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Du Cai

Publications and source records attributed to Du Cai.

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Spatial Transcriptomics-Guided Alignment Enhances Molecular Profiling in Pathology Foundation Model

Comprehensive molecular profiling is essential for modern precision oncology but remains hindered by prohibitive costs, specimen exhaustion, and protracted turnaround times. While pathology foundation models (PFMs) have demonstrated potential for inferring molecular phenotypes from routine hematoxylin and eosin (H&E) whole-slide images (WSIs), current architectures primarily rely on vision-centric self-supervised learning or vision-language alignment, lacking the spatially resolved molecular supervision required to connect subtle morphological features with underlying genomic alterations. Spatial transcriptomics (ST) emerges as a transformative technology that enables transcriptomic quantification within intact tissue sections, thereby preserving the precise spatial link between histology and molecular profiles. In this study, we present a Spatial Transcriptomics-guided Alignment framework for Molecular Profiling (STAMP), which endows PFMs with intrinsic molecular awareness. To support this paradigm, we curated HumanST-1k, a human ST dataset spanning diverse anatomical organs and sequencing platforms. This atlas yields 1.8 million pairs of H&E patches and corresponding transcriptomic profiles, providing a corpus that links histological structures with their molecular states. To mitigate the technical noise inherent to raw transcriptomics, STAMP applies a pathway-informed alignment strategy that aggregates transcriptomic data into biologically functional pathways, which are subsequently integrated into PFMs via parameter-efficient fine-tuning. This alignment enriches the representation space of PFMs and unlocks their capacity to resolve sub-visual molecular signatures. The clinical utility of these augmented representations was validated through a multi-tier evaluation framework.

cs.LG

A Deployment-Friendly Foundational Framework for Efficient Computational Pathology

Pathology foundation models (PFMs) generalize well across computational pathology tasks but remain costly for gigapixel whole-slide image analysis. Here, we present LitePath, a deployment-friendly framework that addresses model over-parameterization and patch-level redundancy. LitePath combines LiteFM, a compact model distilled from Virchow2, H-Optimus-1 and UNI2 using 190 million patches, with the Adaptive Patch Selector for task-specific patch selection. Compared with Virchow2, LitePath uses 28x fewer parameters and 403.5x fewer FLOPs. On an NVIDIA Jetson Orin Nano Super, it processes 208 slides per hour, 104.5x faster than Virchow2, and consumes 0.36 kWh per 3,000 slides, 171x less energy than Virchow2 on an RTX 3090 GPU. We evaluated LitePath on 45 multicenter cohorts across four organs and 33 tasks, comprising 37 classification and 8 survival cohorts, including 33 internal, 10 external and 2 prospective cohorts, with 17,837 slides from 9,977 patients disjoint from the pretraining data. Among 22 PFMs, LitePath achieved the best average rank (6.56 vs. 6.58 for Virchow2), retained 99.71% of Virchow2's Macro-AUC across classification cohorts, and improved mean C-index by 2.14 percentage points across survival cohorts (71.91% vs. 69.77%). We further introduce the Deployability Score (D-Score), a weighted geometric mean of normalized task performance and FLOPs. LitePath achieved the highest D-Score (0.8455), outperforming H0-mini (0.7723) and Virchow2 (0.7297). In a randomized paired crossover study of four pathologists and 120 cases, LitePath increased diagnostic accuracy by 4.1-15.8 percentage points and reduced diagnostic time by 10.9-14.2%. These results demonstrate rapid, cost-effective and energy-efficient pathology image analysis on accessible hardware while maintaining competitive performance.

cs.CV

PathBench: A comprehensive comparison benchmark for pathology foundation models towards precision oncology

The emergence of pathology foundation models has revolutionized computational histopathology, enabling highly accurate, generalized whole-slide image analysis for improved cancer diagnosis, and prognosis assessment. While these models show remarkable potential across cancer diagnostics and prognostics, their clinical translation faces critical challenges including variability in optimal model across cancer types, potential data leakage in evaluation, and lack of standardized benchmarks. Without rigorous, unbiased evaluation, even the most advanced PFMs risk remaining confined to research settings, delaying their life-saving applications. Existing benchmarking efforts remain limited by narrow cancer-type focus, potential pretraining data overlaps, or incomplete task coverage. We present PathBench, the first comprehensive benchmark addressing these gaps through: multi-center in-hourse datasets spanning common cancers with rigorous leakage prevention, evaluation across the full clinical spectrum from diagnosis to prognosis, and an automated leaderboard system for continuous model assessment. Our framework incorporates large-scale data, enabling objective comparison of PFMs while reflecting real-world clinical complexity. All evaluation data comes from private medical providers, with strict exclusion of any pretraining usage to avoid data leakage risks. We have collected 15,888 WSIs from 8,549 patients across 10 hospitals, encompassing over 64 diagnosis and prognosis tasks. Currently, our evaluation of 19 PFMs shows that Virchow2 and H-Optimus-1 are the most effective models overall. This work provides researchers with a robust platform for model development and offers clinicians actionable insights into PFM performance across diverse clinical scenarios, ultimately accelerating the translation of these transformative technologies into routine pathology practice.

cs.CV