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Record W4409598465 · doi:10.1016/j.gim.2025.101446

Evaluating the return of additional findings from the 100,000 Genomes Project: A mixed-methods study exploring participant experiences of receiving secondary findings from genomic sequencing

2025· article· en· W4409598465 on OpenAlexaff
Bethany Stafford‐Smith, Morgan Daniel, Michelle Peter, Jana Gurasashvili, Rashida Baptiste, Xavier Bracke-Manzanares, Lamprini Georgiou, Adele Green-Armytage, Blanche Griffin, Bethany Lumborg, Ben Paternoster, Emma Smith, Meena Balasubramanian, Lucy Bownass, Paul Brennan, Ruth Cleaver, Virginia Clowes, Philandra Costello, Bianca DeSouza, Louise Dubois, Angela George, Elaine George, Rachel Harrison, Lara Hawkes, Steve E. Humphries, Alan Jones, Elizabeth A. V. Jones, Alison Kraus, Deborah Holiday, Meriel McEntagart, Suresh Somarathi, Amy E. Taylor, Vishakha Tripathi, Stephen Morris, Lyn S. Chitty, Melissa Hill

Bibliographic record

VenueGenetics in Medicine · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Rare Diseases
Canadian institutionsSt. Thomas Hospital
FundersNIHR Great Ormond Street Hospital Biomedical Research CentreDepartment of Health and Social CareBritish Heart FoundationUniversité Catholique de LouvainUniversity College London Hospitals NHS Foundation TrustNational Institute for Health and Care ResearchHeart of England NHS Foundation Trust
KeywordsComputational biologyGenomic sequencingGenomePersonal genomicsGenomicsMedicineBiologyGeneticsData scienceComputer scienceGene

Abstract

fetched live from OpenAlex

PURPOSE: The 100,000 Genomes Project participants could consent to receive additional findings (AFs) for variants associated with susceptibility to cancer and familial hypercholesterolemia. Here, we evaluate stakeholder experiences to inform clinical practice. METHODS: Mixed-methods study conducted at 18 sites across England that comprised a cross-sectional survey and interviews with participants who received a positive AF (PAF) and interviews with participants who had no AFs (NAF). RESULTS: There were 146 surveys followed by 35 interviews with PAF participants and 29 interviews with NAF participants. Surveys found that PAF results were seen as useful and would influence health management (82%). Most (90%) had shared their result with family members. Experiences differed by PAF type; cancer PAF participants were often initially shocked and anxious and found telling family members challenging compared with participants with a familial hypercholesterolemia PAF. Although most experiences of NAF results were positive, some misunderstandings were identified. Participants supported returning AFs when offering genome sequencing. CONCLUSION: Patient experiences of receiving AFs were primarily positive, and there is support for offering AFs routinely. Considerations for offering AFs in clinical practice include adapting approaches tailored to individual conditions and greater support for people with a NAF result.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.046
metaresearch head score (Gemma)0.092
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Qualitative · Consensus signal: Qualitative
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.046
Threshold uncertainty score0.244

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0460.092
Meta-epidemiology (narrow)0.0000.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0040.003
Scholarly communication0.0040.003
Open science0.0010.006
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.116
GPT teacher head0.403
Teacher spread0.287 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designQualitative
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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