RT Journal Article
SR Electronic
T1 Topological Data Analysis of PAM50 and 21-Gene Breast Cancer Assays
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 480723
DO 10.1101/480723
A1 James C. Mathews
A1 Saad Nadeem
A1 Maryam Pouryahya
A1 Joseph O. Deasy
A1 Allen Tannenbaum
YR 2018
UL http://biorxiv.org/content/early/2018/11/28/480723.abstract
AB This study uses new techniques of topological data analysis to demonstrate the relationship between breast cancer assays and important biological modules. Specifically, we map the landscape of breast tumor molecular states and integrate the information provided by the PAM50 intrinsic subtypes and the 21-gene Oncotype DX Recurrence Score. We modify the Mapper tool, which provides a visual network representation of a dataset in high dimensions, to allow us to incorporate relevant gene sets and stratification functions informed by pre-existing research on breast tumor profiling, mammary basal and luminal-epithelial cell types, and prognostication schemes. This customized tool is utilized to analyze mRNA profiles of TCGA (The Cancer Genome Atlas) breast tumors, METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) breast tumors, and GTEx (Genotype-Tissue Expression) normal mammary tissue samples. The unsupervised analysis locates the basal-like, HER2-enriched, normal-like, Luminal A, and Luminal B breast tumor subtypes along a graphical summary of the breast tumor mRNA expression profiles along assay-relevant genes. The method illuminates the inherent stratification of breast cancer types that is implied by the effectiveness of the Oncotype DX and PAM50 gene sets.