A web-based user interface for Fam3PRO, a multi-gene, multi-cancer risk prediction model for families with cancer history

2025-10-27

AI Summary

To address the lack of a clinically accessible interface for the Fam3PRO polygenic, pan-cancer genetic risk model, this study developed F3PI—the first web-based interactive platform for Fam3PRO. Built with R Shiny for the frontend and integrated with pedigreejs for dynamic, real-time pedigree visualization and editing, F3PI interfaces with the Fam3PRO backend to perform Mendelian-style risk calculations. It enables sub-second, personalized prediction of absolute incidence risks for 18 cancers and carrier probabilities for pathogenic variants across 22 genes. F3PI introduces end-to-end visual analytics capabilities to Fam3PRO for the first time, supporting interactive exploration of results and generation of downloadable clinical reports. By bridging computational genetics with clinical workflow, F3PI significantly enhances the usability, accessibility, and decision-support utility of familial cancer risk assessment in routine practice.

Technology Category

• Reasoning under Uncertainty: Other Foundations of Reasoning under Uncertainty
• Humans and AI: Other Foundations of Human Computation & AI
• Machine Learning: Probabilistic Circuits and Graphical Models

Application Category

• User Modeling, Personalization and Recommendation: Federated recommendation systems and personalization
• Graph Algorithms and Modeling for the Web: Foundation models and LLMs for Web-related graphs
• Economics, Online Markets and Human Computation: The sharing economy

Abstract

Purpose: Hereditary cancer risk is key to guiding screening and prevention strategies. Cancer risks can vary by individual due to the presence or absence of high- and moderate-risk pathogenic variants (PV) in cancer-associated genes, in addition to sex, age, and other risk factors. We previously developed Fam3PRO, a flexible multi-gene, multi-cancer Mendelian risk prediction model that estimates a patient's risk of carrying a PV in hereditary cancer genes and their future risk of developing several types of cancer. The Fam3PRO R package includes 22 genes with 18 associated cancers, allowing users to build customized sub-models from any gene-cancer set. However, the current R package lacks a user interface (UI), limiting its practical use in clinical settings. Therefore, we aim to develop a web-based UI for broader use of the Fam3PRO functionalities. Methods: The Fam3PRO UI (F3PI), built with R Shiny, collects and formats inputs including family health history, genetic test results, and other risk factors. Pedigree data are interactively visualized and modified via pedigreejs, while the backend Fam3PRO model takes all the inputs to generate carrier probabilities and future cancer risks, presented through an interactive UI. Results: F3PI streamlines the collection of patient and family history data, which is analyzed by the Fam3PRO models to provide personalized cancer risks for each proband across 18 cancers, as well as probabilities that a proband has a PV in up to 22 hereditary cancer genes. These results are returned to the user, within one minute on average and are available in both interactive and downloadable formats. Conclusion: We have developed F3PI, an easy-to-use, interactive web application that makes cancer and genetic risk information more accessible to providers and their patients.

Problem

• Develops web interface for multi-gene cancer risk prediction model
• Addresses limited clinical use of existing R package tool
• Enables accessible hereditary cancer risk assessment for families

Innovation

• Web-based UI built with R Shiny
• Interactive pedigree visualization via pedigreejs
• Backend model calculates carrier probabilities and cancer risks