Access to research resources
Cancer researchers with appropriate regulatory approval have the opportunity to request ZERO samples and data via an application process. Resources that may be requested include:
- primary and patient-derived xenograft cells and tissues
- WGS, RNAseq and methylation array data.
Applications received are reviewed by the ZERO Research Committee, with an expected response time of 6 weeks. Patient consent to share collected samples and data is sought at the time of enrolment on the ZERO national clinical trial, and all collected material is deidentified to maintain participant privacy and confidentiality.
Please note that in certain circumstances, the material may need to be recalled for clinical use (such as to enable clinicians to enrol patients onto other trials).
By the end of 2020, approximately 400 patients diagnosed with high-risk cancers (expected survival <30%) from all eight paediatric oncology centres around Australia will have been recruited to the ZERO national clinical trial. From 2021 the trial is being expanded to include children with lower risk cancers, and by the end of 2023, it will include all children and young people diagnosed with cancer in Australia.
After giving informed consent, patients enrolled onto the ZERO national clinical trial provide both germline samples and tumour samples (either fresh, fresh frozen, or formalin-fixed embedded) for analysis by means of molecular profiling, in vitro drug screening and in vivo drug modelling.
Excess tissue and nucleic acids samples from participants who have consented to future research are available through application to the ZERO Research Committee. Applications are assessed on a range of factors, including the merit of research proposals and availability of samples.
Data from sample analysis and testing
Researchers are invited to complete a data access application form to gain access to comprehensive omics and high throughput screening datasets, together with minimal clinical information to support high-level integrative analysis. This application is based on the exacting standards of the European Genome-Phenome Archive. VCF, BAM, FASTQ, TXT and BED data are available.
ZERO data is primarily comprised of:
- whole genome sequencing (WGS)
- RNA sequencing (RNASeq)
- methylation array data
- aggregate base clinical information from children with high-risk cancer of various tissue origins.
In addition, the successful generation of in vitro cell culture gives rise to drug screening data and, in turn, patient-derived xenografts (PDXs) enable in vivo drug efficacy data to be made available. (Note: Targeted sequencing was routinely performed on samples obtained earlier in the Program; however, it is now only completed on samples where the material is found to be insufficient for WGS.)
Whole-genome sequencing (WGS) is performed on Illumina HiSeq X sequencers at the Garvan Institute of Medical Research (Sydney, Australia) under clinically accredited conditions (ISO15189). Tumour DNA is sequenced to 90-120x depth and matched germline to 30-40x depth. Reads are aligned to the hs37d5 reference genome using BWA, and variant files generated using best practice pipelines to make results comparable with other cohorts.
Whole transcriptome RNA Sequencing (80M read pairs) is performed on either the Illumina NovaSeq 6000 or NextSeq500 platform at Murdoch Children’s Institute, Melbourne (MCRI). Associated bioinformatics analysis for fusion transcripts and global gene expression are conducted through local pipelines at MCRI and Children’s Cancer Institute.
Methylation analysis using Illumina’s Infinium Human Methylation EPIC BeadChip is performed on the Illumina iScan. The EPIC BeadChip assesses methylation at over 850,000 CpGs throughout the human genome.