Attractor Landscape Analysis Reveals a Reversion Switch in the Transition of Colorectal Tumorigenesis

Abstract

A cell fate change such as tumorigenesis incurs critical transition. It remains a longstanding challenge whether the underlying mechanism can be unraveled and a molecular switch that can reverse such transition is found. Here a systems framework, REVERT, is presented with which can reconstruct the core molecular regulatory network model and a reversion switch based on single-cell transcriptome data over the transition process is identified. The usefulness of REVERT is demonstrated by applying it to single-cell transcriptome of patient-derived matched organoids of colon cancer and normal colon. REVERT is a generic framework that can be applied to investigate various cell fate transition phenomena.

Keywords: attractor landscape analysis; cancer reversion; colon cancer; critical transition; dynamic network model; patient‐derived organoid; single cell transcriptome data.