Abstract
BACKGROUND: Clustering is a fundamental problem in statistics and has broad applications in various areas. Traditional clustering methods treat features equally and ignore the potential structure brought by the characteristic difference of features. Especially in cancer diagnosis and treatment, several types of biological features are collected and analyzed together. Treating these features equally fails to identify the heterogeneity of both data structure and cancer itself, which leads to incompleteness and inefficacy of current anti-cancer therapies. OBJECTIVES: In this paper, we propose a clustering framework based on hierarchical heterogeneous data with prior pairwise relationships. The proposed clustering method fully characterizes the difference of features and identifies potential hierarchical structure by rough and refined clusters. RESULTS: The refined clustering further divides the clusters obtained by the rough clustering into different subtypes. Thus it provides a deeper insight of cancer that can not be detected by existing clustering methods. The proposed method is also flexible with prior information, additional pairwise relationships of samples can be incorporated to help to improve clustering performance. Finally, well-grounded statistical consistency properties of our proposed method are rigorously established, including the accurate estimation of parameters and determination of clustering structures. CONCLUSIONS: Our proposed method achieves better clustering performance than other methods in simulation studies, and the clustering accuracy increases with prior information incorporated. Meaningful biological findings are obtained in the analysis of lung adenocarcinoma with clinical imaging data and omics data, showing that hierarchical structure produced by rough and refined clustering is necessary and reasonable.