{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328830"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Temporal control of sgRNA library activation unlocks large-scale in vivo CRISPR screens","description":"Functional genomics screens have revealed cancer gene dependencies, but cell culture misses vulnerabilities driven by the tumor microenvironment. We implemented CRISPR-StAR (Stochastic Activation by Recombination), an inducible pooled screening system that activates gene knockout after tumor engraftment and provides matched internal controls for guide-level normalization. Using barcode-embedded sequencing and Bayesian analysis, we screened a 30,000-sgRNA library in A549 xenografts and achieved reproducible dropout and enrichment phenotypes using just ~30 tumors. Across additional xenograft models, single tumors yielded reliable functional annotation for ~1,000 genes leveraging within-tumor normalization. Comparing in vivo and in vitro screens uncovered tumor-suppressor effects detectable only in vivo; for example KMT2C and KMT2D knockouts produced contrasting tumor growth and transcriptional programs. Together with our R analysis package, CRISPR-StAR enables scalable in vivo dependency mapping that complements in vitro resources and reduces animal use up to sevenfold versus conventional dropout screens, improving overall methodological rigor at genome-scale clonal resolution.","dates":{"publication":"2026/04/29"},"accession":"GSE328830","cross_references":{"GSM":["GSM9690411","GSM9690415","GSM9690414","GSM9690413","GSM9690412","GSM9690418","GSM9690417","GSM9690416"],"GPL":["30173"],"GSE":["328830"],"taxon":["Homo sapiens"]}}