Familial Hypercholesterolemia (FH) is a genetic disorder characterized by elevated levels of Low-Density Lipoprotein (LDL) cholesterol or its associated genes. Early-stage and accurate categorization of FH is of significance allowing for timely interventions to mitigate the risk of life-threatening conditions. Conventional diagnosis approach, however, is complex, costly, and a challenging interpretation task even for experienced clinicians resulting in high underdiagnosis rates. Although there has been a recent surge of interest in using Machine Learning (ML) models for early FH detection, existing solutions only consider a binary classification task solely using classical ML models. Despite its significance, application of Deep Learning (DL) for FH detection is in its infancy, possibly, due to categorical nature of the underlying clinical data. The paper addresses this gap by introducing the FH-TabNet, which is a multi-stage tabular DL network for multi-class (Definite, Probable, Possible, and Unlikely) FH detection. The FH-TabNet initially involves applying a deep tabular data learning architecture (TabNet) for primary categorization into healthy (Possible/Unlikely) and patient (Probable/Definite) classes. Subsequently, independent TabNet classifiers are applied to each subgroup, enabling refined classification. The model's performance is evaluated through 5-fold cross-validation illustrating superior performance in categorizing FH patients, particularly in the challenging low-prevalence subcategories.

In a study published in the journal Nature Communications, scientists at IBM, the Broad Institute of MIT and Harvard, and health tech company Color detail evidence that the presence of genetic mutations isn't a reliable precursor to genetic diseases. They claim diseases can be so greatly influenced by other factors that the risk in carriers is sometimes as low as in that in noncarriers. The research -- which stems from a larger, three-year collaboration between IBM Research and the Broad Institute that was announced in 2019 -- aims to support clinicians leveraging data to better identify patients at serious risk for conditions like cardiovascular disease. Insights could be useful in making health care and prevention decisions, helping clinicians choose whether to recommend imaging or more drastic surgical interventions, like mastectomies. In the course of the study, an IBM-led team developed models that analyze a person's genetic risk factors, clinical health records, and biomarker data to more accurately predict the onset of conditions like heart attacks, sudden cardiac death, and atrial fibrillation.

A Stanford University-led team of scientists has developed a machine learning tool that can analyse electronic healthcare records (EHR) to identify individuals who are likely to have familial hypercholesterolemia (FH), an underdiagnosed genetic cause of elevated low-density lipoprotein (LDL) cholesterol, which puts patients at a 20-fold increased risk of coronary artery disease. In separate test runs the classifier, described today in npj Digital Medicine, correctly identified more than 80% of cases--its positive predictive value (PPV)--and demonstrated 99% specificity. The team says the classifier could help to flag up patients who are most likely to have FH, so that they and their families can undergo further genetic testing. "Theoretically, when someone comes into the clinic with high cholesterol or heart disease, we would run this algorithm," said Nigam Shah, MBBS, PhD, Stanford University associate professor of medicine and biomedical data science. "If they're flagged, it means there's an 80% chance that they have FH. Those few individuals could then get sequenced to confirm the diagnosis and could start an LDL-lowering treatment right away."