Robust model-based clustering with gene ranking

TL;DR

This paper introduces a robust clustering method using penalized Student's t mixtures combined with bootstrap-based gene ranking, effectively handling noise and outliers in gene expression data to identify meaningful biological subgroups.

Contribution

It proposes a novel penalized Student's t mixture model with a bootstrap procedure for gene ranking, improving robustness and interpretability in gene expression clustering.

Findings

Performs well with outliers and heavy-tailed distributions

Accurately identifies informative genes with high sensitivity

Enhances model selection accuracy

Abstract

Cluster analysis of biological samples using gene expression measurements is a common task which aids the discovery of heterogeneous biological sub-populations having distinct mRNA profiles. Several model-based clustering algorithms have been proposed in which the distribution of gene expression values within each sub-group is assumed to be Gaussian. In the presence of noise and extreme observations, a mixture of Gaussian densities may over-fit and overestimate the true number of clusters. Moreover, commonly used model-based clustering algorithms do not generally provide a mechanism to quantify the relative contribution of each gene to the final partitioning of the data. We propose a penalised mixture of Student's t distributions for model-based clustering and gene ranking. Together with a bootstrap procedure, the proposed approach provides a means for ranking genes according to their contributions to the clustering process. Experimental results show that the algorithm performs well comparably to traditional Gaussian mixtures in the presence of outliers and longer tailed distributions. The algorithm also identifies the true informative genes with high sensitivity, and achieves improved model selection. An illustrative application to breast cancer data is also presented which confirms established tumor subclasses.