LynchRisk: a Bayesian network to estimate the probability of Lynch syndrome based on pedigree and tumor characteristics
Lefebvre, A.; Benusiglio, P.; Nuel, G.
Show abstract
Background: Current Lynch syndrome (LS) prediction models do not account for detailed family structure and tumour mismatch repair (MMR) status. We developed LynchRisk, a Bayesian model that estimates individualized LS probability from pedigree, cancer history and tumour MMR test results. Methods: LynchRisk combines Mendelian inheritance, age- and sex-specific cancer hazards, affected and unaffected relatives, and detailed MMR status. Parameters were derived from the literature. Results: In two simulated cases of probands with LS-associated cancers, family structure and MMR status markedly changed LS probability estimates, with implications for germline testing decisions. LynchRisk also identified situations in which a negative germline result might be considered sufficient to rule out LS or, conversely, prompt further investigations such as somatic MMR or long-read sequencing. Discussion: LynchRisk gives individualized LS probability by combining clinical, family, and tumour data at different stages of the diagnostic process. Further work will focus on recalibrating cancer hazard functions, validating model performance through simulations, and developing an R package for use by interested research groups.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Multi-Platform Curation in the Development of ACMG/AMP Specifications for Von Hippel Lindau (VHL) Disease 91%
- Classification of Variants of Reduced Penetrance in High Penetrance Cancer Susceptibility Genes: Framework for Genetics Clinicians and Clinical Scientists by CanVIG-UK (Cancer Variant Interpretation Group-UK) 90%
- AVADA Enables Automated Genetic Variant Curation Directly from the Full Text Literature 90%
Similar papers in this journal
- A Comprehensive Epithelial Tubo-Ovarian Cancer Risk Prediction Model Incorporating Genetic and Epidemiological Risk Factors 92%
- The PS4-Likelihood Ratio Calculator: Flexible allocation of evidence weighting for case-control data in variant classification 92%
- Validation of the BOADICEA Model in a Prospective Cohort of BRCA1/2 Pathogenic Variant Carriers 91%
Similar papers in this journal
- Using Family History Data to Improve the Power of Association Studies: Application to Cancer in UK Biobank 92%
- Statistics to prioritize rare variants in family-based sequencing studies with disease subtypes 92%
- Benchmarking statistical methods for analyzing parent-child dyads in genetic association studies 91%
Similar papers in this journal
Similar papers in this journal
- The Causal Pivot: A Structural Approach to Genetic Heterogeneity and Variant Discovery in Complex Diseases 91%
- Evidence-based calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for clinical use of PP3/BP4 criteria 90%
- The contribution of coding variants to the heritability of multiple cancer types using UK Biobank whole-exome sequencing data 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.