{"entity": "publication", "iuid": "6e4add0553434fad9bcdef0ea5b6e455", "timestamp": "2026-10-24T09:22:58.035Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6e4add0553434fad9bcdef0ea5b6e455.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6e4add0553434fad9bcdef0ea5b6e455"}}, "title": "A Multi-Omic Phenobank Reveals Axes of Glioblastoma Growth, Invasion, and Therapeutic Vulnerability.", "authors": [{"family": "Krona", "given": "Cecilia", "initials": "C"}, {"family": "Kundu", "given": "Soumi", "initials": "S"}, {"family": "Rosen", "given": "Emil", "initials": "E"}, {"family": "Kruse", "given": "Filippa", "initials": "F"}, {"family": "Skepp\u00e5s", "given": "Madeleine", "initials": "M"}, {"family": "Baba\u010di\u0107", "given": "Haris", "initials": "H"}, {"family": "Larsson", "given": "Ida", "initials": "I"}, {"family": "Elfineh", "given": "Ludmila", "initials": "L"}, {"family": "L\u00fc", "given": "Maya Jeje Schuan", "initials": "MJS"}, {"family": "Conde", "given": "Maria Escriva", "initials": "ME"}, {"family": "Elgendy", "given": "Ramy", "initials": "R"}, {"family": "Dave", "given": "Zankruti", "initials": "Z"}, {"family": "Doroszko", "given": "Milena", "initials": "M"}, {"family": "Rut-Halldorsdottir", "given": "Katrin", "initials": "K"}, {"family": "Cao", "given": "Xiaofang", "initials": "X"}, {"family": "Ramachandra", "given": "Rashmi", "initials": "R"}, {"family": "Olausson", "given": "Karl Holmberg", "initials": "KH"}, {"family": "Nilsson", "given": "Mats", "initials": "M"}, {"family": "Weischenfeldt", "given": "Joachim", "initials": "J"}, {"family": "Wikstr\u00f6m", "given": "Johan", "initials": "J"}, {"family": "Pernemalm", "given": "Maria", "initials": "M"}, {"family": "Sundstr\u00f6m", "given": "Anders", "initials": "A"}, {"family": "Uppman", "given": "Irem", "initials": "I"}, {"family": "Mangukiya", "given": "Hitesh Bhagavanbhai", "initials": "HB"}, {"family": "Nelander", "given": "Sven", "initials": "S"}], "type": "journal article", "published": "2026-10-12", "journal": {"title": "Neuro-oncology", "issn": "1523-5866", "issn-l": "1522-8517"}, "abstract": "Glioblastoma (GBM) invasion is clinically decisive but difficult to model systematically. Existing patient-derived xenograft (PDX) resources rarely couple reproducible in vivo invasion phenotypes with matched multi-omic profiles at scale, limiting mechanistic insight and phenotype-informed therapeutic hypotheses.\n\nWe established the HGCC Phenobank, comprising 65 patient-derived GBM stem-like cultures with matched multi-omic profiling and orthotopic engraftment in 449 mice. Blinded histopathology quantified ten invasion traits per case. These phenotypes were integrated with RNA sequencing, DNA methylation, and mass-spectrometry-based proteomics. Multi-Omic Factor Analysis (MOFA) identified latent molecular programs. Phenotype-specific RNA signatures were matched to LINCS drug-perturbation profiles and validated in 3D gliomasphere and ex vivo brain-slice assays.\n\nTwo dominant, reproducible invasion modes emerged across models: diffuse parenchymal infiltration and perivascular/condensed growth. Proneural cultures formed more aggressive tumors in immunodeficient mice, and mouse survival showed a modest correlation with patient survival in matched cases (Pearson r=0.1832, p=0.045). MOFA identified 15 latent factors; Factor 1, marked by ASCL1/OLIG1/OLIG2 programs across multiple molecular layers, was associated with increased tumor formation and diffuse invasion in mice. Higher Factor 1 scores were associated with significantly longer postoperative survival in both the matched patient cohort (p = 0.00018) and TCGA (p = 0.017), although Factor 1 was not associated with survival of the xenografted mice. Drug-signature matching separated mechanisms targeting diffuse versus perivascular invasion. Experimental validation confirmed phenotype-selective sensitivities, and inhibitors PIK-75 and buparlisib suppressed invasion dynamics across representative models in 3D and brain-slice assays.\n\nThe HGCC Phenobank provides the first openly available PDX resource that systematically links GBM invasion phenotypes to multi-omic programs and therapeutic predictions. This framework enables reproducible model selection, mechanistic dissection of invasion modes, and phenotype-guided therapeutic discovery.", "doi": "10.1093/neuonc/noag255", "pmid": "42865025", "labels": {"National Genomics Infrastructure": "Service", "NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "8911843"}], "notes": [], "created": "2026-10-23T12:23:00.110Z", "modified": "2026-10-23T12:23:00.120Z"}