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Transcriptomic foundation models pretrained with masked language modeling can achieve low pretraining loss yet produce poor cell representations for downstream tasks. We introduce whole-cell expression decoding (WCED), where models…

Cell identity encompasses various semantic aspects of a cell, including cell type, pathway information, disease information, and more, which are essential for biologists to gain insights into its biological characteristics. Understanding…

Genomics · Quantitative Biology 2024-06-12 Suyuan Zhao , Jiahuan Zhang , Yushuai Wu , Yizhen Luo , Zaiqing Nie

Single-cell omics technologies have transformed our understanding of cellular diversity by enabling high-resolution profiling of individual cells. However, the unprecedented scale and heterogeneity of these datasets demand robust frameworks…

Cell type identification from single-cell transcriptomic data is a common goal of single-cell RNA sequencing (scRNAseq) data analysis. Neural networks have been employed to identify cell types from scRNAseq data with high performance.…

Genomics · Quantitative Biology 2020-05-11 Xishuang Dong , Shanta Chowdhury , Uboho Victor , Xiangfang Li , Lijun Qian

Single-cell foundation models (scFMs) have demonstrated state-of-the-art performance on various tasks, such as cell-type annotation and perturbation response prediction, by learning gene regulatory networks from large-scale transcriptome…

Machine Learning · Computer Science 2025-09-19 Sosuke Hosokawa , Toshiharu Kawakami , Satoshi Kodera , Masamichi Ito , Norihiko Takeda

Large language models (LLMs) have shown strong ability in generating rich representations across domains such as natural language processing and generation, computer vision, and multimodal learning. However, their application in biomedical…

Genomics · Quantitative Biology 2025-09-30 Luxuan Zhang , Douglas Jiang , Qinglong Wang , Haoqi Sun , Feng Tian

The integration of single-cell proteomic data is often hindered by the fragmented nature of targeted antibody panels. To address this limitation, we introduce scpFormer, a transformer-based foundation model designed for single-cell…

Quantitative Methods · Quantitative Biology 2026-04-23 Qifeng Zhou , Lei Yu , Yuzhi Guo , Yuwei Miao , Hehuan Ma , Wenliang Zhong , Lin Xu , Junzhou Huang

Single-cell RNA sequencing has transformed biology by enabling the measurement of gene expression at cellular resolution, providing information for cell types, states, and disease contexts. Recently, single-cell foundation models have…

Machine Learning · Computer Science 2025-10-13 Oussama Kharouiche , Aris Markogiannakis , Xiao Fei , Michail Chatzianastasis , Michalis Vazirgiannis

Understanding the biological mechanisms of disease is crucial for medicine, and in particular, for drug discovery. AI-powered analysis of genome-scale biological data holds great potential in this regard. The increasing availability of…

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…

Single-cell multi-omics (scMulti-omics) refers to the paired multimodal data, such as Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), where the regulation of each cell was measured from different modalities, i.e.…

Machine Learning · Computer Science 2024-10-18 Dian Meng , Bohao Xing , Xinlei Huang , Yanran Liu , Yijun Zhou , Yongjun xiao , Zitong Yu , Xubin Zheng

Single-cell foundation models such as scGPT represent a significant advancement in single-cell omics, with an ability to achieve state-of-the-art performance on various downstream biological tasks. However, these models are inherently…

Machine Learning · Computer Science 2025-07-15 Steven Palayew , Bo Wang , Gary Bader

Recent advancements in single-cell multi-omics, particularly RNA-seq, have provided profound insights into cellular heterogeneity and gene regulation. While pre-trained language model (PLM) paradigm based single-cell foundation models have…

Genomics · Quantitative Biology 2026-01-12 Haoran Wang , Xuanyi Zhang , Shuangsang Fang , Longke Ran , Ziqing Deng , Yong Zhang , Yuxiang Li , Shaoshuai Li

Recent studies have demonstrated the feasibility of modeling single-cell data as natural languages and the potential of leveraging powerful large language models (LLMs) for understanding cell biology. However, a comprehensive evaluation of…

Quantitative Methods · Quantitative Biology 2025-05-14 Fan Zhang , Tianyu Liu , Zhihong Zhu , Hao Wu , Haixin Wang , Donghao Zhou , Yefeng Zheng , Kun Wang , Xian Wu , Pheng-Ann Heng

We present the use of single-cell entropy (scEntropy) to measure the order of the cellular transcriptome profile from single-cell RNA-seq data, which leads to a method of unsupervised cell type classification through scEntropy followed by…

Quantitative Methods · Quantitative Biology 2020-02-18 Jingxin Liu , You Song , Jinzhi Lei

Large language models (LLMs) have demonstrated remarkable advancements, primarily due to their capabilities in modeling the hidden relationships within text sequences. This innovation presents a unique opportunity in the field of life…

Genomics · Quantitative Biology 2024-12-25 Cong Li , Qingqing Long , Yuanchun Zhou , Meng Xiao

Cytology is essential for cancer diagnostics and screening due to its minimally invasive nature. However, the development of robust deep learning models for digital cytology is challenging due to the heterogeneity in staining and…

Computer Vision and Pattern Recognition · Computer Science 2025-04-21 Vedrana Ivezić , Ashwath Radhachandran , Ekaterina Redekop , Shreeram Athreya , Dongwoo Lee , Vivek Sant , Corey Arnold , William Speier

Despite the inherent limitations of existing Large Language Models in directly reading and interpreting single-cell omics data, they demonstrate significant potential and flexibility as the Foundation Model. This research focuses on how to…

Genomics · Quantitative Biology 2024-02-21 Cong Li , Meng Xiao , Pengfei Wang , Guihai Feng , Xin Li , Yuanchun Zhou

Large language models excel at interpreting complex natural language instructions, enabling them to perform a wide range of tasks. In the life sciences, single-cell RNA sequencing (scRNA-seq) data serves as the "language of cellular…

Computation and Language · Computer Science 2025-01-16 Yin Fang , Xinle Deng , Kangwei Liu , Ningyu Zhang , Jingyang Qian , Penghui Yang , Xiaohui Fan , Huajun Chen

The anti-cancer immune response relies on the bindings between T-cell receptors (TCRs) and antigens, which elicits adaptive immunity to eliminate tumor cells. This ability of the immune system to respond to novel various neoantigens arises…

Quantitative Methods · Quantitative Biology 2025-11-11 Xing Fang , Chenpeng Yu , Shiye Tian , Hui Liu
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