Thoughts and perspectives of metagenome sequencing as a diagnostic tool for infectious disease: an interpretive phenomenological study

Background Effective infectious disease diagnostics (IDD) are vital for informing clinical decision-making regarding the treatment and patient management of disease and infections. Conventional clinical methods rely upon culture-dependent techniques, and there has been little shift in the acceptance and integration of culture-independent sequencing methods into routine clinical IDD. This study explored stakeholders’ experiences within IDD, including those working in clinical settings and those conducting research at the forefront of microbial genomics. We aimed to identify factors driving the development and implementation of metagenome sequencing as a routine diagnostic. Methods Virtual semi-structured interviews were conducted with purposively selected individuals involved in IDD. The interviews explored the experiences of implementing metagenome sequencing as a diagnostic tool and decisions about which diagnostics are used for identifying bacteria-causing infections. Thematic analysis was used to analyse the data, and an Interpretive Phenomenological approach was used throughout. Results Ten individuals were interviewed between July 2021 and October 2021, including Clinical scientists, consultants, and professors in academia. Their experience ranged from no knowledge of metagenome sequencing to an expert understanding of the phenomenon. Five themes emerged: Diagnostic Choice, Infrastructure, Open Data Sharing, COVID-19, and Communication. Participants recognised the need for new diagnostics to be implemented to overcome the limitations of current diagnostic approaches but highlighted the barriers to integrating new diagnostics into clinical settings, such as the impact on clinical decision-making, accreditation, and cost. However, participants felt that lessons could be learnt from using metagenomics in COVID-19 and how other diagnostic platforms have been integrated into clinical settings over the last 20 years. Conclusions The study provided clear evidence to address the knowledge gap in current literature and practice for developing and implementing metagenome sequencing as a potential IDD. The knowledge of new and upcoming genomic diagnostic testing is not equally distributed throughout the UK, impacting the understanding and drive to integrate metagenome sequencing into routine clinical diagnostics. Improvements in access to new diagnostics could improve patient treatment and management and positively impact public health. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study is funded by the National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Gastrointestinal Infections, a partnership between the UK Health Security Agency, the University of Liverpool and the University of Warwick. The views expressed are those of the author(s) and not necessarily those of the NIHR, the UK Health Security Agency or the Department of Health and Social Care. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study gained ethical approval from the Institute of Life Course and Medical Sciences Research Ethics Committee at the University of Liverpool (Ethical review reference 9855). All methods were carried out following relevant guidelines. All participants were provided with an information sheet and provided written consent before participating in this study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The dataset (which includes individual transcripts) is not publicly available due to confidentiality. * IDD : Infectious disease diagnostics mNGS : Metagenomic next-generation sequencing PCR : Polymerase Chain Reaction MALDI-TOF : Matrix-assisted laser desorption-ionization time of flight mass spectrometry IPA : Interpretive phenomenological approach COREQ : Consolidated criteria for reporting qualitative research