Cancer classification and pathway discovery using non-negative matrix factorization

Zexian Zeng, Andy H. Vo, Chengsheng Mao, Susan E Clare*, Seema Ahsan Khan, Yuan Luo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Objectives: Extracting genetic information from a full range of sequencing data is important for understanding disease. We propose a novel method to effectively explore the landscape of genetic mutations and aggregate them to predict cancer type. Design: We applied non-smooth non-negative matrix factorization (nsNMF) and support vector machine (SVM) to utilize the full range of sequencing data, aiming to better aggregate genetic mutations and improve their power to predict disease type. More specifically, we introduce a novel classifier to distinguish cancer types using somatic mutations obtained from whole-exome sequencing data. Mutations were identified from multiple cancers and scored using SIFT, PP2, and CADD, and collapsed at the individual gene level. nsNMF was then applied to reduce dimensionality and obtain coefficient and basis matrices. A feature matrix was derived from the obtained matrices to train a classifier for cancer type classification with the SVM model. Results: We have demonstrated that the classifier was able to distinguish four cancer types with reasonable accuracy. In five-fold cross-validations using mutation counts as features, the average prediction accuracy was 80% (SEM = 0.1%), significantly outperforming baselines and outperforming models using mutation scores as features. Conclusion: Using the factor matrices derived from the nsNMF, we identified multiple genes and pathways that are significantly associated with each cancer type. This study presents a generic and complete pipeline to study the associations between somatic mutations and cancers. The proposed method can be adapted to other studies for disease status classification and pathway discovery.

Original languageEnglish (US)
Article number103247
JournalJournal of Biomedical Informatics
StatePublished - Aug 2019


  • Cancer
  • Classification
  • Non-negative matrix factorization
  • Pathway
  • Somatic mutation
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Health Informatics
  • Computer Science Applications


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