Quantitative Issues in Cancer Research Working Seminar

Luca Pinello, Ph.D.
Associate Professor of Pathology, Harvard Medical School

“Computational Methods to Understand Gene Regulation Based on Single-Cell and CRISPR Genome Editing Data”

ABSTRACT: Single-cell and CRISPR technologies have opened new opportunities to understand principles of gene regulation.

In this talk I will first present how to design and analyze recent CRISPR tiling screens using computational methods we have recently developed. Tiling perturbations allow a powerful and high-throughput functional interrogation of non-coding elements throughout the genome. Functional mapping can be achieved by densely tiling single guide RNAs (sgRNAs) across a non-coding region of interest, where each sgRNA enables linking a unique, genomic location to an observable phenotype. Tiling screens provide the capability to discover functional non-coding regions and to dissect their critical elements thereby enabling a powerful characterization of genetic variants involved in traits or diseases.

Then I will present STREAM, a computational method for single-cell analysis of transcriptomic and epigenomic data. This method can be used to disentangle complex cellular types and states in development, differentiation or in perturbation studies. It can accurately detect cellular hierarchies and recover complex developmental trajectories. In addition, it provides informative and intuitive visualizations to highlight important genes or other features that can be used as markers to define sub-populations and rare cell types.