biostudies-literatureBlick TQueensland Children's HospitalWesley Research InstituteCooper Rice-Brading Foundation, AustraliaRichie's Rainbow FoundationUniversity of QueenslandNational Breast Cancer FoundationMedical Research Future FundAustralian Academy of SciencesPA Research Foundationlqag007https://www.ebi.ac.uk/biostudies/studies/S-EPMC12838529biostudies-literatureUnknown8(1)We developed Standardised Minimum 3D Distance (SM3DD), an entirely cell segmentation/annotation-free approach to the analysis of spatial RNA datasets, using it to compare lung tissue from 16 clinically normal individuals to that of 18 SARS-CoV-2 patients who died from acute respiratory distress syndrome. RNA spatial coordinates were determined using the CosMx™ Spatial Molecular Imager (Bruker Spatial Biology, US). For each individual transcript location, we calculated the three-dimensional distances to the nearest transcript of each transcript type, standardising the distances to each transcript type. Mean SM3DDs were compared between normal and SARS-CoV-2 patients. Notably, hierarchical clustering of the directional log10(P) values organized genes by functionality, making it easier to intNAR genomics and bioinformaticsSM3DD with segmented PCA: a comprehensive method for interpreting 3D spatial transcriptomics.PMC1283852920194852023/IIRS0063Belz GTNam ALiang YBlick TGuimaraes PSFFraser JFMartins APCMonkman JKilgallon AKulasinghe Ade Noronha LNagashima STan CWKillingbeck EELeon MMachado-Souza CKim YCooper CPan LSouza-Fonseca-Guimaraes FfalseSM3DD with segmented PCA: a comprehensive method for interpreting 3D spatial transcriptomics.We developed Standardised Minimum 3D Distance (SM3DD), an entirely cell segmentation/annotation-free approach to the analysis of spatial RNA datasets, using it to compare lung tissue from 16 clinically normal individuals to that of 18 SARS-CoV-2 patients who died from acute respiratory distress syndrome. RNA spatial coordinates were determined using the CosMx™ Spatial Molecular Imager (Bruker Spatial Biology, US). For each individual transcript location, we calculated the three-dimensional distances to the nearest transcript of each transcript type, standardising the distances to each transcript type. Mean SM3DDs were compared between normal and SARS-CoV-2 patients. Notably, hierarchical clustering of the directional log10(P) values organized genes by functionality, making it easier to int2026-01-01T00:00:00Z2026 Mar2026-06-12T03:19:28.69Z2026-06-12T03:11:51.993ZS-EPMC128385294160873310.1093/nargab/lqag007