Training machine learning models to detect rare inborn errors of metabolism (IEMs) based on GC-MS urinary...

Gas chromatography-mass spectrometry (GC-MS) has been shown to be a potentially efficient metabolic profiling platform in urine analysis. However, the widespread use of GC-MS for inborn errors of metabolism (IEM) screening is constrained by the rarity of IEM in population, and the difficult and specialized complexity of the interpretation of GC-MS organic acid profiles.

Based on 355,197 GC-MS test cases accumulated from 2013 to 2021 in China, a random forest-based machine learning model was proposed, trained, and evaluated. Weighted undersampling or oversampling data processing and staged modeling strategies were used to handle the highly imbalanced data and improve the ability of the model to identify different types of rare IEM cases.

In the first-stage model, which only identified positive cases without discriminating the specific IEM, the screening sensitivity was 0.938 (or 0.991 if abnormal cases were also included). The average sensitivity of the second-stage models that classify 11 particular IEMs is 0.992, with an average specificity and accuracy of 0.944 and 0.969, respectively. The SHAP values visualized for each model explain the basis for the differential diagnosis made by the model.

With sufficient high-quality data, machine learning models can provide high-sensitivity GC-MS interpretation and greatly improve the efficiency and quality of GC-MS based IEM screening.