Pseudotime Based Discovery of Breast Cancer Heterogeneity Breast cancer is highly sporadic and heterogeneous in nature. Even the patients with same clinical stage do not cluster together in terms of genomic profiles such as mRNA expression. In order to prevent and cure breast cancer completely, it is essential to decipher the detailed heterogeneity of breast cancer at genomic level. Putting the cancer patients on a time scale, which represents the trajectory of cancer development, may help discover the detailed heterogeneity. This in turn would help establish the mechanisms for prevention and complete cure of breast cancer. The goal of this study is to discover the heterogeneity of breast cancer by ordering the cancer patients using pseudotime. This is achieved through two objectives: First, a computational framework is developed to place the cancer patients on a time scale, meaning construct a trajectory of cancer development, by inferring pseudotime from static mRNA expression data; Second, discovering breast cancer heterogeneity at different time periods of the trajectory using statistical and machine learning techniques. In this study, the trajectory of breast cancer progression was constructed using static mRNA expression profiles of 1072 breast cancer patients by inferring pseudotime. Three sets of key genes discovered using supervised machine learning techniques are used to develop the trajectories. The first set of genes are PAM50 genes which is available in literature. The second and third sets of genes were discovered in the present study using the clinical stages of breast cancer (StageI, StageII, StageIII, and StageIV). The proposed computational framework has the capability of deciphering heterogeneity in breast cancer at a granular level. The results also show the existence of multiple parallel trajectories at different time periods of cancer development or progression.

Investigating a Breast Cancer Gene Expression Data Using a Novel Clustering Approach Historically, breast cancer has been perceived as a disease with varying histological and clinical features. Breast cancer tumor classification is important in disease prognosis and prediction because different breast tumors respond differently to different treatments and have different survival rates. Gene expression profiling studies have increasingly been motivated in the past decades to develop a good classification of breast cancer in molecular subtypes, which can improve the standard clinical assessments by providing extra prognostic information. In this research, one of the most comprehensive breast cancer gene expression datasets is analyzed by applying a novel clustering approach to predict the breast cancer subtypes. The novel unsupervised clustering approach initially model the gene expression data as a network and employ a community detection method to identify network clusters. This method utilizes an efficient problem specific metaheuristic algorithm to optimize the modularity value and identify clusters of breast cancer samples with similar characteristics that presents different subtypes of breast cancer. To assess the significant of the newly defined breast cancer subtypes, we compared our findings with three breast cancer subtyping methods.