Interpreting human cellular and genetic variation with perturb-seq

Abstract: The genomics era has produced a wealth of observational data from human populations and cohorts, associating molecular and genetic variation with complex phenotypes. Yet, we still struggle to understand causal pathways from genes to cellular and tissue functions to human traits. First, I will present our work on using perturb-seq in primary immune cells to predict the signatures and regulators of human T cell states (Zhu*, Dann* et al. 2026, Cell). Here perturbation signatures enabled us to model T cell states observed in population-scale transcriptomic atlases, nominating regulators of T cell polarization and of age-related phenotypes. Second, I will present PhenoBridge, a framework for jointly modeling perturb-seq and gene–trait association data to identify the gene programs driving complex phenotypes.

Biography: I am an Helen Hay Whitney and EMBO postdoctoral fellow working with Jonathan Pritchard at Stanford University and Alex Marson at the Gladstone Institute of Genomic Immunology. Here I work on experimental genetic perturbations in primary immune cells to understand how natural genetic variation shapes cellular variation. Previously, I did my PhD at the University of Cambridge, working between the groups of Sarah Teichmann at the Wellcome Sanger Institute and John Marioni at the EMBL European Bioinformatics Institute. Here I developed methods for detection of disease-associated cells in scRNA-seq data, and applied them to understand immune cell variation in health and disease. I am also part of the core team of the scverse consortium of foundational tools for analysis of omics data in life sciences, where I work on governance and community initiatives.