Computational Biology Seminar
Customizing single cell applications to interrogate mechanisms of acquired drug resistance in cancer
We have recently developed a simple forward genetic screening method that can be used to identify genes associated with a specific cellular phenotype. This method utilizes a transposon mutagenesis approach to generate a genetically diverse population of cells with distinct transposon-tagged mutations. Various selection methods are then used to identify cells with the desired phenotype, and rapid transposon insertion site profiling then identifies candidate genes associated with the selected phenotype. We have recently applied this method to identify drivers of resistance to targeted oncology drugs. More recently, we have developed a novel approach to perform transposon insertion site profiling within the 10X Multiomic method such that we are able to obtain transposon insertion site, ATAC-seq, and gene expression profiles from individual cells. This novel approach provides the potential to perform phenotype-driven genetics screens at the single cell level.
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