haCCA: multi-module Integration of spot-based spatial transcriptomes and metabolomesDownload PDF Download PDF ArticleOpen accessPublished: 17 January 2026Jing Xu ORCID: orcid.org/0009-0004-7045-81611,2,3 na1,Xiao-Tian Shen1,4 na1,Chen Zhang1,4 na1,Xiao-Yun Zhang5,Zhou-Qing Chen6,Hu-Liang Jia1,4 &…Lu-Yu Yang3,4 Communications Biology , Article number: (2026) Cite this article We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.SubjectsChemical biologyData integrationMetabolomicsAbstractSpatial transcriptomes and Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) measures mRNA expression and mass-to-charge (m/z) spectra on thousands of spots along with the spatial coordinates. Integrating spatial transcriptomes and MALDI-MSI is challenge due to no shared coordinates or features. We present \({haCCA}\), a workflow to integrate spatial transcriptomes and metabolomes.\(h{aCCA}\) take advantage of modified spatial registration and shared latent space constructed by CCA(Canonical Correlation Analysis)-mediated transfer of high-correlated feature pairs. It enables the simultaneous spatial profiling of metabolites and transcriptome across neighbor tissue section. We tested \({haCCA}\) on pseudo and real data, proving that \(h{aCCA}\) improved the integration accuracy than existing methods. We further applicated \(h{aCCA}\) on a custom dataset from Akt/Yap driven Padi4-/-ICC model which lacks neutrophil extracellular traps(NETs) and revealing the spatial distribution of both mRNA and metabolites,enabled both in situ and in vivo exploration of the metabolic alteration effect of NETs on ICC. A Python package was developed to facilitate its use.Data availabilityThe MALDI mass spectrometry imaging (MALDI-MSI) data and spatial transcriptomics data generated in this study have been deposited in the figshare database (https://doi.org/10.6084/m9.figshare.28320587). Details of the public datasets used in this study are available in the “Methods” section.Code availabilityAll code for the haCCA workflow and analyses presented in this manuscript is publicly available without restrictions at GitHub: https://github.com/LittleLittleCloud/haCCA. https://doi.org/10.5281/zenodo.1778597031.ReferencesVandereyken, K. et al. Methods and applications for single-cell and spatial multi-omics. Nat. Rev. Genet. 24, 494–515 (2023).Google Scholar Vicari, M.M. et al. Spatial Multimodal Analysis of Transcriptomes and Metabolomes in Tissues Mendeley Data, V1, https://doi.org/10.17632/w7nw4km7xd.1 (2023).Argelaguet, R. et al. Computational principles and challenges in single-cell data integration. Nat. 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This manuscript was supported by Natural science foundation of Shanghai (No. 24ZR1408800 to L.-Y.Y.), the National Natural Science Foundation of China (No. 82002532 to L.-Y.Y., No 82201445 to Z.-Q.C., No 82503435 to X.-T.S.), China Postdoctoral Science Foundation (2024M750533 to X.-T.S.), Shanghai Anticancer Association Chuying Project (SACA-CY22C10 to X.-T.S.).Author informationAuthor notesThese authors contributed equally: Jing Xu, Xiao-Tian Shen, Chen Zhang.Authors and AffiliationsDepartment of General Surgery, Huashan Hospital, Fudan University, Shanghai, ChinaJing Xu, Xiao-Tian Shen, Chen Zhang & Hu-Liang JiaDepartment of Dermatology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine No, Shanghai, ChinaJing XuDepartment of Dermatology, Huashan Hospital, Fudan University, Shanghai, ChinaJing Xu & Lu-Yu YangCancer Metastasis Institute, Fudan University, Shanghai, ChinaXiao-Tian Shen, Chen Zhang, Hu-Liang Jia & Lu-Yu YangMicrosoft Co Seattle, Seattle, WA, USAXiao-Yun ZhangDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaZhou-Qing ChenAuthorsJing XuView author publicationsSearch author on:PubMed Google ScholarXiao-Tian ShenView author publicationsSearch author on:PubMed Google ScholarChen ZhangView author publicationsSearch author on:PubMed Google ScholarXiao-Yun ZhangView author publicationsSearch author on:PubMed Google ScholarZhou-Qing ChenView author publicationsSearch author on:PubMed Google ScholarHu-Liang JiaView author publicationsSearch author on:PubMed Google ScholarLu-Yu YangView author publicationsSearch author on:PubMed Google ScholarContributionsLu-Yu Yang, Zhou-Qing Chen and Hu-Liang Jia designed and supervised the study and revised the manuscript; Jing Xu, Xiao-Tian Shen and Chen Zhang performed the experiments, Xiao-Yun Zhang and Xiao-Tian Shen write the code and provided helps in experimental techniques as well as data analysis, Xiao-Tian Shen prepared the manuscript.Corresponding authorsCorrespondence to Zhou-Qing Chen, Hu-Liang Jia or Lu-Yu Yang.Ethics declarationsCompeting interestsThe authors declare no competing interests.Peer reviewPeer review informationCommunications Biology thanks Chin Wee Tan and Joe Wandy for their contribution to the peer review of this work. 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