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

TL;DR

This paper introduces a user-friendly web interface for the Fam3PRO model, enabling clinicians to easily assess multi-gene, multi-cancer hereditary risks using family history and genetic data.

Contribution

The development of a web-based UI for Fam3PRO enhances its practical application in clinical settings, making complex genetic risk predictions accessible and interactive.

Findings

Risk assessments generated within one minute

Interactive visualization of pedigree data

Personalized cancer risk and gene carrier probability outputs

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.