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High-Information Phenotypic Characterization of the Effect of Ionizing Radiation on Human Cells Using Rich Phenotypes From Perturb-Seq.

Title/Author: High-Information Phenotypic Characterization of the Effect of Ionizing Radiation on Human Cells Using Rich Phenotypes From Perturb-Seq.

General Note: Source: Dissertations Abstracts International, Volume: 86-06, Section: B.

Abstracts/Etc: 요약Ionizing radiation is employed broadly in oncology, but has a narrow therapeutic window arising from nonspecifically induced genomic damage in both healthy and cancerous cells. We employ genome-scale CRISPRi perturb-seq across millions of human cells alongside proliferation screens to profile all expressed genes' effect on heterogenous cellular responses to ionizing radiation in the human chronic myelogenous leukemia cell line K562. We identify undercharacterized radiation sensitizing genes and leverage rich transcriptomic phenotypes to assign putative functional roles based on clustering. We find perturbations which induce radiation-specific responses in single-cell transcriptomic phenotypes like cell cycle state and chromosomal instability, and show how the stressor environment reveals the role of regulatory programs invisible without radiation. A followup validation perturb-seq experiment was used to determine the replicability and broader applicability of these findings, bolstering our confidence in our generation of high-quality transcriptomic profiles to CRISPRi perturbation and ionizing radiation.

Added Entry-Corporate Name: University of California, San Francisco Biological and Medical Informatics

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