Best practice recommendations for bioinformatics approaches applied to high-throughput sequencing for rare disease and cancer diagnosis within the United Kingdom National Health Service

Background<br/>Establishing best practice recommendations helps to increase consistency, equity and innovation in clinical genomics services. Bioinformatics approaches are a core component of clinical genomics services that utilize high-throughput genomic sequencing applied in the diagnosis of rare disorders and cancer. Whilst a broad range of international recommendations exist for genomic diagnostic testing and genetic variant classification, the current United Kingdom (UK)-specific best practice recommendations for bioinformatics approaches applied in this context are outdated.<br/><br/>Methods<br/>We assembled a team of bioinformaticians and scientists with diverse expertise in rare disease and cancer genomics applied in clinical diagnostics within the UK National Health Service. Through structured discussion, polls and surveys we developed an updated set of best practice recommendations for bioinformatics approaches applied to high-throughput genomic sequencing in clinical genomic testing.<br/><br/>Results<br/>We provide best practice recommendations across the spectrum of activities within a clinical genomics bioinformatics pipeline, including quality control, primary, secondary and tertiary analysis approaches, and shared knowledge bases. We also comment on issues related to software development and maintenance. The recommendations can be applied to multiple sequencing technologies and encompass both targeted and whole genome sequencing approaches applied to germline and tumour DNA samples.<br/><br/>Conclusion<br/>The best practice recommendations outlined in this study provide a national framework for adoption and innovation of bioinformatics approaches across diverse clinical genomic testing strategies in the UK National Health Service.