Table 3. Summary of considerations for reporting metagenomic findings.

Consideration	Point of Relevance	Criteria for reporting to research participant	Recommendation
1. Need to discriminate between environmental contamination, and true presence of a microbe in a clinical sample;	Pre-analytical	There must be reasonable certainty that an organism identified is a pathogen	Organisms that may reflect environmental contamination should not be reported.
2. Need to discriminate between commensal flora (harmless to the host) vs pathogenic organisms (associated with a disease phenotype);	Pre-analytical Clinical evaluation	There must be reasonable certainty that an organism identified is a pathogen	Organisms that may represent commensal flora should not be reported. Reporting should be reserved for organisms that cause serious and persistent infection.
3. Long time delays may occur between acquisition of a clinical sample and identification of microbial reads through the metagenomic pipeline;	Clinical evaluation	Identification of a pathogen must occur within a period deemed timely for appropriate clinical intervention	After a time lapse of weeks/months, feedback to the participant is not relevant for the majority of pathogens. Reporting should be reserved for conditions that influence treatment decisions.
4. Quality controls are required for metagenomic sequencing of pathogen DNA;	Analytical	Sequencing platform is currently not validated for clinical diagnostics, so the majority of pathogen sequence data should not be reported to participant	Over time, consider developing positive controls for microbial identification from metagenomic sequencing platforms. Sterility of sample handling and sequencing environment needs to be assured.
5. Quality controls required for bioinformatic processing of sequencing data;	Analytical	Bioinformatic platform is currently not validated for clinical diagnostics, so the majority of pathogen sequence data should not be reported to participant	Over time, pathogen-specific and tissue- specific algorithms are required (e.g. to specify what number and % of reads, length and depth of coverage of a micro-organism’s genome) to report its presence in the sample. A designated pathogen database of reference genomes should be developed
6. Identification of a pathogen may have implications for contacts of the participant;	Clinical Evaluation	Confirmation of a specific pathogen would have consequences for testing/ treating family members or sexual contacts	Identification of blood-borne viruses should be reported, as contacts/family members should be offered screening ± treatment if infection is confirmed
7. Special considerations may arise if biohazard organisms are identified or reported (potential impact on laboratory staff, patient’s clinical teams, family members, and the wider community);	Clinical Evaluation	There must be reasonable certainty that an organism identified is a pathogen, has been correctly identified, within an appropriate time-frame for clinical action	Reporting biohazard organisms could cause high anxiety and cost affecting a wide number of people. Reporting should only be undertaken in keeping with points 1–6 above.
8. Need to differentiate between results that may have impact for an individual patient, versus those that could underpin future patient-stratified medicine or provide longer-term insights into pathophysiology of disease	Clinical Evaluation	The presence of a micro- organism should only be reported to the participant/ clinician if it will change current clinical management.	Organisms that may be important in disease pathogenesis (e.g. oncoviruses) should be recorded for research purposes but not reported back to individual participants.