Center for Cancer Systems Therapeutics (CaST)
Molecular Profiling Core
Core Leader: Peter Sims
A technical requirement for achieving the scientific goals of the Columbia Center for Cancer Systems Therapeutics (CaST) will be access to cost-effective cutting-edge molecular profiling, high-throughput screening, and single-cell analysis tools utilizing robotics and microfluidics. The Molecular Profiling Core (MPC) provides three key capabilities that leverage the resources of the JP Sulzberger Columbia Genome Center’s next-generation sequencing and high-throughput screening facilities.
PLATESeq is a novel platform for integrating high-throughput screening with genome-wide expression profiling. It enables inexpensive, low-depth RNASeq for each well in a perturbation screen using the same automation that produces the screen. Using the CaST regulatory network approach to modeling cancer, computational analysis of PLATESeq data takes advantage of previously inferred gene interactions to reduce noise and therefore to reduce the coverage requirements for profiling gene activity across a screen by deep sequencing.
The Molecular Profiling Core also provides a highly multiplexed, microfluidic implementation of PLATESeq that produces expression profiles across hundreds of single cells in parallel. This platform allows CaST investigators to identify the cellular phenotypes that underlie heterogeneous responses to perturbations.
Single-cell whole genome sequencing
The Molecular Profiling Core has also developed a pipeline that combines microscopy-based single cell isolation with whole genome amplification for single-cell whole genome sequencing. Single-cell genomics allows CaST investigators, particularly in Project 2, to identify genetic alterations that co-occur or occur exclusively in specific subpopulations of cancer cells.