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1.
  • Owe-Larsson, Björn, et al. (författare)
  • Increased plasma levels of thioredoxin-1 in patients with first episode psychosis and long-term schizophrenia.
  • 2011
  • Ingår i: Progress in neuro-psychopharmacology & biological psychiatry. - 1878-4216. ; 35:4, s. 1117-21
  • Tidskriftsartikel (refereegranskat)abstract
    • Excessive level of radicals and/or dysfunctional antioxidant response, oxidative stress, is implicated in the pathogenesis of schizophrenia. A condition of oxidative stress has been detected in the brain, peripheral tissues and fluids including plasma. Plasma thioredoxin-1 (Trx1) is well characterized and a putative marker for oxidative stress and recently shown to be increased in plasma at the onset of schizophrenia. The present study aimed to explore whether Trx1 can be used as a marker to identify schizophrenic patients at the time-point when patients have their first episode of psychosis as compared to patients with long-term schizophrenia and mentally healthy patients, respectively. Plasma samples obtained from 18 patients at first episode of psychosis, from 49 long-term schizophrenic patients and from 20 mentally healthy controls (admitted with minor physical injury to the general ward) where analyzed by ELISA for Trx1. The patients with first episode of psychosis were diagnosed at least 6months later and shown to constitute various psychotic syndromes, including schizophrenia, or affective disorder. The concentration of Trx1 in the patients with first episode of psychosis was 1.5±1.0ng/ml and 0.8±0.6ng/ml in controls. In the long-term schizophrenic patients the plasma concentration was 1.5±0.7. The differences between the groups of acute psychotic or long-term schizophrenia patients to controls were significant (p<0.016 and p<0.001, respectively). Our data indicate that Trx1 may not be used as an early marker to identify schizophrenic patients in a mixed population of first episode psychotic patients. Further, Trx1 did not discriminate with reliable accuracy patients with psychotic disorder from mentally healthy controls on an individual basis due to overlap in levels of Trx1. However, our observations show that psychotic patients in general are in a significant long-term condition of oxidative stress, with possible implications for the profound morbidity and mortality found in this patient population.
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2.
  • Uhlen, Mathias, et al. (författare)
  • The human secretome
  • 2019
  • Ingår i: Science signaling. - : NLM (Medline). - 1937-9145 .- 1945-0877. ; 12:609
  • Tidskriftsartikel (refereegranskat)abstract
    • The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
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3.
  • Danielsson, Frida, et al. (författare)
  • Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model
  • 2013
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 110:17, s. 6853-6858
  • Tidskriftsartikel (refereegranskat)abstract
    • The transformation of normal cells to malignant, metastatic tumor cells is a multistep process caused by the sequential acquirement of genetic changes. To identify these changes, we compared the transcriptomes and levels and distribution of proteins in a four-stage cell model of isogenically matched normal, immortalized, transformed, and metastatic human cells, using deep transcriptome sequencing and immunofluorescence microscopy. The data show that similar to 6% (n = 1,357) of the human protein-coding genes are differentially expressed across the stages in the model. Interestingly, the majority of these genes are down-regulated, linking malignant transformation to dedifferentiation. The up-regulated genes are mainly components that control cellular proliferation, whereas the down-regulated genes consist of proteins exposed on or secreted from the cell surface. As many of the identified gene products control basic cellular functions that are defective in cancers, the data provide candidates for follow-up studies to investigate their functional roles in tumor formation. When we further compared the expression levels of four of the identified proteins in clinical cancer cohorts, similar differences were observed between benign and cancer cells, as in the cell model. This shows that this comprehensive demonstration of the molecular changes underlying malignant transformation is a relevant model to study the process of tumor formation.
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4.
  • Fagerberg, Linn, et al. (författare)
  • Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
  • 2014
  • Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
  • Tidskriftsartikel (refereegranskat)abstract
    • Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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5.
  • Fagerberg, Linn, et al. (författare)
  • Contribution of Antibody-based Protein Profiling to the Human Chromosome-centric Proteome Project (C-HPP)
  • 2013
  • Ingår i: Journal of Proteome Research. - : The American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:6, s. 2439-2448
  • Tidskriftsartikel (refereegranskat)abstract
    • A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease. Here, we report on the protein evidence for all genes predicted from the genome sequence based on manual annotation from literature (UniProt), antibody-based profiling in cells, tissues and organs and analysis of the transcript profiles using next generation sequencing in human cell lines of different origins. We estimate that there is good evidence for protein existence for 69% (n = 13985) of the human protein-coding genes, while 23% have only evidence on the RNA level and 7% still lack experimental evidence. Analysis of the expression patterns shows few regards to protein evidence is visualized in a chromosome-centric manner as part of a new version of the Human Protein Atlas (www.proteinatlas.org).
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6.
  • Geiger, T., et al. (författare)
  • Initial quantitative proteomic map of 28 mouse tissues using the SILAC mouse
  • 2013
  • Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 12:6, s. 1709-1722
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying the building blocks of mammalian tissues is a precondition for understanding their function. In particular, global and quantitative analysis of the proteome of mammalian tissues would point to tissue-specific mechanisms and place the function of each protein in a whole-organism perspective. We performed proteomic analyses of 28 mouse tissues using high-resolution mass spectrometry and used a mix of mouse tissues labeled via stable isotope labeling with amino acids in cell culture as a "spike-in" internal standard for accurate protein quantification across these tissues. We identified a total of 7,349 proteins and quantified 6,974 of them. Bioinformatic data analysis showed that physiologically related tissues clustered together and that highly expressed proteins represented the characteristic tissue functions. Tissue specialization was reflected prominently in the proteomic profiles and is apparent already in their hundred most abundant proteins. The proportion of strictly tissue-specific proteins appeared to be small. However, even proteins with household functions, such as those in ribosomes and spliceosomes, can have dramatic expression differences among tissues. We describe a computational framework with which to correlate proteome profiles with physiological functions of the tissue. Our data will be useful to the broad scientific community as an initial atlas of protein expression of a mammalian species.
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7.
  • Kampf, C., et al. (författare)
  • The human liver-specific proteome defined by transcriptomics and antibody-based profiling
  • 2014
  • Ingår i: FASEB Journal. - 1530-6860 .- 0892-6638. ; 28:7, s. 2901-2914
  • Tidskriftsartikel (refereegranskat)abstract
    • Human liver physiology and the genetic etiology of the liver diseases can potentially be elucidated through the identification of proteins with enriched expression in the liver. Here, we combined data from RNA sequencing (RNA-Seq) and antibody-based immunohistochemistry across all major human tissues to explore the human liver proteome with enriched expression, as well as the cell type-enriched expression in hepatocyte and bile duct cells. We identified in total 477 protein-coding genes with elevated expression in the liver: 179 genes have higher expression as compared to all the other analyzed tissues; 164 genes have elevated transcript levels in the liver shared with at least one other tissue type; and an additional 134 genes have a mild level of increased expression in the liver. We identified the precise localization of these proteins through antibody-based protein profiling and the subcellular localization of these proteins through immunofluorescent-based profiling. We also identified the biological processes and metabolic functions associated with these proteins, investigated their contribution in the occurrence of liver diseases, and identified potential targets for their treatment. Our study demonstrates the use of RNA-Seq and antibody-based immunohistochemistry for characterizing the human liver proteome, as well as the use of tissue-specific proteins in identification of novel drug targets and discovery of biomarkers.
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8.
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9.
  • Magnusson, Kristina, et al. (författare)
  • SATB2 in Combination With Cytokeratin 20 Identifies Over 95% of all Colorectal Carcinomas
  • 2011
  • Ingår i: American Journal of Surgical Pathology. - : Lippincott Williams & Wilkins. - 0147-5185 .- 1532-0979. ; 35:7, s. 937-948
  • Tidskriftsartikel (refereegranskat)abstract
    • The special AT-rich sequence-binding protein 2 (SATB2), a nuclear matrix-associated transcription factor and epigenetic regulator, was identified as a tissue type-specific protein when screening protein expression patterns in human normal and cancer tissues using an antibody-based proteomics approach. In this respect, the SATB2 protein shows a selective pattern of expression and, within cells of epithelial lineages, SATB2 expression is restricted to glandular cells lining the lower gastrointestinal tract. The expression of SATB2 protein is primarily preserved in cancer cells of colorectal origin, indicating that SATB2 could function as a clinically useful diagnostic marker to distinguish colorectal cancer (CRC) from other types of cancer. The aim of this study was to further explore and validate the specific expression pattern of SATB2 as a clinical biomarker and to compare SATB2 with the well-known cytokeratin 20 (CK20). Immunohistochemistry was used to analyze the extent of SATB2 expression in tissue microarrays with tumors from 9 independent cohorts of patients with primary and metastatic CRCs (n = 1882). Our results show that SATB2 is a sensitive and highly specific marker for CRC with distinct positivity in 85% of all CRCs, and that SATB2 and/or CK20 was positive in 97% of CRCs. In conclusion, the specific expression of SATB2 in a large majority of CRCs suggests that SATB2 can be used as an important complementary tool for the differential diagnosis of carcinoma of unknown primary origin.
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10.
  • Thul, Peter J., et al. (författare)
  • A subcellular map of the human proteome
  • 2017
  • Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 356:6340
  • Tidskriftsartikel (refereegranskat)abstract
    • Resolving the spatial distribution of the human proteome at a subcellular level can greatly increase our understanding of human biology and disease. Here we present a comprehensive image-based map of subcellular protein distribution, the Cell Atlas, built by integrating transcriptomics and antibody-based immunofluorescence microscopy with validation by mass spectrometry. Mapping the in situ localization of 12,003 human proteins at a single-cell level to 30 subcellular structures enabled the definition of the proteomes of 13 major organelles. Exploration of the proteomes revealed single-cell variations in abundance or spatial distribution and localization of about half of the proteins to multiple compartments. This subcellular map can be used to refine existing protein-protein interaction networks and provides an important resource to deconvolute the highly complex architecture of the human cell.
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