Neurological, neurodegenerative, and psychiatric disorders impose substantial morbidity and disability worldwide, yet their molecular basis remains incompletely understood, in part due to limited access to human brain tissue. The Danish Brain Collection, comprising brains from individuals who lived in Danish psychiatric institutions from the 1940s to the 1980s, represents a unique but largely untapped resource for retrospective molecular investigation. Here, we assess the feasibility of extracting and sequencing DNA and RNA from decades-old FFPE brain tissue.
We systematically evaluate how extraction and library preparation strategies influence nucleic acid yield and quality, and show that RNA end-repair prior to library preparation substantially enhances transcript diversity, improving data quality from highly degraded samples. Despite extensive fragmentation, we recover biologically informative transcriptomic profiles, including protein-coding and microRNA expression profiles that retain tissue-specific signatures. These results establish the Danish Brain Collection as a viable resource for genomic and transcriptomic analyses and demonstrate the broader potential of archival FFPE tissues for large-scale molecular studies.
EM-S acknowledges financial support from the Villum Fonden (Villum Experiment project no. 57875). NO is supported by the European Regional Development Fund project “Functional Omics Analysis of Metabolic Diseases to Advance Drug Discovery Research Excellence in LIOS - TARGETWISE” (no. 1.1.1.5/2/24/A/003). CK acknowledges financial support to this project through The Danish Association of Biomedical Laboratory Scientists.
Caroline Robinson Christiansen, Emily Hansen Firoozfard, Christina Kjær and Emilio Mármol-Sánchez contributed equally to this work. Department of Technology, Faculty of Health and Technology, University College Copenhagen, Copenhagen, Denmark Caroline Robinson Christiansen, Emily Hansen Firoozfard & Christina Kjaer Center for Evolutionary Hologenomics, GLOBE Institute, University of Copenhagen, Copenhagen, Denmark Caroline Robinson Christiansen, Emily Hansen Firoozfard, M. Mak & Emilio Mármol-Sánchez Department of Pathology, Rigshospitalet, The Capital Region of Denmark, Copenhagen, Denmark Metabolic Research Group, Latvian Institute of Organic Synthesis, Riga, Latvia University Museum, NTNU, Trondheim, Norway Department of Pathology, Esbjerg Hospital, University Hospital of Southern Denmark, Esbjerg, Denmark Department of Regional Health Research, University of Southern Denmark, Odense, Denmark BRIDGE (Brain Research - Inter Disciplinary Guided Excellence), Department of Clinical Research, University of Southern Denmark, Odense, Denmark Correspondence to Christina Kjaer or Emilio Mármol-Sánchez.
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