| # Dataset: X-Atlas/Pisces |
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| X-Atlas/Pisces is the largest CRISPRi Perturb-seq compendium to date, comprising |
| **25.6 million perturbed single-cell transcriptomes** across 7 biologically diverse contexts. |
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| ## Screens |
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| | Screen | Cell Type | Perturbations | Perturbed Cells | Median KD % | |
| |--------|-----------|--------------|----------------|-------------| |
| | HCT116 | Colorectal cancer | 18,924 | 3.4M | 70% | |
| | HEK293T | Kidney epithelial | 18,312 | 4.5M | 48% | |
| | HepG2 | Hepatocellular carcinoma | 9,735 | 2.6M | 85% | |
| | iPSC | Induced pluripotent stem cells | 10,095 | 4.2M | 82% | |
| | Jurkat Resting | T lymphoblastic leukemia | 10,872 | 2.8M | 79% | |
| | Jurkat Active | CD3/CD28-stimulated T cells | 10,878 | 2.8M | 71% | |
| | iPSC Multi-Diff | Multi-lineage differentiation | 12,175 | 5.1M | 96% | |
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| ## Data Access |
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| Test perturbation sets (held-out genes from HepG2 and iPSC, plus full Jurkat Resting/Active screens) |
| are available on HuggingFace: |
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| [:hugging: Xaira-Therapeutics/X-Atlas-Pisces](https://huggingface.co/datasets/Xaira-Therapeutics/X-Atlas-Pisces){ .md-button } |
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| ## Format |
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| Data is provided as `.h5ad` files (AnnData format) with: |
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| - `.X` — log-normalized expression (log1p CP10k) |
| - `.obs["perturbation"]` — gene target of CRISPRi knockdown |
| - `.obs["is_control"]` — boolean flag for non-targeting controls |
| - `.var_names` — ENSEMBL gene IDs |
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| ## Context-Dependent Biology |
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| A key finding from X-Atlas/Pisces is that perturbation effects are strongly context-dependent. |
| Hierarchical clustering of perturbation effect profiles (F1 scores from a per-perturbation |
| binary classifier) reveals three classes: |
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| - **Context-independent**: core essential machinery (e.g., mitochondrial ribosome subunits, |
| oxidative phosphorylation) — enriched in shared metabolic functions |
| - **Context-specific**: lineage-defining regulators — enriched in cell-type-specific pathways |
| (e.g., hypoxia response in HepG2, neural crest differentiation in iPSC) |
| - **Conserved proximal / variable distal**: perturbations where the direct consequence is |
| consistent but downstream cascades diverge by context |
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| This context-dependence motivates X-Cell's cross-attention architecture, which conditions |
| predictions on multi-modal biological priors rather than learning context-invariant representations. |
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