Predicting spatial gene expression from hematoxylin and eosin (H\&E)-stained images offers a cost-effective alternative to spatial transcriptomics (ST). However, existing methods treat H\&E images as generic visual inputs and ignore their intrinsic biological hierarchy, where spatially organized cell types collectively form functional tissue microenvironments that govern local gene expression programs. To bridge this gap, we formulate H\&E-to-ST prediction as a cross-modal semantic translation task and propose Path2ST, a hierarchically grounded autoregressive framework featuring three key components: (i) a Hierarchical Cell-Tissue Conditioning mechanism that fuses explicit and implicit cellular features with tissue-level semantic representations to construct hierarchical conditioning signals; (ii) a Scale-Adaptive Autoregressive Generation process over a hierarchical semantic vocabulary, enabling coarse-to-fine, biologically consistent expression synthesis; and (iii) SpectraLoss, a full-spectrum objective that jointly enforces ordinal fidelity, models transcriptional bursts, and aligns semantic structures with cell types. Extensive experiments on three datasets demonstrate state-of-the-art performance, validating that Path2ST generates highly accurate and spatially coherent transcriptomic profiles. The related code is released at https://github.com/RuochenLiu23/Path2ST.
Existing generative models for earth observation (EO) predominantly rely on fine-tuning natural image priors, which limits their scalability and introduces perspective biases that conflict with geospatial constraints. To address this, we introduce GeoCore-9B, a 9-billion-parameter generative foundation model, which is the first of its scale to be trained from scratch exclusively on EO data. Unlike previous EO foundation models, GeoCore-9B is built upon a Flow Matching-based Diffusion Transformer (DiT) and natively conditions generation on text descriptions and continuous geospatial metadata, including ground sample distances, latitudes, and longitudes. To overcome the convergence and spatial disorientation challenges of training at this scale, we propose a Geospatial Semantic Alignment loss. This objective distills structural Earth surface priors (e.g., terrain and urban areas) from a frozen specialist teacher network, constraining the diffusion latent trajectory during training without adding inference overhead. Pre-trained on the global-scale Git-10M dataset, GeoCore-9B demonstrates strong downstream versatility. Beyond standard proxy generative tasks, we show that GeoCore-9B can be effectively adapted for practical EO applications, including highly challenging tasks such as cloud removal and SAR-to-optical cross-modal translation. Extensive evaluations confirm that GeoCore-9B establishes new state-of-the-art performance in both visual fidelity and geographic structural accuracy.
Joseph Boyd, Matthew Lyon, Martino Mansoldo +2q-bio.GN cs.AI
Spatial transcriptomics (ST) is a powerful tool for exploring biological properties dependent on structure, proximity, and interaction in tissue. The methods underpinning ST are developing rapidly but are limited in their ability to profile many thousands of genes at a subcellular scale. Although dissociated from tissue, it is known that the whole-transcriptome readouts of cells in single-cell RNA sequencing (scRNA-seq) retain information about their former in situ neighbourhoods, motivating computational methods to recover it. While paired ST and scRNA-seq datasets are scarce, each modality in its own right is abundantly available. We therefore propose to perform cross-modal translation between unpaired ST and scRNA-seq data. In this work we show that a single-cell foundation model can perform this translation via adversarial fine-tuning. We demonstrate that our method performs favourably against methods built for multi-omics translation.