Nathalie Groot is a senior Biological Sciences major at Virginia Polytechnic Institute and State University. She researched how patient data is represented by cell lines in terms of driver gene mutation patterns.
Cancer cell lines are widely used to research novel cancer therapeutics. However, immortalization and growth of cells in culture can induce genomic changes, which can alter mutation patterns in the genomes of cell lines, causing variation from patient tumors. These genetic differences between cell lines and patient cancers have the capacity to alter the efficacy of therapeutics. BSRP provided me with tools that not only will advance my career, allowed me to meet lifelong friends, and taught me how to be a better researcher. I have come out of this program as a better scientist, collaborator, and as a Broadie.Therefore, it is important to make sure that cell lines and patient data align. Using two databases, the Cancer Cell Line Encyclopedia, CCLE, and The Cancer Genome Atlas, TCGA, cell line data will be compared to patient data to determine whether the cell lines accurately represent mutation patterns present in patient tumors. Specifically, driver genes and their pattern of co-occurrence and mutual exclusivity will be compared. Co-occurrence is the tendency for these genes to mutate together more frequently than individually; mutual exclusivity is the tendency to mutate separately more often than together. Overall, the CCLE was found to generally follow TCGA’s trend, but with a high number of false positives for mutual exclusivity. The conclusion was that CCLE needs more cell line data to determine mutual exclusivity trends. CCLE’s data showed weaker correlation and more insignificant comparisons for both co-occurrence and mutual exclusivity than TCGA. Eventually, this data can be used to ensure the accuracy of cell models, as well as provide a list of good co-occurring drug targets, and a list of poor mutually exclusive drug targets.
Project: How Well do Cell Lines Represent Patient Data’s Pattern of Mutual Exclusivity and Co-Occurrence in Driver Genes?
Mentor: Lei Shi, PhD, Bardeesy Lab