TF Perturb-seq
Mapping transcription factor regulation across human biosystems (IGVF)
A computational analysis pipeline and resource built for the IGVF Consortium’s Pillar Project on transcription factor (TF) Perturb-seq. The goal: systematically perturb TFs across multiple human cell systems and measure single-cell transcriptomic responses to learn how each TF shapes gene regulation in context.
My contribution focuses on (1) integrating perturbation-response data across biosystems, (2) building evaluation frameworks for the inferred gene programs, and (3) connecting the measured TF effects back to regulatory sequence models.
Why this matters
Most of what we know about TF function comes from a patchwork of studies in different cell lines using different assays. A uniform, genome-scale perturbation of TFs — measured in comparable ways across many biosystems — gives us a chance to (a) build mechanistic models of gene regulation that generalize beyond a single context, and (b) ground-truth the predictions of sequence-based deep learning models like EUGENe.