{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:26:14Z","timestamp":1788279974244,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"49","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The molecular pathogenesis of infectious diseases and cancer is orchestrated by nanoscale of host and microbial RNA transcripts within the tissue microenvironment. Nevertheless, spatially resolving the comprehensive transcriptional landscape within complex clinical tissues, like formalin\u2010fixed paraffin\u2010embedded (FFPE) specimens, still poses a formidable challenge. Here, we present spRandom\u2010seq, a random primer\u2010based spatial total RNA sequencing technology designed to spatially resolve complete transcriptomes from host, bacteria, and even nanoscale viruses in FFPE tissues. Capitalizing on the random primer design, our technology not only facilitated the discovery of specific lncRNAs and alternative splicing events in mouse brain and olfactory bulb, but also delineated pronounced spatial heterogeneity in clinical FFPE sections\u2014across distinct tumor regions in breast cancer and microbial infection sites in\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    \u2010infected tissues. Importantly, integrated analysis of host and viral RNAs in FFPE samples from hepatitis B virus (HBV)\u2011positive hepatocellular carcinoma (HCC) demonstrated that complement and coagulation pathways were specifically activated across expansive HBV\u2011infected tumor areas, which also exhibited an increased burden of copy number variations (CNVs). Owing to its compatibility with existing spatial transcriptomics platforms and minimal operational complexity, spRandom\u2010seq represents a practical and scalable approach for clinical pathology applications and infection diagnostics.\n                  <\/jats:p>","DOI":"10.1002\/smll.74487","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:48:52Z","timestamp":1784630932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatial Total RNA Sequencing of Formalin\u2010Fixed Paraffin\u2010Embedded Tissue by spRandom\u2010seq"],"prefix":"10.1002","volume":"22","author":[{"given":"Yuan","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine of The First Affiliated Hospital &amp; Liangzhu Laboratory Zhejiang University School of Medicine  Hangzhou China"},{"name":"M20 Genomics  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaye","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine of The First Affiliated Hospital &amp; Liangzhu Laboratory Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunji","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Biomedical Engineering and Instrument Science Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery and Liver Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexiao","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine of The First Affiliated Hospital &amp; Liangzhu Laboratory Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhu","sequence":"additional","affiliation":[{"name":"M20 Genomics  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haide","family":"Chen","sequence":"additional","affiliation":[{"name":"M20 Genomics  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyi","family":"Zhu","sequence":"additional","affiliation":[{"name":"M20 Genomics  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Dong","sequence":"additional","affiliation":[{"name":"M20 Genomics  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liang","sequence":"additional","affiliation":[{"name":"M20 Genomics  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong","family":"Liu","sequence":"additional","affiliation":[{"name":"M20 Genomics  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziye","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine of The First Affiliated Hospital &amp; Liangzhu Laboratory Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"M20 Genomics  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2820-4243","authenticated-orcid":false,"given":"Yongcheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine of The First Affiliated Hospital &amp; Liangzhu Laboratory Zhejiang University School of Medicine  Hangzhou China"},{"name":"College of Biomedical Engineering and Instrument Science Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010021\u201001131\u2010y"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1706920115"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.84"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi4882"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adr0932"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010023\u201001988\u20101"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010023\u201001979\u20102"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010025\u201001170\u20108"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010025\u201001181\u20105"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201040137\u20109"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201038409\u20105"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.08.008"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010016\u20100904\u20105"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","unstructured":"G.Prezza T.Heckel S.Dietrich C.Homberger A. 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