{
  "abstract": "Understanding the pathological significance of protein glycosylation and translating disease-associated glycan alterations into diagnostic and therapeutic opportunities require integrated analysis of glycans, their carrier glycoproteins, and spatial context. Here, we present an expanded multimodal glycoprotein analysis framework incorporating lectin-assisted imaging mass cytometry (Lectin-IMC) for stepwise discovery and spatial validation of disease-associated glyco-niches. Disease-associated glycans identified by laser microdissection-assisted lectin microarray (LMD-LMA) tissue glycome mapping are spatially evaluated by Lectin-IMC in relation to cell types and tissue microenvironments, and candidate carrier glycoproteins identified by MS-based glycoproteomics are subsequently incorporated for higher-order evaluation of glycan-protein-cell type relationships. Multiplex panel design is guided by LMA-based assessment of lectin-lectin interactions and biologically informed probe selection. Using a dilated cardiomyopathy model, we constructed a five-lectin panel centered on Wisteria floribunda agglutinin (WFA), which recognizes fibrosis-associated asialo N-glycans identified previously. Glycan-dependent WFA detection was validated by competitive inhibition and PNGase F treatment, and WFA-reactive glycans were spatially associated with fibrotic regions containing ACTA2VIM myofibroblast-like cells. Among six extracellular matrix glycoprotein candidates identified in WFA-binding fractions, periostin showed the strongest spatial correspondence with WFA-positive regions by pixel-based quantitative analysis and was further associated with ACTA2VIMWFA fibrotic microenvironments. The optimized Lectin-IMC panel was also transferable to a human FFPE cardiomyopathy specimen. Collectively, Lectin-IMC provides intuitive spatial visualization and interpretability of glycan-protein-cell type relationships and serves as an on-tissue spatial validation and prioritization layer within an iterative multimodal framework in which spatially defined glyco-niches can guide subsequent proteomic or glycoproteomic discovery.",
  "abstract_shown": true,
  "affiliations": [
    "National Institute of Advanced Industrial Science and Technology (AIST)"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "C. Nagai-Okatani"
    },
    {
      "name": "U. Horiuchi"
    },
    {
      "name": "P. Boottanun"
    },
    {
      "name": "K. Miyako"
    },
    {
      "name": "A. Kuno"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d6jkd5nyste42.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.19.752828",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.19.752828v1.full",
  "id": "d6jkd5nyste42",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.19.752828v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "1312|Glycosylation and Glycoproteins Research"
    ]
  ],
  "openalex": "W7213981682",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.19.752828v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d6jkd5nyste42.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:43Z",
      "native_id": "10.64898/2026.09.19.752828",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.19.752828v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Glycosylation and Glycoproteins Research",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Lectin-Assisted Imaging Mass Cytometry (Lectin-IMC) Enables Spatial Validation of Disease-Associated Glyco-Niches within a Multimodal Glycoprotein Analysis Framework",
  "title_text": "Lectin-Assisted Imaging Mass Cytometry (Lectin-IMC) Enables Spatial Validation of Disease-Associated Glyco-Niches within a Multimodal Glycoprotein Analysis Framework",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:43Z",
  "url": "https://research.draconitic.com/paper/d6jkd5nyste42",
  "venue": "bioRxiv",
  "versions": []
}