Expert knowledge-based weighted K-means clustering for polycystic ovary syndrome phenotype identification

Background Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disease condition that affects 8%–13% of the female population worldwide. Its clinical heterogeneity makes the binary approach to phenotyping less effective for the biological significance of such phenotypic groups and the personalized management of PCOS. To overcome this issue, we present the expert knowledge-based weighted K -means (EKWKM) approach. Objective The proposed EKWKM is a new, weakly supervised phenotyping approach that uses structured clinical knowledge along with mutual information (MI)-based feature weighting, whereby the feature weighting process is weakly supervised, but clustering is unsupervised. Methods The EKWKM was benchmarked using a clinical dataset ( n = 541, 41 features) and a large-scale population study ( n = 120,000). A grid search was performed for K ∈ {2, 3, 4} and α = 0.1–0.9. The silhouette score (95% bootstrap confidence interval), the adjusted Rand index (ARI), and the Davies–Bouldin (DB) index were used to quantify cluster quality. Biomarker importance was measured using the Kruskal–Wallis test with Benjamini–Hochberg correction and ϵ 2 effect size. Results The most effective clinical model ( K = 2, α = 0.9) achieved a silhouette score of 0.3606. The model also achieved ARI = 0.9780 ± 0.0362 and DB = 1.1480 and identified 13 significant biomarkers. The population survey acted as a negative control dataset [random forest area under the curve (AUC) = 0.4974 ± 0.0096] and demonstrated no phenotypic signal. Cross-dataset transfer decreased Cramér’s V from 0.497 to 0.006, which confirmed that EKWKM did not add false patterns. The main part of the clustering was due to data-driven MI, as confirmed by the ablation analysis. Expert knowledge improved clustering robustness. Conclusion EKWKM formed clinically meaningful and Rotterdam-based PCOS phenotype clusters. In contrast, the population survey clusters formed symptom-reporting patterns and are not meaningful PCOS phenotypes.