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D-SPIN constructs regulatory network models from scRNA-seq revealing organizing principles of perturbation response

GSE327727 Homo sapiens Expression profiling by high throughput sequencing; Other 194 samples Submitted 2026/05/11 Platform GPL24676Platform GPL20301Platform GPL15520
Summary
Gene regulatory networks modulate the expression of the genome in response to signals and environmental conditions. Reconstructions of such networks can reveal the control principles cells use to maintain homeostasis and execute cell-state transitions. Here, we introduce a computational framework, D-SPIN, that infers mechanistically interpretable and generative models of gene regulatory networks from single-cell mRNA-seq datasets collected across thousands of perturbation conditions. The models explain how perturbations modulate cell state proportions by reconfiguring underlying regulatory interactions. Using large Perturb-seq and drug-response datasets, D-SPIN models reveal key regulators of cell-fate decisions and the coordination of distant cellular pathways in response to gene knockdowns and drug treatments, elucidate how combinations of immunomodulatory drugs induce combinatorial cell states through additive recruitment of gene expression programs, and simulate shifts in immune cell population structures across unobserved drug dosage combinations. D-SPIN provides a computational framework for revealing principles of cellular information processing and physiological control.
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Direct links to NCBI, no account and no request form: the whole study as GSE327727_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 194 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1449626 and SRA study SRP690278. Searching any of these in the dataset finder brings you back here.

Study design
40 conditions, each sampled once — no replicated groups

Read from the first 40 of 194 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.

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