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  • 1.
    Agaton, Charlotta
    et al.
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Unneberg, Per
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Sievertzon, Maria
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Holmberg, Anders
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Ehn, Maria
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Larsson, Magnus
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Odeberg, Jacob
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Uhlén, Mathias
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Gene expression analysis by signature pyrosequencing2002Ingår i: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 289, nr 1-2, s. 31-39Artikel i tidskrift (Refereegranskat)
    Abstract [en]

     We describe a novel method for transcript profiling based on high-throughput parallel sequencing of signature tags using a non-gel-based microtiter plate format. The method relies on the identification of cDNA clones by pyrosequencing of the region corresponding to the 3'-end of the mRNA preceding the poly(A) tail. Simultaneously, the method can be used for gene discovery, since tags corresponding to unknown genes can be further characterized by extended sequencing. The protocol was validated using a model system for human atherosclerosis. Two 3'-tagged cDNA libraries, representing macrophages and foam cells, which are key components in the development of atherosclerotic plaques, were constructed using a solid phase approach. The libraries were analyzed by pyrosequencing, giving on average 25 bases. As a control, conventional expressed sequence tag (EST) sequencing using slab gel electrophoresis was performed. Homology searches were used to identify the genes corresponding to each tag. Comparisons with EST sequencing showed identical, unique matches in the majority of cases when the pyrosignature was at least 18 bases. A visualization tool was developed to facilitate differential analysis using a virtual chip format. The analysis resulted in identification of genes with possible relevance for development of atherosclerosis. The use of the method for automated massive parallel signature sequencing is discussed.

  • 2. Agerberth, B
    et al.
    Gunne, H
    Odeberg, Jacob
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Kogner, P
    Boman, H G
    Gudmundsson, G H
    FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis.1995Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 92, nr 1, s. 195-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PR-39, a proline/arginine-rich peptide antibiotic, has been purified from pig intestine and later shown to originate in the bone marrow. Intending to isolate a clone for a human counterpart to PR-39, we synthesized a PCR probe derived from the PR-39 gene. However, when this probe was used to screen a human bone marrow cDNA library, eight clones were obtained with information for another putative human peptide antibiotic, designated FALL-39 after the first four residues. FALL-39 is a 39-residue peptide lacking cysteine and tryptophan. All human peptide antibiotics previously isolated (or predicted) belong to the defensin family and contain three disulfide bridges. The clone for prepro-FALL-39 encodes a cathelin-like precursor protein with 170 amino acid residues. We have postulated a dibasic processing site for the mature FALL-39 and chemically synthesized the putative peptide. In basal medium E, synthetic FALL-39 was highly active against Escherichia coli and Bacillus megaterium. Residues 13-34 in FALL-39 can be predicted to form a perfect amphiphatic helix, and CD spectra showed that medium E induced 30% helix formation in FALL-39. RNA blot analyses disclosed that the gene for FALL-39 is expressed mainly in human bone marrow and testis.

  • 3.
    Ahmadian, Afshin
    et al.
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Gharizadeh, B.
    O'Meara, D.
    Odeberg, Jacob
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Genotyping by apyrase-mediated allele-specific extension2001Ingår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 29, nr 24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This report describes a single-step extension approach suitable for high-throughput single-nucleotide polymorphism typing applications. The method relies on extension of paired allele-specific primers and we demonstrate that the reaction kinetics were slower for mismatched configurations compared with matched configurations. In our approach we employ apyrase, a nucleotide degrading enzyme, to allow accurate discrimination between matched and mismatched primer-template configurations. This apyrase-mediated allele-specific extension (AMASE) protocol allows incorporation of nucleotides when the reaction kinetics are fast (matched 3'-end primer) but degrades the nucleotides before extension when the reaction kinetics are slow (mismatched 3'-end primer). Thus, AMASE circumvents the major limitation of previous allele-specific extension assays in which slow reaction kinetics will still give rise to extension products from mismatched 3'-end primers, hindering proper discrimination. It thus represents a significant improvement of the allele-extension method. AMASE was evaluated by a bioluminometric assay in which successful incorporation of unmodified nucleotides is monitored in real-time using an enzymatic cascade.

  • 4.
    Ahmadian, Afshin
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Ren, Z P
    Williams, Cecilia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Pontén, F
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Pontén, J
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Lundeberg, Joakim
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Genetic instability in the 9q22.3 region is a late event in the development of squamous cell carcinoma.1998Ingår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 17, nr 14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Squamous cell carcinoma (SCC) of the skin represents a group of neoplasms which is associated with exposure to UV light. Recently, we obtained data suggesting that invasive skin cancer and its precursors derive from one original neoplastic clone. Here, the analysis were extended by loss of heterozygosity (LOH) analysis in the chromosome 9q22.3 region. A total of 85 samples, taken from twenty-two sections of sun-exposed sites, corresponding to normal epidermis, morphological normal cells with positive immuno-staining for the p53 protein (p53 patches), dysplasias, cancer in situ (CIS) and squamous cell carcinomas (SCC) of the skin were analysed. Overall, about 70% of p53 patches had mutations in the p53 gene but not LOH in the p53 gene or 9q22.3 region. Approximately 70% of the dysplasias showed p53 mutations of which about 40% had LOH in the p53 region but not in the 9q22.3 region. In contrast, about 65% of SCC and CIS displayed LOH in the 9q22.3 region, as well as frequent (80%) mutations and/or LOH in the p53 gene. These findings strongly suggest that alterations in the p53 gene is an early event in the progression towards SCC, whereas malignant development involves LOH and alterations in at least one (or several) tumor suppressor genes located in chromosome 9q22.3.

  • 5.
    Andersen, Malin
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Engström, Pär
    Lithwick, Stuart
    Arenillas, David
    Eriksson, Per
    Lenhard, Boris
    Wasserman, Wyeth
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    In silico detection of sequence variations modifying transcriptional regulation2008Ingår i: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 4, nr 1, s. e5-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN ( regulatory analysis of variation in enhancers). The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation.

  • 6.
    Andersen, Malin
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Fisher, Rachel
    Holmberg, Kristina
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Samnegård, Ann
    Hamsten, Anders
    Eriksson, Per
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    In silico prediction of regulatory SNPs in the CD36 gene and evaluation of their effect in a clinical study for coronary artery diseaseManuskript (Övrigt vetenskapligt)
  • 7.
    Andersen, Malin
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Lenhard, Boris
    Whatling, Carl
    Eriksson, Per
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Alternative promoter usage of the membrane glycoprotein CD362006Ingår i: BMC Molecular Biology, ISSN 1471-2199, E-ISSN 1471-2199, Vol. 7, s. 8-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: CD36 is a membrane glycoprotein involved in a variety of cellular processes such as lipid transport, immune regulation, hemostasis, adhesion, angiogenesis and atherosclerosis. It is expressed in many tissues and cell types, with a tissue specific expression pattern that is a result of a complex regulation for which the molecular mechanisms are not yet fully understood. There are several alternative mRNA isoforms described for the gene. We have investigated the expression patterns of five alternative first exons of the CD36 gene in several human tissues and cell types, to better understand the molecular details behind its regulation.

    Results: We have identified one novel alternative first exon of the CD36 gene, and confirmed the expression of four previously known alternative first exons of the gene. The alternative transcripts are all expressed in more than one human tissue and their expression patterns vary highly in skeletal muscle, heart, liver, adipose tissue, placenta, spinal cord, cerebrum and monocytes. All alternative first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins. The alternative promoters lack TATA-boxes and CpG islands. The upstream region of exon 1b contains several features common for house keeping gene and monocyte specific gene promoters.

    Conclusion: Tissue-specific expression patterns of the alternative first exons of CD36 suggest that the alternative first exons of the gene are regulated individually and tissue specifically. At the same time, the fact that all first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins may suggest that the alternative first exons are coregulated in this cell type and environmental condition. The molecular mechanisms regulating CD36 thus appear to be unusually complex, which might reflect the multifunctional role of the gene in different tissues and cellular conditions.

  • 8. Andersson, T.
    et al.
    Borang, S.
    Larsson, M.
    Wirta, V.
    Wennborg, A.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Odeberg, Jacob
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Novel candidate genes for atherosclerosis are identified by representational difference analysis-based transcript profiling of cholesterol-loaded macrophages2001Ingår i: Pathobiology (Basel), ISSN 1015-2008, E-ISSN 1423-0291, Vol. 69, nr 6, s. 304-314Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To analyze the early gene expression in macrophages accompanying the phenotypic changes into foam cells upon exposure to oxidized low-density lipoprotein. To identify candidate genes and markers for further studies into the pathogenesis of atherosclerosis. Methods: Cells of the monocytic cell line THP-1 were activated by PMA and exposed to oxidized low-density lipoprotein. Gene expression profiles were investigated after 24 h, using a solid phase cDNA representational difference analysis (RDA) method and shotgun sequencing. Results were verified by microarray hybridization, and analyzed in the virtual chip display of a novel software tool for transcript profile exploration. Results: By comparing transcript profiles of exposed/unexposed cells, 1,984 transcript sequences, representing a total of 921 genes with altered expression levels in response to oxidized low-density lipoprotein exposure, were identified. Genes that are central to cell cycle control and proliferation, inflammatory response, and of pathways not previously implicated in atherosclerosis were identified. The data obtained is also made available on-line at http:// biobase.biotech.kth.se/thp1a for further exploration. Conclusion: The identification of new candidate genes for atherosclerotic disease through RDA-based transcript profiling facilitates further functional genomic studies in coronary artery disease. Candidate genetic polymorphism markers of potential clinical relevance can be identified by filtering information in genome variation databases through the virtual chip analysis of the transcript profiles and subsequently tested in association studies.

  • 9. Andersson, T.
    et al.
    Borang, S.
    Unneberg, P.
    Wirta, V.
    Thelin, A.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Odeberg, Jacob
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Shotgun sequencing and microarray analysis of RDA transcripts2003Ingår i: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 310, s. 39-47Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Monitoring of differential gene expression is an important step towards understanding of gene function. We describe a comparison of the representational difference analysis (RDA) subtraction process with corresponding microarray analysis. The subtraction steps are followed in a quantitative manner using a shotgun cloning and sequencing procedure that includes over 1900 gene sequences. In parallel, the enriched transcripts are spotted onto microarrays facilitating large scale hybridization analysis of the representations and the difference products. We show by the shotgun procedure that there is a high diversity of gene fragments represented in the iterative RDA products (92-67% singletons) with a low number of shared sequences (<9%) between subsequent subtraction cycles. A non redundant set of 1141 RDA clones were immobilized on glass slides and the majority of these clones (97%) gave repeated good fluorescent signals in a subsequent hybridization of the labelled and amplified original cDNA. We observed only a low number of false positives (<2%) and a more than twofold differential expression for 32% (363) of the immobilized RDA clones. In conclusion, we show that by random sequencing of the difference products we obtained an accurate transcript profile of the individual steps and that large-scale confirmation of the obtained transcripts can be achieved by microarray analysis.

  • 10. Andersson, T.
    et al.
    Unneberg, P.
    Nilsson, Peter
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Odeberg, Jacob
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Quackenbush, J.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Monitoring of representational difference analysis subtraction procedures by global microarrays2002Ingår i: BioTechniques, ISSN 0736-6205, E-ISSN 1940-9818, Vol. 32, nr 6, s. 1348-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Various approaches to the study of differential gene expression are applied to compare cell lines and tissue samples in a wide range of biological contexts. The compromise between focusing on only the important genes in certain cellular processes and achieving a complete picture is critical for the selection of strategy. We demonstrate how global microarray technology can be used for the exploration of the differentially expressed genes extracted through representational difference analysis (RDA). The subtraction of ubiquitous gene fragments from the two samples was demonstrated using cDNA microarrays including more than 32 000 spotted, PCR-amplified human clones. Hybridizations indicated the expression of 9100 of the microarray elements in a macrophage/foam cell atherosclerosis model system, of which many were removed during the RDA process. The stepwise subtraction procedure was demonstrated to yield an efficient enrichment of gene fragments overrepresented in either sample (18% in the representations, 86% after the first subtraction, and 88% after the second subtraction), many of which were impossible to detect in the starting material. Interestingly, the method allowed for the observation of the differential expression of several members of the low-abundant nuclear receptor gene family. We also observed a certain background level in the difference products of nondifferentially expressed gene fragments, warranting a verification strategy for selected candidate genes. The differential expression of several genes was verified by real-time PCR.

  • 11.
    Andrade, Jorge
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Andersen, Malin
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Berglund, Lisa
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Applications of grid computing in genetics and proteomics2007Ingår i: Applied Parallel Computing: State Of The Art In Scientific Computing / [ed] Kagstrom, B; Elmroth, E; Dongarra, J; Wasniewski, J, 2007, Vol. 4699, s. 791-798Konferensbidrag (Refereegranskat)
    Abstract [en]

    The potential for Grid technologies in applied bioinformatics is largely unexplored. We have developed a model for solving computationally demanding bioinformatics tasks in distributed Grid environments, designed to ease the usability for scientists unfamiliar with Grid computing. With a script-based implementation that uses a strategy of temporary installations of databases and existing executables on remote nodes at submission, we propose a generic solution that do not rely on predefined Grid runtime environments and that can easily be adapted to other bioinformatics tasks suitable for parallelization. This implementation has been successfully applied to whole proteome sequence similarity analyses and to genome-wide genotype simulations, where computation time was reduced from years to weeks. We conclude that computational Grid technology is a useful resource for solving high compute tasks in genetics and proteomics using existing algorithms.

  • 12.
    Andrade, Jorge
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Andersen, Malin
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Sillén, Anna
    Graff, Caroline
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    The use of grid computing to drive data-intensive genetic research2007Ingår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 15, nr 6, s. 694-702Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In genetics, with increasing data sizes and more advanced algorithms for mining complex data, a point is reached where increased computational capacity or alternative solutions becomes unavoidable. Most contemporary methods for linkage analysis are based on the Lander-Green hidden Markov model (HMM), which scales exponentially with the number of pedigree members. In whole genome linkage analysis, genotype simulations become prohibitively time consuming to perform on single computers. We have developed 'Grid-Allegro', a Grid aware implementation of the Allegro software, by which several thousands of genotype simulations can be performed in parallel in short time. With temporary installations of the Allegro executable and datasets on remote nodes at submission, the need of predefined Grid run-time environments is circumvented. We evaluated the performance, efficiency and scalability of this implementation in a genome scan on Swedish multiplex Alzheimer's disease families. We demonstrate that 'Grid-Allegro' allows for the full exploitation of the features available in Allegro for genome-wide linkage. The implementation of existing bioinformatics applications on Grids (Distributed Computing) represent a cost-effective alternative for addressing highly resource-demanding and data-intensive bioinformatics task, compared to acquiring and setting up clusters of computational hardware in house (Parallel Computing), a resource not available to most geneticists today.

  • 13.
    Andrade, Jorge
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Berglund, Lisa
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Using Grid Technology for Computationally Intensive Applied Bioinformatics Analyses2006Ingår i: In Silico Biology, ISSN 1386-6338, Vol. 6, nr 6, s. 495-504Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    For several applications and algorithms used in applied bioinformatics, a bottle neck in terms of computational time may arise when scaled up to facilitate analyses of large datasets and databases. Re-codification, algorithm modification or sacrifices in sensitivity and accuracy may be necessary to accommodate for limited computational capacity of single work stations. Grid computing offers an alternative model for solving massive computational problems by parallel execution of existing algorithms and software implementations. We present the implementation of a Grid-aware model for solving computationally intensive bioinformatic analyses exemplified by a blastp sliding window algorithm for whole proteome sequence similarity analysis, and evaluate the performance in comparison with a local cluster and a single workstation. Our strategy involves temporary installations of the BLAST executable and databases on remote nodes at submission, accommodating for dynamic Grid environments as it avoids the need of predefined runtime environments (preinstalled software and databases at specific Grid-nodes). Importantly, the implementation is generic where the BLAST executable can be replaced by other software tools to facilitate analyses suitable for parallelisation. This model should be of general interest in applied bioinformatics. Scripts and procedures are freely available from the authors.

  • 14.
    Berglund, Lisa
    et al.
    KTH, Skolan för bioteknologi (BIO).
    Andrade, Jorge
    KTH, Skolan för bioteknologi (BIO).
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO).
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO).
    The epitope space of the human proteome2008Ingår i: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 17, nr 4, s. 606-613Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the post-genome era, there is a great need for protein-specific affinity reagents to explore the human proteome. Antibodies are suitable as reagents, but generation of antibodies with low cross-reactivity to other human proteins requires careful selection of antigens. Here we show the results from a proteomewide effort to map linear epitopes based on uniqueness relative to the entire human proteome. The analysis was based on a sliding window sequence similarity search using short windows (8, 10, and 12 amino acid residues). A comparison of exact string matching (Hamming distance) and a heuristic method (BLAST) was performed, showing that the heuristic method combined with a grid strategy allows for whole proteome analysis with high accuracy and feasible run times. The analysis shows that it is possible to find unique antigens for a majority of the human proteins, with relatively strict rules involving low sequence identity of the possible linear epitopes. The implications for human antibody-based proteomics efforts are discussed.

  • 15. Borang, S.
    et al.
    Andersson, T.
    Thelin, A.
    Larsson, M.
    Odeberg, Jacob
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Monitoring of the subtraction process in solid-phase representational difference analysis: characterization of a candidate drug2001Ingår i: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 271, nr 2, s. 183-192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study, we have applied and evaluated a modified cDNA representational difference analysis (RDA) protocol based on magnetic bead technology to study the molecular effects of a candidate drug (N,N'-diacetyl-L-cystine, DiNAC) in a model for atherosclerosis. Alterations in a gene expression profile induced by DiNAC were investigated in a human monocytic cell line (THP-1) differentiated into macrophage-like cells by lipopolysaccharide and further exposed to DiNAC. Three rounds of subtraction have been performed and the difference products from the second and third rounds have been characterized in detail by analysis of over 1000 gene sequences. Two protocols for analysis of the subtraction products have been evaluated, a shotgun approach and size selection of both distinct fragments and band-patterned smear. We demonstrate that in order to obtain a representative view of the most abundant gene fragments, the shotgun procedure is preferred. The obtained sequences were analyzed against the UniGene and Expressed Gene Anatomy Database (EGAD) databases and the results were visualized and analyzed with the ExProView software enabling rapid pair-wise comparison and identification of individual genes or functional groups of genes with altered expression levels. The identified differentially expressed gene sequences were comprised of both genes with known involvement in atherosclerosis or cholesterol biosynthesis and genes previously not implicated in these processes. The applicability of a solid-phase shotgun RDA protocol, combined with virtual chip monitoring, results in new starting points for characterization of novel candidate drugs.

  • 16.
    Boräng, Stina
    et al.
    KTH, Tidigare Institutioner, Bioteknologi.
    Andersson, Tove
    KTH, Tidigare Institutioner, Bioteknologi.
    Thelin, A.
    Odeberg, Jacob
    KTH, Tidigare Institutioner, Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner, Bioteknologi.
    Vascular gene expression in atherosclerotic plaque-prone regions analyzed by representational difference analysis2004Ingår i: Pathobiology (Basel), ISSN 1015-2008, E-ISSN 1423-0291, Vol. 71, nr 2, s. 107-114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Atherosclerotic plaques are known to develop and progress where the endothelium is subjected to turbulent blood flow. We have applied cDNA representational difference analysis (RDA) to study vascular gene expression in mouse aorta in a model for atherosclerosis. Methods: Gene expression profiles were investigated in plaque-prone and plaque-resistant localizations in the ascending aorta and arch in 8-week-oldApoE-/- and LDLR-/- mice. Total RNA was extracted and two rounds of subtraction were performed; the difference products were characterized in detail by shotgun cloning and analysis of more than 2,700 gene sequences. Results: The identified differentially expressed gene sequences include both genes with known involvement in vascular gene expression and genes previously not implicated in vascular processes. For example, CD36 and caveolin, previously reported for their participation in the progression of atherosclerosis, were found to have an increased expression in vessel localizations thought to be especially susceptible to plaque formation. Conclusions: This report provides new in vivo information of expressed genes that can be useful for further investigations of the molecular mechanisms in focal localization of atherosclerosis.

  • 17. Bruzelius, M.
    et al.
    Bottai, M.
    Sabater-Lleal, M.
    Strawbridge, R. J.
    Bergendal, A.
    Silveira, A.
    Sundstrom, A.
    Kieler, H.
    Hamsten, A.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska University Hospital Solna, Sweden; Karolinska Institutet, Sweden .
    Predicting venous thrombosis in women using a combination of genetic markers and clinical risk factors2015Ingår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, nr 2, s. 219-227Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundFamily history of venous thromboembolism (VTE) has been suggested to be more useful in risk assessment than thrombophilia testing. ObjectivesWe investigated established genetic susceptibility variants for association with VTE and evaluated a genetic risk score in isolation and combined with known trigger factors, including family history of VTE. Patients/MethodA total of 18 single nucleotide polymorphisms (SNPs) selected from the literature were genotyped in 2835 women participating in a Swedish nationwide case-control study (the ThromboEmbolism Hormone Study [TEHS]). Association with VTE was assessed by odds ratios (ORs) with 95% confidence interval (CI) using logistic regression. Clinical and genetic predictors that contributed significantly to the fit of the logistic regression model were included in the prediction models. SNP-SNP interactions were investigated and incorporated into the models if found significant. Risk scores were evaluated by calculating the area under the receiver-operating characteristics curve (AUC). ResultsSeven SNPs (F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446) with four SNP-SNP interactions contributed to the genetic risk score for VTE, with an AUC of 0.66 (95% CI, 0.64-0.68). After adding clinical risk factors, which included family history of VTE, the AUC reached 0.84 (95% CI, 0.82-0.85). The goodness of fit of the genetic and combined scores improved when significant SNP-SNP interaction terms were included. ConclusionPrediction of VTE in high-risk individuals was more accurate when a combination of clinical and genetic predictors with SNP-SNP interactions was included in a risk score.

  • 18. Bruzelius, M.
    et al.
    Iglesias, Maria Jesus
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sanchez-Rivera, Laura
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Gyorgy, B.
    Souto, J. C.
    Franberg, M.
    Fredolini, Claudia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Strawbridge, R. J.
    Holmström, M.
    Hamsten, A.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Silveira, A.
    Soria, J. M.
    Smadja, D. M.
    Butler, L. M.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Morange, P. -E
    Trégouët, D. -A
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska University Hospital, Sweden; Karolinska Institutet, Sweden.
    PDGFB, a new candidate plasma biomarker for venous thromboembolism: Results from the VEREMA affinity proteomics study2016Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 128, nr 23, s. e59-e66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a clear clinical need for high-specificity plasma biomarkers for predicting risk of venous thromboembolism (VTE), but thus far, such markers have remained elusive. Utilizing affinity reagents from the Human Protein Atlas project and multiplexed immuoassays, we extensively analyzed plasma samples from 2 individual studies to identify candidate protein markers associated with VTE risk. We screened plasma samples from 88 VTE cases and 85 matched controls, collected as part of the Swedish ¡°Venous Thromboembolism Biomarker Study,¡± using suspension bead arrays composed of 755 antibodies targeting 408 candidate proteins. We identified significant associations between VTE occurrence and plasma levels of human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1), von Willebrand factor (VWF), glutathione peroxidase 3 (GPX3), and platelet-derived growth factor β (PDGFB). For replication, we profiled plasma samples of 580 cases and 589 controls from the French FARIVE study. These results confirmed the association of VWF and PDGFB with VTE after correction for multiple testing, whereas only weak trends were observed for HIVEP1 and GPX3. Although plasma levels of VWF and PDGFB correlated modestly (p ~ 0.30) with each other, they were independently associated with VTE risk in a joint model in FARIVE (VWF P < .001; PDGFB P 5 .002). PDGF was verified as the target of the capture antibody by immunocapture mass spectrometry and sandwich enzyme-linked immunosorbent assay. In conclusion, we demonstrate that high-throughput affinity plasma proteomic profiling is a valuable research strategy to identify potential candidate biomarkers for thrombosis-related disorders, and our study suggests a novel association of PDGFB plasma levels with VTE.

  • 19. Bruzelius, M.
    et al.
    Iglesias, Maria Jesus
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Tregouet, D. A.
    Souto, J. C.
    Holmström, M.
    Frånberg, M.
    Strawbridge, R. J.
    Sabater-Lleal, M.
    Sennblad, B.
    Silveira, A.
    Soria, J. M.
    Morange, P. E.
    Butler, L.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hamsten, A.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Verema - an affinity proteomics study to identify and translate plasma biomarkers for venous thromboembolism2015Ingår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, s. 954-954Artikel i tidskrift (Refereegranskat)
  • 20. Bruzelius, M.
    et al.
    Ljungqvist, M.
    Bottai, M.
    Bergendal, A.
    Strawbridge, R. J.
    Silveira, A.
    Kieler, H.
    Hamsten, A.
    Laerfars, G.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    F11 is associated with recurrent event of VTE in women: a prospective cohort study2015Ingår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, s. 198-198Artikel i tidskrift (Refereegranskat)
  • 21. Bruzelius, Maria
    et al.
    Ljungqvist, Maria
    Bottai, Matteo
    Bergendal, Annica
    Strawbridge, Rona J.
    Holmstrom, Margareta
    Silveira, Angela
    Kieler, Helle
    Hamsten, Anders
    Larfars, Gerd
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska Institutet & Karolinska universitetssjukhus, Sweden.
    F11 is associated with recurrent VTE in women A prospective cohort study2016Ingår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 115, nr 2, s. 406-414Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genetic associations for the reoccurrence of venous thromboembolism (VTE) are not well described. Our aim was to investigate if common genetic variants, previously found to contribute to the prediction of first time thrombosis in women, were associated with risk of recurrence. The Thromboembolism Hormone Study (TEHS) is a Swedish nationwide case-control study (2002-2009). A cohort of 1,010 women with first time VTE was followed up until a recurrent event, death or November 2011. The genetic variants in F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446 were assessed together with clinical variables. Recurrence rate was calculated as the number of events over the accumulated patient-time. Cumulative recurrence was calculated by Kaplan-Meier curve. Cox proportional-hazard model was used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) between groups. A total of 101 recurrent events occurred during a mean follow-up time of five years. The overall recurrence rate was 20 per 1,000 person-years (95 % CI; 16-24). The recurrence rate was highest in women with unprovoked first event and obesity. Carriers of the risk alleles of F5 rs6025 (HR=1.7 (95 % CI; 1.1-2.6)) and F11 rs2289252 (HR=1.8 (95 % CI; 1.1-3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at five years follow-up. In conclusion, F5 rs6025 and F11 rs2289252 contributed to the risk of recurrent VTE and the combination is of potential clinical relevance for risk prediction.

  • 22. Bruzelius, Maria
    et al.
    Strawbridge, Rona J.
    Tregouet, David-Alexandre
    Wiggins, Kerri L.
    Gertow, Karl
    Sabater-Lleal, Maria
    Ohrvik, John
    Bergendal, Annica
    Silveira, Angela
    Sundstrom, Anders
    Kieler, Helle
    Syvanen, Ann-Christine
    Smith, Nicholas L.
    Morange, Pierre-Emmanuel
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Coagulation Unit, Hematology Centre; Atherosclerosis Research Unit, Centre for Molecular Medicine Karolinska University Hospital Solna, Sweden.
    Hamsten, Anders
    Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism2014Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 134, nr 2, s. 426-432Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case-control study (n = 2753) from Sweden. Materials and Methods: 39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression. Results: Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181). Conclusions: It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.

  • 23. Butler, L. M.
    et al.
    Hallström, Björn Mikael
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Fagerberg, Linn
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Pontén, F.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Renné, T.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Analysis of Body-wide Unfractionated Tissue Data to Identify a Core Human Endothelial Transcriptome2016Ingår i: Cell Systems, ISSN 2405-4712, Vol. 3, nr 3, s. 287-301.e3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endothelial cells line blood vessels and regulate hemostasis, inflammation, and blood pressure. Proteins critical for these specialized functions tend to be predominantly expressed in endothelial cells across vascular beds. Here, we present a systems approach to identify a panel of human endothelial-enriched genes using global, body-wide transcriptomics data from 124 tissue samples from 32 organs. We identified known and unknown endothelial-enriched gene transcripts and used antibody-based profiling to confirm expression across vascular beds. The majority of identified transcripts could be detected in cultured endothelial cells from various vascular beds, and we observed maintenance of relative expression in early passage cells. In summary, we describe a widely applicable method to determine cell-type-specific transcriptome profiles in a whole-organism context, based on differential abundance across tissues. We identify potential vascular drug targets or endothelial biomarkers and highlight candidates for functional studies to increase understanding of the endothelium in health and disease.

  • 24. Cheung, Louisa
    et al.
    Andersen, Malin
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Gustavsson, Carolina
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Biokemi.
    Fernández-Pérez, Leandro
    Norsteds, Gunnar
    Tollet-Egnell, Petra
    Hormonal and nutritional regulation of alternative CD36 transcripts in rat liver: a role for growth hormone in alternative exon usage2007Ingår i: BMC Molecular Biology, ISSN 1471-2199, E-ISSN 1471-2199, Vol. 8, nr 60, s. 12-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: CD36 is a multiligand receptor involved in various metabolic pathways, including cellular uptake of long-chain fatty acids. Defect function or expression of CD36 can result in dyslipidemia or insulin resistance. We have previously shown that CD36 expression is female-predominant in rat liver. In the present study, hormonal and nutritional regulation of hepatic CD36 expression was examined in male and female rats. Since alternative transcription start sites have been described in murine and human Cd36, we investigated whether alternative CD36 transcripts are differentially regulated in rat liver during these conditions.

    Results: Sequence information of the rat Cd36 5'-UTR was extended, showing that the gene structure of Cd36 in rat is similar to that previously described in mouse with at least two alternative first exons. The rat Cd36 exon 1a promoter was sequenced and found to be highly similar to murine and human Cd36. We show that alternative first exon usage is involved in the female-predominant expression of CD36 in rat liver and during certain hormonal states that induce CD36 mRNA abundance. Estrogen treatment or continuous infusion of growth hormone (GH) in male rats induced CD36 expression preferentially through the exon 1a promoter. Old age was associated with increased CD36 expression in male rats, albeit without any preferential first exon usage. Intermittent GH treatment in old male rats reversed this effect. Mild starvation (12 hours without food) reduced CD36 expression in female liver, whereas its expression was increased in skeletal muscle.

    Conclusion: The results obtained in this study confirm and extend our previous observation that GH is an important regulator of hepatic CD36, and depending on the mode of treatment (continuous or intermittent) the gene might be either induced or repressed. We suggest that the effects of continuous GH secretion in females (which is stimulatory) and intermittent GH secretion in males (which is inhibitory) explains the sex-different expression of this gene. Furthermore, a female-specific repression of hepatic CD36 in response to food deprivation was found, which was in contrast to a stimulatory effect in skeletal muscle. This demonstrates a tissue-specific regulation of Cd36.

  • 25. dos Remedios, Cristobal G.
    et al.
    Estigoy, Colleen
    Cameron, Darryl
    Ho, Joshua W. K.
    Herbert, Benjamin
    Padula, Matthew
    Pickford, Russel
    Guilhaus, Michael
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Ponten, Fredrik
    Proteomics of the Human Cardiac Intercalated Disc: A More Complex Multi-Functional Structure than was Previously Thought2010Ingår i: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 98, nr 3, s. 755A-756AArtikel i tidskrift (Övrigt vetenskapligt)
  • 26.
    Dusart, Philip
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Fagerberg, Linn
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Perisic, L.
    Civelek, M.
    Struck, Eike
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hedin, U.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Trégouët, D. -A
    Renné, T.
    Odeberg, Jacob
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO). Coagulation Unit, Centre for Hematology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
    Butler, Lynn M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO). Clinical Chemistry and Blood Coagulation, Department of Molecular Medicine and Surgery, Karolinska Institute, SE-171 76, Stockholm, Sweden Institute for Clinical Chemistry and Laboratory Medicine, University Medical Centre Hamburg-Eppendorf, D-20246, Hamburg, Germany.
    A systems-approach reveals human nestin is an endothelial-enriched, angiogenesis-independent intermediate filament protein2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, nr 1, artikel-id 14668Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The intermediate filament protein nestin is expressed during embryonic development, but considered largely restricted to areas of regeneration in the adult. Here, we perform a body-wide transcriptome and protein-profiling analysis to reveal that nestin is constitutively, and highly-selectively, expressed in adult human endothelial cells (EC), independent of proliferative status. Correspondingly, we demonstrate that it is not a marker for tumour EC in multiple malignancy types. Imaging of EC from different vascular beds reveals nestin subcellular distribution is shear-modulated. siRNA inhibition of nestin increases EC proliferation, and nestin expression is reduced in atherosclerotic plaque neovessels. eQTL analysis reveals an association between SNPs linked to cardiovascular disease and reduced aortic EC nestin mRNA expression. Our study challenges the dogma that nestin is a marker of proliferation, and provides insight into its regulation and function in EC. Furthermore, our systems-based approach can be applied to investigate body-wide expression profiles of any candidate protein. 

  • 27.
    Edsgärd, Daniel
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Iglesias, Maria Jesus
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska University Hospital, Sweden; Karolinska Institutet, Sweden .
    Reilly, Sarah-Jayne
    Hamsten, Anders
    Tornvall, Per
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska University Hospital, Sweden; Karolinska Institutet, Sweden; .
    Emanuelsson, Olof
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    GeneiASE: Detection of condition-dependent and static allele-specific expression from RNA-seq data without haplotype information2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 21134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Allele-specific expression (ASE) is the imbalance in transcription between maternal and paternal alleles at a locus and can be probed in single individuals using massively parallel DNA sequencing technology. Assessing ASE within a single sample provides a static picture of the ASE, but the magnitude of ASE for a given transcript may vary between different biological conditions in an individual. Such condition-dependent ASE could indicate a genetic variation with a functional role in the phenotypic difference. We investigated ASE through RNA-sequencing of primary white blood cells from eight human individuals before and after the controlled induction of an inflammatory response, and detected condition-dependent and static ASE at 211 and 13021 variants, respectively. We developed a method, GeneiASE, to detect genes exhibiting static or condition-dependent ASE in single individuals. GeneiASE performed consistently over a range of read depths and ASE effect sizes, and did not require phasing of variants to estimate haplotypes. We observed condition-dependent ASE related to the inflammatory response in 19 genes, and static ASE in 1389 genes. Allele-specific expression was confirmed by validation of variants through real-time quantitative RT-PCR, with RNA-seq and RT-PCR ASE effect-size correlations r = 0.67 and r = 0.94 for static and condition-dependent ASE, respectively.

  • 28. Estigoy, C. B.
    et al.
    Pontén, F.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Herbert, B.
    Guilhaus, M.
    Charleston, M.
    Ho, J. W. K.
    Cameron, D.
    dos Remedios, C. G.
    Intercalated discs: Multiple proteins perform multiple functions in non-failing and failing human hearts2009Ingår i: Biophysical Reviews, ISSN 1867-2450, Vol. 1, nr 1, s. 43-49Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The intercalated disc (ICD) occupies a central position in the transmission of force, electrical continuity and chemical communication between cardiomyocytes. Changes in its structure and composition are strongly implicated in heart failure. ICD functions include: maintenance of electrical continuity across the ICD; physical links between membranes and the cytoskeleton; intercellular adhesion; maintenance of ICD structure and function; and growth. About 200 known proteins are associated with ICDs, 40% of which change in disease. We systemically reviewed cardiac immunohistochemical data on the Human Protein Atlas (HPA) web site, ExPASy protein binding data and published papers on ICDs. We identified 43 proteins not previously reported, and confirmed 37 proteins that have previously been described. In addition, 102 proteins not present on the HPA web site but were described in ICDs in the literature. We group these into clusters that demonstrate functionally interactive groups of proteins demonstrating that ICDs play a key role in cardiomyocyte function.

  • 29.
    Fagerberg, Linn
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hallström, Björn M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Oksvold, Per
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Kampf, C.
    Djureinovic, D.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Habuka, Masato
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Tahmasebpoor, S.
    Danielsson, A.
    Edlund, K.
    Asplund, A.
    Sjöstedt, E.
    Lundberg, E.
    Szigyarto, Cristina Al-Khalili
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Skogs, Marie
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ottosson Takanen, J.
    Berling, H.
    Tegel, Hanna
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Mulder, J.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lindskog, C.
    Danielsson, Frida
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mardinoglu, A.
    Sivertsson, Åsa
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Von Feilitzen, Kalle
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Forsberg, Mattias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Zwahlen, Martin
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Olsson, I.
    Navani, S.
    Huss, Mikael
    Nielsen, Jens
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Pontén, F.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics2014Ingår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 13, nr 2, s. 397-406Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 30.
    Fagerberg, Linn
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Oksvold, Per
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Skogs, Marie
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Älgenäs, C.
    Lundberg, Emma
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Pontén, F.
    Sivertsson, Åsa
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Odeberg, Jacob
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Klevebring, Daniel
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Kampf, C.
    Asplund, A.
    Sjöstedt, E.
    Al-Khalili Szigyarto, C.
    Edqvist, P. -H
    Olsson, I.
    Rydberg, U.
    Hudson, P.
    Ottosson Takanen, J.
    Berling, H.
    Björling, Lisa
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Tegel, Hanna
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Rockberg, J.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Navani, S.
    Jirström, K.
    Mulder, J.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Zwahlen, Martin
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hober, Sophia
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Forsberg, Mattias
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Von Feilitzen, Kalle
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Contribution of antibody-based protein profiling to the human chromosome-centric proteome project (C-HPP)2013Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 12, nr 6, s. 2439-2448Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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 tissue-specific proteins and approximately half of the genes expressed in all the analyzed cells. The status for each gene with 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).

  • 31. Gudmundsson, G H
    et al.
    Agerberth, B
    Odeberg, Jacob
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Bergman, T
    Olsson, B
    Salcedo, R
    The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes.1996Ingår i: European Journal of Biochemistry, ISSN 0014-2956, E-ISSN 1432-1033, Vol. 238, nr 2, s. 325-32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The peptide FA-LL-37, previously termed FALL-39, was originally predicted from on ORF of a cDNA clone isolated from a human bone marrow library. This peptide was synthesized and found to have antibacterial activity. We have now characterized and sequenced the complete gene for FA-LL-37, termed FALL39. It is a compact gene of 1963 bp with four exons. Exons 1-3 code for a signal sequence and the cathelin region. Exon 4 contains the information for the mature antibacterial peptide. Our results indicate that FALL39 is the only member of the cathelin gene family present in the human genome. Potential binding sites for acute-phase-response factors are identified in the promoter and in intron 2. A possible role for the cytokine interleukin-6 in the regulation of FALL 39 is discussed. Anti-(FA-LL-37) IgG located the peptide in granulocytes and we isolated the mature peptide from these cells after degranulation. Structural analysis determined the mature peptide to be LL-37. To obtain LL-37 for antibacterial assays, synthetic FA-LL-37 was degraded with dipeptidyl-peptidase I. This analysis showed that mature LL-37 is a potent antibacterial peptide.

  • 32.
    Habuka, Masato
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska University Hospital, Sweden .
    Fagerberg, Linn
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hallström, Björn M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Kampf, Caroline
    Edlund, Karolina
    Sivertsson, Åsa
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Yamamoto, Tadashi
    Pontén, Fredrik
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska University Hospital, Sweden.
    The Kidney Transcriptome and Proteome Defined by Transcriptomics and Antibody-Based Profiling2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 12, s. e116125-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To understand renal functions and disease, it is important to define the molecular constituents of the various compartments of the kidney. Here, we used comparative transcriptomic analysis of all major organs and tissues in the human body, in combination with kidney tissue micro array based immunohistochemistry, to generate a comprehensive description of the kidney-specific transcriptome and proteome. A special emphasis was placed on the identification of genes and proteins that were elevated in specific kidney subcompartments. Our analysis identified close to 400 genes that had elevated expression in the kidney, as compared to the other analysed tissues, and these were further subdivided, depending on expression levels, into tissue enriched, group enriched or tissue enhanced. Immunohistochemistry allowed us to identify proteins with distinct localisation to the glomeruli (n=11), proximal tubules (n=120), distal tubules (n=9) or collecting ducts (n=8). Among the identified kidney elevated transcripts, we found several proteins not previously characterised or identified as elevated in kidney. This description of the kidney specific transcriptome and proteome provides a resource for basic and clinical research to facilitate studies to understand kidney biology and disease.

  • 33. Holmberg, K.
    et al.
    Persson, M. L.
    Uhlén, Mathias
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Pyrosequencing analysis of thrombosis-associated risk markers2005Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 51, nr 8, s. 1549-1552Artikel i tidskrift (Refereegranskat)
  • 34.
    Iglesias, Maria Jesus
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Bruzelius, M.
    Hong, M-Gwan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Tregouet, D. A.
    Perisic, L.
    Frånberg, M.
    Parini, P.
    Ganna, A.
    Ingelsson, E.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hedin, U.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Silveira, A.
    Morange, P. E.
    Hamsten, A.
    Schwenk, JM, Jochen
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    An affinity proteomics study for plasma biomarker candidates of cardiovascular disease in venous thromboembolism2015Ingår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, s. 956-956Artikel i tidskrift (Refereegranskat)
  • 35. Iglesias, Maria Jesus
    et al.
    Reilly, Sarah-Jayne
    Emanuelsson, Olof
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sennblad, Bengt
    Najafabadi, Mohammad Pirmoradian
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Folkersen, Lasse
    Mälarstig, Anders
    Lagergren, Jens
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Eriksson, Per
    Hamsten, Anders
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Combined Chromatin and Expression Analysis Reveals Specific Regulatory Mechanisms within Cytokine Genes in the Macrophage Early Immune Response2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 2, s. e32306-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS). To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches - gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of upregulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the chromatin level for specific genes and this study highlights the level of fine-tuning that occurs in the immune response.

  • 36.
    Karlöf, Eva
    et al.
    Karolinska Univ Hosp, Dept Vasc Surg, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, L8 03, SE-17176 Stockholm, Sweden..
    Seime, Till
    Karolinska Inst, Dept Mol Med & Surg, L8 03, SE-17176 Stockholm, Sweden..
    Dias, Nuno
    Skane Univ Hosp, Dept Vasc Surg, Vasc Ctr, Malmo, Sweden..
    Lengquist, Mariette
    Karolinska Inst, Dept Mol Med & Surg, L8 03, SE-17176 Stockholm, Sweden..
    Witasp, Anna
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, Stockholm, Sweden..
    Almqvist, Hakan
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Kronqvist, Malin
    Karolinska Inst, Dept Mol Med & Surg, L8 03, SE-17176 Stockholm, Sweden..
    Gadin, Jesper R.
    Karolinska Inst, Dept Med, Ctr Mol Med, Stockholm, Sweden..
    Odeberg, Jacob
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Maegdefessel, Lars
    Karolinska Inst, Dept Med, Ctr Mol Med, Stockholm, Sweden.;Tech Univ Munich, Klinikum Klinikum Rechts Isar Isar, Dept Vasc & Endovasc Surg, Munich, Germany..
    Stenvinkel, Peter
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, Stockholm, Sweden..
    Matic, Ljubica Perisic
    Karolinska Inst, Dept Mol Med & Surg, L8 03, SE-17176 Stockholm, Sweden..
    Hedin, Ulf
    Karolinska Univ Hosp, Dept Vasc Surg, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, L8 03, SE-17176 Stockholm, Sweden..
    Correlation of computed tomography with carotid plaque transcriptomes associates calcification with lesion-stabilization2019Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 288, s. 175-185Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: Unstable carotid atherosclerosis causes stroke, but methods to identify patients and lesions at risk are lacking. We recently found enrichment of genes associated with calcification in carotid plaques from asymptomatic patients. Here, we hypothesized that calcification represents a stabilising feature of plaques and investigated how macro-calcification, as estimated by computed tomography (CT), correlates with gene expression profiles in lesions. Methods: Plaque calcification was measured in pre-operative CT angiographies. Plaques were sorted into high- and low-calcified, profiled with microarrays, followed by bioinformatic analyses. Immunohistochemistry and qPCR were performed to evaluate the findings in plaques and arteries with medial calcification from chronic kidney disease patients. Results: Smooth muscle cell (SMC) markers were upregulated in high-calcified plaques and calcified plaques from symptomatic patients, whereas macrophage markers were downregulated. The most enriched processes in high-calcified plaques were related to SMCs and extracellular matrix (ECM) organization, while inflammation, lipid transport and chemokine signaling were repressed. These findings were confirmed in arteries with high medial calcification. Proteoglycan 4 (PRG4) was identified as the most upregulated gene in association with plaque calcification and found in the ECM, SMA+ and CD68+/TRAP + cells. Conclusions: Macro-calcification in carotid lesions correlated with a transcriptional profile typical for stable plaques, with altered SMC phenotype and ECM composition and repressed inflammation. PRG4, previously not described in atherosclerosis, was enriched in the calcified ECM and localized to activated macrophages and smooth muscle-like cells. This study strengthens the notion that assessment of calcification may aid evaluation of plaque phenotype and stroke risk.

  • 37.
    Käller, Max
    et al.
    KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Hultin, Emilie
    KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Holmberg, Kristina
    KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Persson, Marie-Louise
    Clinical Chemistry Laboratory, Blekinge Hospital, Karlskrona.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Lundeberg, Joakim
    KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Ahmadian, Afshin
    KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Comparison of PrASE and Pyrosequencing for SNP Genotyping2006Ingår i: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 7, s. 291-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is an imperative need for SNP genotyping technologies that are cost-effective per sample with retained high accuracy, throughput and flexibility. We have developed a microarray-based technique and compared it to Pyrosequencing. In the protease-mediated allele-specific extension (PrASE), the protease constrains the elongation reaction and thus prevents incorrect nucleotide incorporation to mismatched 3'-termini primers.

    Results: The assay is automated for 48 genotyping reactions in parallel followed by a tag-microarray detection system. A script automatically visualizes the results in cluster diagrams and assigns the genotypes. Ten polymorphic positions suggested as prothrombotic genetic variations were analyzed with Pyrosequencing and PrASE technologies in 442 samples and 99.8 % concordance was achieved. In addition to accuracy, the robustness and reproducibility of the technique has been investigated.

    Conclusion: The results of this study strongly indicate that the PrASE technology can offer significant improvements in terms of accuracy and robustness and thereof increased number of typeable SNPs.

  • 38. Lahermo, P.
    et al.
    Liljedahl, U.
    Alnaes, G.
    Axelsson, T.
    Brookes, A. J.
    Ellonen, P.
    Groop, P. H.
    Hallden, C.
    Holmberg, D.
    Holmberg, K.
    Keinanen, M.
    Kepp, K.
    Kere, J.
    Kiviluoma, P.
    Kristensen, V.
    Lindgren, C.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Osterman, P.
    Parkkonen, M.
    Saarela, J.
    Sterner, M.
    Stromqvist, L.
    Talas, U.
    Wessman, M.
    Palotie, A.
    Syvanen, A. C.
    A quality assessment survey of SNP genotyping laboratories2006Ingår i: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 27, nr 7, s. 711-714Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To survey the quality of SNP genotyping, a joint Nordic quality assessment (QA) round was organized between 11 laboratories in the Nordic and Baltic countries. The QA round involved blinded genotyping of 47 DNA samples for 18 or six randomly selected SNPs. The methods used by the participating laboratories included all major platforms for small, to medium-size SNP genotyping. The laboratories used their standard procedures for SNP assay design, genotyping, and quality control. Based on the joint results from all laboratories, a consensus genotype for each DNA sample and SNP was determined by the coordinator of the survey, and the results from each laboratory were compared to this genotype. The overall genotyping accuracy achieved in the survey was excellent. Six laboratories delivered genotype data that were in full agreement with the consensus genotype. The average accuracy per SNP varied from 99.1 to 100% between the laboratories, and it was frequently 100% for the majority of the assays for which SNP genotypes were reported. Lessons from the survey are that special attention should be given to the quality of the DNA samples prior to genotyping, and that a conservative approach for calling the genotypes should be used to achieve a high accuracy. Hum Mutat 27(7), 711-714,2006.

  • 39. Li, A.
    et al.
    Estigoy, C.
    Raftery, M.
    Cameron, D.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Pontén, F.
    Lal, S.
    dos Remedios, C. G.
    Heart research advances using database search engines, human protein atlas and the sydney heart bank2013Ingår i: Heart, Lung and Circulation, ISSN 1443-9506, E-ISSN 1444-2892, Vol. 22, nr 10, s. 819-826Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    This Methodological Review is intended as a guide for research students who may have just discovered a human "novel" cardiac protein, but it may also help hard-pressed reviewers of journal submissions on a "novel" protein reported in an animal model of human heart failure. Whether you are an expert or not, you may know little or nothing about this particular protein of interest. In this review we provide a strategic guide on how to proceed. We ask: How do you discover what has been published (even in an abstract or research report) about this protein? Everyone knows how to undertake literature searches using PubMed and Medline but these are usually encyclopaedic, often producing long lists of papers, most of which are either irrelevant or only vaguely relevant to your query. Relatively few will be aware of more advanced search engines such as Google Scholar and even fewer will know about Quertle. Next, we provide a strategy for discovering if your "novel" protein is expressed in the normal, healthy human heart, and if it is, we show you how to investigate its subcellular location. This can usually be achieved by visiting the website "Human Protein Atlas" without doing a single experiment. Finally, we provide a pathway to discovering if your protein of interest changes its expression level with heart failure/disease or with ageing.

  • 40. Liem, David A.
    et al.
    Nsair, Ali
    Setty, Shaun P.
    Cadeiras, Martin
    Wang, Ding
    Maclellan, Robb
    Lotz, Chris
    Lin, Amanda J.
    Tabaraki, Jason
    Li, Hua
    Ge, Junbo
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Pontén, Fredrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Larson, Erik
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mulder, Jan
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundberg, Emma
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Weiss, James N.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ping, Peipei
    Deng, Mario C.
    Molecular- and Organelle-Based Predictive Paradigm Underlying Recovery by Left Ventricular Assist Device Support2014Ingår i: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 7, nr 2, s. 359-366Artikel i tidskrift (Refereegranskat)
  • 41. Lindstrom, A.
    et al.
    Odeberg, Jacob
    KTH, Tidigare Institutioner, Bioteknologi.
    Albert, J.
    Pyrosequencing for detection of lamivudine-resistant hepatitis B virus2004Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 42, nr 10, s. 4788-4795Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chronic hepatitis B virus (HBV) infection can cause severe liver disease, including cirrhosis and hepatocellular carcinoma. Lamivudine is a relatively recent alternative to alpha interferon for the treatment of HBV infection, but unfortunately, resistance to lamivudine commonly develops during monotherapy. Lamivudine-resistant HBV mutants display specific mutations in the YMDD (tyrosine, methionine, aspartate, aspartate) motif of the viral polymerase (reverse transcriptase [rt]), which is the catalytic site of the enzyme, i.e., methionine 204 to isoleucine (rtM204I) or valine (rtM204V). The latter mutation is often accompanied by a compensatory leucine-to-methionine change at codon 180 (rtL180M). In the present study, a novel sequencing method, pyrosequencing, was applied to the detection of lamivudine resistance mutations and was compared with direct Sanger sequencing. The new pyrosequencing method had advantages in terms of throughput. Experiments with mixtures of wild-type and resistant viruses indicated that pyrosequencing can detect minor sequence variants in heterogeneous virus populations. The new pyrosequencing method was evaluated with a small number of patient samples, and the results showed that the method could be a useful tool for the detection of lamivudine resistance in the clinical setting.

  • 42. Ljungqvist, Maria
    et al.
    Holmstrom, Margareta
    Kieler, Helle
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska University Hospital, Sweden.
    Larfars, Gerd
    Cardiovascular disease and mortality after a first episode of venous thromboembolism in young and middle-aged women2016Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 138, s. 80-85Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Patients with a history of venous thromboembolism (VTE) seem to have an increased risk of arterial cardiovascular disease (CVD). Objectives: To evaluate the risk of CVD and overall mortality after a first episode of VTE in women and to assess common risk factors for VTE and CVD. Patients/methods: We performed a cohort study inviting 1433 women with a previous VTE (exposed) and 1402 women without VTE (unexposed). The cohort was derived from TEHS, a Swedish population-based case-control study on risk factors for VTE in women age 18-64 years. The women were recruited in 2002-2009. During 2011 information on CVD and mortality was obtained from a questionnaire and from the Swedish Patient Register and the Cause of Death Register. Hazard ratios (HR) for CVD and their 95% confidence intervals (CI) were calculated using Cox regression. In multivariate analyses we adjusted for age, smoking, diabetes mellitus, hypertension and body mass index. Results: 2108 (75%) women (mean age 47 +/- 13 years) accepted participation. During the total follow up of 11,920 person years 35 (3.2%, 95% CI 0.7-2.1) among the exposed and 14 (1.4%, 95% CI 0.2-4.3) among the unexposed had any CVD event. The adjusted HR for CVD was 2.0 (95% CI 1.1-3.9) the adjusted HR for mortality was 2.3 (95% CI 1.2-4.6) Conclusion: Women with a previous VTE had a two-fold increased risk of CVD and overall mortality. Adjusting for cardiovascular risk factors only modestly changed the estimates.

  • 43. Magnusson, V.
    et al.
    Johanneson, B.
    Lima, G.
    Odeberg, Jacob
    KTH, Tidigare Institutioner, Bioteknologi.
    Alarcon-Segivuam, D.
    Alarcon-Riquelme, M. E.
    S. L. E. Genetics Collaboration Grp,
    Both risk alleles for Fc gamma RIIA and Fc gamma RIIIA are susceptibility factors for SLE: a unifying hypothesis2004Ingår i: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 5, nr 2, s. 130-137Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to analyze in families with SLE for the presence of linkage and the structure and transmission of haplotypes containing alleles for the low-affinity Fcgamma receptors. The Fcgamma receptor polymorphisms FcgammaRIIA-131R/H, FcgammaRIIIA176F/ V and FcgammaRIIIB-NA1/2 and a polymorphism in the FcgammaRIIB gene were genotyped with RFLP, allele-specific PCR or pyrosequencing. Individual SNPs and haplotypes were tested for linkage in multicase families and for association using contingency tables, transmission disequilibrium test and affected family-based control groups in Swedish and Mexican single-case families. No linkage or association could be detected using the FcgammaR polymorphisms in the multicase families. However, an association was found for both FcgammaRIIA-131R and IIIA-176F alleles in the single-case families, but not for IIIB or IIB. Allelic association to SLE was found for a haplotype that included both risk alleles, but not in haplotypes where only one or the other was present. We propose that FcgammaRIIA-131R and FcgammaRIIIA-176F are both risk alleles for SLE transmitted primarily, but not exclusively on a single major haplotype that behaves functionally in a situation similar to that of compound heterozygozity.

  • 44. Magnusson, V
    et al.
    Zunec, R
    Odeberg, Jacob
    KTH, Tidigare Institutioner, Bioteknologi.
    Sturfelt, G
    Truedsson, L
    Alarcon-Riquelme, M E
    Polymorphisms of the Fc gamma receptor type IIB gene are not associated with systemic lupus erythematosus in the Swedish population2004Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 50, nr 4, s. 1348-1350Artikel i tidskrift (Refereegranskat)
  • 45. Matic, L. P.
    et al.
    Iglesias, Maria Jesus
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Vesterlund, M.
    Lengquist, M.
    Hong, Mun-Gwan
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Saieed, S.
    Sanchez-Rivera, Laura
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Berg, M.
    Razuvaev, A.
    Kronqvist, M.
    Lund, K.
    Caidahl, K.
    Gillgren, P.
    Pontén, F.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Hansson, G. K.
    Paulsson-Berne, G.
    Fagman, E.
    Roy, J.
    Hultgren, R.
    Bergström, G.
    Lehtiö, J.
    Odeberg, Jacob
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Hedin, U.
    Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage2018Ingår i: JACC: Basic to Translational Science, ISSN 2452-302X, Vol. 3, nr 4, s. 464-480Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Clinical tools to identify individuals with unstable atherosclerotic lesions are required to improve prevention of myocardial infarction and ischemic stroke. Here, a systems-based analysis of atherosclerotic plaques and plasma from patients undergoing carotid endarterectomy for stroke prevention was used to identify molecular signatures with a causal relationship to disease. Local plasma collected in the lesion proximity following clamping prior to arteriotomy was profiled together with matched peripheral plasma. This translational workflow identified biliverdin reductase B as a novel marker of intraplaque hemorrhage and unstable carotid atherosclerosis, which should be investigated as a potential predictive biomarker for cardiovascular events in larger cohorts.

  • 46. Odeberg, J. M.
    et al.
    Andrade, J.
    Holmberg, K.
    Hoglund, P.
    Malmqvist, U.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    UGT1A polymorphisms in a Swedish cohort and a human diversity panel, and the relation to bilirubin plasma levels in males and females2006Ingår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 62, nr 10, s. 829-837Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The objective of this study was to investigate the prevalence of different polymorphisms and haplotypes associated with individual variations in pharmacokinetics and drug toxicity in the uridine-diphosphate glucuronosyl transferase (UGT) 1A gene in a Swedish cohort (248 healthy volunteers) and in 14 different ethnic groups. We also estimated UGT1A genotype-dependent glucuronidation efficiency using the endogenous substrate bilirubin as an indicator. Methods: Pyrosequencing-based genotyping assays were used to determine the different polymorphisms and haplotypes. Results: Haplotype analysis of the UGT1A1 (*1*28), UGT1A6 (*1*2), and UGT1A7(*1*2*3*4) allelic variants showed that three major haplotypes constituted 84% of the allelic variants in the cohort. We identified 15 haplotypes altogether from all groups, including previously undescribed haplotypes.Testing for the association of genotype and total bilirubin levels (nonfasting) in plasma disclosed that homozygous carriers of the TA allele, irrespective of haplotype combinations, had increased levels of bilirubin compared with noncarriers, but a gender-associated difference was observed. Conclusions: In a Swedish cohort, several genetic variants in the UGT1A gene are common, but prevalence in a population may differ because of ethnicity. A phenotype based on bilirubin levels has limitations in serving as an indicator of pharmacogenetic differences in glucuronidation due to the influence of gender. Because of possible substrate overlap regarding different UGT1A isoforms, determination of haplotypes of potential cis-acting polymorphisms in the UGT1A gene should be considered in pharmacogenetic association studies regarding drugs that undergo glucuronidation.

  • 47.
    Odeberg, Jacob
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Analysis of human gene transcripts: Identification and characterisation based on homology and differential expression1998Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
  • 48.
    Odeberg, Jacob
    et al.
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Ahmadian, Afshin
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Williams, C
    Pontén, F.
    Uhlén, Mathias
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Direct sequencing of the ZNF 189 gene promotor reveals artifact hot spot mutations.Manuskript (preprint) (Övrigt vetenskapligt)
  • 49.
    Odeberg, Jacob
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Freitag, M.
    Odeberg, H.
    Rastam, L.
    Lindblad, U.
    Severity of acute coronary syndrome is predicted by interactions between fibrinogen concentrations and polymorphisms in the GPIIIa and FXIII genes2006Ingår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 4, nr 4, s. 909-912Artikel i tidskrift (Refereegranskat)
  • 50.
    Odeberg, Jacob
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska University Hospital, Sweden.
    Freitag, Michael
    Forssell, Henrik
    Vaara, Ivar
    Persson, Marie-Louise
    Odeberg, Hakan
    Halling, Anders
    Rastam, Lennart
    Lindblad, Ulf
    Influence of pre-existing inflammation on the outcome of acute coronary syndrome: a cross-sectional study2016Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, nr 1, artikel-id e009968Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Inflammation is a well-established risk factor for the development of coronary artery disease (CAD) and acute coronary syndrome (ACS). However, less is known about its influence on the outcome of ACS. The aim of this study was to determine if blood biomarkers of inflammation were associated specifically with acute myocardial infarction (MI) or unstable angina (UA) in patients with ACS. Design: Cross-sectional study. Setting: Patients admitted to the coronary care unit, via the emergency room, at a central county hospital over a 4-year period (1992-1996). Participants: In a substudy of Carlscrona Heart Attack Prognosis Study (CHAPS) of 5292 patients admitted to the coronary care unit, we identified 908 patients aged 30-74 years, who at discharge had received the diagnosis of either MI (527) or UA (381). Main outcome measures: MI or UA, based on the diagnosis set at discharge from hospital. Results: When adjusted for smoking, age, sex and duration of chest pain, concentrations of plasma biomarkers of inflammation (high-sensitivity C reactive protein >2 mg/L (OR=1.40 (1.00 to 1.96) and fibrinogen (p for trend=0.035)) analysed at admission were found to be associated with MI over UA, in an event of ACS. A strong significant association with MI over UA was found for blood cell markers of inflammation, that is, counts of neutrophils (p for trend <0.001), monocytes (p for trend <0.001) and thrombocytes (p for trend=0.021), while lymphocyte count showed no association. Interestingly, eosinophil count (p for trend=0.003) was found to be significantly lower in patients with MI compared to those with UA. Conclusions: Our results show that, in patients with ACS, the blood cell profile and degree of inflammation at admission was associated with the outcome. Furthermore, our data suggest that a pre-existing low-grade inflammation may dispose towards MI over UA.

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