LFSPROShiny: an interactive R/Shiny app for prediction and visualization of cancer risks in families with deleterious germlineTP53mutations

Abstract

AbstractPurposeLFSPRO is an R library that implements risk prediction models for Li-Fraumeni syndrome (LFS), a genetic disorder characterized by deleterious germline mutations in theTP53gene. To facilitate the use of these models in clinics, we developed LFSPROShiny, an interactive R/Shiny interface of LFSPRO that allows genetic counselors (GCs) to perform risk predictions without any programming components, and further visualize the risk profiles of their patients to aid the decision-making process.MethodsLFSPROShiny implements two models that have been validated on multiple LFS patient cohorts: a competing-risk model that predicts cancer-specific risks for the first primary, and a recurrent-event model that predicts the risk of a second primary tumor. Starting with a visualization template, we keep regular contact with GCs, who ran LFSPROShiny in their counseling sessions, to collect feedback and discuss potential improvement. Upon receiving the family history as input, LFSPROShiny renders the family into a pedigree, and displays the risk estimates of the family members in a tabular format. The software offers interactive overlaid side-by-side bar charts for visualization of the patients’ cancer risks relative to the general population.ResultsWe walk through a detailed example to illustrate how GCs can run LFSPROShiny in clinics, from data preparation to downstream analyses and interpretation of results with an emphasis on the utilities that LFSPROShiny provides to aid decision making.ConclusionSince Dec 2021, we have applied LFSPROShiny to over 100 families from counseling sessions at MD Anderson Cancer Center. Our study suggests that software tools with easy-to-use interfaces are crucial for the dissemination of risk prediction models in clinical settings, hence serving as a guideline for future development of similar models.