A Pan-Cancer Single-Cell Atlas to Evaluate Tumor Identity, Cell Line Concordance, and Dependency Mapping
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ABSTRACT: Bulk RNA sequencing enables pan-cancer transcriptional analyses, but obscures cancer cell-specific programs due to admixture with nonmalignant cells, limiting direct comparison between experimental models and human tumors. Single-cell RNA sequencing (scRNA-seq) overcomes these limitations, yet biological interpretability of public datasets is often compromised by variable data quality, inconsistent annotation, and atlas-scale aggregation strategies that favor data volume over biological coherence. We therefore developed a stringent integration framework that prioritizes representative malignant transcriptional states. Using Mahalanobis distance-based selection in batch-corrected latent space, we constructed a pan-cancer atlas of 135,441 high-quality malignant cells from 494 samples spanning 36 adult and pediatric cancer types. Atlas-derived signatures were used to assess tumor–cell line concordance and project ElasticNet models trained on DepMap CRISPR screens to infer cancer-specific gene dependencies. Together, the scTumor Atlas provides a scalable framework for tumor identity inference, cancer cell line benchmarking, and systematic identification of genetic vulnerabilities.
ORGANISM(S): Homo sapiens
PROVIDER: GSE319327 | GEO | 2026/07/24
REPOSITORIES: GEO
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