arXiv Machine Learning

One Method Does Not Fit All: A Large-Scale Benchmark of Imputation Methods for Single-Cell RNA Sequencing Data

The study evaluates 16 imputation methods for single‑cell RNA sequencing across 10 protocols, 6 downstream tasks, and 30 datasets. It finds that traditional methods generally perform better across many tasks, while deep learning approaches show more variability. No single method consistently outperforms others, and strong numerical recovery does not always improve biological interpretation.

arXiv AI
Sep 21

A Hybrid Computational Intelligence Framework for scRNA-seq Imputation: Integrating scRecover and Random Forests

The paper introduces SCR-MF, a two‑stage workflow for single‑cell RNA sequencing imputation that first detects dropout events with scRecover and then imputes missing values using the non‑parametric missForest algorithm. Benchmarking on public and simulated datasets shows that SCR‑MF delivers robust, interpretable results that match or surpass existing methods while maintaining biological fidelity. Runtime analysis indicates that SCR‑MF balances accuracy with computational efficiency, making it well suited for mid‑scale single‑cell studies.

By Ali Anaissi, Deshao Liu, Yuanzhe Jia, Weidong Huang, Widad Alyassine, Junaid Akram
arXiv AI
Oct 1

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 Machine Learning
Sep 18

Transcriptomic Models for Immunotherapy Response Prediction Show Limited Cross-cohort Generalisability

The study evaluated nine transcriptomic models—five bulk RNA‑seq and four single‑cell RNA‑seq—designed to predict response to immune checkpoint inhibitors. Across independent datasets, bulk models performed near chance while single‑cell models offered only modest gains, and pathway analyses revealed inconsistent biomarker signals. The results highlight the limited cross‑cohort robustness and biological consistency of current transcriptomic ICI predictors.

By Yuheng Liang, Lucy Chhuo, Ahmadreza Argha, Nona Farbehi, Lu Chen, Roohallah Alizadehsani, Mehdi Hosseinzadeh, Min Yang, Thantrira Porntaveetusm, Youqiong Ye, Hamid Alinejad-Rokny
arXiv AI
Aug 3

ELISA: An Interpretable Hybrid Generative AI Agent for Expression-Grounded Discovery in Single-Cell Genomics

arXiv:2603. 11872v3 Announce Type: replace-cross Abstract: Translating single-cell RNA sequencing (scRNA-seq) data into mechanistic biological hypotheses remains a critical bottleneck, as agentic AI systems lack direct access to transcriptomic representations while expression foundation models remain opaque to natural language.

By Omar Coser
arXiv Machine Learning
Jun 9

Integrating gene regulatory priors into Transformer attention with scTransformer for interpretable scRNA-seq analysis

arXiv:2606. 09558v1 Announce Type: cross Abstract: Motivation: Transformer-based models are increasingly applied to large-scale single-cell transcriptomics, showing strong performance through self-supervised learning on millions of cells.

By Mikele Milia, Louis Fabrice Tshimanga, Henning Mueller, Manfredo Atzori, Barbara Di Camillo
arXiv AI
5d ago

scAnyOmics: Foundation-Model Distillation for Any-to-Any Completion of Multi-omics Virtual Cells

scAnyOmics is a generative framework that distills knowledge from a frozen single-cell foundation model into a multimodal student model, integrating scRNA‑seq, protein‑marker measurements, and scATAC‑seq into a shared representation. It enables cross‑modal prediction and reconstruction of missing modalities, and was evaluated on 690,880 cells from six studies, outperforming baseline methods on held‑out donor data. The framework also supports applications such as cell‑type annotation, perturbation‑response prediction, and biological age estimation, providing a unified approach for integrating incomplete single‑cell multi‑omics data and transferring pretrained biological knowledge.

By Zhaoqi Song, Ye Du, Yusuke Iwasawa, Yutaka Matsuo, Qian Niu
arXiv AI
1d ago

MUSS: A Multi-scale and Sequence-based Model for Single-cell Gene Regulation

arXiv:2611.08086v1 Announce Type: new Abstract: Modeling gene regulation in single cells requires jointly representing DNA sequence, chromatin accessibility, and gene expression across regulatory sca...

By Kangjie Zheng, Amirhossein Vahidi, Liying Jin, Joseph Clarke, Vijaya Baskar MS, Connor Rogerson, Mengji Zhang, Muzlifah Haniffa, Anshul Kundaje, Mo Lotfollahi