ANNUAL REPORT 2017/2018 ANNUAL REPORT AGRF 2017/2018 2
AGRF IMPROVES QUALITY OF LIFE THROUGH EXCEPTIONAL LIFE SCIENCE.
AGRF is a not-for-profit organisation, committed to quality and innovation. We actively seek to partner and share our knowledge and expertise in genomics. Through our national network, AGRF provides access to innovative and leading technologies, enabling genomics in the biomedical, agricultural and environmental domains. From single gene analysis to whole genome sequencing, AGRF provides a full range of genomic capabilities and services with complementary bioinformatics across the entire biological spectrum, to academia, healthcare and commercial industries.
www.agrf.org.au ABN 63 097 086 292 © Australian Genome Research Facility Ltd 2018. ANNUAL REPORT AGRF 2017/2018 3
CONTENTS
Chairman’s Message & A Word from our CEO 04-05
Our Vision, Mission & Values 06-07
Our Team 08-09
Spotlight - Chris Noune and Microbiome 10-11
The Genetics of Epilepsy 12-13
A Key Partner 14-15
Spotlight - Our Clinical Team 16-17
Zero Childhood Cancer 18-19
About Our Clients 20-21
Celebrating 20 Years of AGRF 22-25
Leading Through Innovation 26-27
Single Cell Analysis of Breast Cancer 28-29
Events & Engagement 30-31
Overcoming Anxiety 32-33
Black Tiger Shrimp Transcriptome 34
Our Bioinformatics Team 35
Proudly Supporting Academic Research 36-37
Publications 38-39
Our Board of Directors 40-41
Our Executive Team & Our Funding Partners 42-43 ANNUAL REPORT AGRF 2017/2018 4
CHAIRMAN’S MESSAGE
In 2017/2018 AGRF continued to deliver on our mission of providing “national quality state-of-the-art genomic services to Australia’s researchers and industry”. AGRF maintains Australia’s most comprehensive and distributed array of genomic platforms and capabilities to meet the diversified needs of the biomedical, agricultural, and environmental research and industry domains.
AGRF’s transformation strategy continued in 2017/2018 to ensure we are positioned to meet the needs of the Australian genomics community. The key initiative in this context was the relocation of AGRF’s Melbourne laboratories to the Victorian Comprehensive Cancer Centre (VCCC) and engaging with the pathology community in developing solutions to the future needs of Australian clinical genomics. Of particular significance in 2017/2018 was our achievement of ISO15189 Accreditation for Medical Testing Laboratories. With over 20 years of genomics expertise, AGRF now delivers NATA accredited workflows for clinical genomic applications, including genome-wide genotyping, Whole Exome Sequencing, and Sanger sequencing.
In 2017/2018, we moved into the second year of our growth strategy with critical initiatives to underpin all aspects of AGRF’s growth, culture, diversification of platforms and services, promotion, and governance. This included the welcoming of new leadership and operational staff in critical areas of Business & Market Development, Research Partnerships, and Science & Technology, as well AGRF’s operational areas of People & Culture, Laboratory Services, and Finance & Business Services. It is exciting to see throughout this report, the It is pleasing to report the 2017/2018 financial diverse work that AGRF has supported throughout year again delivered a positive result with both this financial year, particularly across the research revenues and EBITA above budget. The credit areas of Epilepsy, Childhood Cancer, Mental Health, for this is due to the AGRF management and staff Breast Cancer, and Aquaculture. We are proud to who continued to deliver the most commendable support our clients across all disciplines and look dedication and persistence in response to the forward to working with them again in 2018/2019. complex challenges of increasing competition, restraints and uncertainties in government 2018/2019 will no doubt be an exciting year. The funding and continued technological advances. transitioning initiatives of the past year have primed AGRF for the transformation and growth vision I thank my fellow Board Directors for their and agenda we have set. The AGRF Board looks continued unstinting contribution and enthusiasm forward to working with management, staff and our to AGRF’s mission and continuing success. research and industry clients and collaborators in this pursuit, with the aim of providing Australia’s The continuing contribution of Bioplatforms leading genomics solutions across the biomedical, Australia (BPA) to many of AGRF’s activities is also agricultural and environmental domains. acknowledged and greatly appreciated. ANNUAL REPORT AGRF 2017/2018 5
A WORD FROM OUR CEO
2017/2018 was an important year for AGRF as we implemented our five-year strategy to “grow through transformation”. Our move to the VCCC allowed us to co-locate our Melbourne teams in support of our ‘One AGRF’ culture. With clever design and attention to detail we have created an environment promoting engagement, collaboration, and creative thinking, all of which is supported by the wonderful space and natural light offered on level 13. The move to the VCCC allows AGRF to continue our strategic imperative of leading, enabling, and supporting clinical genomics as a key partner.
Beyond clinical genomics and biomedical activity, AGRF also supports agricultural and environmental genomics. This includes improvements to livestock and crops, right through to monitoring our environment.
Early access to technology is increasingly becoming a source of competitive advantage for researchers globally. In 2016, we recognised the importance of this, and founded the Genomics Innovation Hub (GIH), in partnership with the University of Melbourne, the Peter MacCallum Cancer Centre, the Walter and Eliza Hall Institute, the Murdoch Children’s Research Institute, and BioPlatforms Australia.
In the past year, the GIH has completed a number of projects in collaboration with Our clinically accredited services include researchers, including the exciting area of Whole Exome Sequencing, Single Nucleotide single cell genomics, with work recently Polymorphism Array Genotyping, and Sanger published in Nature Medicine by Professor Sequencing. We are also in the final stages of Sherene Loi, Medical Oncologist at the VCCC. securing accreditation for our Whole Genome Sequencing services. Our clinically accredited In May 2018, the Federal government expertise combined with in-house bioinformatics announced a $500M investment through the and curation capability allows AGRF to be a Australian Genomics Health Futures Mission, key partner in clinical genomics. This is further to “help save or transform the lives of more supported by our active memberships and than 200,000 Australians through research partnerships with the Australian, Melbourne and into better testing, diagnosis and treatment”. Queensland Genomic Health Alliances, where AGRF is excited to support this national AGRF has been involved in a number of key agenda. projects.
Furthermore, as part of our strategic “growth I take this opportunity to express my gratitude to through transformation” vision, AGRF has our supporters and partners who have entrusted secured ISO15189 Clinical Accreditation for us with their projects, and have allowed us to Medical Testing. This is a great opportunity continue to deliver genomics expertise for over for us to continue to expand our offerings to 20 years. I would also like to thank our AGRF include clinical-grade genomics services in staff for their contributions and dedication over our expanding portfolio. the year. ANNUAL REPORT AGRF 2017/2018 6
OUR VISION
To be a key enabler of world-class genomic science.
OUR VALUES
innovation integrity respect
We embrace genomic We always act in the We honour challenges with best interests of our individuality and curiosity, novel stakeholders and appreciate our approaches and AGRF as a whole. working relationships. world class technologies.
Putting our valued staff in the spotlight AGRF launched a staff Recognition Awards Program in February 2018 which provides an opportunity to ‘shine the spotlight’ on an individual, team or group of people for their work that is aligned with our Values in Practice. ANNUAL REPORT AGRF 2017/2018 7
OUR MISSION
To provide Australia with a world standard, research integrated capability, delivering genomic solutions to the biomedical, agricultural, and environmental sectors to address key scientific questions.
excellence client focused collaboration & teamwork
We are proud of our We are committed to We build inclusive quest to be delivering exceptional and valued outstanding in services, all of the relationships in everything we do. time. pursuit of shared goals.
Our new AGRF Recognition Awards Program aligns AGRF’s Values in Practice to the nomination criteria. Launching this program is part of the 2017 – 2022 strategic goal: to collectively promote and foster a high performing ‘One AGRF’ culture, and an environment where achievements and contributions are noticed, appreciated and celebrated. ANNUAL REPORT AGRF 2017/2018 8
15 58% languages spoken by staff with our staff parents not born in Australia 36%
staff not born in Australia
DIVERSITY DRIVING INNOVATION
We employ more than 70 highly skilled staff, with a broad range of skills and diverse backgrounds. We wanted to highlight that diversity here.
11% Baby Boomers 32% Generation X 57% Generation Y born 1946-1964 born 1965 - 1979 born 1980 - 1994 ANNUAL REPORT AGRF 2017/2018 9
OUR NATIONAL NETWORK
Our Melbourne Team
Our Brisbane Team Our Perth Team
Our Sydney Team Our Adelaide Team
ANNUAL REPORT AGRF 2017/2018 10
83 sequencing runs CHRIS NOUNE LABORATORY SUPERVISOR MICROBIAL PROFILING & CUSTOM AMPLICON NEXT GENERATION SEQUENCING
AGRF has provided me with great opportunities and skills in the short time I have been here. I don’t think I would have had the opportunities given to me in such a short time at any other workplace.
“Chris Noune is a valued member of our In the future, I see AGRF’s NGS (Next Generation Sequencing) team and the AGRF family as a whole. Microbial Profiling transitioning Starting at AGRF in January 2018, Chris to Third Generation Sequencing recently moved from our Brisbane lab to our Melbourne lab to take up the role to provide clients with higher of Laboratory Supervisor for Microbial Profiling and Custom Amplicon NGS. taxonomic resolution.
Chris has been instrumental in setting up a rigorous automated workflow for our Microbial Profiling service and has transitioned it into a “well-oiled machine”.
Chris is also an active contributor at conferences and symposia, having Some of the interesting Microbial Profiling work we’ve run this this year presented at the University year includes: of Queensland Winter School in Mathematical and Computational • identifying bacteria on frog skin Biology, and also given a guest lecture • identifying bird species destroyed by domesticated cats for the Queensland University of • analysing the bacterial composition of patient Technology Masters of Diagnostic gastrointestinal tracts Genomics. • analysing bacteria in wine and wine sediment
ANNUAL REPORT AGRF 2017/2018 11
MICROBIOME ANALYSIS THROUGH MICROBIAL PROFILING
AGRF’s Microbial Profiling service is a method of identifying the relative proportion of organisms present in a mixed community. This community may be the microorganisms within your own body. Our own microbiome serves a number of functions, including ensuring proper functioning of our immune system. AGRF is powering the use of diversity profiling for industrial clients to solve real world problems. - Emily Scholes, Monash University
2017/2018 MICROBIOME AT A GLANCE
8,862 client samples 83 sequencing runs >1 terabases generated
50% 40% 24%
batches containing bacterial batches containing bacterial batches containing 16S ribosomal subunit (variable 16S ribosomal subunit fungi (ITS) target regions 1-3) target (variable regions 3-4) target
Chris Noune with Mr Frank McGuire, Parliamentary Secretary for Medical Research, showing him our automation in action. ANNUAL REPORT AGRF 2017/2018 12
THE GENETICS OF EPILEPSY
Hypothalamic hamartoma is an unusual benign brain tumour associated with drug-resistant epilepsy in early life. Patients develop subcortical gelastic seizures, often in the neonatal period, that if untreated frequently evolve into an epileptic encephalopathy with refractory generalised seizures. Surgical resection of these tumours is the only effective treatment leading to seizure freedom in over half of patients. Little is known about the genetic architecture of hamartoma tumours.
Associate Professor Michael Hildebrand, Head of the Translational Neurogenetics Laboratory at the Epilepsy Research Centre (Melbourne Brain Centre) has published work in the leading international journal American Journal of Human Genetics (Hildebrand et al., 2016 99(2):423- 9). The work was published with teams from the Austin and the Royal Children’s Hospitals in Melbourne, as well as Columbia University in New York, and involved a comprehensive search for somatic mutations of hamartoma tissue from 38 patients. With AGRF’s sequencing assistance, Associate Professor Hildebrand’s team carried out whole exome sequencing analysis, followed by chromosomal microarray and targeted resequencing.
Somatic mutations were identified in 14 patients in genes involving regulation of the sonic-hedgehog (Shh) pathway. This work supports the idea that hypothalamic hamartoma is a developmental ‘pathway’ brain disease. Professor Ingrid Scheffer, Austin Hospital’s Director of Paediatrics Photograph first published on Austin Health website.
our whole exome sequencing service ANNUAL REPORT AGRF 2017/2018 13
This phenomenon is reminiscent of the remarkable contribution of various mTOR pathway gene mutations to malformations of cortical Published in the development realised through similar clinico-molecular studies with privileged brain tissue over the last few years. American Journal The Austin Hospital’s Director of Paediatrics, Professor Ingrid Scheffer of Human Genetics (shown left) is a leading paediatric neurologist treating patients with hypothalamic hamartoma. Professor Scheffer was awarded the 2018 Fellow of the Royal Society, the 2014 Prime Minister’s Prize for Science, and the 2012 Asia-Pacific L’Oreal-UNESCO for Women in Science Laureate, for her groundbreaking work on the genetics of epilepsy.
We have chosen AGRF to provide our genomics services over the last 6 years because they reliably provide high quality data, efficient turnaround times, downstream bioinformatics analysis, and competitive pricing. For this study, AGRF provides robust gene chip and high-depth exome data generated from precious tumour and blood samples to facilitate somatic mutation detection. - Associate Professor Michael Hildebrand, PhD
Epilespy awareness is represented by lavender
your partners at AGRF ANNUAL REPORT AGRF 2017/2018 14
A KEY PARTNER: LEADING, ENABLING & SUPPORTING CLINICAL GENOMICS
In 2017/2018, AGRF Melbourne moved into a purpose-built facility at the Victorian Comprehensive Cancer Centre (VCCC). The move to the VCCC allows AGRF to continue our strategic imperative of leading, enabling and supporting clinical genomics as a key partner.
We are excited to support the clinical genomic activities of our VCCC building partners, our Melbourne Biomedical Precinct partners, and our national and international partners. ANNUAL REPORT AGRF 2017/2018 15
With clever design and attention to detail we have created an environment promoting engagement, collaboration and creative thinking, all of which is supported by the wonderful space and natural light offered on level 13.
Dr. Kirby Siemering (AGRF’s Executive - Science & Technology) with Dr. Alan Finkel (Australia’s Chief Scientist). ANNUAL REPORT AGRF 2017/2018 16
CLINICAL SPOTLIGHT
READS VARIANTS
10,754,077,995 BASES 5,076,609
CLINICAL EXOME CLINICAL VARIANTS 10 billion reads of clinical exome data has been 1,613,111,699,250 5 million variants have sequenced on our been sent for curation to NovaSeq 6000 platforms our clinical partners CLINICAL DATA 1.6 trillion bases of clinical DNA have been analysed through our pipelines ANNUAL REPORT AGRF 2017/2018 17
MEET OUR CLINICAL GENOMICS TEAM
In 2017/2018, AGRF secured an accreditation expansion to deliver clinical genomics to the medical sector.
In June 2018, AGRF was formally accredited as a medical testing laboratory. With a dedicated team to provide clinical genomics, AGRF has focused on delivering a streamlined service that can be partnered with pathology organisations to expand this type of testing within the national healthcare networks. With expertise in Next Generation Sequencing technologies, Clinical Bioinformatics, and Variant Curation, AGRF delivers innovative, robust and reproducible medical testing services with the sensitivity required to meet NATA and NPAAC requirements.
With a variant calling pipeline that has a strong focus on sample traceability, integrity, and accuracy, we have benchmarked our pipeline both nationally and internationally. Our expertise, coupled with a suite of sequencing platforms, enables AGRF to tailor tests to the needs of our pathology partners.
We are now in the final stages of further expanding our clinical genomic services to include Whole Genome Sequencing.
Left to Right: Alexis Lucattini, Matthew Tinning, Melanie O’Keefe, Matthew Stevens, Lesley Gray & Ashley George.
With over 20 years of genomics expertise AGRF now delivers NATA accredited workflows for your Clinical Genomic applications, including targeted panels, genome-wide Genotyping, Whole Genome and Whole Exome Sequencing, and Sanger Sequencing.
ACCREDITATION OUR CLINICAL SERVICES
Our Flagship Melbourne Laboratory is now Whole Genome Sequencing accredited as an ISO15189 Medical Testing Exome Enrichment & Sequencing Laboratory, for clinical-grade genomics services. Variant Calling Pipeline DNA Sequencing In addition, AGRF has many services accredited Microsatellite Fine-Mapping by the National Association of Testing Authorities, Custom Genotyping Australia (NATA) and operates in compliance with Fragment Separation / Analysis the International Standard ISO/IEC 17025:2005 in the field of Life Sciences. SNP Array Genotyping Sanger Sequencing ANNUAL REPORT AGRF 2017/2018 18
ZERO CHILDHOOD CANCER The Zero Childhood Cancer program is the most ambitious and comprehensive child cancer research program ever undertaken in Australia. The program demonstrates unprecedented collaboration, uniquely bringing together clinicians from all eight child cancer treatment centres throughout Australia, together with 14 leading national research partners, to deliver Australia’s first ever personalised medicine program for children with high-risk or relapsed cancer.
The aim of the program is to assess the feasibility of a diagnostic platform (including molecular profiling - Whole Genome Sequencing, RNA-Seq and methylation analysis, in vitro high-throughput drug screening and in vivo drug efficacy studies) to identify potential tumour targets with the aim of better matching novel targeted therapies for children with high risk cancers.
Recommendations based on the evidence of findings are decided by a Multidisciplinary Tumour Board (MTB) and then reported to treating oncologists in a clinically actionable timeframe. The program is now 13 months into its national precision medicine trial for children with high risk cancer, with over 120 children enrolled.
In light of a number of high impact publications demonstrating the importance of methylation analysis to determine molecular tumour types in children with high-risk brain cancers, the Zero Childhood Cancer program has recently decided to incorporate methylation analysis into their molecular profiling pipeline.
“Given the extremely small size of paediatric brain tumour biopsies, we often have a very small amount Biljana Dumevska and the Zero Childhood Cancer Team of DNA for each patient and so we conducted
our methylation service ANNUAL REPORT AGRF 2017/2018 19
two test chips with AGRF to test different concentrations of DNA that would give us high quality data with a low DNA input amount,” First Recipient of Biljana Dumevska says. “Following this test, we are now conducting methylation testing for childhood brain cancer patients enrolled in the Australian Brain program and then running the data through a tumour classifer program developed in Germany, to help determine the right diagnosis, and Cancer Mission therefore optimal treatment, for these patients.” Funds To date, approximately 67% of patients in the Zero Childhood Cancer program are receiving a recommendation. They have conducted methylation analysis on a subset of the brain tumour patients to date, but have already demonstrated the value of this testing when incorporated into the whole genome and whole transcriptome RNA sequencing data to the MTB to assist them in their recommendation decisions.
AGRF have a strong reputation for high-quality service and we were confident our precious patient samples would be handled appropriately. AGRF also provided technical support and advice before we ran our test chips, which was helpful to us. AGRF have been responsive, professional and good value for money (given we are research-funded), and have delivered high quality reproducible data to us in the test chips and subsequent patient samples. We look forward to working even more closely with AGRF in the future. - Biljana Dumevska, Laboratory Operations Coordinator
Childhood Cancer awareness is represented by yellow
your partners at AGRF ANNUAL REPORT AGRF 2017/2018 20
OUR INTERNATIONAL CLIENTS
In the last financial year, we provided services to more than 450 research and commercial organisations, delivering services to more than 3,000 clients and collaborators. Our clients are split across all types of organisations, from universities and medical research institutes, to government, industry, hospitals, and more. Twelve percent of those clients are international clients, which is a testament to our reliable, secure and quality-driven data.
> 9,000 samples received from our international cients
5% 12% 13% 65%
SANGER MICROBIAL NEXT GEN GENOTYPING PROFILING SEQUENCING ANNUAL REPORT AGRF 2017/2018 21
A YEAR IN NUMBERS
Our Clients (%) Numbers of Samples
Government Industry / Commercial Medical Research Institutes Publicly Funded Research Agencies Universities Genetic Identifications Genotyping Microbiomes Next Generation Sequencing Nucleic Acid Extraction Sanger
Our Clients by Industry (%)
Agriculture Biomedical Diagnostics Environmental other
WAR AND PEACE If each base sequenced by AGRF was a letter in a book, it would fill 35.6 million copies of War and Peace. ANNUAL REPORT AGRF 2017/2018 22
Melbourne & Brisbane Nodes opened. Find us at: Victorian Comprehensive Cancer Centre in Melbourne, and The University of Queensland in Brisbane
Wayne Ward National Facilities & Foundation Procurement Manager established
“The people at AGRF are Chromosome 22 what make us an awesome sequenced organisation. I’m proud of our continued success, and our ability to provide clients access to cutting-edge technologies.” AGRF established JOINED APRIL 6, 1998
Melanie O’Keefe National Quality Manager
1997 1998 1999 2000
“As a leader in the early adoption of technologies, AGRF is at the forefront of what is possible, and we are contributing to exciting advances in genomic science.”
JOINED APRIL 28, 1998 search engine founded Phuong Nguyen Summer Olympics Laboratory Technician Marie Everest held in Sydney Sanger & Genotyping NGS Pre PCR Laboratory Supervisor
“I love the friendly environment at AGRF, it feels like another “I love the people. I love that my job is constantly family in my life, and so I have evolving with technology. I love the opportunities been devoted to this family.” that I have been given to grow as a member of the AGRF team. I love that we get amazing ‘toys’ to work JOINED JULY 27, 1998 with. And did I mention that I love the people?”
JOINED OCTOBER 19, 1998 ANNUAL REPORT AGRF 2017/2018 23
CELEBRATING 20 YEARS OF AGRF
Facebook launched
Human Chimpanzee genome genome published published Our first High Our MicroArray Performance Printing Service Computing launched cluster
2001 2002 2003 2004 2005 2006
Our first Applied Our first Our Client Biosystems 3730s Sequenom Portal installed installed launched
Rat genome published
YouTube platform launched
Adelaide Node opened. Find us at: The University of Adelaide ANNUAL REPORT AGRF 2017/2018 24
CELEBRATING 20 YEARS OF AGRF
Sydney Node opened. Find us at: Westmead Institute of Medical Research
Tammar wallaby Neanderthal genome published genome with AGRF as a published partner Our first Our first Our first illumina illumina Roche 454s iScans HiSeq 2500 installed installed installed
2007 2008 2009 2010 2011 2012
Our first Our first illumina Our first illumina GAIIs HiSeq 2000 illlumina installed installed MiSeq installed
First comprehensive AGRF partners with the analysis of cancer ARC Centre of Excellence genomes published for Coral Reef Studies to sequence and assemble the first animal genome in Australia: the Staghorn Coral
Apple launches first iPhone
Perth Node opened. Find us at: Harry Perkins Institute of Medical Research ANNUAL REPORT AGRF 2017/2018 25 International Wheat Genome Sequencing Consortium published the wheat genome with AGRF contributing to chromosome 7A via a BPA Framework Initiative
US Supreme Court Aboriginal Heritage rules naturally Project wins a Eureka occuring DNA Prize, with AGRF as a cannot be patented Adelaide is the sequencing partner Our first High Our first final AGRF lab Performance illumina to be NATA Genomics Computing NextSeq accredited to Innovation Hub clustered file installed ISO17025:2005 launched system
2013 2014 2015 2016 2017 2018
Our first Our first single Our first 10x Our first illumina AGRF attains 40Gb High Performance Genomics NovaSeq 6000 ISO15189 network Computing node with Chromium platforms installed Accreditation for interface 1.5TB of RAM installed Medical Testing
AGRF partners with the ARC Research Hub for Advanced Breeding to transform prawn aquaculture Completed our Our first Oxford first PacBio Nanopore Sequel run Technologies PromethION Our Flagship Laboratory in Melbourne officially opened by Australia’s Chief Scientist, Dr. Alan Finkel ANNUAL REPORT AGRF 2017/2018 26
LEADING THROUGH INNOVATION
We are excited to be able to deliver 30x Whole Genome coverage with Long-Read Sequencing, now possible with a single ONT PromethION flow cell.
The Oxford Nanopore Technologies (ONT) PromethION is a highly scalable, single-molecule, real- time, long-read sequencer. This platform, known as nanopore sequencing, enables on-demand long-read sequencing for large numbers of samples.
We can easily visualise haplotype structural variation information with the 10x Genomics Chromium.
As part of GIH and Melbourne Genomics Health Alliance, we’ve had hands-on experience with the latest technology from 10x Genomics. Linked-Reads, developed by 10x Genomics, leverages microfluidics to partition cells or DNA molecules and prepare sequencing libraries in parallel such that all fragments produced within a partition share a common barcode. ANNUAL REPORT AGRF 2017/2018 27
We can explore alternative splicing of highly accurate full-length transcripts with the latest developments from Pacific Biosciences.
The Pacific Biosciences (PacBio) Sequel is a single- molecule, real-time, long-read sequencer. In partnership with Walter and Eliza Hall Institute, AGRF has developed a range of robust and reproducible methodologies for long-read sequencing on the PacBio Sequel, and we will be offering this as a service in the next financial year.
200 single cell Record 101GB samples analysed from a single by Single Cell PromethION RNA-Seq flow cell
targeted regions full-le Record 24.6GB per PacBio structural variation repetitve regions SMRT cell ucleotide variation haplotype phasing RNA e variants isoforms fusion transcripts epigentic difications transcriptomes single cell somatic mutations methylation profiles de novo assembly epigenetics alternative splicing coding regions ANNUAL REPORT AGRF 2017/2018 28
SINGLE CELL ANALYSIS OF BREAST CANCER
With breast cancer diagnoses on the rise, recent research led by Dr. Bhupinder Pal has provided fresh insights into the molecular changes in breast development, which will help develop highly specific and personalised treatments for breast cancer patients. Over the past decade, Dr. Pal’s work with AGRF has generated detailed molecular and genomic information on a wide range of tissues generated from mouse models, clinical samples, and patient derived xenografts (PDXs) that has helped many ongoing pre-clinical studies and research projects aimed at identifying novel biomarkers for breast cancer.
In a study recently published in Nature Communications, Dr. Pal’s group used the 10x Chromium platform at AGRF to reveal novel cell surface markers and previously unknown rare epithelial cell populations. This has advanced our knowledge of mammary epithelial cellular hierarchy.
“Currently, we are using innovative molecular and genomic techniques to generate high-resolution transcriptomic/genomic maps of breast tumour tissues from different stages of breast cancer”, Dr. Pal says. “This approach will allow us to resolve the molecular heterogeneity in breast tumour cells representing major subtypes, characterise the tumour microenvironment, and identify genetic alterations that are responsible for cancer progression. These studies will form the basis for developing highly specific and personalised treatments for breast cancer patients.”
Dr. Bhupinder Pal
our single cell sequencing service ANNUAL REPORT AGRF 2017/2018 29
Dr. Pal states that AGRF’s strategic location in the Parkville precinct Another Genomics and capacity to provide access to a wide variety of the latest NGS platforms is a big incentive for collaboration. For example, our recently Innovation Hub acquired high-throughput NovaSeq sequencing platform helped them to screen dozens of single-cell transcriptome libraries in a short time, Success Story! without worrying about batch effects.
Dr. Pal received his PhD degree from the University of Melbourne and is currently the Head of the Cancer and Single Cell Genomics Laboratory in the Translational Breast Cancer Program at the Olivia Newton-John Cancer Research Institute. He has extensively used single cell methods to understand the lineage relationships in mammary epithelial cells, tease out rare and intermediate cell sub- types, and identify early molecular events that mark pre-cancerous cells in breast tissues.
We have utilised AGRF services ranging from Sanger-based sequencing of plasmids to the latest high-throughput Next Gen sequencing. The arrival of Australia’s first 10x Chromium platform at AGRF in 2016, allowed us to have early access to the latest single cell RNA-Seq technology. We were able to quickly and reliably interrogate the transcriptome of thousands of mammary epithelial cells isolated from different developmental stages and publish the results. - Dr Bhupinder Pal
Breast cancer awareness is represented by pink
your partners at AGRF ANNUAL REPORT AGRF 2017/2018 30
EVENTS & ENGAGEMENT STEP NAME 01
5 AGRICULTURE & ENVIRONMENT EVENTS 20 CONFERENCES
6 MEETINGS 6 CLINICAL EVENTS 7 SPECIAL INTEREST GROUPS ANNUAL REPORT AGRF 2017/2018 31
STEP NAME 01 STEP NAME 04
8 7 SYMPOSIA INNOVATION EVENTS
2 LAUNCHES
4 WORKSHOPS 13 EDUCATION EVENTS
16 SCIENTIFIC EVENTS ANNUAL REPORT AGRF 2017/2018 32
OVERCOMING ANXIETY
Dr. Irina Baetu at the University of Adelaide is researching how our brain relates cause and effect. She is focusing on the link between genetic variance and cognitive functions, and how these differences might contribute to psychopathology. Dr. Baetu says, “I have always been fascinated by individual differences in cognitive performance and how these affect our daily lives. What I find even more interesting is that some of these individual differences, and less stable characteristics such as temporary moods, are determined by our neurobiology”. Now, Dr. Baetu is working on gaining a better understanding of the neurobiological mechanisms that determine specific cognitive functions and emotion regulation. While scientists have made great discoveries in neurobiology, there is still much that is unknown. Irina is working to contribute to understanding the links between neurobiology and cognitive performance, including understanding the role of genetic variation in cognitive phenotypes.
With a particular interest in ‘fear learning’, Irina notes that while learning allows us to associate neutral cues with subsequent events so that we can anticipate those events in the future and prepare for them, excessive learning can actually lead to cognitive dysfunction. She says, “In particular, excessive fear of stimuli that signal the occurrence of aversive events seems to contribute to vulnerability to anxiety disorders”.
Using AGRF’s Single Nucleotide Polymorphism MassArray service, Irina’s work aims to discover the relationship between Dr. Irina Baetu genetic variance and specific fear learning mechanisms. This work has clinical implications – if the genetic markers for increased fear learning can be identified, then we can determine whether an individual is at risk of developing anxiety disorders.
our genotyping service ANNUAL REPORT AGRF 2017/2018 33
Dr Baetu notes that “these genetic markers can also be used to identify people with an anxiety disorder, who are likely to be resistant to traditional behavioural therapies that rely on teaching the patient to extinguish, or ‘unlearn’, their acquired fears, such as cognitive Published in behavioural therapy”. Neuroimage With her research investigating the relationship between specific cognitive functions and genetic variation, genomics becomes very important. It can help predict important outcomes, such as how susceptible an individual may be to certain disorders. In turn, treatment outcomes may be predicted from these studies. Additionally, information about how variations in specific genes relate to cognitive performance can give us clues about potential neurotransmitter systems that are involved in these functions, and therefore opens up new avenues for future research.
In 2010, Dr. Baetu was awarded the New Investigator Award by the American Psychological Association, Division of Experimental Psychology. She was also awarded a Discovery Early Career Researcher Award by the Australian Research Council in 2014 to carry out research investigating genetic individual differences in learning.
I have used AGRF’s services for several projects since 2014 and was always satisfied with their prompt service and their advice. Their partnership has enabled me to incorporate genomics in my work. - Dr. Irina Baetu
Anxiety awareness is represented by teal
your partners at AGRF ANNUAL REPORT AGRF 2017/2018 34
BLACK TIGER PRAWN TRANSCRIPTOME
A sub-program of the ARC Research Hub for Advanced Prawn Breeding, elucidation of the black tiger prawn transcriptome, was identified as a key genomic resource required for an advanced genomically-guided breeding program for the aquaculture industry.
The main objective of the program was to reconstruct the black tiger prawn transcriptome to help understand the genes driving key developmental events and commercially important traits during farming. The transcriptome will also be useful in annotating the full Published in Nature’s draft of the genome, needed for advanced genetic mapping of traits and breeding. Scientific Reports
The experiment was designed and executed through close collaboration between AGRF wet lab scientists and bioinformaticians, and other Hub partners, culminating in the publication of the assembled transcriptome in Nature’s Scientific Reports (Huerlimann et al., 2018).
AGRF and Hub partners are continuing to improve and polish the transcriptome assembly using state- of-the-art long-read sequencing technologies. The Pacific Biosciences Sequel platform has been used to generate Iso-Seq reads to map an improved version of the transcriptome which will be included in a major publication describing the assembly of the black tiger prawn genome. ANNUAL REPORT AGRF 2017/2018 35
OUR BIOINFORMATICS TEAM
Our AGRF bioinformatics team consists of six expert bioinformaticians with PhD or Masters degrees from diversified backgrounds, including bioinformatics, biomedicine, molecular biology, statistics, computer science, and physics. With such a diverse team, we provide expert bioinformatics services to cater to clients working in a broad range of applications for human, plant, animal, bacteria and virus samples. We support our clients by providing four categories of work: 1. Essential data processing after sequencing, such as demulitplexing, QC and contamination checks; 2. Standard bioinformatics analyses with well-tested mature pipelines; 3. Customised bioinformatics analyses tailored to the clients’ requirements; and 4. Collaboration on large projects, including complex genome assembly.
With our diversified team and extensive experience, we are capable of providing solutions for challenging biological questions. Our mission is to provide the highest standard of bioinformatics support to maximise the value of our sequencing data. genotyping by sequencing
copy number variants multi loci sequence typing population genetics
Nanopore methylation web app development metagenomics pipeline development CRISPR Linked-Reads genome assembly array analysis microbiome sanger sequencing PacBio genome visual
clinical exome ATAC Seq RNA-Seq transcriptome assembly microsatellite microbial profiling whole exome sequencing ANNUAL REPORT AGRF 2017/2018 36
Justin Crockett Laboratory Technician Next Generation Sequencing ANNUAL REPORT AGRF 2017/2018 37
PROUDLY SUPPORTING ACADEMIC RESEARCH
AGRF has proudly supported academic research for more than 20 years. In 2017/2018, AGRF worked with 36 of Australia’s 41 universities. We understand that having early access to cutting-edge technologies gives our clients a competitive advantage and we are proud to enable genomics in the biomedical, agricultural and environmental domains.
AUSTRALIAN CAPITAL TERRITORY Australian National University University of Canberra
NEW SOUTH WALES Charles Sturt University Macquarie University Southern Cross University University of New England University of New South Wales University of Newcastle University of Sydney University of Technology Sydney University of Wollongong Western Sydney University
QUEENSLAND Central Queensland University VICTORIA Griffith University Deakin University James Cook University Federation University Queensland University of Technology La Trobe University University of Queensland Monash University University of Southern Queensland RMIT University University of the Sunshine Coast Swinburne University of Technology University of Melbourne Victoria University SOUTH AUSTRALIA Flinders University University of Adelaide WESTERN AUSTRALIA University of South Australia Curtin University Edith Cowan University Murdoch University TASMANIA University of Notre Dame University of Tasmania University of Western Australia ANNUAL REPORT PUBLICATIONS 4. 3. 1. 5. 6. 2. 8. 7.
retinal ganglioncells. Powell, J. E.,Hewitt,A.(2018).SinglecellRNAsequencing ofstemcell-derived W., Kulkarni, T., Sluch,V. M.,Jabbari,J. S.,Chamling,X.,Zack,D. J., Pébay, A., Daniszewski, M.,Senabouth,A.,Nguyen,Q. H., Crombie, D. E.,Lukowski, S. mammary glandbysingle-cellRNAprofiling. J. E.(2017).Constructionofdevelopmentallineage relationships inthemouse N., Liu,K.H.,Jackling,F. C.,Davis,M.J., Lindeman,G.J., Smyth,G.K.,Visvader, Pal, B.,Chen,Y., Vaillant, F., Jamieson,P., Gordon,L.,Rios,A.C.,Wilcox, S.,Fu, promoter methylation. cardiac a-actin(Actc1)expressioninearlyadultskeletal musclecorrelateswith D. Boutilier, J., Taylor, R.,Ram, R.,McNamara,E.,Nguyen,Q., Goullée, H.,Chandler, Variation inabundanceofpredictedresistancegenesthe Bayer, P. E.,Golicz,A.A.,Tirnaz,S.,Chan,C.K.K.,Edwards,D., Batley, J. (2018). resistance topotatovirusY. Ryadg locusonchromosomeXIfromAndigenapotatoesconferringextreme F., Bartolini,I.,Ghislain,M.(2018).Molecularandgenetic characterizationofthe Del Rosario Herrera,M.,JaraVidalon,L.,Montenegro, J. D., Riccio, C.,Guzman, ( Global DNAMethylationpatternscanplayaroleindefining terroiringrapevine J., Metcalfe, A.,Stephen, J. R.,DeBei,R.,Collins,C.,Lopez, C.M.R.(2017). Xie, H.,Konate, M.,Sai,N.,Tesfamicael, K.G.,Cavagnaro, T., Gilliham,M.,Breen, 6(Jun), 1–22. pangenome. Mechanisms. Best practicedatalifecycleapproachesforthe sciences. F., Watson-Haigh, N.S.,Wyres, K.L.,.Young, N.D., Schneider, M.V. (2018). Keeble-Gagnère, G.,Korhonen, P. K.,Neish,P., Prestes,P. R.,Richardson,M. J. H.,Dayalan,S.,Gladman,Hangartner, S.B.,Hayden,H.L.,Ho, W. W. H., B., Roessner, U., Russell, K.,Seemann,T., Treloar, A.,Tyagi, S.,Christiansen, Griffin, P.C.,Khadake, J., LeMay, K.S., Lewis,S.E., Orchard,S., Pask,A., Pope, 89(Jun), 455–465. Southern Oceanfeedinggroundsofhumpbackwhales. Application ofamulti-disciplinaryapproachtoreveal population structureand L., Robbins, J., Steel, D., Tremlett, J., Vindenes,S.,Constantine, R.(2018). A., Gallego, R.,Garrigue, C.,Ivashchenko, Y., Jarman,S.,Lindsay, R.,Pallin, D. Riekkola, L.,Zerbini,A.,Andrews,O., Andrews-Goff, V., Baker, C.S.,Chandler, 1938. Vitis vinifera cv. Shiraz cv. vinifera Vitis , Mehta,M.,Balmer, L.,Laing, N.,Morahan,G.,Nowak, K.(2017).Variable , Childerhouse, S.,Clapham,P., Dodémont,R.,Donnelly, D., Friedlaender, THE POWER OFPARTNERSHIP genomic researchinAustralia. and connectionsallowustoupholdourmissionofbeingakey enablerof bodies, hostinstitutes,andthegreaterresearchcommunity. Thesepartnerships organisations throughoutAustralia. Thisincludespartnershipswithourfunding As partoftheAustralian genomicscommunity, weworkwithawidevarietyof
1860(10),1025-1036. Plant Biotechnology. Plant Scientific Data Scientific Miochimica et Biophysica Acta (BBA) - Gene Regulatory Regulatory Gene - (BBA) Acta Biophysica et Miochimica ). Frontiers in Plant Science. Plant in Frontiers 38 Theoretical and Applied Genetics. Applied and Theoretical 7(5),1–12. . 5(Feb),1–9. Nature Communications. Nature 8(Oct),1–16 Ecological Indicators. Ecological Co-authored papers Brassica oleracea Brassica F1000Research. 131(9),1925– AGRF 2017/2018 8(1),1–13.
ANNUAL REPORT AGRF 2017/2018 39
We are passionate about research and take great pride in seeing research work that is supported by our services being published. Where appropriate, please acknowledge the contributions of AGRF in your publications, simply by including the following sentence in your acknowledgements section: The authors acknowledge use of the services and facilities of AGRF.
AGRF mentions PUBLICATIONS
1. Marques, F. Z., Nelson, E., Chu, P., Horlock, D., Fiedler, A., Ziemann, M., Tan, J. K., Kuruppu, S., Rajapakse, N. W., El-Osta, A., Mackay, C. R., Kaye, D. M. (2017). High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in DOCA-salt hypertensive mice. Circulation. 135(10), 964–977. 2. Combes, A., Phipson, B., Zappia, L., Lawlor, K., Er, P., X., Oshlack, A., Little, M. (2017). High throughput single cell RNA-seq of developing mouse kidney and human kidney organoids reveals a roadmap for recreating the kidney. BioRxiv. (Dec), 1–44. 3. Goonetilleke, S. N., March, T. J., Wirthensohn, M. G., Arús, P., Walker, A. R., Mather, D. E. (2018). Genotyping by Sequencing in Almond: SNP Discovery, Linkage Mapping, and Marker Design. G3: Genes, Genomes, Genetics. 8(1), 161–172. 4. Bradford, T., Pickett, M., Donnellan, S., Gardner, M., Schofield, J. (2018). Conservation genomics of an endangered subspecies of Southern Emu-Wren, Stipiturus malachurus (Passeriformes: Maluridae). Emu Austral Ornithology. 118(3), 258–268. 5. Poddar, N., Sen, R., Martin, G. J. O. (2018). Glycerol and nitrate utilisation by marine microalgae Nannochloropsis salina and Chlorella sp. and associated bacteria during mixotrophic and heterotrophic growth. Algal Research. 33(May), 298–309. 6. Savas, P., Virassamy, B., Ye, C., Salim, A., Mintoff, C. P., Caramia, F., Salgado, R., Byrne, D. J., Teo, Z. L., Dushyanthen, S., Byrne, A., Wein, L., Luen, S. J., Poliness, C., Nightingale, S. S., Skandarajah, A. S., Gyorki, D. E., Thornton, C. M., Beavis, P. A., Fox, S. B., Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), Darcy, P. K., Speed, T. P., Mackay, L. K., Neeson, P. J., Loi, S. (2018). Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis. Nature Medicine. 24(7), 986–993. ANNUAL REPORT AGRF 2017/2018 40
OUR BOARD OF DIRECTORS
In 2017/2018, AGRF was governed by eight directors, led by Professor Robert Lewis. The Directors are responsible for overseeing policy, strategic direction, and risk management.
In 2017/2018, our Directors were:
Professor Robert Lewis Chairman BSc (Hons), DSc (honoris causa), FTSE, FSARDI, PSM Member of the Finance, Audit & HR Committee
Professor Lewis is an Honorary Fellow of the South Australian Research and Development Institute and a Fellow of the Australian Academy of Technological Sciences and Engineering. Professor Lewis provides extensive guidance as the Chairman of the AGRF Board. He is also a member of the Finance, Audit & HR Committee. Professor Lewis contributes as a liaison with the agricultural and environmental sectors and is AGRF’s representative for Genomics Australia.
Professor Nick Samaras Deputy Chairman and Company Secretary BSc (Hons), PhD, MBA, FAIM, FAICD, FWCLP Member of the Finance, Audit & HR Committee
Professor Samaras is the Chairman of Genetic Signatures Ltd. He has extensive experience in the global life sciences and advises the AGRF Board on current technological advances, market trends and industry engagement. In addition, he had the role of AGRF’s Company Secretary from October 2016 to August 2017.
Dr Irene Kourtis Managing Director PhD, GDipLaw, GAICD
Dr Kourtis was the Chief Executive Officer of AGRF until 31 October 2018, and had an extensive background leading strategy, operations, change and business growth. Commencing as Managing Director of the AGRF Board in April 2017, she managed the performance of the organisation, the Board’s strategy, and the formulation and successful implementation of AGRF company policy.
Dr John Bell BSc, MSc, PhD, FTSE, FRACI, Comp I.E. Aust, MAICD
Dr Bell is a Senior Associate with ACIL Allen Consulting and a Senior Policy Adviser to the Australian Academy of Technological Sciences and Engineering, with previous experience working as the Deputy Secretary and Chief Science Advisor in the Department of Industry and Science. Dr Bell provides an invaluable service to the AGRF Board as a government liaison and advisor.
our governance ANNUAL REPORT AGRF 2017/2018 41
Professor Gabrielle Belz BVBiol, BVSc, PhD, DVSc, FAHMS, MAICD
Professor Belz is an NHMRC Senior Research Fellow. She joined the AGRF Board in May 2017 as a representative from the Walter and Eliza Hall Institute of Medical Research and The University of Melbourne. With over 20 years of experience in medical research, Professor Belz provides significant knowledge and expertise to the AGRF.
Mr Andrew Macdonald Chairman of the Finance, Audit & HR Committee BSc, BBus, CPA, MAICD
Mr Macdonald has over 25 years of commercial experience, working across the biotechnology, technology and finance sectors in Australia, the US and the UK. In his role as Chair of the Finance, Audit & HR Committee, Mr Macdonald provides significant contributions in the areas of business and finance.
Professor Benjamin Kile Member of the Finance, Audit & HR Committee BSc (Hons), LLB (Mon), PhD
Professor Kile was the representative from the Walter and Eliza Hall Institute of Medical Research until April 2017, when he relocated to Monash University as the Head of the Department of Anatomy and Developmental Biology. His key contribution to the Board has been to act as an independent director and intermediary to the medical research sector.
Professor Brandon Wainwright AM BSc (Hons), PhD
Professor Wainwright is the Director of the Institute for Molecular Bioscience at The University of Queensland. As well as acting as a representative of The University of Queensland, he provides services to the AGRF Board as a liaison with the Queensland Government.
Professor Ingrid Winship MBChB, MD (Human Genetics), FRACP, FACD, FAICD
Professor Winship has a Doctorate of Medicine (MD) Human Genetics from the University of Cape Town (1981) and accreditation as a Clinical Geneticist from the Human Genetics Society of Australasia (1995). She has more than 35 years’ experience working in medicine and clinical genetics, bringing a wealth of knowledge and expertise to AGRF.
your partners at AGRF ANNUAL REPORT AGRF 2017/2018 42
OUR EXECUTIVE TEAM
Our Executive Team is responsible for the strategic management and leadership of AGRF, ensuring that we remain an innovative and accountable world class genomics facility.
In 2017/2018, our Executive Team included:
Irene Kourtis PhD : Chief Executive Officer
Karen Jenkins : Executive - People & Culture - leading AGRF’s Human Resources strategy to support our staff and our ‘One AGRF’ culture.
Maria Ricci : Executive - Business & Market Development - driving business opportunities in the clinical, applied and commercial sectors, and leading the Sales & Marketing team.
Stephan Scheffer : Executive - Finance & Business Services - leading AGRF’s financial activities and governance, information technology and procurement sections.
Kirby Siemering PhD : Executive - Science & Technology - leading innovation, scientific and technology strategy across the organisation and with our valued clients.
Justin Stockmyer : Executive - Laboratory Operations - leading the day-to-day operation and quality management of AGRF services.
L-R: Irene Kourtis, Justin Stockmyer, Kirby Siemering, Maria Ricci, Karen Jenkins, & David Benallack (joined August 2018, as Executive - Finance & Business Services) ANNUAL REPORT AGRF 2017/2018 43
OUR FUNDING PARTNERS
The work we do is made possible with the support of our funding partners. We thank the Commonwealth Government infrastructure funding schemes, administered through NCRIS and Bioplatforms Australia.
The BPA Data Framework Initiatives are delivering large-scale ‘omics data to support national research efforts. These are nationally collaborative programs to create new datasets and ultimately offer them as a public resource.
To ensure relevance and strategic value, all datasets are generated with the collective support and expert guidance of leading researchers, industry specialists and government bodies. This has the advantage of drawing together existing resources and knowledge and has also been successful in seeding new linkages and research partnerships.
AGRF has played a key role in providing data, expertise, and bioinformatics support for the following projects:
1. Stem Cells: This is a multi-omics project (transcriptomics, proteomics and metabolomics) of stem-cell differentiation. AGRF has performed transcriptomics (whole transcriptome or mRNA and small RNA) of bulk stem cell populations as well as single cell transcriptomics (10x Genomics Chromium). 2. Antibiotic Resistant Pathogens (Sepsis): This is a multi-omics project (genomics, transcriptomics, proteomics and metabolomics) of several antibiotic-resistant pathogens. AGRF has performed transcriptomics of multiple bacterial strains grown under several conditions. 3. Oz Mammal Genomes: The aim of this genomics initiative is to build reference quality genomes for 10 Australian mammals, and study genomics diversity of Australian mammals including several threatened species. AGRF has contributed to both projects through Linked-Reads sequencing (10x Genomics Chromium) for de novo assembly, and Genotyping by Sequencing (GBS) of three threatened species. 4. Marine Microbes: This is a study of the microbial ecology of Australian marine environments. AGRF has performed meta-genome and meta-transcriptome sequencing for this project. 5. DNA Barcoding: This project used traditional DNA barcoding as well as NGS methods to study genetic diversity of several Australian environments. AGRF has performed conventional DNA barcode sequencing via Sanger as well as low-coverage shotgun sequencing and GBS for this project. 6. Reef Future Genomics (ReFuGe): The aim of this genomics initiative is to build reference quality genomes of several coral and symbiodinium species and associated microbial symbionts. AGRF has contributed to de novo assembly though sequencing of paired-end and long mate-pair libraries. 7. Biomes of Australian Soil Environments (BASE): This project is a study of the microbial ecology of soil environments across Australia. AGRF has performed amplicon sequencing and metagenome sequencing for this project. 8. Wheat Chr7a: AGRF has performed shotgun sequencing of tiled BAC libraries from chromosome 7a as part for the International Wheat Genome Sequencing Consortium. This work was recently published in Genome Biology. 9. Melanoma: Sequencing of a large cohort of Australian melanoma patients. 10. Wheat Varieties and Pathogens: Sequencing of several wheat varieties and wheat pathogens. ANNUAL REPORT
AGRF improves quality of life through exceptional life science.
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