待翻译：Response Magnitude as a Dominant Signal for Held-Out CRISPRi Perturbation Effect Prediction

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--> [Submitted on 31 Jul 2026] Title:Response Magnitude as a Dominant Signal for Held-Out CRISPRi Perturbation Effect Prediction View a PDF of the paper titled Response Magnitude as a Dominant Signal for Held-Out CRISPRi Perturbation Effect Prediction, by Mehrdad Shoeibi and Niloofar Yousefi View PDF HTML (experimental) Abstract:Predicting the magnitude of a CRISPRi perturbation's transcriptomic effect on held-out target genes is an important open problem in single-cell biology. Recent work has documented that simple baselines often match or exceed deep perturbation predictors on related protocols. We study this phenomenon on the Virtual Cell Challenge (VCC) benchmark under a strict held-out target-gene split, identify the specific low-dimensional signal that drives the gap, and characterize how it transfers across cell types. The target is the log Anderson-Darling distance from non-targeting controls, which is strongly predictable from four deterministic scalar functions of the 2,000-dimensional input. A deep MLP encoder with direct access to the full input collapses toward the marginal training mean, and standard remedies do not close the gap. A linear regression on the four magnitude scalars alone exceeds the strongest x-only classical model, while a Random Forest on the input plus the four scalars substantially outperforms our deep proof-of-concept encoder. Two pre-specified controls attribute the magnitude gain to per-row alignment rather than added dimensionality. Under zero-shot transfer to two external CRISPRi screens evaluated against a target-gene endpoint rebuilt from single-cell data, magnitude-only predictors transfer positively whereas expression-only predictors are negative or unresolved. Exposing magnitude to the deep encoder improves transfer over its expression-only counterpart, yet the encoder does not outperform a four-scalar linear regression on the same features. We also find that the Anderson-Darling column distributed with these screens measures transcriptome-wide response breadth rather than target-gene effect strength, so evaluating transfer against it scores a different outcome. Comments: 27 pages, 8 figures, 8 tables Subjects: Machine Learning (cs.LG); Artificial Intelligence (cs.AI) Cite as: arXiv:2608.00152 [cs.LG] (or arXiv:2608.00152v1 [cs.LG] for this version) https://doi.org/10.48550/arXiv.2608.00152 arXiv-issued DOI via DataCite Submission history From: Mehrdad Shoeibi [view email] [v1] Fri, 31 Jul 2026 17:09:26 UTC (195 KB) Full-text links: Access Paper: View a PDF of the paper titled Response Magnitude as a Dominant Signal for Held-Out CRISPRi Perturbation Effect Prediction, by Mehrdad Shoeibi and Niloofar Yousefi View PDF HTML (experimental) TeX Source view license Current browse context: cs.LG new | recent | 2026-08 Change to browse by: cs cs.AI References & Citations NASA ADS Google Scholar Semantic Scholar Loading... Data provided by: Bibliographic Tools Bibliographic and Citation Tools Bibliographic Explorer Toggle Bibliographic Explorer (What is the Explorer?) Connected Papers Toggle Connected Papers (What is Connected Papers?) Litmaps Toggle Litmaps (What is Litmaps?) scite.ai Toggle scite Smart Citations (What are Smart Citations?) Code, Data, Media Code, Data and Media Associated with this Article alphaXiv Toggle alphaXiv (What is alphaXiv?) Links to Code Toggle CatalyzeX Code Finder for Papers (What is CatalyzeX?) DagsHub Toggle DagsHub (What is DagsHub?) GotitPub Toggle Gotit.pub (What is GotitPub?) Huggingface Toggle Hugging Face (What is Huggingface?) ScienceCast Toggle ScienceCast (What is ScienceCast?) Demos Demos Replicate Toggle Replicate (What is Replicate?) Spaces Toggle Hugging Face Spaces (What is Spaces?) Spaces Toggle TXYZ.AI (What is TXYZ.AI?) Related Papers Recommenders and Search Tools Link to Influence Flower Influence Flower (What are Influence Flowers?) Core recommender toggle CORE Recommender (What is CORE?) IArxiv recommender toggle IArxiv Recommender (What is IArxiv?) Author Venue Institution Topic About arXivLabs arXivLabs: experimental projects with community collaborators arXivLabs is a framework that allows collaborators to develop and share new arXiv features directly on our website. Both individuals and organizations that work with arXivLabs have embraced and accepted our values of openness, community, excellence, and user data privacy. arXiv is committed to these values and only works with partners that adhere to them. Have an idea for a project that will add value for arXiv's community? Learn more about arXivLabs. Which authors of this paper are endorsers? | Disable MathJax (What is MathJax?)