{"about":{"site":"https://codewithpapers.app","non_affiliation":"Code with Papers and Syntology are not affiliated with, endorsed by, or sponsored by Papers with Code, Meta, or the pwc-archive mirror.","licence":"CC BY-SA 4.0","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","attribution":"https://codewithpapers.app/attribution","modified":"archive material modified by Syntology; see the attribution page"},"url":"/paper/learning-causal-representations-of-single","title":"Learning Causal Representations of Single Cells via Sparse Mechanism Shift Modeling","arxiv_id":"2211.03553","date":"2022-11-07","proceeding":null,"authors":["Romain Lopez","Nataša Tagasovska","Stephen Ra","Kyunghyn Cho","Jonathan K. Pritchard","Aviv Regev"],"abstract":"Latent variable models such as the Variational Auto-Encoder (VAE) have become a go-to tool for analyzing biological data, especially in the field of single-cell genomics. One remaining challenge is the interpretability of latent variables as biological processes that define a cell's identity. Outside of biological applications, this problem is commonly referred to as learning disentangled representations. Although several disentanglement-promoting variants of the VAE were introduced, and applied to single-cell genomics data, this task has been shown to be infeasible from independent and identically distributed measurements, without additional structure. Instead, recent methods propose to leverage non-stationary data, as well as the sparse mechanism shift assumption in order to learn disentangled representations with a causal semantic. Here, we extend the application of these methodological advances to the analysis of single-cell genomics data with genetic or chemical perturbations. More precisely, we propose a deep generative model of single-cell gene expression data for which each perturbation is treated as a stochastic intervention targeting an unknown, but sparse, subset of latent variables. We benchmark these methods on simulated single-cell data to evaluate their performance at latent units recovery, causal target identification and out-of-domain generalization. Finally, we apply those approaches to two real-world large-scale gene perturbation data sets and find that models that exploit the sparse mechanism shift hypothesis surpass contemporary methods on a transfer learning task. We implement our new model and benchmarks using the scvi-tools library, and release it as open-source software at https://github.com/Genentech/sVAE.","url_abs":"https://arxiv.org/abs/2211.03553v4","url_pdf":"https://arxiv.org/pdf/2211.03553v4.pdf","source":{"archive":"pwc-archive (Hugging Face), CC BY-SA 4.0","snapshot":"2025-07-28","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","row_kind":"abstracts"},"code_links":[{"paper_slug":"learning-causal-representations-of-single","repo_url":"https://github.com/genentech/svae","is_official":1,"mentioned_in_paper":1,"mentioned_in_github":1,"framework":"pytorch","reach":null}],"tasks":[{"task_slug":"disentanglement","task_name":"Disentanglement"},{"task_slug":"domain-generalization","task_name":"Domain Generalization"},{"task_slug":"transfer-learning","task_name":"Transfer Learning"}],"methods":[],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"atlas_url":"https://app.syntology.ai/?focus=2211.03553","mcp":{"get_harvested_code_for_paper":{"arxiv_id":"2211.03553"}},"developers":"https://syntology.ai/developers","read_at":"2026-09-24T18:15:14+00:00","read_at_is":"when the build read Syntology's graph, not when any sample ran","claim":"Per-sample execution status on synthesized fixtures; not a correctness claim about the paper. 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