Feature-weighted ordinal classification for predicting drug response in multiple Myeloma

Abstract

Motivation: Ordinal classification problems arise in a variety of real-world applications, in which samples need to be classified into categories with a natural ordering. An example of classifying high-dimensional ordinal data is to use gene expressions to predict the ordinal drug response, which has been increasingly studied in pharmacogenetics. Classical ordinal classification methods are typically not able to tackle high-dimensional data and standard high-dimensional classification methods discard the ordering information among the classes. Existing work of high-dimensional ordinal classification approaches usually assume a linear ordinality among the classes. We argue that manually-labeled ordinal classes may not be linearly arranged in the data space, especially in high-dimensional complex problems.

Results: We propose a new approach that can project high-dimensional data into a lower discriminating subspace, where the innate ordinal structure of the classes is uncovered. The proposed method weights the features based on their rank correlations with the class labels and incorporates the weights into the framework of linear discriminant analysis. We apply the method to predict the response to two types of drugs for patients with Multiple Myeloma, respectively. A comparative analysis with both ordinal and nominal existing methods demonstrates that the proposed method can achieve a competitive predictive performance while honoring the intrinsic ordinal structure of the classes. We provide interpretations on the genes that are selected by the proposed approach to understand their drug-specific response mechanisms.

Availability and implementation: The data underlying this article are available in the Gene Expression Omnibus Database at https://www.ncbi.nlm.nih.gov/geo/ and can be accessed with accession number GSE9782 and GSE68871. The source code for FWOC can be accessed at https://github.com/pisuduo/Feature-Weighted-Ordinal-Classification-FWOC.