Cancer molecular subtyping using limited multi-omics data with missingness.

Abstract

Diagnosing cancer subtypes is a prerequisite for precise treatment. Existing multi-omics data fusion-based diagnostic solutions build on the requisite of sufficient samples with complete multi-omics data, which is challenging to obtain in clinical applications. To address the bottleneck of collecting sufficient samples with complete data in clinical applications, we proposed a flexible integrative model (CancerSD) to diagnose cancer subtype using limited samples with incomplete multi-omics data. CancerSD designs contrastive learning tasks and masking-and-reconstruction tasks to reliably impute missing omics, and fuses available omics data with the imputed ones to accurately diagnose cancer subtypes. To address the issue of limited clinical samples, it introduces a category-level contrastive loss to extend the meta-learning framework, effectively transferring knowledge from external datasets to pretrain the diagnostic model. Experiments on benchmark datasets show that CancerSD not only gives accurate diagnosis, but also maintains a high authenticity and good interpretability. In addition, CancerSD identifies important molecular characteristics associated with cancer subtypes, and it defines the Integrated CancerSD Score that can serve as an independent predictive factor for patient prognosis.