Subtype Characterization of Ovarian Cancer Cell Lines Using Machine Learning and Network Analysis: A Pilot Study

Rama Krishna Thelagathoti, Dinesh S. Chandel, Chao Jiang, Wesley A. Tom, Gary Krzyzanowski, Appolinaire Olou, M. Rohan Fernando

Background/Objectives: Ovarian cancer is a heterogeneous malignancy with molecular subtypes that strongly influence prognosis and therapy. High-dimensional mRNA data can capture this biological diversity, but its complexity and noise limit robust subtype characterization. Furthermore, current classification approaches often fail to reflect subtype-specific transcriptional programs, underscoring the need for computational strategies that reduce dimensionality and identify discriminative molecular features. Methods: We designed a multi-stage feature selection and network analysis framework tailored for high-dimensional transcriptomic data. Starting with ~65,000 mRNA features, we applied unsupervised variance-based filtering and correlation pruning to eliminate low-information genes and reduce redundancy. The applied supervised Select-K Best filtering further refined the feature space. To enhance robustness, we implemented a hybrid selection strategy combining recursive feature elimination (RFE) with random forests and LASSO regression to identify discriminative mRNA features. Finally, these features were then used to construct a gene co-expression similarity network. Results: This pipeline reduced approximately 65,000 gene features to a subset of 83 discriminative transcripts, which were then used for network construction to reveal subtype-specific biology. The analysis identified four distinct groups. One group exhibited classical high-grade serous features defined by TP53 mutations and homologous recombination deficiency, while another was enriched for PI3K/AKT and ARID1A-associated signaling consistent with clear cell and endometrioid-like biology. A third group displayed drug resistance-associated transcriptional programs with receptor tyrosine kinase activation, and the fourth demonstrated a hybrid profile bridging serous and endometrioid expression modules. Conclusions: This pilot study shows that combining unsupervised and supervised feature selection with network modeling enables robust stratification of ovarian cancer subtypes.