QCB Seminar Nir Yosef, Weizmann Institute of Science Monday, April 4, 2022 11:00 a.m. - 12:00 p.m. (****Please note time!****) Host: Yuri Pritykin Location: Virtual seminar Contact Sara Thibeault at [ mailto:thibeault@princeton.edu | thibeault@princeton.edu ] for seminar link “Mapping paths of tumor evolution with single cell phylogenetics” Single-cell genomics provides a powerful set of tools for dissecting temporal processes such as cell differentiation and tumor development from snapshots of asynchronous ensembles of cells. A promising addition to this set of technologies utilizes Cas9- induced mutations as a way of recording lineage information in each cell, thus providing a way to infer the tree (phylogeny) by which individual cells are related. In this talk, I will describe our work on analytical tools for inference of such lineage trees and their joint analysis with the cells’ transcriptomes. I will demonstrate the utility of these tools and the Cas9 lineage tracing system for studying the Kras;Trp53 (KP) mouse model of lung adenocarcinoma, in which progenies of single transformed cells are traced up to the stage of aggressive and metastatic tumors. We will consider different ways by which a concomitant view of cell lineage trees and transcriptomes can be used to shed new light on the trajectories of cell states that are traversed during tumor development, the dynamics and regulation of sub-clonal selection and expansion, and the origins of metastases. Bio: Nir Yosef received his PhD in Computer Science from Tel Aviv University and then completed a postdoctoral training at the Broad Institute, where he worked on transcriptional regulation of T cell differentiation. Nir joined the faculty at UC Berkeley in 2014, where he has most recently served as an Associate Professor of Computer Science and a core member at the Center of Computational Biology. Since January 2022, Nir is an Associate Professor at the Department of Systems Immunology at the Weizmann Institute of Science. The Yosef lab is developing data- centric approaches for studying how changes in transcription are associated with molecular and cellular phenotypes in immunity and cancer. In that capacity, the lab is developing and applying computational tools that leverage single cell genomics, with the goal of better understanding the factors that contribute to variability between cells, (e.g, metabolism, chromatin structure) and their broader implications (e.g., in autoimmunity). A second area of research is studying regulatory regions in the genome, based on chromatin profiles and massively parallel reporter assays.