Quasi-linear score for capturing heterogeneous structure in biomarkers

BMC Bioinformatics. 2017 Jun 19;18(1):308. doi: 10.1186/s12859-017-1721-x.

Abstract

Background: Linear scores are widely used to predict dichotomous outcomes in biomedical studies because of their learnability and understandability. Such approaches, however, cannot be used to elucidate biodiversity when there is heterogeneous structure in target population.

Results: Our study was focused on describing intrinsic heterogeneity in predictions. Because heterogeneity can be captured by a clustering method, integrating different information from different clusters should yield better predictions. Accordingly, we developed a quasi-linear score, which effectively combines the linear scores of clustered markers. We extended the linear score to the quasi-linear score by a generalized average form, the Kolmogorov-Nagumo average. We observed that two shrinkage methods worked well: ridge shrinkage for estimating the quasi-linear score, and lasso shrinkage for selecting markers within each cluster. Simulation studies and applications to real data show that the proposed method has good predictive performance compared with existing methods.

Conclusions: Heterogeneous structure is captured by a clustering method. Quasi-linear scores combine such heterogeneity and have a better predictive ability compared with linear scores.

Keywords: Discriminant analysis; Heterogeneity; Kolmogorov-Nagumo average; Prediction.

MeSH terms

  • Algorithms*
  • Biomarkers / analysis
  • Biomarkers / metabolism*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cluster Analysis
  • Discriminant Analysis
  • Female
  • Humans
  • Likelihood Functions
  • Logistic Models
  • Neoplasm Metastasis
  • Transcriptome

Substances

  • Biomarkers