The Topology of Mutated Driver Pathways

TL;DR

This paper introduces a topological framework to analyze and compare the structure of mutated driver pathways in different cancers, revealing distinct topological properties for AML and GBM.

Contribution

It presents a novel topological approach to understand the relationships among cancer pathways and compares their structures across different cancer types.

Findings

AML pathways form a homotopy sphere

GBM pathways form a genus-2 surface

Topological differences suggest distinct pathway organizations

Abstract

Much progress has been made, and continues to be made, towards identifying candidate mutated driver pathways in cancer. However, no systematic approach to understanding how candidate pathways relate to each other for a given cancer (such as Acute myeloid leukemia), and how one type of cancer may be similar or different from another with regard to their respective pathways (Acute myeloid leukemia vs. Glioblastoma multiforme for instance), has emerged thus far. Our work attempts to contribute to the understanding of {\em space of pathways} through a novel topological framework. We illustrate our approach, using mutation data (obtained from TCGA) of two types of tumors: Acute myeloid leukemia (AML) and Glioblastoma multiforme (GBM). We find that the space of pathways for AML is homotopy equivalent to a sphere, while that of GBM is equivalent to a genus-2 surface. We hope to trigger new types of questions (i.e., allow for novel kinds of hypotheses) towards a more comprehensive grasp of cancer.