Computational Analyses Connect Small-Molecule Sensitivity to Cellular Features Using Large Panels of Cancer Cell Lines.

Rees MG, Seashore-Ludlow B, Clemons PA.

Systems Chemical Biology: Book Chapter

January 01, 2019

We recently pioneered several analyses of small-molecule sensitivity data collected from large-scale perturbation of hundreds of cancer cell lines with hundreds of small molecules, with cell viability measured as a readout of compound sensitivity. We performed these studies using cancer cell lines previously annotated with cellular, genomic, and basal gene-expression features. By combining small-molecule sensitivity data with these other datasets, we identified new candidate biomarkers of sensitivity, gained insights into small-molecule mechanisms of action, and proposed candidate hypotheses for cancer dependencies (including candidate combination therapies). Nevertheless, given the size of these datasets, we expect that many connections between cellular features and small-molecule sensitivity remain underexplored. In this chapter, we provide a step-by-step account of foundational data-analysis methods underlying our published studies, including working MATLAB code applied to our own public datasets. These procedures will allow others to repeat analyses of our data with new parameters, in additional contexts, and to adapt our procedures to their own datasets.

 

Rees MG, Seashore-Ludlow B, Clemons PA. Computational Analyses Connect Small-Molecule Sensitivity to Cellular Features Using Large Panels of Cancer Cell Lines. In: Ziegler S, Waldmann H. (eds) Systems Chemical Biology. Methods in Molecular Biology. New York, NY: Humana Press; 2019;1888:233-254.

Program:
CTD²
Last updated: June 05, 2019