InfoGlobe: Local-and-Global Information-Preserving Statistical Manifold Learning for Single-Cell Transcriptomics
Cheng Wang, Jinpu Cai, Chongxiao Mao, Yuxuan Wang, Xinzhu Jiang, Yunhao Qiao, Luqi Yang, Luting Zhou
ICML 2026 regular
Abstract (source: OpenReview · © authors)
Geometry-preserving dimension reduction is critical for single-cell transcriptomics, where low-dimensional distances should reflect biological divergence between cell types along the transcriptomic manifold. Due to inadequate metrics, the global structure is not sufficiently preserved in the low-dimensional manifold in standard dimension reduction regimes. We model RNA counts as Multinomial samples, leveraging their hierarchical closure property: gene-level counts refine functional gene-group counts via nested Multinomial distributions. Extending Chentsov's Theorem, we show that the Fisher-Rao metric on coarse (gene-group) and fine (gene) statistical manifolds is isometric. Following this isometry property, we propose InfoGlobe, an information-preserving statistical manifold learning framework that projects cells from high-dimensional hyperspheres (full transcriptome) to low-dimensional hyperspheres (functional groups) while preserving information geometry. Embeddings on the low-dimensional sphere explicitly represent Multinomial distributions by functional gene groups. Benchmarks demonstrate superior preservation of local-and-global cell-type geodesic distances, automatic and robust gene-group discovery, nuanced cell subtype resolution without manual feature engineering and natural batch effect mitigation without explicit alignments.
Keywords
Metadata from BioTender-max/icml2026-ai-bio (CC0-1.0). Phở does not host any PDF; links point back to the source.
Related
Scalable Single-Cell Gene Expression Generation with Latent Diffusion Models
Giovanni Palla, Sudarshan Babu, Payam Dibaeinia, James D Pearce +4
Computational modeling of single-cell gene expression is crucial for understanding cellular processes, but generating realistic expression profiles remains a major challenge. This…
Beyond Independent Genes: Learning Module-Inductive Representations for Single-Cell Gene Perturbation Prediction
Jiafa Ruan, Ruijie Quan, Xu Liyang, Zongxin Yang +1
Predicting transcriptional responses to genetic perturbations is a central problem in functional genomics. In practice, perturbation responses are rarely gene-independent but…
Effects of Structural Reward Shaping on Biophysical Properties in RL-Trained Plasmid Generators
McClain Thiel, Angus G. Cunningham, Chris P Barnes
We compare the efficacy and distributional effects of supervised fine-tuning (SFT) and reinforcement learning (RL) post-training for PlasmidGPT, a foundation model for…