Potential for diagnosis of infectious disease from the 100,000 Genomes Project Metagenomic Dataset: Recommendations for reporting results

Wellcome Open Research

article

Gkikas Magiorkinis¹  Philippa C. Matthews²  Susan E. Wallace⁵  Katie Jeffery²  Kevin Dunbar⁶  Richard Tedder⁷  Jean L. Mbisa⁶  Bernadette Hannigan⁶  Effy Vayena⁹  Peter Simmonds²  Daniel S. Brewer^1,10  Abraham Gihawi^1,10  Ghanasyam Rallapalli^1,10  Lea Lahnstein^1,12  Tom Fowler^1,12  Christine Patch^1,12  Fiona Maleady-Crowe^1,12  Anneke Lucassen^1,13  Colin Cooper^1,10 

[1] Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens;University of Oxford;Oxford University Hospitals NHS Foundation Trust;Oxford Biomedical Research Centre, John Radcliffe Hospital;University of Leicester;Public Health England;Imperial College London;University of Cambridge;Swiss Federal Institute of Technology;University of East Anglia;Earlham Institute;Genomics England;Faculty of Medicine, University of Southampton

关键词: metagenomics;    full-genome sequencing;    pathogens;    incidental findings;   

DOI  :  10.12688/wellcomeopenres.15499.1

学科分类：内科医学

来源: Wellcome

【 摘 要 】

The identification of microbiological infection is usually a diagnostic investigation, a complex process that is firstly initiated by clinical suspicion. With the emergence of high-throughput sequencing (HTS) technologies, metagenomic analysis has unveiled the power to identify microbial DNA/RNA from a diverse range of clinical samples (1). Metagenomic analysis of whole human genomes at the clinical/research interface bypasses the steps of clinical scrutiny and targeted testing and has the potential to generate unexpected findings relating to infectious and sometimes transmissible disease. There is no doubt that microbial findings that may have a significant impact on a patient’s treatment and their close contacts should be reported to those with clinical responsibility for the sample-donating patient. There are no clear recommendations on how such findings that are incidental, or outside the original investigation, should be handled. Here we aim to provide an informed protocol for the management of incidental microbial findings as part of the 100,000 Genomes Projectwhich may have broader application in this emerging field. As with any other clinical information, we aim to prioritise the reporting of data that are most likely to be of benefit to the patient and their close contacts. We also set out to minimize risks, costs and potential anxiety associated with the reporting of results that are unlikely to be of clinical significance. Our recommendations aim to support the practice of microbial metagenomics by providing a simplified pathway that can be applied to reporting the identification of potential pathogens from metagenomic datasets. Given that the ambition for UK sequenced human genomes over the next 5 years has been set to reach 5 million and the field of metagenomics is rapidly evolving, the guidance will be regularly reviewed and will likely adapt over time as experience develops.

【 授权许可】

CC BY