PAST: A multimodal single-cell foundation model for histopathology and spatial transcriptomics in cancer

While pathology foundation models have transformed cancer image analysis, they often lack integration with molecular data at single-cell resolution, limiting their utility for precision oncology. Here, we present PAST, a pan-cancer single-cell foundation model trained on 20 million paired histopathology images and single-cell transcriptomes spanning multiple tumor types and tissue contexts. By jointly encoding cellular morphology and gene expression, PAST learns unified cross-modal representations that capture both spatial and molecular heterogeneity at the cellular level. This approach enables accurate prediction of single-cell gene expression, virtual molecular staining, and multimodal survival analysis directly from routine pathology slides. Across diverse cancers and downstream tasks, PAST consistently exceeds the performance of existing approaches, demonstrating robust generalizability and scalability. Our work establishes a new paradigm for pathology foundation models, providing a versatile tool for high-resolution spatial omics, mechanistic discovery, and precision cancer research.

Fast on the Easy, Deep on the Hard: Efficient Reasoning via Powered Length Penalty

Large language models (LLMs) have demonstrated significant advancements in reasoning capabilities, performing well on various challenging benchmarks. Techniques like Chain-of-Thought prompting have been introduced to further improve reasoning. However, these approaches frequently generate longer outputs, which in turn increase computational latency. Although some methods use reinforcement learning to shorten reasoning, they often apply uniform penalties without considering the problem's complexity, leading to suboptimal outcomes. In this study, we seek to enhance the efficiency of LLM reasoning by promoting conciseness for simpler problems while preserving sufficient reasoning for more complex ones for accuracy, thus improving the model's overall performance. Specifically, we manage the model's reasoning efficiency by dividing the reward function and including a novel penalty for output length. Our approach has yielded impressive outcomes in benchmark evaluations across three datasets: GSM8K, MATH500, and AIME2024. For the comparatively simpler datasets GSM8K and MATH500, our method has effectively shortened output lengths while preserving or enhancing accuracy. On the more demanding AIME2024 dataset, our approach has resulted in improved accuracy.

ChromFound: Towards A Universal Foundation Model for Single-Cell Chromatin Accessibility Data

The advent of single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) offers an innovative perspective for deciphering regulatory mechanisms by assembling a vast repository of single-cell chromatin accessibility data. While foundation models have achieved significant success in single-cell transcriptomics, there is currently no foundation model for scATAC-seq that supports zero-shot high-quality cell identification and comprehensive multi-omics analysis simultaneously. Key challenges lie in the high dimensionality and sparsity of scATAC-seq data, as well as the lack of a standardized schema for representing open chromatin regions (OCRs). Here, we present \textbf{ChromFound}, a foundation model tailored for scATAC-seq. ChromFound utilizes a hybrid architecture and genome-aware tokenization to effectively capture genome-wide long contexts and regulatory signals from dynamic chromatin landscapes. Pretrained on 1.97 million cells from 30 tissues and 6 disease conditions, ChromFound demonstrates broad applicability across 6 diverse tasks. Notably, it achieves robust zero-shot performance in generating universal cell representations and exhibits excellent transferability in cell type annotation and cross-omics prediction. By uncovering enhancer-gene links undetected by existing computational methods, ChromFound offers a promising framework for understanding disease risk variants in the noncoding genome.