title: Defining the Human Brain Proteome Using Transcriptomics and Antibody-Based Profiling with a Focus on the Cerebral Cortex.
abstract: The mammalian brain is a complex organ composed of many specialized cells, harboring sets of both common, widely distributed, as well as specialized and discretely localized proteins. Here we focus on the human brain, utilizing transcriptomics and public available Human Protein Atlas (HPA) data to analyze brain-enriched (frontal cortex) polyadenylated messenger RNA and long non-coding RNA and generate a genome-wide draft of global and cellular expression patterns of the brain. Based on transcriptomics analysis of altogether 27 tissues, we have estimated that approximately 3% (n=571) of all protein coding genes and 13% (n=87) of the long non-coding genes expressed in the human brain are enriched, having at least five times higher expression levels in brain as compared to any of the other analyzed peripheral tissues. Based on gene ontology analysis and detailed annotation using antibody-based tissue micro array analysis of the corresponding proteins, we found the majority of brain-enriched protein coding genes to be expressed in astrocytes, oligodendrocytes or in neurons with molecular properties linked to synaptic transmission and brain development. Detailed analysis of the transcripts and the genetic landscape of brain-enriched coding and non-coding genes revealed brain-enriched splice variants. Several clusters of neighboring brain-enriched genes were also identified, suggesting regulation of gene expression on the chromatin level. This multi-angle approach uncovered the brain-enriched transcriptome and linked genes to cell types and functions, providing novel insights into the molecular foundation of this highly specialized organ.
authors.affiliation: Science for Life Laboratory, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden; Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Evelina
authors.initials: E
authors.lastname: Sjöstedt
authors.affiliation: Science for Life Laboratory, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Linn
authors.initials: L
authors.lastname: Fagerberg
authors.affiliation: Science for Life Laboratory, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Björn M
authors.initials: BM
authors.lastname: Hallström
authors.affiliation: Science for Life Laboratory, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Häggmark
authors.affiliation: Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mitsios
authors.affiliation: Science for Life Laboratory, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.affiliation: Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.affiliation: Science for Life Laboratory, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Mulder
mesh_terms: D000906:Antibodies / Q000737:chemistry*; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D040081:Protein Array Analysis / Q000379:methods*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D017423:Sequence Analysis, RNA / Q000379:methods; D059467:Transcriptome / Q000235:genetics*
chemical_list: D000906:Antibodies; D020543:Proteome