{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:01:27Z","timestamp":1780542087077,"version":"3.54.1"},"reference-count":40,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MPs"],"abstract":"<jats:p>Accurate deconvolution of bulk transcriptomes is essential for characterizing the breast cancer tumor microenvironment (TME), yet existing reference matrices incompletely capture tumor-specific cellular diversity. Here, we developed breast cancer\u2013specific multiresolution CIBERSORTx signature matrices from single-cell RNA sequencing data and systematically evaluated their analytical performance and interpretability. Major-, minor-, and subset-level matrices were constructed and assessed using pseudo-bulk mixtures and pure cell profiles, while biological and clinical coherence were evaluated in TCGA-BRCA and the I-SPY2 cohort. All matrices demonstrated high accuracy in reconstructing pseudo-bulk compositions, with performance declining at finer resolution. Spillover increased with granularity but was largely restricted within related lineages. Lineage-wise deconvolution modestly reduced spillover but consistently decreased accuracy, highlighting the importance of cross-lineage transcriptional contrast. In external datasets, most inferred cell populations showed biologically coherent associations with canonical markers and pathways, whereas some fine-resolution subsets exhibited non-canonical patterns, likely reflecting intra-lineage trade-offs or context-dependent transcriptional states. In the I-SPY2 cohort, plasmablasts and selected myeloid populations were positively associated with pathological complete response, whereas fibroblastic and perivascular-like populations showed negative associations. These findings establish a validated and interpretable resource for breast cancer TME deconvolution and clarify its performance characteristics and limitations.<\/jats:p>","DOI":"10.3390\/mps9030088","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:08:02Z","timestamp":1780535282000},"page":"88","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Multiresolution Breast Cancer CIBERSORTx Resource Validated for Accuracy, Interpretive Limits, and Biological and Clinical Coherence in Tumor Microenvironment Deconvolution"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6934-8588","authenticated-orcid":false,"given":"Toru","family":"Hanamura","sequence":"first","affiliation":[{"name":"Department of Breast Oncology, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Takase","sequence":"additional","affiliation":[{"name":"Department of Life Science Support, Research Innovation Center, University Hospitals Sector, Tokai University, Isehara 259-1193, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1404-1570","authenticated-orcid":false,"given":"Masanori","family":"Oshi","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6732-8527","authenticated-orcid":false,"given":"Naoki","family":"Niikura","sequence":"additional","affiliation":[{"name":"Department of Breast Oncology, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/S0140-6736(16)31891-8","article-title":"Breast cancer","volume":"389","author":"Harbeck","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12943-023-01805-y","article-title":"Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer","volume":"22","author":"Ye","year":"2023","journal-title":"Mol. 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