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

PLoS One. 2018 Sep 14;13(9):e0203824. doi: 10.1371/journal.pone.0203824. eCollection 2018.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Artificial Intelligence
  • Breast Neoplasms / classification
  • Breast Neoplasms / genetics
  • Cluster Analysis
  • Female
  • Gene Expression Profiling / methods*
  • Genetic Heterogeneity
  • Humans
  • Machine Learning
  • Male
  • Neoplasms / classification*
  • Neoplasms / genetics*
  • Stomach Neoplasms / classification
  • Stomach Neoplasms / genetics
  • Transcriptome / genetics

Grants and funding

This work was supported by a Start-up Grant for New Faculty (7200455), VPRT grant (9610337) at the City University of Hong Kong, a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. CityU 21101115) and grants from The Science Technology and Innovation Committee of Shenzhen Municipality (JCYJ20170307091256048 and JSGG20151030110921727) awarded to Xin Wang.