Zhuhao Wu

Adina Scheinfeld, Haotan Zhang, Shang Mu et al.

Light sheet fluorescence microscopy (LSM) enables high-resolution, three-dimensional (3D) imaging of biological specimens, providing rich volumetric data for studying cellular organization, pathology, and vascular networks. However, the size, dimensionality, and annotation burden of LSM data make supervised deep learning approaches costly and difficult to scale. Additionally, despite the abundance of unannotated LSM volumes, foundation models for this modality remain underexplored due to computational challenges and the complexity of volumetric representation learning. In this work, we introduce a 3D foundation model for LSM data, pretrained on a large curated collection of 3D images spanning multiple organisms, stains, and imaging protocols. We learn transferable volumetric representations by jointly optimizing for masked reconstruction and image-text alignment. The pretrained backbone drastically reduces the annotation burden, enabling efficient, few-shot adaptation for varied downstream tasks. We evaluate this approach on downstream segmentation, classification, and deblurring. Our results demonstrate consistent improvements over baselines, (1) when measured using standard evaluation metrics and (2) when rigorously assessed by domain experts. This highlights the potential of foundation model pretraining to reduce annotation requirements while improving performance across diverse LSM analysis tasks. Pretrained model weights and code for pretraining and finetuning are publicly available: https://github.com/AdinaScheinfeld/lsm_fm_public_repo.git.

Rongbin Li, Wenbo Chen, Zhao Li et al.

Single-cell RNA sequencing has transformed our ability to identify diverse cell types and their transcriptomic signatures. However, annotating these signatures-especially those involving poorly characterized genes-remains a major challenge. Traditional methods, such as Gene Set Enrichment Analysis (GSEA), depend on well-curated annotations and often perform poorly in these contexts. Large Language Models (LLMs) offer a promising alternative but struggle to represent complex biological knowledge within structured ontologies. To address this, we present BRAINCELL-AID (BRAINCELL-AID: https://biodataai.uth.edu/BRAINCELL-AID), a novel multi-agent AI system that integrates free-text descriptions with ontology labels to enable more accurate and robust gene set annotation. By incorporating retrieval-augmented generation (RAG), we developed a robust agentic workflow that refines predictions using relevant PubMed literature, reducing hallucinations and enhancing interpretability. Using this workflow, we achieved correct annotations for 77% of mouse gene sets among their top predictions. Applying this approach, we annotated 5,322 brain cell clusters from the comprehensive mouse brain cell atlas generated by the BRAIN Initiative Cell Census Network, enabling novel insights into brain cell function by identifying region-specific gene co-expression patterns and inferring functional roles of gene ensembles. BRAINCELL-AID also identifies Basal Ganglia-related cell types with neurologically meaningful descriptions. Hence, we create a valuable resource to support community-driven cell type annotation.