Dataset: X-Atlas/Pisces

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.

Screens

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%

Data Access

Test perturbation sets (held-out genes from HepG2 and iPSC, plus full Jurkat Resting/Active screens) are available on HuggingFace:

Xaira-Therapeutics/X-Atlas-Pisces

Format

Data is provided as .h5ad files (AnnData format) with:

• .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

Context-Dependent Biology

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:

• 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

This context-dependence motivates X-Cell's cross-attention architecture, which conditions predictions on multi-modal biological priors rather than learning context-invariant representations.