Performance and clinical utility of a new supervised machine-learning pipeline in detecting rare ciliopathy patients based on deep phenotyping from electronic health records and semantic similarity

Rare diseases affect approximately 400 million people worldwide. Many of them suffer from delayed diagnosis. Among them, NPHP1-related renal ciliopathies need to be diagnosed as early as possible as potential treatments have been recently investigated with promising results. Our objective was to develop a supervised machine learning pipeline for the detection of NPHP1 ciliopathy patients from a large number of nephrology patients using electronic health records (EHRs).

We designed a pipeline combining a phenotyping module re-using unstructured EHR data, a semantic similarity module to address the phenotype dependence, a feature selection step to deal with high dimensionality, an undersampling step to address the class imbalance, and a classification step with multiple train-test split for the small number of rare cases. The pipeline was applied to thirty NPHP1 patients and 7231 controls and achieved good performances (sensitivity 86% with specificity 90%). A qualitative review of the EHRs of 40 misclassified controls showed that 25% had phenotypes belonging to the ciliopathy spectrum, which demonstrates the ability of our system to detect patients with similar conditions.

Our pipeline reached very encouraging performance scores for pre-diagnosing ciliopathy patients. The identified patients could then undergo genetic testing. The same data-driven approach can be adapted to other rare diseases facing underdiagnosis challenges.