arXiv Machine Learning

scCBGM: Interpretable Single-Cell Counterfactual Editing

arXiv:2606. 07760v1 Announce Type: new Abstract: Understanding cellular phenotypes and how they respond to perturbations is critical for disease biology and therapeutic design.

arXiv AI
3d ago

CellMSA: Context Modeling for Single-Cell Representation Learning

CellMSA introduces a novel single‑cell representation learning framework that leverages a multiple‑sequence‑alignment‑inspired context model. For each target cell, it retrieves relevant cells across batches and related cell types, summarizing cross‑cell patterns into a context‑dependent gene‑pair representation that is fed into a pair‑aware encoder. Pretraining on a massive human single‑cell corpus (≈109 million cells) and subsequent benchmarks demonstrate consistent performance gains over existing methods.

By Suyuan Zhao, Minghao Liu, Yizhen Luo, Zaiqing Nie
arXiv AI
3d ago

scTrilemma: Balancing Identity, Invariance, and Fidelity in Single-Cell Representation Learning

The paper introduces scTrilemma, a latent-bottleneck variational autoencoder designed to address the representation trilemma in single‑cell RNA‑seq data: preserving biological identity and state, remaining robust to nuisance context, and retaining gene‑level variation for expression analysis. scTrilemma routes expression‑derived variation to the embedding, decoder, or prior, gating gene tokens by expression and conditioning the prior on unlabeled pseudo‑bulk context, all under a single reconstruction objective without target annotations. In zero‑shot evaluations on successive CZ CELLxGENE Census releases, scTrilemma simultaneously satisfies all three demands, maintaining biological state, differential‑expression, and pathway structure across multiple disease settings, and latent interventions show context can be removed with minimal impact on other demands.

By Yunhak Oh, Yoonho Lee, Junseok Lee, Namkyeong Lee, Sang-Yeon Hwang, Yinhua Piao, Hyomin Kim, Seonghwan Kim, Jaechang Lim, Woo Youn Kim, Sungsoo Ahn, Chanyoung Park
arXiv AI
Aug 12

JEPA-DNA: Grounding Genomic Foundation Models through Joint-Embedding Predictive Architectures

arXiv:2602. 17162v3 Announce Type: replace Abstract: Genomic Foundation Models (GFMs) typically rely on Masked Language Modeling (MLM) or Next-Token Prediction (NTP) to learn the "Laws of Nature".

By Ariel Larey, Elay Dahan, Amit Bleiweiss, Raizy Kellerman, Guy Leib, Omri Nayshool, Dan Ofer, Tal Zinger, Dan Dominissini, Gideon Rechavi, Nicole Bussola, Simon Lee, Shane O'Connell, Dung Hoang, Marissa Wirth, Alexander W. Charney, Nati Daniel, Yoli Shavit
arXiv AI
Sep 15

Towards a knowledge-enhanced single-cell foundation model

The paper introduces scKITE, a single-cell foundation model that incorporates biological knowledge—cell-level text annotations and gene-level regulatory information—into a shared Transformer encoder via lightweight auxiliary decoders used only during pretraining. This approach provides a new scaling dimension beyond merely increasing data size, enabling the model to achieve superior performance on diverse downstream tasks with only 179,067 pretraining samples, less than 0.5% of the data used by previous strong scFMs. The study demonstrates that knowledge-enhanced pretraining can yield significant gains while reducing computational cost.

By Hanqing Zhang, Jie Bao, Mei Ma, Shuai Liu, Jiaying Ma, Jiaguan Liu, Jiaxiao Li, Zhenbo Li, Wenwen Gong, Zhijun Ca