iSPHYNCS: Unsupervised clustering in questionnaires and metadata reveals distinct subtypes in the narcolepsy borderland
Abstract
Objective: The international Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (iSPHYNCS) is a multicenter study aimed at identifying novel biomarkers for central disorders of hypersomnolence (CDH). We analyzed questionnaires and metadata to uncover distinct clusters of participants and explore phenotypic variability within CDH.
Methods: Data were collected from 227 patients with CDH and 33 healthy controls. Participants completed validated clinical questionnaires and study-specific questions addressing CDH-related symptoms such as excessive daytime sleepiness, fatigue, cataplexy, disrupted sleep, and sleep paralysis. Demographic metadata (age, gender, BMI) were included. After excluding participants with missing over 30% of data (n = 40), missing values were imputed using a multiple random forest algorithm. A robust clustering pipeline was employed: (1) random sampling of 60% of the dataset, (2) dimensionality reduction via UMAP, (3) K-means clustering, and (4) consensus clustering across 500 iterations. Post hoc analysis was performed to identify biomarkers in data not used for clustering.
Results: We identified four distinct clusters. One predominantly comprised healthy controls, while another primarily contained individuals with narcolepsy type 1 (NT1). Two clusters represented predominantly the narcolepsy borderland group (NBL), with one distinctly characterized by higher symptom severity and psychiatric comorbidities.
Conclusions: The clustering pipeline…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 227 participants or records.
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