- This document has been developed under the auspices of the Royal College of Pathologists of Australasia, and is hosted by RCPA Quality Assurance Programs, as a service to the pathology community.
- The recommendations presented in this document do not carry regulatory authority.
- This document does not purport to provide legal advice. This document is offered in good faith, but no liability is accepted for consequences arising from its use.
- This is Version 1.0 of the document. It will be updated as required. You can check the version date of the page you are reading at the foot of the page.
- Editor of v1.0 - Graeme Suthers email. As of January 2014, the Editor for the next edition is Melody Caramins email
- Please refer to the Discussion tab above for comments or suggestions from readers that could improve this Chapter.
In March 2011, the Royal College of Pathologists of Australasia (RCPA) held a workshop on the implementation of "next generation sequencing" in diagnostic laboratories across Australia. As noted in the Report from the workshop, there was agreement that a guideline be developed for diagnostic labs wanting to implement next generation sequencing. The goal was to develop a tool that would assist such labs identify the issues to be addressed to ensure that the high quality of medical genetic testing across Australia is maintained. As yet, there is no accreditation standard for the implementation of next generation sequencing in Australian diagnostic laboratories. This document may become the basis for such a standard in the future.
The development of these guidelines was under the auspices of the Genetics Advisory Committee of the College, with the Chair of the Committee, Graeme Suthers email, acting as Project Coordinator. Separate writing committees were developed to address each of the topics/chapters listed above. The committees had nominees from the RCPA, Faculty of Science of the RCPA, and HGSA. Other experts were also co-opted. The term "next generation sequencing" was subsequently changed to "massively parallel sequencing" as the technology in this domain is changing repeatedly.
A draft of this document was discussed at a workshop held in Sydney in September 2012. Attendees included members of the writing groups, other nominees from stakeholder organisations, and co-opted experts. The document was launched at the College's Annual Scientific Meeting, Pathology Update, in February 2013 in Melbourne, Victoria.
2 Why Wiki?
We chose to present this document in the "Wiki" format for a number of reasons.
- First, placing the document on the web makes it readily available for anyone to access.
- Second, we recognise that this field is changing rapidly, and the document will need frequent updates to keep it relevant. The Wiki format allows for frequent changes. The date of the last change to a Chapter is shown at the foot of each page.
- Third, this format allows people to add comments, corrections, suggestions, and examples to improve the document. We encourage you to engage with us in this way (refer to the Discussion of each Chapter at Top Left).
- Finally, the security provisions of the Wiki format allow us to protect the text. The text of each Chapter can only be edited by the Chapter Editors. The suggestions you make will be reviewed by the relevant Chapter Editor and potentially incorporated in subsequent updates to that Chapter. Hence you can be assured that the text as shown has been reviewed by the Editor responsible.
There are separate Chapters in this document for
This list of "chapters" is included at the top of each page for easy navigating. You can also create a PDF of each Chapter by clicking on the "printable version" button on the left of your screen.
Please note: This document is not a guide to next generation sequencing or to accreditation per se. The goal of this document is to identify issues that require consideration, and to direct readers to resources that may help them address those issues. This document should be regarded as a checklist of issues to be considered, with suggestions regarding relevant resources.
Each of the Chapters of the document (or "pages", as they are viewed here) has a hierarchy of headings. The headings form the basis for the Table of Contents at the beginning of each Page. The headings also provide a consistent structure across the entire document.
- A Level 1 heading is the name of the Chapter or Page.
- A Level 2 heading identifies a section that deals with a large topic.
- A Level 3 heading is used for recommendations.
- A Level 4 heading identifies a supplementary section that might list references or technical details.
Each heading may be followed by text which is the commentary on that section.
This document consists of a series of recommendations, with commentary to explain and direct readers to resources. The recommendations represent a checklist of issues that need to be considered by a laboratory seeking accreditation for diagnostic massively parallel sequencing.
It is important to note that these recommendations do not carry the weight of Standards and Guidelines in NPAAC reference materials. This document does not have the regulatory authority of an NPAAC document.
This document represents the commitment and expertise of many people. It is hard to trace who was responsible for this specific idea, or that useful turn of phrase. We are particularly grateful to the Editors of each Chapter of Version 1.0,
- Bev Rowbotham (Ethical and legal issues)
- Bing Yu (Wet Lab)
- David Thorburn (Bioinformatics)
- Damien Bruno (Reporting)
- Richard Allcock (IT infrastructure)
and to their long suffering colleagues who helped draw this together.
Funding for the workshop in Sydney at which a draft of this document was reviewed was provided by the Australian Department of Health & Ageing. Their support is noted with appreciation, as is the assistance of the RCPA QAP Pty Ltd in hosting this website.
Special thanks to the the following Chapter Editors of Version 1: We also acknowledge with thanks the contributions of those who attended the Sydney workshop in person or by correspondence:
David Abbott, Richard Allcock, Bruce Bennetts, Daniel Bourke, Frank Bowling, Damien Bruno, Michael Buckley, Leslie Burnett, Melody Caramins, Don Chalmers, John Christodoulou, Joe Daniel, Mark Davis, Vicki Dong, Kerry Emslie, Kelly Ewen-White, Andrew Fellowes, Simon Foote, Jozef Gecz, Andy Griffin, Sean Grimmond, Kumari Hallwirth-Pillay, James Harraway, Marcus Hinchcliffe, Brett Kennedy , Craig Kennedy, Michael Legg, Scott Mead, Cliff Meldrum, Melanie O'Keefe, Greg Peters, Jason Pinner, Michael Ralston, John Rasko, David Ravine, Tony Roscioli, Bronwen Ross, Bev Rowbotham, Barney Rudzki, Hamish Scott, Rodney Scott, Tim Smith, Graeme Suthers, Thorsten Theis, Mervyn Thomas, David Thorburn, Ron Trent, Vanessa Tyrrell, Alastair Wilson, Bing Yu, and Sui Yu.
If you reference this document, please cite it as follows: Royal College of Pathologists of Australasia (RCPA). Implementation of Massively Parallel Sequencing in Diagnostic Medical Genetic Testing. http://pathwiki.rcpaqap.com.au/pathwiki/index.php/Introduction [date accessed].
This section lists some of the documents which address quality issues in genomic sequencing generally. More specific references are provided in subsequent sections of this document.
- Gargis et al., Assuring the quality of next-generation sequencing in clinical laboratory practice. Nat Biotechnol 2012 Nov;30(11):1033-6. doi: 10.1038/nbt.2403. PubMed PMID: 23138292
- CDC. Next Generation Sequencing: Standardization of Clinical Testing (Nex-StoCT) Working Groups.
- CDC. Next-generation Sequencing: Standardization of Clinical Testing (Nex-StoCT) Workgroup Principles and Guidelines.
- Weiss et al. Best Practice Guidelines for the Use of Next Generation Sequencing (NGS) Applications in Genome Diagnostics: A National Collaborative Study of Dutch Genome Diagnostic Laboratories. Hum Mutat 2013 Jun 17. PubMed PMID: 23776008.
- Schrijver et al. Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology. J Mol Diagn 2012 Nov;14(6):525-40.
- Next Generation Sequencing (NGS) guidelines for somatic genetic variant detection. New York State Department of Health, August 10 2012.
- Rehm et al. ACMG clinical laboratory standards for next-generation sequencing. Genet Med 2013 Jul 25. doi: 10.1038/gim.2013.92. [Epub ahead of print PubMed PMID: 23887774.]