Dissecting cancer heterogeneity based on dimension reduction of transcriptomic profiles using extreme learning machines.

Abstract

It is becoming increasingly clear that major malignancies such as breast, colorectal and gastric cancers are not single disease entities, but comprising multiple cancer subtypes of distinct molecular properties. Molecular subtyping has been widely used to dissect inter-tumor biological heterogeneity, in relation to clinical outcomes. A key step of this methodology is to perform unsupervised classification of gene expression profiles, which, however, often suffers challenges of high-dimensionality, feature redundancy as well as noise and irrelevant information. To overcome these limitations, we propose ELM-CC, which employs hidden observation features obtained from extreme learning machines (ELMs) for cancer classification. To demonstrate the effectiveness and usefulness, we applied ELM-CC for gastric and ovarian cancer subtyping. Comparing with the widely-used consensus clustering method, our approach demonstrated much better clustering performance and identified molecular subtypes that are much more clinically relevant.