PT  - JOURNAL ARTICLE
AU  - S. Huang
TI  - Modeling non-genetic dynamics of cancer cell states measured by single-cell analysis: Uncovering bifurcations that explain why treatment either kills a cancer cell or makes it resistant
AID  - 10.1101/574848
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 574848
4099  - http://biorxiv.org/content/early/2019/03/12/574848.short
4100  - http://biorxiv.org/content/early/2019/03/12/574848.full
AB  - Single-cell transcriptomics offers a new vista on non-genetic tumor cell plasticity, a neglected aspect of cancer. The gene expression state of each cell is governed by the gene regulatory network which represents a high-dimensional non-linear dynamical system that generates multiple stable attractor states and undergoes destabilizing bifurcations, manifest as critical transitions. Modeling clonal cell population as statistical ensembles of the same dynamical system, a index IC is derived for detecting destabilization towards critical transitions in single-cell molecular profiles. Therapy-induced bifurcation explains why treatment backfires: a drug-treated cell is imposed the binary choice to either apoptose or become a cancer-stem cell.