-100% of all mitochondrial genomes. Once the heteroplasmy of a pathogenic mutation increases above a clinical threshold in a given tissue, symptoms of a mitochondrial disease can appear. Ms Clare Puttick and Dr Mark Cowley have developed mity, a mitochondrial variant analysis pipeline, for sensitive characterisation of heteroplasmy from WGS data, from blood, or other tissues. They have developed this pipeline in collaboration with colleagues Dr Kishore Kumar, Dr Ryan Davis, Dr Lisa Riley, Prof Carolyn Sue, and Prof John Christodoulou.

Product development and clinical applications

KCCG combines disease-focussed, and methods-development research to develop the analytical capability to diagnose new diseases, or new types of genomic variation (eg CNV and SV). 


Australian Parkinson's Mission
Neuroscience Division (Parkinsons & Neurodegeneration), Antony Cooper

WGS of Skeletal Dysplasias
Translational Bone group, Andreas Zankl

Genomic determinants of bone mineral density
Osteoporosis & Translational Research group, John Eisman

External collaborations

Sydney Children’s Hospital Network
Elizabeth (Emma) Palmer, Rani Sachdev

Kolling Insitute of Medical Research
Carolyn Sue, Ryan Davis

Genetics of Learning Disabilities (GOLD)
Mike Field

Murdoch Children’s Research Institute
John Christodoulou

Victor Chang Cardiac Research Institute
Diane Fatkin, Sally Dunwoodie, Eleni Giannoulatou

ANZAC Institute and Molecular Medicine Lab, Concord Hospital
Garth Nicholson

St Vincent’s Hospital
Tim Furlong, Kathy Wu