{
  "abstract": "Background 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 use high-throughput genomic sequencing applied in the diagnosis of rare disorders and cancer. While a broad range of international recommendations exist for genomic diagnostic testing and genetic variant classification, the current UK-specific best practice recommendations for bioinformatics approaches applied in this context are outdated.Methods We assembled a team of bioinformaticians and scientists with diverse expertise in rare disease and cancer genomics applied in clinical diagnostics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.Results 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.Conclusion 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.",
  "authors": [
    {
      "affiliations": [
        "Genomics England Limited, London, UK",
        "Division of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"
      ],
      "name": "Jamie M Ellingford"
    },
    {
      "affiliations": [
        "All Wales Medical Genomics Service, Cardiff, UK"
      ],
      "name": "Erik Waskiewicz"
    },
    {
      "affiliations": [
        "NHS North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK"
      ],
      "name": "Ashley J Pritchard"
    },
    {
      "affiliations": [
        "Genomics England Limited, London, UK"
      ],
      "name": "Javier Lopez"
    },
    {
      "affiliations": [
        "South West Genomic Laboratory Hub, University Hospitals Bristol NHS FoundationTrust, Bristol, UK"
      ],
      "name": "Rebecca Morgan"
    },
    {
      "affiliations": [
        "North West Genomic Laboratory Hub, Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Oxford Road, Manchester, UK"
      ],
      "name": "Emily Ley"
    },
    {
      "affiliations": [
        "Central and South Genomic Laboratory Hub, Birmingham Women’s Hospital, Mindelsohn Way, Birmingham, UK"
      ],
      "name": "Matt Lyon"
    },
    {
      "affiliations": [
        "Genomics England Limited, London, UK"
      ],
      "name": "Alona Sosinsky"
    },
    {
      "affiliations": [
        "Genomics England Limited, London, UK"
      ],
      "name": "Dalia Kasperaviciute"
    },
    {
      "affiliations": [
        "East Genomics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK",
        "NHS England, London, UK"
      ],
      "name": "Joo Wook Ahn"
    }
  ],
  "title": "Best practice recommendations for bioinformatics approaches applied to high-throughput sequencing for rare disease and cancer diagnosis within the UK National Health Service",
  "uid": "a99d279c-e265-5f1e-89de-9a4c89ae2375"
}