{"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/sc-otgm-single-cell-perturbation-modeling-by","title":"sc-OTGM: Single-Cell Perturbation Modeling by Solving Optimal Mass Transport on the Manifold of Gaussian Mixtures","arxiv_id":"2405.03726","date":"2024-05-06","proceeding":null,"authors":["Andac Demir","Elizaveta Solovyeva","James Boylan","Mei Xiao","Fabrizio Serluca","Sebastian Hoersch","Jeremy Jenkins","Murthy Devarakonda","Bulent Kiziltan"],"abstract":"Influenced by breakthroughs in LLMs, single-cell foundation models are emerging. While these models show successful performance in cell type clustering, phenotype classification, and gene perturbation response prediction, it remains to be seen if a simpler model could achieve comparable or better results, especially with limited data. This is important, as the quantity and quality of single-cell data typically fall short of the standards in textual data used for training LLMs. Single-cell sequencing often suffers from technical artifacts, dropout events, and batch effects. These challenges are compounded in a weakly supervised setting, where the labels of cell states can be noisy, further complicating the analysis. To tackle these challenges, we present sc-OTGM, streamlined with less than 500K parameters, making it approximately 100x more compact than the foundation models, offering an efficient alternative. sc-OTGM is an unsupervised model grounded in the inductive bias that the scRNAseq data can be generated from a combination of the finite multivariate Gaussian distributions. The core function of sc-OTGM is to create a probabilistic latent space utilizing a GMM as its prior distribution and distinguish between distinct cell populations by learning their respective marginal PDFs. It uses a Hit-and-Run Markov chain sampler to determine the OT plan across these PDFs within the GMM framework. We evaluated our model against a CRISPR-mediated perturbation dataset, called CROP-seq, consisting of 57 one-gene perturbations. Our results demonstrate that sc-OTGM is effective in cell state classification, aids in the analysis of differential gene expression, and ranks genes for target identification through a recommender system. It also predicts the effects of single-gene perturbations on downstream gene regulation and generates synthetic scRNA-seq data conditioned on specific cell states.","url_abs":"https://arxiv.org/abs/2405.03726v1","url_pdf":"https://arxiv.org/pdf/2405.03726v1.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":[],"tasks":[{"task_slug":"inductive-bias","task_name":"Inductive Bias"},{"task_slug":"phenotype-classification","task_name":"Phenotype classification"},{"task_slug":"recommendation-systems","task_name":"Recommendation Systems"}],"methods":[{"method_slug":"dropout","method_name":"Dropout"}],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"atlas_url":"https://app.syntology.ai/?focus=2405.03726","mcp":{"get_harvested_code_for_paper":{"arxiv_id":"2405.03726"}},"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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