LLM4Cell: A Survey of Large Language and Agentic Models for Single-Cell Biology

Large language models (LLMs) and emerging agentic frameworks are beginning to transform single-cell biology by enabling natural-language reasoning, generative annotation, and multimodal data integration. However, progress remains fragmented across data modalities, architectures, and evaluation standards. LLM4Cell presents the first unified survey of 58 foundation and agentic models developed for single-cell research, spanning RNA, ATAC, multi-omic, and spatial modalities. We categorize these methods into five families-foundation, text-bridge, spatial, multimodal, epigenomic, and agentic-and map them to eight key analytical tasks including annotation, trajectory and perturbation modeling, and drug-response prediction. Drawing on over 40 public datasets, we analyze benchmark suitability, data diversity, and ethical or scalability constraints, and evaluate models across 10 domain dimensions covering biological grounding, multi-omics alignment, fairness, privacy, and explainability. By linking datasets, models, and evaluation domains, LLM4Cell provides the first integrated view of language-driven single-cell intelligence and outlines open challenges in interpretability, standardization, and trustworthy model development.

MoXGATE: Modality-aware cross-attention for multi-omic gastrointestinal cancer sub-type classification

Cancer subtype classification is crucial for personalized treatment and prognostic assessment. However, effectively integrating multi-omic data remains challenging due to the heterogeneous nature of genomic, epigenomic, and transcriptomic features. In this work, we propose Modality-Aware Cross-Attention MoXGATE, a novel deep-learning framework that leverages cross-attention and learnable modality weights to enhance feature fusion across multiple omics sources. Our approach effectively captures inter-modality dependencies, ensuring robust and interpretable integration. Through experiments on Gastrointestinal Adenocarcinoma (GIAC) and Breast Cancer (BRCA) datasets from TCGA, we demonstrate that MoXGATE outperforms existing methods, achieving 95\% classification accuracy. Ablation studies validate the effectiveness of cross-attention over simple concatenation and highlight the importance of different omics modalities. Moreover, our model generalizes well to unseen cancer types e.g., breast cancer, underscoring its adaptability. Key contributions include (1) a cross-attention-based multi-omic integration framework, (2) modality-weighted fusion for enhanced interpretability, (3) application of focal loss to mitigate data imbalance, and (4) validation across multiple cancer subtypes. Our results indicate that MoXGATE is a promising approach for multi-omic cancer subtype classification, offering improved performance and biological generalizability.

Equitable Skin Disease Prediction Using Transfer Learning and Domain Adaptation

In the realm of dermatology, the complexity of diagnosing skin conditions manually necessitates the expertise of dermatologists. Accurate identification of various skin ailments, ranging from cancer to inflammatory diseases, is paramount. However, existing artificial intelligence (AI) models in dermatology face challenges, particularly in accurately diagnosing diseases across diverse skin tones, with a notable performance gap in darker skin. Additionally, the scarcity of publicly available, unbiased datasets hampers the development of inclusive AI diagnostic tools. To tackle the challenges in accurately predicting skin conditions across diverse skin tones, we employ a transfer-learning approach that capitalizes on the rich, transferable knowledge from various image domains. Our method integrates multiple pre-trained models from a wide range of sources, including general and specific medical images, to improve the robustness and inclusiveness of the skin condition predictions. We rigorously evaluated the effectiveness of these models using the Diverse Dermatology Images (DDI) dataset, which uniquely encompasses both underrepresented and common skin tones, making it an ideal benchmark for assessing our approach. Among all methods, Med-ViT emerged as the top performer due to its comprehensive feature representation learned from diverse image sources. To further enhance performance, we conducted domain adaptation using additional skin image datasets such as HAM10000. This adaptation significantly improved model performance across all models.

PathoLM: Identifying pathogenicity from the DNA sequence through the Genome Foundation Model

Pathogen identification is pivotal in diagnosing, treating, and preventing diseases, crucial for controlling infections and safeguarding public health. Traditional alignment-based methods, though widely used, are computationally intense and reliant on extensive reference databases, often failing to detect novel pathogens due to their low sensitivity and specificity. Similarly, conventional machine learning techniques, while promising, require large annotated datasets and extensive feature engineering and are prone to overfitting. Addressing these challenges, we introduce PathoLM, a cutting-edge pathogen language model optimized for the identification of pathogenicity in bacterial and viral sequences. Leveraging the strengths of pre-trained DNA models such as the Nucleotide Transformer, PathoLM requires minimal data for fine-tuning, thereby enhancing pathogen detection capabilities. It effectively captures a broader genomic context, significantly improving the identification of novel and divergent pathogens. We developed a comprehensive data set comprising approximately 30 species of viruses and bacteria, including ESKAPEE pathogens, seven notably virulent bacterial strains resistant to antibiotics. Additionally, we curated a species classification dataset centered specifically on the ESKAPEE group. In comparative assessments, PathoLM dramatically outperforms existing models like DciPatho, demonstrating robust zero-shot and few-shot capabilities. Furthermore, we expanded PathoLM-Sp for ESKAPEE species classification, where it showed superior performance compared to other advanced deep learning methods, despite the complexities of the task.