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This research introduces MSGR, an AI model that leverages Gene Ontology hierarchies as structural priors to significantly improve the prediction of spatial gene expression from histopathology images. By organizing genes into functional trees rather than treating them as flat vectors, the method effectively captures biological dependencies without requiring modifications to image processing architectures. The results demonstrate that incorporating this specific ontological structure yields consistent performance gains over both unstructured baselines and state-of-the-art generative models across nine datasets.
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Gene Ontology-Guided Hierarchical Spatial Gene Expression Prediction from Histopathology Images

arXiv3 min read

arXiv:2608.00405v1 Announce Type: new Abstract: Predicting spatial gene expression from histopathology images enables large-scale transcriptomic profiling without the cost of direct measurement. Existing methods decode the target gene set as a flat, unstructured vector, ignoring the inter-gene dependencies arising from shared biological pathways and regulatory programs. Without explicit structural guidance, models must infer these dependencies entirely from limited paired data, constraining prediction quality. We propose MSGR (Multi-Scale Gene Refiner), which bridges this gap by incorporating the Gene Ontology (GO), a curated functional hierarchy of genes, as an explicit structural prior. MSGR organizes target genes into a four-level GO tree. Its GO-guided decoder then progressively refines predictions from coarse functional domains to fine individual genes via residual corrections under scale-weighted supervision. Operating solely on the gene side, the GO-guided decoder serves as a seamless plug-in replacement that consistently improves existing architectures without requiring any image-side modifications. Extensive experiments on nine datasets from the HEST-1k benchmark provide empirical evidence for two central claims: GO-structured decoding consistently outperforms flat decoding, even against a state-of-the-art generative baseline, and the gain is attributable to biological ontology structure rather than hierarchical decomposition per se, as confirmed by a +0.027 margin over a structurally equivalent random hierarchy.

Abstract:Predicting spatial gene expression from histopathology images enables large-scale transcriptomic profiling without the cost of direct measurement. Existing methods decode the target gene set as a flat, unstructured vector, ignoring the inter-gene dependencies arising from shared biological pathways and regulatory programs. Without explicit structural guidance, models must infer these dependencies entirely from limited paired data, constraining prediction quality. We propose MSGR (Multi-Scale Gene Refiner), which bridges this gap by incorporating the Gene Ontology (GO), a curated functional hierarchy of genes, as an explicit structural prior. MSGR organizes target genes into a four-level GO tree. Its GO-guided decoder then progressively refines predictions from coarse functional domains to fine individual genes via residual corrections under scale-weighted supervision. Operating solely on the gene side, the GO-guided decoder serves as a seamless plug-in replacement that consistently improves existing architectures without requiring any image-side modifications. Extensive experiments on nine datasets from the HEST-1k benchmark provide empirical evidence for two central claims: GO-structured decoding consistently outperforms flat decoding, even against a state-of-the-art generative baseline, and the gain is attributable to biological ontology structure rather than hierarchical decomposition per se, as confirmed by a +0.027 margin over a structurally equivalent random hierarchy.

Accepted by ACM MM 2026. Code: this https URL

Artificial Intelligence (cs.AI); Genomics (q-bio.GN)

arXiv:2608.00405 [cs.AI]

(or arXiv:2608.00405v1 [cs.AI] for this version)

https://doi.org/10.48550/arXiv.2608.00405 Focus to learn more arXiv-issued DOI via DataCite (pending registration)

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Full text under the publisher's open licence · 300 words

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