BACK TO INDEX

Publications of Eduardo D. Sontag jointly with A. Al'Khafaji
Articles in journal or book chapters
  1. K. Johnson, G. Howard, D. Morgan, E. Brenner, A. Gardner, R. Durrett, W. Mo, A. Al'Khafaji, E.D. Sontag, A. Jarrett, T. Yankeelov, and A. Brock. Integrating transcriptomics and bulk time course data into a mathematical framework to describe and predict therapeutic resistance in cancer. Physical Biology, 2020. Note: To appear. Keyword(s): oncology, cancer, chemoresistance, resistance, intratumor heterogeneity, population dynamics, DNA barcoding, evolution.
    Abstract:
    The development of resistance to chemotherapy is a major cause of treatment failure in cancer. Intratumoral heterogeneity and phenotypic plasticity play a significant role in therapeutic resistance. Individual cell measurements such as flow and mass cytometry and single cell RNA sequencing (scRNA-seq) have been used to capture and analyze this cell variability. In parallel, longitudinal treatment-response data is routinely employed in order to calibrate mechanistic mathematical models of heterogeneous subpopulations of cancer cells viewed as compartments with differential growth rates and drug sensitivities. This work combines both approaches: single cell clonally-resolved transcriptome datasets (scRNA-seq, tagging individual cells with unique barcodes that are integrated into the genome and expressed as sgRNA's) and longitudinal treatment response data, to fit a mechanistic mathematical model of drug resistance dynamics for a MDA-MB-231 breast cancer cell line. The explicit inclusion of the transcriptomic information in the parameter estimation is critical for identification of the model parameters and enables accurate prediction of new treatment regimens.



BACK TO INDEX




Disclaimer:

This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders.




Last modified: Thu Sep 24 12:35:48 2020
Author: sontag.


This document was translated from BibTEX by bibtex2html