Assisted gene expression-based clustering with AWNCut

In the research on complex diseases, gene expression (GE) data have been extensively used for clustering samples. The clusters so generated can serve as the basis for disease subtype identification, risk stratification, and many other purposes. With the small sample sizes of genetic profiling studies and noisy nature of GE data, clustering analysis results are often unsatisfactory. In the most recent studies, a prominent trend is to conduct multidimensional profiling, which collects data on GEs and their regulators (copy number alterations, microRNAs, methylation, etc.) on the same subjects. With the regulation relationships, regulators contain important information on the properties of GEs. We develop a novel assisted clustering method, which effectively uses regulator information to improve clustering analysis using GE data. To account for the fact that not all GEs are informative, we propose a weighted strategy, where the weights are determined data-dependently and can discriminate informative GEs from noises. The proposed method is built on the NCut technique and effectively realized using a simulated annealing algorithm. Simulations demonstrate that it can well outperform multiple direct competitors. In the analysis of TCGA cutaneous melanoma and lung adenocarcinoma data, biologically sensible findings different from the alternatives are made.