Alex Marson, Director of the UCSF-Gladstone Institute for Genomic Immunology, shared a post on LinkedIn:
“Today we’re releasing a draft version of the first installment of the Biohub Billion Cell Project. Genome-scale Perturb-Seq in human primary T Cells. CRISPRi knockdown of all expressed genes in >20 million human CD4+ T cells from 4 different blood donors, at rest and at different time points after re-stimulation. We use the massive perturb-seq dataset to uncover regulators driving gene expression signatures observed in human tissue cell atlases and as an interpretative framework for human disease genetics. I think this is going to be a foundational resource for human immunology, genetics, AI modeling of gene function, and immunotherapy development!
Over the past two decades, human population genetics have associated genetic variation to human traits. More recently, single-cell genomic technologies have mapped diverse cell states in human health and disease. Now, perturb-seq in human primary cells has potential to map how genetic variation controls cell states, offering new hope that we can systematically link genome sequences to cell programs to human health outcomes.
This work was led by Ronghui Zhu and Emma Dann and made by possible by a team of so many incredible immunologists and computational biologists working across Gladstone Institutes, Stanford University, UCSF and Biohub.
This is a continuation of a joyous and wildly productive collaboration over most of the past decade with Jonathan Pritchard to integrate human disease genetics with gene regulatory network maps.
Thanks to Biohub for making this possible, especially Bailey Marshall and Jonah Cool and the whole Billion Cell project team who helped us launch the effort.
I’m exciting to share a pre-print of one of the most exciting projects of my career to date.”
Title: Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits
Authors: Ronghui Zhu, Emma Dann, Jun Yan, Justine Reyes Retana, Ryunosuke Goto, Reese Guitche, Lillian Petersen, Mineto Ota, Jonathan Pritchard, Alexander Marson
Read the Full Article.
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