Comparative Study: Queensland Genomics inter-laboratory NGS quality comparison using omnomicsQ
Implementing a world-first inter-laboratory quality comparison with omnomicsQ to ensure high quality data among the members of the Queensland Genomics Genomic Testing Innovation group.
The Challenge
The implementation of high quality, accessible and affordable genomic services into routine clinical health care is a major challenge facing many countries around the world. In tackling this challenge, members of the Queensland Genomics (QG) Genomic Testing Innovation (GTI) group, consisting of public, private and research institutions in Queensland (QLD) Australia, use next generation sequencing (NGS) techniques and funding provided by the QLD Government to bring genomic services to the people of QLD.
Although each institution in the QG GTI alliance has differing testing capabilities, they all work towards the same goal of providing high quality genomic testing
solutions. While each laboratory has carried out its own quality control (QC) analyses, no comparative study of QC had been undertaken to ensure that each of the laboratories in the alliance performed to the same level.
The Solution
The NGS quality management system omnomicsQ was determined to be the ideal solution to the problem, to run a first of its kind collaborative quality study. This
software as a service (SaaS) by Euformatics can be integrated into in-house built pipelines and LIMSs or operated manually through a user interface, which was the case in this context. As an agnostic solution omnomicsQ is able to process data from any sequencer or kit as long as it is in a standardised format, so even though each laboratory in the study had their own specific equipment, it was still possible to analyse their results concurrently and in direct comparison to each other.
Each laboratory was provided with one or more National Institute of Standards and Technology (NIST) reference sample to sequence, the results of which were compared to the reference truth set as well as to those of other laboratories. Due to differing NGS capabilities and test offerings in each laboratory, it would not have been relevant to compare all variant calls with each other; instead, omnomicsQ highlighted a group of 201 genes which were sufficiently covered by all participating laboratories to assess against further detailed quality metrics.
The results of the study demonstrated the high quality of the NGS provision which already exists among the QG GTI laboratories. Single Nucleotide Variant (SNV or SNP) calling was measured at a sensitivity of over 96.6% in all laboratories, while the average read depth for all the samples assessed was over 87x. This is particularly positive when considering the range of panels assessed, from targeted panel sequencing all the way to full exome. omnomicsQ also allowed the participating laboratories to compare their quality metrics to other users of the software around the world, helping them to benchmark their results not only against each other, but to the wider NGS community.
The Context
Establishing strong quality processes and checks for NGS solutions becomes ever more important as our understanding of genetic diseases continues to grow. Indeed, in Australia where 6-8% of the population are affected by a rare genetic disease, this is particularly valuable. For the QG GTI members, effectively demonstrating that their NGS provision is already of a high quality drives trust within the sector in Australia, brings additional funding and clarifies that capabilities within Queensland are well-suited to the needs of the population.
Currently, quality control for NGS often ends at pipeline validation and coverage analysis; there are limited international guidelines on how laboratories should ensure that their data is at the highest quality it can be every time a sample is run.
omnomicsQ provides a solution that brings all of these metrics together; being able to demonstrate quality in NGS data is one crucial step towards laboratory accreditation and omnomicsQ can provide laboratories with the data to pursue this goal.
Most importantly in this context, demonstrating a high level of NGS data quality means that QG can already start reducing the burden on the Queensland healthcare system by lowering treatment times and resource levels to bring about quicker and more targeted diagnoses. omnomicsQ made it easy to conduct a comparative quality assessment and help strengthen ties between the laboratories as well as offering an educative process for continued improvement of genomic services.
Profile
The Queensland Genomics Health Alliance (Queensland Genomics) is a five-year program (2016-2021) funded by the Queensland Government to lay the foundations to support genomic medicine in Queensland’s health system. Through Queensland Genomics, the Queensland Government is investing $25million in clinical and capability building activities.
Current clinical areas include: rare disease, epilepsy, cancer and infectious disease.
The focus for capability building activities is on: educating the clinical workforce; genomic sequencing results used to benefit patients; genomic data management; legal and social policy; community awareness and advocacy, and; building evidence to move genomics research findings into practice.
The QG GTI alliance consisted of 5 laboratories from the public, private and research sectors, each with their own genomic speciality, ranging from whole exome sequencing to targeted panels.
Rachael Mehrtens
Project Manager, Pathology Queensland
omnomicsQ allowed us to thoroughly examine our NGS data quality, and clearly highlight our successes and opportunities for development. Together with the expertise of the Euformatics team, the software gave us everything we needed to carry out this world-first comparative study.
References
1. Rare Voices – https://www.rarevoices.org.au/page/15/what-is-a-raredisease
For more information visit:
www.queenslandgenomics.org