Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar 21;61(4):305-312.
doi: 10.1136/jmg-2023-109645.

Recommendations for laboratory workflow that better support centralised amalgamation of genomic variant data: findings from CanVIG-UK national molecular laboratory survey

Sophie Allen #  1 , Lucy Loong #  1 , Alice Garrett  1   2 , Bethany Torr  1 , Miranda Durkie  3 , James Drummond  4 , Alison Callaway  5 , Rachel Robinson  6 , George J Burghel  7 , Helen Hanson  1   2 , Joanne Field  8 , Trudi McDevitt  9 , Terri P McVeigh  10 , Tina Bedenham  11 , Christopher Bowles  12 , Kirsty Bradshaw  13 , Claire Brooks  14 , Samantha Butler  15 , Juan Carlos Del Rey Jimenez  2 , Lorraine Hawkes  16 , Victoria Stinton  17 , Suzanne MacMahon  18   19 , Martina Owens  12 , Sheila Palmer-Smith  20 , Kenneth Smith  21 , James Tellez  22 , Mikel Valganon-Petrizan  18   19 , Erik Waskiewicz  20 , Michael Yau  16 , Diana M Eccles  23   24 , Marc Tischkowitz  25 , Shilpi Goel  26   27 , Fiona McRonald  26 , Antonis C Antoniou  28 , Eva Morris  29 , Steven Hardy  26 , Clare Turnbull  30   10
Affiliations

Recommendations for laboratory workflow that better support centralised amalgamation of genomic variant data: findings from CanVIG-UK national molecular laboratory survey

Sophie Allen et al. J Med Genet. .

Abstract

Background: National and international amalgamation of genomic data offers opportunity for research and audit, including analyses enabling improved classification of variants of uncertain significance. Review of individual-level data from National Health Service (NHS) testing of cancer susceptibility genes (2002-2023) submitted to the National Disease Registration Service revealed heterogeneity across participating laboratories regarding (1) the structure, quality and completeness of submitted data, and (2) the ease with which that data could be assembled locally for submission.

Methods: In May 2023, we undertook a closed online survey of 51 clinical scientists who provided consensus responses representing all 17 of 17 NHS molecular genetic laboratories in England and Wales which undertake NHS diagnostic analyses of cancer susceptibility genes. The survey included 18 questions relating to 'next-generation sequencing workflow' (11), 'variant classification' (3) and 'phenotypical context' (4).

Results: Widely differing processes were reported for transfer of variant data into their local LIMS (Laboratory Information Management System), for the formatting in which the variants are stored in the LIMS and which classes of variants are retained in the local LIMS. Differing local provisions and workflow for variant classifications were also reported, including the resources provided and the mechanisms by which classifications are stored.

Conclusion: The survey responses illustrate heterogeneous laboratory workflow for preparation of genomic variant data from local LIMS for centralised submission. Workflow is often labour-intensive and inefficient, involving multiple manual steps which introduce opportunities for error. These survey findings and adoption of the concomitant recommendations may support improvement in laboratory dataflows, better facilitating submission of data for central amalgamation.

Keywords: Clinical Laboratory Techniques; Genetic Testing; Genetics; Genomics; Molecular Diagnostic Techniques.

PubMed Disclaimer

Conflict of interest statement

Competing interests: MD and TM have received honoraria from AstraZeneca and MSD for contributions as expert assessors in the GenQA/EMQN GTACT schemes: Ensuring accurate classification of BRCA1, BRCA2 and other HRR gene variants. ACA is the creator of BOADICEA, licensed by Cambridge Enterprise, and receives royalties from Cambridge University. TPM is a council member for the UK Cancer Genetics Group, and has received honoraria from AstraZeneca and Novartis, and consulting fees from Roche as an Expert Advisor for the National Molecular Tumour Board (Ireland). DME was co-applicant on an AstraZeneca Research Grant (2021–2023), is on the University of Southampton Executive Board and is the Non-Executive Director of UHS NHS Foundation Trust. CT has received honoraria from AstraZeneca and MSD for educational activities and scientific boards, which are donated in full to charity.

Figures

Figure 1
Figure 1
Responses from each laboratory for multiple choice questions pertaining to variant workflow from NGS pipelines to the LIMS. (A,B) All laboratory responses describing the method of transfer from NGS pipeline output to LIMS, and how this information is stored within the LIMS. (C) Visual description of differing LIMS storage formats. (D) All laboratory responses describing which detected variants are stored within an LIMS. CSG, cancer susceptibility gene; LIMS, Laboratory Information Management System; NGS, next-generation sequencing; QC, quality control.
Figure 2
Figure 2
Comparison of testing context information captured by each laboratory before and after the National Test Directory was implemented. LIMS, Laboratory Information Management System.
See this image and copyright information in PMC

References

    1. Annual report of the chief medical officer 2016: generation genome. Office of the Chief Medical Officer, Department of Health; 2017.
    1. Accelerating genomic medicine in the NHS. A strategy for embedding genomics in the NHS over the next 5 years. NHS England, 2022.
    1. Landmark strategy launched to cement UK’s position as global leader in genomics. Department of Health and Social Care, 2020.
    1. NHS-England . National genomic test directory. 2023.
    1. Karczewski KJ, Francioli LC, Tiao G. The mutational constraint spectrum quantified from variation in 141,456 humans. Genomics [Preprint]. 10.1101/531210 - DOI - PMC - PubMed