Digitala Vetenskapliga Arkivet

Ändra sökning
Avgränsa sökresultatet
3456789 251 - 300 av 697
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 251.
    Hu, Francis Jingxin
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Volk, Anna-Luisa
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Persson, Helena
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Lund University, Sweden.
    Säll, Anna
    Borrebaeck, Carl
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Rockberg, Johan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Combination of phage and Gram-positive bacterial display of human antibody repertoires enables isolation of functional high affinity binders2018Ingår i: New Biotechnology, ISSN 1871-6784, E-ISSN 1876-4347, Vol. 45, s. 80-88Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Surface display couples genotype with a surface exposed phenotype and thereby allows screening of gene-encoded protein libraries for desired characteristics. Of the various display systems available, phage display is by far the most popular, mainly thanks to its ability to harbour large size libraries. Here, we describe the first use of a Gram-positive bacterial host for display of a library of human antibody genes which, when combined with phage display, provides ease of use for screening, sorting and ranking by flow cytometry. We demonstrate the utility of this method by identifying low nanomolar affinity scFv fragments towards human epidermal growth factor receptor 2 (HER2). The ranking and performance of the scFv isolated by flow sorting in surface-immobilised form was retained when expressed as soluble scFv and analysed by biolayer interferometry, as well as after expression as full-length antibodies in mammalian cells. We also demonstrate the possibility of using Gram-positive bacterial display to directly improve the affinity of the identified binders via an affinity maturation step using random mutagenesis and flow sorting. This combined approach has the potential for a more complete scan of the antibody repertoire and for affinity maturation of human antibody formats.

  • 252.
    Hu, Francis Jingxin
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Volk, Anna-Luisa
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Persson, Helena
    Department of Immunotechnology, Lund University, Medicon Village (Bldg 406), 223 81 Lund, Sweden..
    Säll, Anna
    Department of Immunotechnology, Lund University, Medicon Village (Bldg 406), 223 81 Lund, Sweden..
    Borrebaeck, Carl
    Department of Immunotechnology, Lund University, Medicon Village (Bldg 406), 223 81 Lund, Sweden..
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Rockberg, Johan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Phage and Gram-positive bacterial display of human antibody repertoires enables isolation of functional high affinity bindersIngår i: New Biotechnology, ISSN 1871-6784, E-ISSN 1876-4347Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Surface display couples genotype with a surface exposed phenotype and thereby allows for screening of gene-encoded protein libraries for desired characteristics. Of the various display systems, phage display is by far the most popular, mainly thanks to its ability to harbor large library sizes. Here, we describe the first use of a grampositive host for display of a library of human antibody genes. The method allows for swift generation of binders by combining phage and gram-positive display, for its ease of use for screening, sorting and ranking by flow cytometry. We demonstrate the utility of this method by identifying specific low nanomolar scFv towards human HER2. The ranking and performance of the scFv isolated by flow sorting in surface immobilized form was retained when expressed as soluble scFv and analyzed by biolayer interferometry as well as after expression as full-length antibodies in mammalian cells. We also show the possibility to use gram-positive display to directly improve the affinity of the identified binders via an affinity maturation step using random mutagenesis and flow sorting. We believe this combined approach has the potential for a more complete scan of the antibody repertoire and for swift affinity maturation of human antibody formats.

  • 253.
    Huang, Jinrong
    et al.
    Lars Bolund Inst Regenerat Med, Shenzhen, Peoples R China.;Qingdao Europe Adv Inst Life Sci, Qingdao, Peoples R China.;Univ Copenhagen, Dept Biol, Lab Genom & Mol Biomed, Copenhagen, Denmark.;Aarhus Univ, Dept Biomed, Aarhus, Denmark.;Aarhus Univ Hosp, Steno Diabet Ctr Aarhus, Aarhus, Denmark..
    Lin, Lin
    Aarhus Univ Hosp, Steno Diabet Ctr Aarhus, Aarhus, Denmark..
    Dong, Zhanying
    Lars Bolund Inst Regenerat Med, Shenzhen, Peoples R China.;Qingdao Europe Adv Inst Life Sci, Qingdao, Peoples R China..
    Yang, Ling
    Lars Bolund Inst Regenerat Med, Shenzhen, Peoples R China.;Qingdao Europe Adv Inst Life Sci, Qingdao, Peoples R China..
    Zheng, Tianyu
    Lars Bolund Inst Regenerat Med, Shenzhen, Peoples R China.;Qingdao Europe Adv Inst Life Sci, Qingdao, Peoples R China..
    Gu, Weiwang
    Wuyi Univ, Sch Biotechnol & Hlth Sci, Jiangmen, Peoples R China..
    Zhang, Yan
    Wuhan Univ, Renmin Hosp, Dept Clin Lab, Wuhan, Hubei, Peoples R China..
    Yin, Tailang
    Wuhan Univ, Renmin Hosp, Dept Clin Lab, Wuhan, Hubei, Peoples R China..
    Sjöstedt, Evelina
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Mulder, Jan
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Kristiansen, Karsten
    Bolund, Lars
    Lars Bolund Inst Regenerat Med, Shenzhen, Peoples R China.;Qingdao Europe Adv Inst Life Sci, Qingdao, Peoples R China.;Aarhus Univ, Dept Biomed, Aarhus, Denmark..
    Luo, Yonglun
    Lars Bolund Inst Regenerat Med, Shenzhen, Peoples R China.;Qingdao Europe Adv Inst Life Sci, Qingdao, Peoples R China.;Aarhus Univ, Dept Biomed, Aarhus, Denmark..
    A porcine brain-wide RNA editing landscape2021Ingår i: Communications Biology, E-ISSN 2399-3642, Vol. 4, nr 1, artikel-id 717Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR enzymes, is an essential post-transcriptional modification. Although hundreds of thousands of RNA editing sites have been reported in mammals, brain-wide analysis of the RNA editing in the mammalian brain remains rare. Here, a genome-wide RNA-editing investigation is performed in 119 samples, representing 30 anatomically defined subregions in the pig brain. We identify a total of 682,037 A-to-I RNA editing sites of which 97% are not identified before. Within the pig brain, cerebellum and olfactory bulb are regions with most edited transcripts. The editing level of sites residing in protein-coding regions are similar across brain regions, whereas region-distinct editing is observed in repetitive sequences. Highly edited conserved recoding events in pig and human brain are found in neurotransmitter receptors, demonstrating the evolutionary importance of RNA editing in neurotransmission functions. Although potential data biases caused by age, sex or health status are not considered, this study provides a rich resource to better understand the evolutionary importance of post-transcriptional RNA editing. Huang et al performed a genome-wide RNA editing investigation in the porcine brain in which they found over 680,000 A-to-I RNA editing sites. They identified conserved recoding events between pig and human brains thus providing an extensive resource to aid our understanding of the evolutionary importance of post-transcriptional RNA editing.

  • 254. Huang, Mingtao
    et al.
    Bai, Yunpeng
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. East China University of Science and Technology, China.
    Sjöström, Staffan L.
    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.
    Liu, Zihe
    Petranovic, Dina
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Technical University of Denmark, Denmark .
    Jönsson, Håkan N.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Andersson Svahn, Helene
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nielsen, Jens
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Chalmers University of Technology, Sweden; Technical University of Denmark, Denmark.
    Microfluidic screening and whole-genome sequencing identifies mutations associated with improved protein secretion by yeast2015Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, nr 34, s. E4689-E4696Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    There is an increasing demand for biotech-based production of recombinant proteins for use as pharmaceuticals in the food and feed industry and in industrial applications. Yeast Saccharomyces cerevisiae is among preferred cell factories for recombinant protein production, and there is increasing interest in improving its protein secretion capacity. Due to the complexity of the secretory machinery in eukaryotic cells, it is difficult to apply rational engineering for construction of improved strains. Here we used highthroughput microfluidics for the screening of yeast libraries, generated by UV mutagenesis. Several screening and sorting rounds resulted in the selection of eight yeast clones with significantly improved secretion of recombinant α-amylase. Efficient secretion was genetically stable in the selected clones. We performed wholegenome sequencing of the eight clones and identified 330 mutations in total. Gene ontology analysis of mutated genes revealed many biological processes, including some that have not been identified before in the context of protein secretion. Mutated genes identified in this study can be potentially used for reverse metabolic engineering, with the objective to construct efficient cell factories for protein secretion. The combined use of microfluidics screening and whole-genome sequencing to map the mutations associated with the improved phenotype can easily be adapted for other products and cell types to identify novel engineering targets, and this approach could broadly facilitate design of novel cell factories.

  • 255.
    Hudson, Elton P.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Nikoshkov, Andrej
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Rockberg, Johan
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Automated Solid-Phase Subcloning Based on Beads Brought into Proximity by Magnetic Force2012Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 7, nr 5, s. e37429-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the fields of proteomics, metabolic engineering and synthetic biology there is a need for high-throughput and reliable cloning methods to facilitate construction of expression vectors and genetic pathways. Here, we describe a new approach for solid-phase cloning in which both the vector and the gene are immobilized to separate paramagnetic beads and brought into proximity by magnetic force. Ligation events were directly evaluated using fluorescent-based microscopy and flow cytometry. The highest ligation efficiencies were obtained when gene- and vector-coated beads were brought into close contact by application of a magnet during the ligation step. An automated procedure was developed using a laboratory workstation to transfer genes into various expression vectors and more than 95% correct clones were obtained in a number of various applications. The method presented here is suitable for efficient subcloning in an automated manner to rapidly generate a large number of gene constructs in various vectors intended for high throughput applications.

  • 256.
    Hudson, Elton P.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Rockberg, Johan
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Multiplex epitope mapping using bacterial surface display reveals both linear and conformational epitopes2012Ingår i: Scientific Reports, ISSN 2045-2322, Vol. 2, s. 706-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    As antibody-based diagnosis and therapy grow at an increased pace, there is a need for methods which rapidly and accurately determine antibody-antigen interactions. Here, we report a method for the multiplex determination of antibody epitopes using bacterial cell-surface display. A protein-fragment library with 107 cell clones, covering 60 clinically-relevant protein targets, was created and characterized with massively parallel sequencing. Using this multi-target fragment library we determined simultaneously epitopes of commercial monoclonal and polyclonal antibodies targeting PSMA, EGFR, and VEGF. Off-target binding was observed for one of the antibodies, which demonstrates the method's ability to reveal cross-reactivity. We exemplify the detection of structural epitopes by mapping the therapeutic antibody Avastin. Based on our findings we suggest this method to be suitable for mapping linear and structural epitopes of monoclonal and polyclonal antibodies in a multiplex fashion and could find applicability in serum profiling as well as other protein-protein interaction studies.

  • 257. Hudson, Thomas J.
    et al.
    Anderson, Warwick
    Aretz, Axel
    Barker, Anna D.
    Bell, Cindy
    Bernabe, Rosa R.
    Bhan, M. K.
    Calvo, Fabien
    Eerola, Iiro
    Gerhard, Daniela S.
    Guttmacher, Alan
    Guyer, Mark
    Hemsley, Fiona M.
    Jennings, Jennifer L.
    Kerr, David
    Klatt, Peter
    Kolar, Patrik
    Kusuda, Jun
    Lane, David P.
    Laplace, Frank
    Lu, Youyong
    Nettekoven, Gerd
    Ozenberger, Brad
    Peterson, Jane
    Rao, T. S.
    Remacle, Jacques
    Schafer, Alan J.
    Shibata, Tatsuhiro
    Stratton, Michael R.
    Vockley, Joseph G.
    Watanabe, Koichi
    Yang, Huanming
    Yuen, Matthew M. F.
    Knoppers, M.
    Bobrow, Martin
    Cambon-Thomsen, Anne
    Dressler, Lynn G.
    Dyke, Stephanie O. M.
    Joly, Yann
    Kato, Kazuto
    Kennedy, Karen L.
    Nicolas, Pilar
    Parker, Michael J.
    Rial-Sebbag, Emmanuelle
    Romeo-Casabona, Carlos M.
    Shaw, Kenna M.
    Wallace, Susan
    Wiesner, Georgia L.
    Zeps, Nikolajs
    Lichter, Peter
    Biankin, Andrew V.
    Chabannon, Christian
    Chin, Lynda
    Clement, Bruno
    de Alava, Enrique
    Degos, Francoise
    Ferguson, Martin L.
    Geary, Peter
    Hayes, D. Neil
    Johns, Amber L.
    Nakagawa, Hidewaki
    Penny, Robert
    Piris, Miguel A.
    Sarin, Rajiv
    Scarpa, Aldo
    van de Vijver, Marc
    Futreal, P. Andrew
    Aburatani, Hiroyuki
    Bayes, Monica
    Bowtell, David D. L.
    Campbell, Peter J.
    Estivill, Xavier
    Grimmond, Sean M.
    Gut, Ivo
    Hirst, Martin
    Lopez-Otin, Carlos
    Majumder, Partha
    Marra, Marco
    Ning, Zemin
    Puente, Xose S.
    Ruan, Yijun
    Stunnenberg, Hendrik G.
    Swerdlow, Harold
    Velculescu, Victor E.
    Wilson, Richard K.
    Xue, Hong H.
    Yang, Liu
    Spellman, Paul T.
    Bader, Gary D.
    Boutros, Paul C.
    Flicek, Paul
    Getz, Gad
    Guigo, Roderic
    Guo, Guangwu
    Haussler, David
    Heath, Simon
    Hubbard, Tim J.
    Jiang, Tao
    Jones, Steven M.
    Li, Qibin
    Lopez-Bigas, Nuria
    Luo, Ruibang
    Pearson, John V.
    Quesada, Victor
    Raphael, Benjamin J.
    Sander, Chris
    Speed, Terence P.
    Stuart, Joshua M.
    Teague, Jon W.
    Totoki, Yasushi
    Tsunoda, Tatsuhiko
    Valencia, Alfonso
    Wheeler, David A.
    Wu, Honglong
    Zhao, Shancen
    Zhou, Guangyu
    Stein, Lincoln D.
    Lathrop, Mark
    Ouellette, B. F. Francis
    Thomas, Gilles
    Yoshida, Teruhiko
    Axton, Myles
    Gunter, Chris
    McPherson, John D.
    Miller, Linda J.
    Kasprzyk, Arek
    Zhang, Junjun
    Haider, Syed A.
    Wang, Jianxin
    Yung, Christina K.
    Cros, Anthony
    Liang, Yong
    Gnaneshan, Saravanamuttu
    Guberman, Jonathan
    Hsu, Jack
    Chalmers, Don R. C.
    Hasel, Karl W.
    Kaan, Terry S. H.
    Knoppers, Bartha M.
    Lowrance, William W.
    Masui, Tohru
    Rodriguez, Laura Lyman
    Vergely, Catherine
    Cloonan, Nicole
    Defazio, Anna
    Eshleman, James R.
    Etemadmoghadam, Dariush
    Gardiner, Brooke B.
    Kench, James G.
    Sutherland, Robert L.
    Tempero, Margaret A.
    Waddell, Nicola J.
    Wilson, Peter J.
    Gallinger, Steve
    Tsao, Ming-Sound
    Shaw, Patricia A.
    Petersen, Gloria M.
    Mukhopadhyay, Debabrata
    DePinho, Ronald A.
    Thayer, Sarah
    Muthuswamy, Lakshmi
    Shazand, Kamran
    Beck, Timothy
    Sam, Michelle
    Timms, Lee
    Ballin, Vanessa
    Ji, Jiafu
    Zhang, Xiuqing
    Chen, Feng
    Hu, Xueda
    Yang, Qi
    Tian, Geng
    Zhang, Lianhai
    Xing, Xiaofang
    Li, Xianghong
    Zhu, Zhenggang
    Yu, Yingyan
    Yu, Jun
    Tost, Joerg
    Brennan, Paul
    Holcatova, Ivana
    Zaridze, David
    Brazma, Alvis
    Egevad, Lars
    Prokhortchouk, Egor
    Banks, Rosamonde Elizabeth
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik.
    Viksna, Juris
    Pontén, Fredrik
    Skryabin, Konstantin
    Birney, Ewan
    Borg, Ake
    Borresen-Dale, Anne-Lise
    Caldas, Carlos
    Foekens, John A.
    Martin, Sancha
    Reis-Filho, Jorge S.
    Richardson, Andrea L.
    Sotiriou, Christos
    van't Veer, Laura
    Birnbaum, Daniel
    Blanche, Helene
    Boucher, Pascal
    Boyault, Sandrine
    Masson-Jacquemier, Jocelyne D.
    Pauporte, Iris
    Pivot, Xavier
    Vincent-Salomon, Anne
    Tabone, Eric
    Theillet, Charles
    Treilleux, Isabelle
    Bioulac-Sage, Paulette
    Decaens, Thomas
    Franco, Dominique
    Gut, Marta
    Samuel, Didier
    Zucman-Rossi, Jessica
    Eils, Roland
    Brors, Benedikt
    Korbel, Jan O.
    Korshunov, Andrey
    Landgraf, Pablo
    Lehrach, Hans
    Pfister, Stefan
    Radlwimmer, Bernhard
    Reifenberger, Guido
    Taylor, Michael D.
    von Kalle, Christof
    Majumder, Partha P.
    Pederzoli, Paolo
    Lawlor, Rita T.
    Delledonne, Massimo
    Bardelli, Alberto
    Gress, Thomas
    Klimstra, David
    Zamboni, Giuseppe
    Nakamura, Yusuke
    Miyano, Satoru
    Fujimoto, Akihiro
    Campo, Elias
    de Sanjose, Silvia
    Montserrat, Emili
    Gonzalez-Diaz, Marcos
    Jares, Pedro
    Himmelbauer, Heinz
    Bea, Silvia
    Aparicio, Samuel
    Easton, Douglas F.
    Collins, Francis S.
    Compton, Carolyn C.
    Lander, Eric S.
    Burke, Wylie
    Green, Anthony R.
    Hamilton, Stanley R.
    Kallioniemi, Olli P.
    Ley, Timothy J.
    Liu, Edison T.
    Wainwright, Brandon J.
    International network of cancer genome projects2010Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, nr 7291, s. 993-998Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

  • 258.
    Häggmark, Anna
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Byström, Sanna
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ayoglu, Burcu
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Qundos, Ulrika
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Khademi, M.
    Olsson, T.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Antibody-based profiling of cerebrospinal fluid within multiple sclerosis2013Ingår i: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 13, nr 15, s. 2256-2267Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antibody suspension bead arrays have proven to enable multiplexed and high-throughput protein profiling in unfractionated plasma and serum samples through a direct labeling approach. We here describe the development and application of an assay for protein profiling of cerebrospinal fluid (CSF). While setting up the assay, systematic intensity differences between sample groups were observed that reflected inherent sample specific total protein amounts. Supplementing the labeling reaction with BSA and IgG diminished these differences without impairing the apparent sensitivity of the assay. We also assessed the effects of heat treatment on the analysis of CSF proteins and applied the assay to profile 43 selected proteins by 101 antibodies in 339 CSF samples from a multiple sclerosis (MS) cohort. Two proteins, GAP43 and SERPINA3 were found to have a discriminating potential with altered intensity levels between sample groups. GAP43 was detected at significantly lower levels in secondary progressive MS compared to early stages of MS and the control group of other neurological diseases. SERPINA3 instead was detected at higher levels in all MS patients compared to controls. The developed assay procedure now offers new possibilities for broad-scale protein profiling of CSF within neurological disorders.

  • 259.
    Häggmark, Anna
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mikus, Maria
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mohsenchian, Atefeh
    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.
    Forsström, Björn
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Gajewska, Beata
    Baranczyk-Kuzma, Anna
    Uhlén, Mathias
    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.
    Kuzma-Kozakiewicz, Magdalena
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Plasma profiling revelas three proteins associated to amyotrophic lateral sclerosis2014Ingår i: Annals of Clinical and Translational Neurology, ISSN 2328-9503, Vol. 1, nr 8, s. 544-553Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease leading to muscular paralysis and death within 3-5 years from onset. Currently, there are no reliable and sensitive markers able to substantially shorten the diagnosis delay. The objective of the study was to analyze a large number of proteins in plasma from patients with various clinical phenotypes of ALS in search for novel proteins or protein profiles that could serve as potential indicators of disease.

    METHODS: Affinity proteomics in the form of antibody suspension bead arrays were applied to profile plasma samples from 367 ALS patients and 101 controls. The plasma protein content was directly labeled and protein profiles obtained using 352 antibodies from the Human Protein Atlas targeting 278 proteins. A focused bead array was then built to further profile eight selected protein targets in all available samples.

    RESULTS: Disease-associated significant differences were observed and replicated for profiles from antibodies targeting the proteins: neurofilament medium polypeptide (NEFM), solute carrier family 25 (SLC25A20), and regulator of G-protein signaling 18 (RGS18).

    INTERPRETATION: Upon further validation in several independent cohorts with inclusion of a broad range of other neurological disorders as controls, the alterations of these three protein profiles in plasma could potentially provide new molecular markers of disease that contribute to the quest of understanding ALS pathology.

    Ladda ner fulltext (pdf)
    fulltext
  • 260.
    Häggmark, Anna
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Neiman, Maja
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Drobin, Kimi
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Zwahlen, Martin
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Schwenk, Jochen M
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Classification of protein profiles from antibody microarrays using heat and detergent treatment.2011Ingår i: New Biotechnology, ISSN 1871-6784, E-ISSN 1876-4347, Vol. 29, nr 5, s. 564-570Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antibody microarrays offer new opportunities for exploring the proteome and to identify biomarker candidates in human serum and plasma. Here, we have investigated the effect of heat and detergents on an antibody-based suspension bead array (SBA) assay using polyclonal antibodies and biotinylated plasma samples. With protein profiles from more than 2300 antibodies generated in 384-plex antibody SBAs, three major classes of heat and detergent susceptibility could be described. The results show that washing of the beads with SDS (rather than Tween) after target binding lowered intensity levels of basically all profiles and that about 50% of the profiles appeared to be lowered to a similar extent by heating of the sample. About 33% of the profiles appeared to be insensitive to heat treatment while another 17% showed a positive influence of heat to yield elevated profiles. The results suggest that the classification of antibodies is driven by the molecular properties of the antibody-antigen interaction and can generally not be predicted based on protein class or Western blot data. The experimental scheme presented here can be used to systematically categorize antibodies and thereby combine antibodies with similar properties into targeted arrays for analysis of plasma and serum.

  • 261.
    Häggmark, Anna
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Zandian, Arash
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Forsström, Björn
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    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.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Autoantibody targets in vaccine-associated narcolepsyManuskript (preprint) (Övrigt vetenskapligt)
  • 262.
    Häggmark-Månberg, Anna
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Zandian, Arash
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Forsström, Björn
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Khademi, Mohsen
    Bomfim, Izaura Lima
    Hellström, Cecilia
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Arnheim-Dahlström, Lisen
    Hallböök, Tove
    Darin, Niklas
    Lundberg, Ingrid E.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Partinen, Markku
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Olsson, Tomas
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Autoantibody targets in vaccine-associated narcolepsy2016Ingår i: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 49, nr 6, s. 421-433Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Narcolepsy is a chronic sleep disorder with a yet unknown cause, but the specific loss of hypocretin-producing neurons together with a strong human leukocyte antigen (HLA) association has led to the hypothesis that autoimmune mechanisms might be involved. Here, we describe an extensive effort to profile autoimmunity repertoires in serum with the aim to find disease-related autoantigens. Initially, 57 serum samples from vaccine-associated and sporadic narcolepsy patients and controls were screened for IgG reactivity towards 10 846 fragments of human proteins using planar microarrays. The discovered differential reactivities were verified on suspension bead arrays in the same sample collection followed by further investigation of 14 antigens in 176 independent samples, including 57 narcolepsy patients. Among these 14 antigens, methyltransferase-like 22 (METTL22) and 5'-nucleotidase cytosolic IA (NT5C1A) were recognized at a higher frequency in narcolepsy patients of both sample sets. Upon sequence analysis of the 14 proteins, polymerase family, member 3 (PARP3), acyl-CoA-binding domain containing 7 (ARID4B), glutaminase 2 (GLS2) and cyclin-dependent kinase-like 1 (CDKL1) were found to contain amino acid sequences with homology to proteins found in the H1N1 vaccine. These findings could become useful elements of further clinical assays that aim towards a better phenotypic understanding of narcolepsy and its triggers.

  • 263.
    Häussler, Ragna S.
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Bendes, Annika
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Iglesias, Maria Jesus
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab. Division of Internal Medicine, University Hospital of North Norway, Tromsø, 9010, Norway.
    Sanchez-Rivera, Laura
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Dodig-Crnkovic, Tea
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Byström, Sanna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Fredolini, Claudia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Birgersson, Elin
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Dale, Matilda
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Edfors, Fredrik
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Fagerberg, Linn
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Rockberg, Johan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Tegel, Hanna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Uhlèn, Mathias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, 2970, Denmark.
    Qundos, Ulrika
    Atlas Antibodies AB, Bromma, 168 69, Sweden.
    Schwenk, Jochen M.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Systematic Development of Sandwich Immunoassays for the Plasma Secretome2019Ingår i: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, artikel-id 1900008Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The plasma proteome offers a clinically useful window into human health. Recent advances from highly multiplexed assays now call for appropriate pipelines to validate individual candidates. Here, a workflow is developed to build dual binder sandwich immunoassays (SIA) and for proteins predicted to be secreted into plasma. Utilizing suspension bead arrays, ≈1800 unique antibody pairs are first screened against 209 proteins with recombinant proteins as well as EDTA plasma. Employing 624 unique antibodies, dilution-dependent curves in plasma and concentration-dependent curves of full-length proteins for 102 (49%) of the targets are obtained. For 22 protein assays, the longitudinal, interindividual, and technical performance is determined in a set of plasma samples collected from 18 healthy subjects every third month over 1 year. Finally, 14 of these assays are compared with with SIAs composed of other binders, proximity extension assays, and affinity-free targeted mass spectrometry. The workflow provides a multiplexed approach to screen for SIA pairs that suggests using at least three antibodies per target. This design is applicable for a wider range of targets of the plasma proteome, and the assays can be applied for discovery but also to validate emerging candidates derived from other platforms.

  • 264. Idborg, Helena
    et al.
    Zandian, Arash
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hellstrom, Cecilia
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mattsson, Cecilia
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Fredolini, Claudia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    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.
    Ayoglu, Burcu
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Neiman, Maja
    Gunnarsson, Iva
    Svenungsson, Elisabet
    Jakobsson, Per-Johan
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    PROTEIN PROFILING IN PLASMA REVEALS MOLECULAR SUBGROUPS IN SYSTEMIC LUPUS ERYTHEMATOSUS2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. A52-A52Artikel i tidskrift (Refereegranskat)
  • 265.
    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)
  • 266.
    Iglesias, Maria Jesus
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. Univ Hosp North Norway, Div Internal Med, Tromso, Norway..
    Kruse, Larissa D.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sanchez-Rivera, Laura
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Enge, Linnea
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Dusart, Philip
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Renne, Thomas
    Univ Med Ctr Hamburg Eppendorf, Inst Clin Chem & Lab Med, Hamburg, Germany.;Royal Coll Surgeons Ireland, Irish Ctr Vasc Biol, Sch Pharm & Biomol Sci, Dublin, Ireland.;Johannes Gutenberg Univ Mainz, Ctr Thrombosis & Hemostasis CTH, Med Ctr, Mainz, Germany..
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Bergstrom, Goran
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden..
    Odeberg, Jacob
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. Univ Hosp North Norway, Div Internal Med, Tromso, Norway.;Arctic Univ Norway, Dept Clin Med, Tromso, Norway.;Karolinska Univ Hosp, Dept Hematol, Coagulat Unit, Stockholm, Sweden..
    Butler, Lynn M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. Karolinska Inst, Dept Mol Med & Surg, Clin Chem & Blood Coagulat Res, SE-17176 Stockholm, Sweden.;Arctic Univ Norway, Dept Clin Med, Tromso, Norway.;Karolinska Univ Hosp, Karolinska Univ Lab, Clin Chem, Stockholm, Sweden..
    Identification of Endothelial Proteins in Plasma Associated With Cardiovascular Risk Factors2021Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 41, nr 12, s. 2990-3004Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Endothelial cell (EC) dysfunction is a well-established response to cardiovascular disease risk factors, such as smoking and obesity. Risk factor exposure can modify EC signaling and behavior, leading to arterial and venous disease development. Here, we aimed to identify biomarker panels for the assessment of EC dysfunction, which could be useful for risk stratification or to monitor treatment response. Approach and Results: We used affinity proteomics to identify EC proteins circulating in plasma that were associated with cardiovascular disease risk factor exposure. Two hundred sixteen proteins, which we previously predicted to be EC-enriched across vascular beds, were measured in plasma samples (N=1005) from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study) pilot. Thirty-eight of these proteins were associated with body mass index, total cholesterol, low-density lipoprotein, smoking, hypertension, or diabetes. Sex-specific analysis revealed that associations predominantly observed in female- or male-only samples were most frequently with the risk factors body mass index, or total cholesterol and smoking, respectively. We show a relationship between individual cardiovascular disease risk, calculated with the Framingham risk score, and the corresponding biomarker profiles. Conclusions: EC proteins in plasma could reflect vascular health status.

  • 267.
    Iglesias, Maria Jesus
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. Division of Internal Medicine, University Hospital of North Norway (UNN), PB100, 9038, Tromsø, Norway; Translational Vascular Research, Department of Clinical Medicine, UiT The Arctic University of Norway, 9019, Tromsø, Norway.
    Sanchez-Rivera, Laura
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Ibrahim-Kosta, Manal
    Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France, HemoVasc (CRB AP-HM HemoVasc).
    Naudin, Clément
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab. Translational Vascular Research, Department of Clinical Medicine, UiT The Arctic University of Norway, 9019, Tromsø, Norway.
    Munsch, Gaëlle
    University of Bordeaux, INSERM, Bordeaux Population Health Research Center, UMR 1219, ELEANOR, Bordeaux, France, ELEANOR.
    Goumidi, Louisa
    Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France, HemoVasc (CRB AP-HM HemoVasc).
    Farm, Maria
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
    Smith, Philip M.
    Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden; Theme of Emergency and Reparative Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Thibord, Florian
    Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA; The Framingham Heart Study, Boston University, Framingham, MA, USA.
    Kral-Pointner, Julia Barbara
    Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
    Hong, Mun-Gwan
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Suchon, Pierre
    Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France, HemoVasc (CRB AP-HM HemoVasc).
    Germain, Marine
    University of Bordeaux, INSERM, Bordeaux Population Health Research Center, UMR 1219, ELEANOR, Bordeaux, France, ELEANOR; Laboratory of Excellence GENMED (Medical Genomics), Bordeaux, France.
    Schottmaier, Waltraud
    Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
    Dusart, Philip
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab. Translational Vascular Research, Department of Clinical Medicine, UiT The Arctic University of Norway, 9019, Tromsø, Norway.
    Boland, Anne
    Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), 91057, Evry, France; Laboratory of Excellence GENMED (Medical Genomics), Evry, France.
    Kotol, David
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Edfors, Fredrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Koprulu, Mine
    MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, CB2 0QQ, UK.
    Pietzner, Maik
    MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, CB2 0QQ, UK; Computational Medicine, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany; Precision Healthcare University Research Institute, Queen Mary University of London, London, UK.
    Langenberg, Claudia
    MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, CB2 0QQ, UK; Computational Medicine, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany; Precision Healthcare University Research Institute, Queen Mary University of London, London, UK.
    Damrauer, Scott M.
    Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA; Department of Surgery and Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
    Johnson, Andrew D.
    Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA; The Framingham Heart Study, Boston University, Framingham, MA, USA.
    Klarin, Derek M.
    VA Palo Alto Healthcare System, Palo Alto, CA, USA; Department of Vascular Surgery, Stanford University School of Medicine, Palo Alto, CA, USA.
    Smith, Nicholas L.
    Department of Epidemiology, University of Washington, Seattle, WA, USA; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA; Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, WA, USA.
    Smadja, David M.
    Hematology Department and Biosurgical Research Lab (Carpentier Foundation), European Georges Pompidou Hospital, Assistance Publique Hôpitaux de Paris, 20 rue Leblanc, Paris, 75015, France, 20 rue Leblanc; Innovative Therapies in Haemostasis, INSERM, Université de Paris, 4 avenue de l’Observatoire, Paris, 75270, France, 4 avenue de l’Observatoire.
    Holmström, Margareta
    Coagulation Unit, Department of Haematology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden, SE-171 76.
    Magnusson, Maria
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Coagulation Unit, Department of Haematology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden, SE-171 76; Department of Clinical Science, Intervention and Technology, Karolinska Institute, 171 77, Stockholm, Sweden, 171 77.
    Silveira, Angela
    Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Renné, Thomas
    Institute for Clinical Chemistry and Laboratory Medicine, University Medical Centre Hamburg-Eppendorf, D-20246, Hamburg, Germany; Center for Thrombosis and Hemostasis (CTH), Johannes Gutenberg University Medical Center, D-, 55131, Mainz, Germany; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin 2, D02 YN77, Ireland.
    Martinez-Perez, Angel
    Genomics of Complex Diseases Group, Research Institute Hospital de la Santa Creu i Sant Pau. IIB Sant Pau, Barcelona, Spain.
    Emmerich, Joseph
    Department of vascular medicine, Paris Saint-Joseph Hospital Group, INSERM 1153-CRESS, University of Paris Cité, 185 rue Raymond Losserand, Paris, 75674, France, 185 rue Raymond Losserand.
    Deleuze, Jean Francois
    Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), 91057, Evry, France; Laboratory of Excellence GENMED (Medical Genomics), Evry, France; Centre D’Etude du Polymorphisme Humain, Fondation Jean Dausset, Paris, France.
    Antovic, Jovan
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
    Soria Fernandez, Jose Manuel
    Genomics of Complex Diseases Group, Research Institute Hospital de la Santa Creu i Sant Pau. IIB Sant Pau, Barcelona, Spain.
    Assinger, Alice
    Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Souto Andres, Joan Carles
    Unitat d’Hemostàsia i Trombosi. Hospital de la Santa Creu i Sant Pau and IIB-Sant Pau, Barcelona, Spain.
    Morange, Pierre Emmanuel
    Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique—Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France, HemoVasc (CRB AP-HM HemoVasc).
    Butler, Lynn M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. Translational Vascular Research, Department of Clinical Medicine, UiT The Arctic University of Norway, 9019, Tromsø, Norway; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
    Trégouët, David Alexandre
    University of Bordeaux, INSERM, Bordeaux Population Health Research Center, UMR 1219, ELEANOR, Bordeaux, France, ELEANOR; Laboratory of Excellence GENMED (Medical Genomics), Bordeaux, France.
    Odeberg, Jacob
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Cellulär och klinisk proteomik. Division of Internal Medicine, University Hospital of North Norway (UNN), PB100, 9038, Tromsø, Norway; Translational Vascular Research, Department of Clinical Medicine, UiT The Arctic University of Norway, 9019, Tromsø, Norway; Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden; Coagulation Unit, Department of Haematology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden, SE-171 76.
    Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism2023Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 14, nr 1, artikel-id 3280Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.

  • 268.
    Jahn, Michael
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. K.
    Vialas, Vital
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Karlsen, Jan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Maddalo, Gianluca
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Edfors, Fredrik
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Forsström, Björn
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Käll, Lukas
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hudson, Elton P.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Growth of Cyanobacteria Is Constrained by the Abundance of Light and Carbon Assimilation Proteins2018Ingår i: Cell Reports, E-ISSN 2211-1247, Vol. 25, nr 2, s. 478-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyanobacteria must balance separate demands for energy generation, carbon assimilation, and biomass synthesis. We used shotgun proteomics to investigate proteome allocation strategies in the model cyanobacterium Synechocystis sp. PCC 6803 as it adapted to light and inorganic carbon (C-i) limitation. When partitioning the proteome into seven functional sectors, we find that sector sizes change linearly with growth rate. The sector encompassing ribosomes is significantly smaller than in E. coli, which may explain the lower maximum growth rate in Synechocystis. Limitation of light dramatically affects multiple proteome sectors, whereas the effect of C-i limitation is weak. Carbon assimilation proteins respond more strongly to changes in light intensity than to C-i. A coarse-grained cell economy model generally explains proteome trends. However, deviations from model predictions suggest that the large proteome sectors for carbon and light assimilation are not optimally utilized under some growth conditions and may constrain the proteome space available to ribosomes.

  • 269. Jakobsen, Lis
    et al.
    Vanselow, Katja
    Skogs, Marie
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Toyoda, Yusuke
    Lundberg, Emma
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Poser, Ina
    Falkenby, Lasse G.
    Bennetzen, Martin
    Westendorf, Jens
    Nigg, Erich A.
    Uhlen, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Hyman, Anthony A.
    Andersen, Jens S.
    Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods2011Ingår i: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 30, nr 8, s. 1520-1535Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Centrosomes in animal cells are dynamic organelles with a proteinaceous matrix of pericentriolar material assembled around a pair of centrioles. They organize the microtubule cytoskeleton and the mitotic spindle apparatus. Mature centrioles are essential for biogenesis of primary cilia that mediate key signalling events. Despite recent advances, the molecular basis for the plethora of processes coordinated by centrosomes is not fully understood. We have combined protein identification and localization, using PCP-SILAC mass spectrometry, BAC transgeneOmics, and antibodies to define the constituents of human centrosomes. From a background of non-specific proteins, we distinguished 126 known and 40 candidate centrosomal proteins, of which 22 were confirmed as novel components. An antibody screen covering 4000 genes revealed an additional 113 candidates. We illustrate the power of our methods by identifying a novel set of five proteins preferentially associated with mother or daughter centrioles, comprising genes implicated in cell polarity. Pulsed labelling demonstrates a remarkable variation in the stability of centrosomal protein complexes. These spatiotemporal proteomics data provide leads to the further functional characterization of centrosomal proteins.

  • 270. Janzi, M.
    et al.
    Ödling, Jenny
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Pan-Hammarstrom, Q.
    Sundberg, Mårten
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Lundeberg, Joakim
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Hammarstrom, L.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Serum microarrays for large scale screening of protein levels2005Ingår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 4, nr 12, s. 1942-1947Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a great need for comprehensive proteomic analysis of large patient cohorts of plasma and serum samples to identify biomarkers of human diseases. Here we describe a new antibody-based proteomic approach involving a reverse array format where serum samples are spotted on a microarray. This enables all samples to be screened for their content of a certain serum protein in a single experiment using target-recognizing antibodies and fluorescently labeled secondary antibodies. The procedure is illustrated with the analysis of the IgA levels in 2009 spotted serum samples, and the data are compared with clinical routine measurements. The results suggest that it is possible to simultaneously screen thousands of complex clinical serum samples for their content of the relative amount of specific serum proteins of clinical relevance.

  • 271.
    Jennbacken, Karin
    et al.
    AstraZeneca, BioPharmaceut R&D, Biosci Cardiovasc, Cardiovasc,Renal & Metab,Res & Early Dev, S-43150 Molndal, Sweden..
    Wagberg, Fredrik
    AstraZeneca, Mechanist Biol & Profiling, Discovery Sci, R&D, S-43150 Molndal, Sweden..
    Karlsson, Ulla
    AstraZeneca, Mechanist Biol & Profiling, Discovery Sci, R&D, S-43150 Molndal, Sweden..
    Eriksson, Jerry
    AstraZeneca, BioPharmaceut R&D, Biosci Cardiovasc, Cardiovasc,Renal & Metab,Res & Early Dev, S-43150 Molndal, Sweden..
    Magnusson, Lisa
    AstraZeneca, BioPharmaceut R&D, Biosci Cardiovasc, Cardiovasc,Renal & Metab,Res & Early Dev, S-43150 Molndal, Sweden..
    Chimienti, Marjorie
    AstraZeneca, BioPharmaceut R&D, Biosci Cardiovasc, Cardiovasc,Renal & Metab,Res & Early Dev, S-43150 Molndal, Sweden..
    Ricchiuto, Piero
    AstraZeneca, R&D, Quantitat Biol, Discovery Sci, Cambridge CB4 0WG, England..
    Bernstroem, Jenny
    AstraZeneca, R&D, Discovery Sci, Discovery Biol, S-43150 Molndal, Sweden..
    Ding, Mei
    AstraZeneca, R&D, Discovery Sci, Discovery Biol, S-43150 Molndal, Sweden..
    Ross-Thriepland, Douglas
    AstraZeneca, R&D, Discovery Sci, Discovery Biol, Cambridge CB4 0WG, England..
    Xue, Yafeng
    AstraZeneca, R&D, Discovery Sci, Struct & Biophys & Fragment Screening, S-43150 Molndal, Sweden..
    Peiris, Diluka
    Attana AB, S-11419 Stockholm, Sweden..
    Aastrup, Teodor
    Attana AB, S-11419 Stockholm, Sweden..
    Tegel, Hanna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Hober, Sophia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Sivertsson, Åsa
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Uhlén, Mathias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Stroemstedt, Per-Erik
    AstraZeneca, Mechanist Biol & Profiling, Discovery Sci, R&D, S-43150 Molndal, Sweden..
    Davies, Rick
    AstraZeneca, R&D, Discovery Sci, Discovery Biol, Cambridge CB4 0WG, England..
    Holmberg Schiavone, Lovisa
    AstraZeneca, R&D, Discovery Sci, Discovery Biol, S-43150 Molndal, Sweden..
    Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells2019Ingår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 20, nr 23, artikel-id 6037Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Paracrine factors can induce cardiac regeneration and repair post myocardial infarction by stimulating proliferation of cardiac cells and inducing the anti-fibrotic, antiapoptotic, and immunomodulatory effects of angiogenesis. Here, we screened a human secretome library, consisting of 923 growth factors, cytokines, and proteins with unknown function, in a phenotypic screen with human cardiac progenitor cells. The primary readout in the screen was proliferation measured by nuclear count. From this screen, we identified FGF1, FGF4, FGF9, FGF16, FGF18, and seven additional proteins that induce proliferation of cardiac progenitor cells. FGF9 and FGF16 belong to the same FGF subfamily, share high sequence identity, and are described to have similar receptor preferences. Interestingly, FGF16 was shown to be specific for proliferation of cardiac progenitor cells, whereas FGF9 also proliferated human cardiac fibroblasts. Biosensor analysis of receptor preferences and quantification of receptor abundances suggested that FGF16 and FGF9 bind to different FGF receptors on the cardiac progenitor cells and cardiac fibroblasts. FGF16 also proliferated naive cardiac progenitor cells isolated from mouse heart and human cardiomyocytes derived from induced pluripotent cells. Taken together, the data suggest that FGF16 could be a suitable paracrine factor to induce cardiac regeneration and repair.

  • 272.
    Jin, Han
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Zhang, Cheng
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Zwahlen, Martin
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    von Feilitzen, Kalle
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Karlsson, Max
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Shi, Mengnan
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Yuan, Meng
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Song, Xiya
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Li, Xiangyu
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Yang, Hong
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Turkez, Hasan
    Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum, Turkey.
    Fagerberg, Linn
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Mardinoglu, Adil
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, UK.
    Systematic transcriptional analysis of human cell lines for gene expression landscape and tumor representation2023Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 14, nr 1, s. 5417-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cell lines are valuable resources as model for human biology and translational medicine. It is thus important to explore the concordance between the expression in various cell lines vis-à-vis human native and disease tissues. In this study, we investigate the expression of all human protein-coding genes in more than 1,000 human cell lines representing 27 cancer types by a genome-wide transcriptomics analysis. The cell line gene expression is compared with the corresponding profiles in various tissues, organs, single-cell types and cancers. Here, we present the expression for each cell line and give guidance for the most appropriate cell line for a given experimental study. In addition, we explore the cancer-related pathway and cytokine activity of the cell lines to aid human biology studies and drug development projects. All data are presented in an open access cell line section of the Human Protein Atlas to facilitate the exploration of all human protein-coding genes across these cell lines.

  • 273.
    Joensson, Haakan
    et al.
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Samuels, M. L.
    Brouzes, E. R.
    Medkova, M.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Andersson Svahn, Helene
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Link, D. R.
    Concurrent multi-sample analysis of low expressed biomarkers on single human cells by enzymatically amplified immunodetection in droplets2008Ingår i: 12th International Conference on Miniaturized Systems for Chemistry and Life Sciences - The Proceedings of MicroTAS 2008 Conference, Chemical and Biological Microsystems Society , 2008, s. 1287-1289Konferensbidrag (Refereegranskat)
    Abstract [en]

    We have developed a novel microfluidic droplet based assay for analysis of low expressed cell surface proteins on individual cells at rates of hundreds of cells/s by antibody coupled enzymatic amplification in monodisperse droplets [1]. Here we expand the method to include concurrent analysis of multiple populations of single cells. We report the validation of the method by analyzing the human monocytic cell line U937 for two low expressed markers, CCR5 and CD19. Comparing our method to standard flow cytometry, we demonstrate increased peak separation, which should allow sorting by these low expressed biomarkers unavailable to flow cytometry.

  • 274. Jogi, Annika
    et al.
    Brennan, Donal J.
    Ryden, Lisa
    Magnusson, Kristina
    Ferno, Marten
    Stal, Olle
    Borgquist, Signe
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Landberg, Goran
    Pahlman, Sven
    Ponten, Fredrik
    Jirstrom, Karin
    Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer2009Ingår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 22, nr 12, s. 1564-1574Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Single-strand RNA-binding proteins (RBPs) are involved in many aspects of RNA metabolism and in the regulation of gene transcription. The RBP RBM3 was recently suggested to be a proto-oncogene in colorectal cancer; however, such a role has not been corroborated by previous studies in the colon or other tumor types, and the prognostic implications of tumor-specific RBM3 expression remain unclear. Mono-specific antibodies against RBM3 were generated. Antibody specificity was confirmed using siRNA gene silencing, western blotting and immunohistochemistry on a panel of breast cancer cell lines. Using tissue microarrays and IHC, RBM3 protein expression was examined in 48 normal tissues and in 20 common cancers. Additional analysis in two independent breast cancer cohorts (n = 1016) with long-term follow-up was also carried out. RBM3 was upregulated in cancer compared to normal tissues. The nuclear expression of RBM3 in breast cancer was associated with low grade (P<0.001), small tumors (P<0.001), estrogen receptor (ER) positivity (P<0.001) and Ki-67 negativity (P<0.001) in both the breast cancer cohorts. An increased nuclear expression of RBM3 was associated with a prolonged overall and recurrence-free survival. The prognostic value was particularly pronounced in hormone receptor-positive tumors and remained significant in multivariate interaction analysis after controlling for tamoxifen treatment (HR: 0.49, 95% CI: 0.30-0.79, P = 0.004). These data strongly indicate that nuclear RBM3 is an independent favorable prognostic factor in breast cancer, and seems to have a specific role in ER-positive tumors. Modern Pathology (2009) 22, 1564-1574; doi:10.1038/modpathol.2009.124; published online 4 September 2009

  • 275.
    Johansson, Camilla
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Hunt, Helian
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Signorelli, Mirko
    Leiden Univ, Math Inst, Leiden, Netherlands..
    Edfors, Fredrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Hober, Andreas
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Svensson, Anne-Sophie
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Tegel, Hanna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Forsström, Björn
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Aartsma-Rus, Annemieke
    Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands..
    Niks, Erik
    Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands..
    Spitali, Pietro
    Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands..
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Al-Khalili Szigyarto, Cristina
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Orthogonal proteomics methods warrant the development of Duchenne muscular dystrophy biomarkers2023Ingår i: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 20, nr 1, artikel-id 23Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Molecular components in blood, such as proteins, are used as biomarkers to detect or predict disease states, guide clinical interventions and aid in the development of therapies. While multiplexing proteomics methods promote discovery of such biomarkers, their translation to clinical use is difficult due to the lack of substantial evidence regarding their reliability as quantifiable indicators of disease state or outcome. To overcome this challenge, a novel orthogonal strategy was developed and used to assess the reliability of biomarkers and analytically corroborate already identified serum biomarkers for Duchenne muscular dystrophy (DMD). DMD is a monogenic incurable disease characterized by progressive muscle damage that currently lacks reliable and specific disease monitoring tools.

    Methods

    Two technological platforms are used to detect and quantify the biomarkers in 72 longitudinally collected serum samples from DMD patients at 3 to 5 timepoints. Quantification of the biomarkers is achieved by detection of the same biomarker fragment either through interaction with validated antibodies in immuno-assays or through quantification of peptides by Parallel Reaction Monitoring Mass Spectrometry assay (PRM-MS).

    Results

    Five, out of ten biomarkers previously identified by affinity-based proteomics methods, were confirmed to be associated with DMD using the mass spectrometry-based method. Two biomarkers, carbonic anhydrase III and lactate dehydrogenase B, were quantified with two independent methods, sandwich immunoassays and PRM-MS, with Pearson correlations of 0.92 and 0.946 respectively. The median concentrations of CA3 and LDHB in DMD patients was elevated in comparison to those in healthy individuals by 35- and 3-fold, respectively. Levels of CA3 vary between 10.26 and 0.36 ng/ml in DMD patients whereas those of LDHB vary between 15.1 and 0.8 ng/ml.

    Conclusions

    These results demonstrate that orthogonal assays can be used to assess the analytical reliability of biomarker quantification assays, providing a means to facilitate the translation of biomarkers to clinical practice. This strategy also warrants the development of the most relevant biomarkers, markers that can be reliably quantified with different proteomics methods.

  • 276.
    Johansson, Camilla
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Schrama, Esther
    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
    Kotol, David
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hober, Andreas
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Koeks, Zaïda
    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
    van de Velde, Nienke
    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
    Verschuuren, Jan J.G.M.
    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Niks, Erik H.
    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
    Edfors, Fredrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Spitali, Pietro
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
    Al-Khalili Szigyarto, Cristina
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Monitoring Biomarker Study in Becker Muscular Dystrophy using Data Independent Acquisition LC-MS/MSManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Becker muscular dystrophy (BMD) is a rare and heterogenous form of dystrophinopathy caused by reduced expression of altered dystrophin protein. Gene therapies and exon-skipping therapies for the more severe form of dystrophinopathy, Duchenne muscular dystrophy (DMD), assumes that by promoting partial dystrophin expression in DMD patients, their disease progression could be reduced. Several studies have identified potential progression biomarkers for DMD and hypothesised in their usefulness in monitoring pharmacodynamic response in gene-therapy clinical trials. However, knowledge of progression changes of blood proteome in BMD is lacking. In this study, we aimed at exploring differences in proteomic changes between DMD and BMD in a prospective longitudinal 4-year study as well as explore what proteins relate to functional performance in BMD patients. Serum from 48 BMD patients and 19 DMD patients were analysed using Data Independent Acquisition Tandem Mass Spectrometry (DIA-MS). Linear mixed effects models identified 17 proteins with altered longitudinal signatures between DMD and BMD, among these CKM, PKM and ALDOA. Furthermore, bikunin (product of AMBP gene), C3 and IGHG2 were found related to functional performance in BMD patients. 

  • 277. Johansson, M. U.
    et al.
    Frick, I. M.
    Nilsson, H.
    Kraulis, P. J.
    Hober, Sophia
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Jonasson, P.
    Linhult, M.
    Nygren, Per-Åke
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Bjorck, L.
    Drakenberg, T.
    Forsen, S.
    Wikstrom, M.
    Structure, specificity, and mode of interaction for bacterial albumin-binding modules2002Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 277, nr 10, s. 8114-8120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have determined the solution structure of an albumin binding domain of protein G, a surface protein of group C and G streptococci. We find that it folds into a left handed three-helix bundle similar to the albumin binding domain of protein PAB from Peptostreptococcus magnus. The two domains share 59% sequence identity, are thermally very stable, and bind to the same site on human serum albumin. The albumin binding site, the first determined for this structural motif known as the GA module, comprises residues spanning the first loop to the beginning of the third helix and includes the most conserved region of GA modules. The two GA modules have different affinities for albumin from different species, and their albumin binding patterns correspond directly to the host specificity of C/G streptococci and P. magnus, respectively. These studies of the evolution, structure, and binding properties of the GA module emphasize the power of bacterial adaptation and underline ecological and medical problems connected with the use of antibiotics.

  • 278. Johansson, T.
    et al.
    Le Quere, A.
    Ahren, D.
    Soderstrom, B.
    Erlandsson, Rikard
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Tunlid, A.
    Transcriptional responses of Paxillus involutus and Betula pendula during formation of ectomycorrhizal root tissue2004Ingår i: Molecular Plant-Microbe Interactions, ISSN 0894-0282, E-ISSN 1943-7706, Vol. 17, nr 2, s. 202-215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In order to obtain information on genes specifically expressed in the ectomycorrhizal symbiosis, 3,555 expressed sequence tags (ESTs) were analyzed from a cDNA library constructed from ectomycorrhiza formed between the basidiomycete Paxillus involutus and birch (Betula pendula). cDNA libraries from saprophytically growing fungus (3,964 ESTs) and from axenic plants (2,532 ESTs) were analyzed in parallel. By clustering all the EST obtained, a nonredundant set of 2,284 unique transcripts of either fungal or plant origin were identified. The expression pattern of these genes was analyzed using cDNA microarrays. The analyses showed that the plant and fungus responded to the symbiosis by altering the expression levels of a number of enzymes involved in carbon metabolism. Several plant transcripts with sequence similarities to genes encoding enzymes in the tricarboxylic cycle and electron transport chain were down regulated as compared with the levels in free-living roots. In the fungal partner, a number of genes encoding enzymes in the lipid and secondary metabolism were down regulated in mycorrhiza as compared with the saprophytically growing mycelium. A substantial number of the ESTs analyzed displayed significant sequence similarities to proteins involved in biotic stress responses, but only a few of them showed differential expression in the mycorrhizal tissue, including plant and fungal metallothioneins and a plant defensin homologue. Several of the genes that were differentially expressed in the mycorrhizal root tissue displayed sequence similarity to genes that are known to regulate growth and development of plant roots and fungal hyphae, including transcription factors and Rho-like GTPases.

  • 279.
    Jonasson, Kalle
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Berglund, Lisa
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    The 6th HUPO Antibody Initiative (HAI) workshop: Sharing data about affinity reagents and other recent developments2010Ingår i: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 10, nr 11, s. 2066-2068Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Human Antibody Initiative (HAI) aims to promote and facilitate the use of antibodies for proteomics research. The 6th workshop for the HUPO Antibody Initiative (HAI) held in September 2009 was co-chaired by Michael Snyder and Mathias Uhlen and discussed several aspects of antibody production, their validation, and attempts to standardise this process, in particular, when subsequently described in the literature. An update on the progress of the Human Protein Atlas was also presented to the attendees.

  • 280. Jonsson, L.
    et al.
    Fridberg, M.
    Wangefjord, S.
    Nodin, B.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Eberhard, J.
    Jirström, K.
    High expression of RBM3 in colorectal cancer is a predictor of improved response to oxaliplatin treatment2012Ingår i: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 61, s. 82-83Artikel i tidskrift (Övrigt vetenskapligt)
  • 281. Jonsson, L.
    et al.
    Hedner, C.
    Gaber, A.
    Korkocic, D.
    Nodin, B.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Eberhard, J.
    Jirström, K.
    High expression of RNA-binding motif protein 3 in esophageal and gastric adenocarcinoma correlates with intestinal metaplasia-associated tumours and independently predicts a reduced risk of recurrence and death2014Ingår i: Biomarker Research, E-ISSN 2050-7771, Vol. 2, nr 1, artikel-id 11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: High nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to correlate with favourable clinicopathological characteristics and a prolonged survival in several cancer forms. Here, we examined the clinicopathological correlates and prognostic significance of RBM3 expression in tumours from a consecutive cohort of upper gastrointestinal adenocarcinoma.Material and methods: Immunohistochemical RBM3 expression was analysed in tissue microarrays with primary radiotherapy- and chemotherapy-naive adenocarcinoma of the esophagus, gastroesophageal junction and stomach (n = 173). In addition paired samples of normal squamous epithelium (n = 53), gastric mucosa (n = 117), Barrett's esophagus/gastric intestinal metaplasia (n = 61) and lymph node metastases (n = 71) were analysed. Kaplan-Meier analysis and Cox proportional hazards modelling was applied to assess the impact of RBM3 expression on overall survival (OS) and recurrence-free survival (RFS).Results: RBM3 expression was similar in primary tumours and lymph node metastases, but significantly higher in primary tumours and metastases arising in a background of intestinal metaplasia compared with cases without intestinal metaplasia (p < 0.001). RBM3 expression was significantly reduced in more advanced tumour stages (p = 0.006). Low RBM3 expression was significantly associated with a shorter OS in cases with radically resected (R0) tumours (HR 2.19, 95% CI 1.33-3.61, p = 0.002) and RFS in curatively treated patients with R0 resection/distant metastasis-free disease (HR = 3.21, 95% CI 1.64-6.30, p = 0.001). These associations remained significant in adjusted analysis (HR = 1.95, 95% CI 1.17-3.25, p = 0.010 for OS and HR = 3.02, 95% CI 1.45-6.29, p = 0.003 for RFS).Conclusion: High expression of RBM3 may signify a subset of upper gastrointestinal cancers arising in a background of intestinal metaplasia and independently predicts a reduced risk of recurrence and death in patients with these cancer forms. These findings are of potential clinical utility and merit further validation. 

  • 282. Jonsson, Liv
    et al.
    Bergman, Julia
    Nodin, Björn
    Manjer, Jonas
    Pontén, Fredrik
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Jirström, Karin
    Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: An analysis of 215 cases from the Malmo Diet and Cancer Study2011Ingår i: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 9, s. 114-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: We have previously reported that expression of the RNA-and DNA-binding protein RBM3 is associated with a good prognosis in breast cancer and ovarian cancer. In this study, the prognostic value of immunohistochemical RBM3 expression was assessed in incident cases of malignant melanoma from a prospective population-based cohort study. Methods: Until Dec 31(st) 2008, 264 incident cases of primary invasive melanoma had been registered in the Malmo Diet and Cancer Study. Histopathological and clinical information was obtained for available cases and tissue microarrays (TMAs) constructed from 226 (85.6%) suitable paraffin-embedded tumours and 31 metastases. RBM3 expression was analysed by immunohistochemistry on the TMAs and a subset of full-face sections. Chi-square and Mann-Whitney U tests were used for comparison of RBM3 expression and relevant clinicopathological characteristics. Kaplan Meier analysis and Cox proportional hazards modelling were used to assess the relationship between RBM3 and recurrence free survival (RFS) and overall survival (OS). Results: RBM3 could be assessed in 215/226 (95.1%) of primary tumours and all metastases. Longitudinal analysis revealed that 16/31 (51.6%) of metastases lacked RBM3 expression, in contrast to the primary tumours in which RBM3 was absent in 3/215 (1.4%) cases and strongly expressed in 120/215 (55.8%) cases. Strong nuclear RBM3 expression in the primary tumour was significantly associated with favourable clinicopathological parameters; i. e. non-ulcerated tumours, lower depth of invasion, lower Clark level, less advanced clinical stage, low mitotic activity and non-nodular histological type, and a prolonged RFS (RR = 0.50; 95% CI = 0.27-0.91) and OS (RR = 0.36, 95% CI = 0.20-0.64). Multivariate analysis demonstrated that the beneficial prognostic value of RBM3 remained significant for OS (RR = 0.33; 95% CI = 0.18-0.61). Conclusions: In line with previous in vitro data, we here show that RBM3 is down-regulated in metastatic melanoma and high nuclear RBM3 expression in the primary tumour is an independent marker of a prolonged OS. The potential utility of RBM3 in treatment stratification of patients with melanoma should be pursued in future studies.

  • 283. Jonsson, Liv
    et al.
    Gaber, Alexander
    Ulmert, David
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Bjartell, Anders
    Jirström, Karin
    High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression2011Ingår i: Diagnostic Pathology, E-ISSN 1746-1596, Vol. 6, s. 91-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: High expression of the RNA-binding protein RBM3 has previously been found to be associated with good prognosis in breast cancer, ovarian cancer, malignant melanoma and colorectal cancer. The aim of this study was to examine the prognostic impact of immunohistochemical RBM3 expression in prostate cancer. Findings: Immunohistochemical RBM3 expression was examined in a tissue microarray with malignant and benign prostatic specimens from 88 patients treated with radical prostatectomy for localized disease. While rarely expressed in benign prostate gland epithelium, RBM3 was found to be up-regulated in prostate intraepithelial neoplasia and present in various fractions and intensities in invasive prostate cancer. High nuclear RBM3 expression was significantly associated with a prolonged time to biochemical recurrence (BCR) (HR 0.56, 95% CI: 0.34-0.93, p = 0.024) and clinical progression (HR 0.09, 95% CI: 0.01-0.71, p = 0.021). These associations remained significant in multivariate analysis, adjusted for preoperative PSA level in blood, pathological Gleason score and presence or absence of extracapsular extension, seminal vesicle invasion and positive surgical margin (HR 0.41, 95% CI: 0.19-0.89, p = 0.024 for BCR and HR 0.06, 95% CI: 0.01-0.50, p = 0.009 for clinical progression). Conclusion: Our results demonstrate that high nuclear expression of RBM3 in prostate cancer is associated with a prolonged time to disease progression and, thus, a potential biomarker of favourable prognosis. The value of RBM3 for prognostication, treatment stratification and follow-up of prostate cancer patients should be further validated in larger studies.

  • 284.
    Jonsson, Malin
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Scheffel, Julia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Larsson, Emma
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Möller, Marit
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Rossi, Gabriella
    Lundqvist, Magnus
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Rockberg, Johan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Uhlén, Mathias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Tegel, Hanna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Kanje, Sara
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Hober, Sophia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    CaRA – A Multi-Purpose Phage Display Library for Selection of Calcium-Regulated Affinity ProteinsManuskript (preprint) (Övrigt vetenskapligt)
  • 285.
    Just, David
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab. Uppsala Univ, Dept Neurosci, Psychiat, Uppsala, Sweden..
    Månberg, Anna
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Mitsios, Nicholas
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Stockmeier, Craig A.
    Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA..
    Rajkowska, Grazyna
    Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA..
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Mulder, Jan
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Feuk, Lars
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden..
    Cunningham, Janet L.
    Uppsala Univ, Dept Neurosci, Psychiat, Uppsala, Sweden..
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Carlstrom, Eva Lindholm
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden..
    Exploring autoantibody signatures in brain tissue from patients with severe mental illness2020Ingår i: Translational Psychiatry, E-ISSN 2158-3188, Vol. 10, nr 1, artikel-id 401Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In recent years, studies have shown higher prevalence of autoantibodies in patients with schizophrenia compared to healthy individuals. This study applies an untargeted and a targeted affinity proteomics approach to explore and characterize the autoantibody repertoire in brain tissues from 73 subjects diagnosed with schizophrenia and 52 control subjects with no psychiatric or neurological disorders. Selected brain tissue lysates were first explored for IgG reactivity on planar microarrays composed of 11,520 protein fragments representing 10,820 unique proteins. Based on these results of ours and other previous studies of autoantibodies related to psychosis, we selected 226 fragments with an average length of 80 amino acids, representing 127 unique proteins. Tissue-based analysis of IgG reactivities using antigen suspension bead arrays was performed in a multiplex and parallel fashion for all 125 subjects. Among the detected autoantigens, higher IgG reactivity in subjects with schizophrenia, as compared to psychiatrically healthy subjects, was found against the glutamate ionotropic receptor NMDA type subunit 2D (anti-GluN2D). In a separate cohort with serum samples from 395 young adults with a wider spectrum of psychiatric disorders, higher levels of serum autoantibodies targeting GluN2D were found when compared to 102 control individuals. By further validating GluN2D and additional potential autoantigens, we will seek insights into how these are associated with severe mental illnesses.

  • 286.
    Jönsson, Håkan
    et al.
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Samuels, Michael L.
    Brouzes, Eric R.
    Medkova, Martina
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Link, Darren R.
    Andersson-Svahn, Helene
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Detection and Analysis of Low-Abundance Cell-Surface Biomarkers Using Enzymatic Amplification in Microfluidic Droplets2009Ingår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 48, nr 14, s. 2518-2521Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Finding the few: Cell-surface proteins are useful disease biomarkers, but current high-throughput methods are limited to detecting cells expressing more than several hundred proteins. Enzymatic amplification in microfluidic droplets (see picture) is a high-throughput method for detection and analysis of cell-surface biomarkers expressed at very low levels on individual human cells. Droplet optical labels allow concurrent analysis of several samples.

  • 287.
    Jönsson, Håkan
    et al.
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Andersson-Svahn, Helene
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Deterministic lateral displacement device for droplet separation by size - Towards rapid clonal selection based on droplet shrinking2010Ingår i: 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2010, MicroTAS 2010: Volume 2, 2010, s. 1355-1357Konferensbidrag (Refereegranskat)
    Abstract [en]

    We present a novel method for robust passive separation of microfluidic droplets by size using deterministic lateral displacement(DLD). We also show that droplets containing Saccharomyces Cervisiae shrink significantly during incubation while droplets containing only yeast media retain their size. We demonstrate the DLD device by sorting out shrunken yeast-cell containing droplets from a 40-fold excess of ∼33% larger yeast-cell-free droplets generated at the same time, suggesting that DLD might be used for clonal selection. The same device also separates 11 μm from 30μm droplets at a rate of 12000droplets/second, more than twofold faster than previously demonstrated passive hydrodynamic separation devices [1].

  • 288.
    Jönsson, Håkan
    et al.
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Andersson-Svahn, Helene
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Droplet size based separation by deterministic lateral displacement: separating droplets by cell-induced shrinking2011Ingår i: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 11, nr 7, s. 1305-1310Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present a novel method for passive separation of microfluidic droplets by size at high throughput using deterministic lateral displacement (DLD). We also show that droplets containing Saccharomyces cerevisiae shrink significantly during incubation while droplets containing only yeast media retain or slightly increase their size. We demonstrate the DLD device by sorting out shrunken yeast-cell containing droplets from 31% larger diameter droplets which were generated at the same time containing only media, present at a >40-fold excess. This demonstrates the resolving power of droplet separation by DLD and establishes that droplets can be separated for a biological property of the droplet contents discriminated by a change of the physical properties of the droplet. Thus suggesting that this technique may be used for e.g. clonal selection. The same device also separates 11 µm from 30 µm droplets at a rate of 12000 droplets per second, more than twofold faster than previously demonstrated passive hydrodynamic separation devices.

  • 289.
    Jönsson, Håkan
    et al.
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Zhang, Chi
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Andersson Svahn, Helene
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    A homogeneous assay for biomolecule interaction analysis in droplets by flourescence polarization2010Ingår i: 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2010, MicroTAS 2010: Volume 3, 2010, s. 1802-1804Konferensbidrag (Refereegranskat)
    Abstract [en]

    We present a novel homogeneous assay for detecting biomolecule interactions in microdroplets by fluorescence polarization (FP) for the first time. The FP assay allows the detection of target biomolecules directly after incubation without removing the detection reagent by separation or washing, making the assay amenable to automation. Using this assay we evaluate protein-protein and drug-DNA interactions. We detect these interactions at concentrations as low as 100nM and 69 pM respectively. This is a proof-of-concept homogeneous labeling assay in droplets for detecting bio-macromolecules.

  • 290.
    Jönsson, Håkan
    et al.
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Zhang, Chi
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Andersson-Svahn, Helene
    KTH, Skolan för bioteknologi (BIO), Nanobioteknologi.
    A Homogeneous Assay for Protein Analysis in Droplets by Fluorescence Polarization2012Ingår i: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 33, nr 3, s. 436-439Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present a novel homogeneous (mix-incubate-read) droplet microfluidic assay for specific protein detection in picoliter volumes by fluorescence polarization (FP), for the first time demonstrating the use of FP in a droplet microfluidic assay. Using an FP-based assay we detect streptavidin concentrations as low as 500?nM and demonstrate that an FP assay allows us to distinguish droplets containing 5?mu M rabbit IgG from droplets without IgG with an accuracy of 95%, levels relevant for hybridoma screening. This adds to the repertoire of droplet assay techniques a direct protein detection method which can be performed entirely inside droplets without the need for labeling of the analyte molecules.

  • 291.
    Jönsson, Malin
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Möller, Marit
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Dorka, Nicolai
    Department of Bioengineering, Stanford University, Stanford.
    Tegel, Hanna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Uhlén, Mathias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Lundberg, Emma
    Department of Bioengineering, Stanford University, Stanford.
    Hober, Sophia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Engineering of calcium-regulated affinity targeting EGFR-expressing cells for efficient internalizationManuskript (preprint) (Övrigt vetenskapligt)
  • 292.
    Jönsson, Malin
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Scheffel, Julia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Larsson, Emma
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinvetenskap.
    Möller, Marit
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Rossi, Gabriella
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Lundqvist, Magnus
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Rockberg, Johan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Uhlén, Mathias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. Department of Protein Science, KTH-Royal Institute of Technology, SE-10691, Stockholm, Sweden.
    Tegel, Hanna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Kanje, Sara
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Hober, Sophia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    CaRA – A multi-purpose phage display library for selection of calcium-regulated affinity proteins2022Ingår i: New Biotechnology, ISSN 1871-6784, E-ISSN 1876-4347, Vol. 72, s. 159-167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Protein activity regulated by interactions with metal ions can be utilized for many different purposes, including biological therapies and bioprocessing, among others. Calcium ions are known to interact with the frequently occurring EF-hand motif, which can alter protein activity upon binding through an induced conformational change. The calcium-binding loop of the EF-hand motif has previously been introduced into a small protein domain derived from staphylococcal Protein A in a successful effort to render antibody binding dependent on calcium. Presented here, is a combinatorial library for calcium-regulated affinity, CaRA, based on this domain. CaRA is the first alternative scaffold library designed to achieve novel target specificities with metal-dependent binding. From this library, several calcium-dependent binders could be isolated through phage display campaigns towards a set of unrelated target proteins (IgE Cε3-Cε4, TNFα, IL23, scFv, tPA, PCSK9 and HER3) useful for distinct applications. Overall, these monomeric CaRA variants showed high stability and target affinities within the nanomolar range. They displayed considerably higher melting temperatures in the presence of 1 mM calcium compared to without calcium. Further, all discovered binders proved to be calcium-dependent, with the great majority showing complete lack of target binding in the absence of calcium. As demonstrated, the CaRA library is highly capable of providing protein-binding domains with calcium-dependent behavior, independent of the type of target protein. These binding domains could subsequently be of great use in gentle protein purification or as novel therapeutic modalities.

  • 293. Kaessmann, H.
    et al.
    Zollner, S.
    Gustafsson, A. C.
    Wiebe, V.
    Laan, M.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Paabo, S.
    Extensive linkage disequilibrium in small human populations in Eurasia2002Ingår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 70, nr 3, s. 673-685Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The extent of linkage disequilibrium (LD) was studied in two small food-gathering populations-Evenki and Saami- and two larger food-producing populations-Finns and Swedes-in northern Eurasia. In total, 50 single-nucleotide polymorphisms (SNPs) from five genes were genotyped using real-time pyrophosphate DNA sequencing, whereas 14 microsatellites were genotyped in two X-chromosomal regions. In addition, hypervariable region I of the mtDNA was sequenced to shed light on the demographic history of the populations. The SNP data, as well as the microsatellite data, reveal extensive levels of LD in Evenki and Saami when compared to Finns and Swedes. mtDNA-sequence variation is compatible with constant population size over time in Evenki and Saami but indicates population expansion in Finns and Swedes. Furthermore, the similarity between Finns and Swedes in SNP allele- and haplotype-frequency distributions indicate that these two populations may share a recent common origin. These findings suggest that populations such as the Evenki and the Saami, rather than the Finns, may be particularly suited for the initial coarse mapping of common complex diseases.

  • 294. Kampf, C.
    et al.
    Andersson, A. -C
    Wester, K.
    Björling, E.
    Uhlen, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Ponten, F.
    Antibody-based tissue profiling as a tool for clinical proteomics2004Ingår i: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 1, nr 3-4, s. 285-299Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Here, we show a strategy for high-throughput antibody-based tissue profiling with the aim to create an atlas of protein expression patterns in normal human tissues and cancer tissues representing the 20 most prevalent cancer types. A set of standardized tissue microarrays (TMAs) was produced to allow for rapid screening of a multitude of different cells and tissues using immunohistochemistry. Eight TMA blocks were produced containing 48 different normal human tissues in triplicate and cancer tissue from 216 individually different tumors in duplicate. Sections from these blocks were immunohistochemically stained using five commercial and five in-house generated antibodies. Digital images for annotation of expression profiles were generated using a semiautomated approach. Five hundred seventy-six images and annotation data corresponding to a total of 30 Gbytes of data were collected for each antibody. The data presented here suggest that antibody-based profiling of protein expression in tissues can be used as a valuable tool in clinical proteomics.

  • 295.
    Kampf, C.
    et al.
    Uppsala Univ, Uppsala, Sweden..
    Bjorling, E.
    KTH.
    Wester, K.
    Uppsala Univ, Uppsala, Sweden..
    Andersson, A.
    Uppsala Univ, Uppsala, Sweden..
    Uhlén, Mathias
    KTH.
    Ponten, F.
    Uppsala Univ, Uppsala, Sweden..
    Mapping the human proteome using tissue microarrays2005Ingår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 4, nr 8, s. S63-S63Artikel i tidskrift (Övrigt vetenskapligt)
  • 296. Kampf, Caroline
    et al.
    Bergman, Julia
    Oksvold, Per
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Asplund, Anna
    Navani, Sanjay
    Wiking, Mikaela
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundberg, Emma
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Pontén, Fredrik
    A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas2012Ingår i: BMC Medicine, E-ISSN 1741-7015, Vol. 10, s. 103-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The complexity of tissue and the alterations that distinguish normal from cancer remain a challenge for translating results from tumor biological studies into clinical medicine. This has generated an unmet need to exploit the findings from studies based on cell lines and model organisms to develop, validate and clinically apply novel diagnostic, prognostic and treatment predictive markers. As one step to meet this challenge, the Human Protein Atlas project has been set up to produce antibodies towards human protein targets corresponding to all human protein coding genes and to map protein expression in normal human tissues, cancer and cells. Here, we present a dictionary based on microscopy images created as an amendment to the Human Protein Atlas. The aim of the dictionary is to facilitate the interpretation and use of the image-based data available in the Human Protein Atlas, but also to serve as a tool for training and understanding tissue histology, pathology and cell biology. The dictionary contains three main parts, normal tissues, cancer tissues and cells, and is based on high-resolution images at different magnifications of full tissue sections stained with H & E. The cell atlas is centered on immunofluorescence and confocal microscopy images, using different color channels to highlight the organelle structure of a cell. Here, we explain how this dictionary can be used as a tool to aid clinicians and scientists in understanding the use of tissue histology and cancer pathology in diagnostics and biomarker studies.

  • 297. Kampf, Caroline
    et al.
    Mardinoglu, Adil
    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.
    Danielsson, Angelika
    Nielsen, Jens
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Chalmers University of Technology, Sweden.
    Pontén, Fredrik
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Defining the human gallbladder proteome by transcriptomics and affinity proteomics2014Ingår i: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 14, nr 21-22, s. 2498-2507Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Global protein analysis of human gallbladder tissue is vital for identification of molecular regulators and effectors of its physiological activity. Here, we employed a genome-wide deep RNA sequencing analysis in 28 human tissues to identify the genes overrepresented in the gallbladder and complemented it with antibody-based immunohistochemistry in 48 human tissues. We characterized human gallbladder proteins and identified 140 gallbladder-specific proteins with an elevated expression in the gallbladder as compared to the other analyzed tissues. Five genes were categorized as enriched, with at least fivefold higher levels in gallbladder, 60 genes were categorized as group enriched with elevated transcript levels in gallbladder shared with at least one other tissue and 75 genes were categorized as enhanced with higher expression than the average expression in other tissues. We explored the localization of the genes within the gallbladder through cell-type specific antibody-based protein profiling and the subcellular localization of the genes through immunofluorescent-based profiling. Finally, we revealed the biological processes and metabolic functions carried out by these genes through the use of GO, KEGG Pathway, and HMR2.0 that is compilation of the human metabolic reactions. We demonstrated the results of the combined analysis of the transcriptomics and affinity proteomics.

  • 298. Kampf, Caroline
    et al.
    Mardinoglu, Adil
    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.
    Edlund, Karolina
    Lundberg, Emma
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Pontén, Fredrik
    Nielsen, Jens
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    The human liver-specific proteome defined by transcriptomics and antibody-based profiling2014Ingår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 28, nr 7, s. 2901-2914Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human liver physiology and the genetic etiology of the liver diseases can potentially be elucidated through the identification of proteins with enriched expression in the liver. Here, we combined data from RNA sequencing (RNA-Seq) and antibody-based immunohistochemistry across all major human tissues to explore the human liver proteome with enriched expression, as well as the cell type-enriched expression in hepatocyte and bile duct cells. We identified in total 477 protein-coding genes with elevated expression in the liver: 179 genes have higher expression as compared to all the other analyzed tissues; 164 genes have elevated transcript levels in the liver shared with at least one other tissue type; and an additional 134 genes have a mild level of increased expression in the liver. We identified the precise localization of these proteins through antibody-based protein profiling and the subcellular localization of these proteins through immunofluorescent-based profiling. We also identified the biological processes and metabolic functions associated with these proteins, investigated their contribution in the occurrence of liver diseases, and identified potential targets for their treatment. Our study demonstrates the use of RNA-Seq and antibody-based immunohistochemistry for characterizing the human liver proteome, as well as the use of tissue-specific proteins in identification of novel drug targets and discovery of biomarkers.

  • 299.
    Kanje, Sara
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Enstedt, Henric
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Dannemeyer, Melanie
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Uhlén, Mathias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Hober, Sophia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Tegel, Hanna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Improvements of a high-throughput protein purification process using a calcium-dependent setup2020Ingår i: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 175, artikel-id 105698Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Human Secretome Project aims to produce and purify all human secreted proteins as full-length. In order to enable this, a robust, gentle and effective purification process is needed, where multiple proteins can be purified in parallel. For this reason, a purification system based on a Protein C-tag and the HPC4 antibody with high affinity to the tag was chosen for purification. The strong binding between the tag and the antibody is specific and calcium-dependent, which allows for mild elution with EDTA. Presented here is a study comparing different protein purification base matrices coupled with the HPC4 antibody, aiming to increase the yield of purified protein and reduce the time for purification. Among the different tested matrices, Capto XP showed a high coupling degree and increased the amount of eluted protein as compared to the control matrix. By moving from batch incubation to direct sample loading and by performing the purification on the aKTAxpress, an automated protein purification process and a high reduction of hands-on sample handling was achieved. This new method also integrates the desalting step in the purification process, and the time for purification and analysis of each sample was decreased from five to three days. Moreover, a new mild method for matrix regeneration was developed using 50 mM EDTA pH 7.5 instead of 0.1 M glycine pH 2. This method was proven to be efficient for regeneration while maintaining the column binding performance even after nine rounds of regeneration.

  • 300.
    Karlsson, Max
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Alvez, Maria Bueno
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Shi, Mengnan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Zhang, Cheng
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Méar, Loren
    Zhong, Wen
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Schutten, Rutger
    Hikmet, Feria
    Digre, Andreas
    Katona, Borbala
    Vuu, Jimmy
    Sjöstedt, Evelina
    Bosic, Martina
    Edfors, Fredrik
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Oksvold, Per
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    von Feilitzen, Kalle
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Zwahlen, Martin
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Forsberg, Mattias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Johansson, Fredric
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Mulder, Jan
    Mardinoglu, Adil
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Sivertsson, Åsa
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Ponten, Fredrik
    Lindskog, Cecilia
    Fagerberg, Linn
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Uhlén, Mathias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Genome-wide single cell annotation of the human protein-coding genesManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    An important quest for the life science community is to deliver a complete annotation of the human building-blocks of life, the genes and the proteins. Here, we report on a genome-wide effort to annotate all protein-coding genes based on single cell transcriptomics data representing all major tissues and organs in the human body, integrated with data from bulk transcriptomics and antibody-based tissue profiling. Altogether, 25 tissues have been analyzed with single cell transcriptomics resulting in genome-wide expression in 444 single cell types using a strategy involving pooling data from individual cells to obtain genome-wide expression profiles of individual cell type. We introduce a new genome-wide classification tool based on clustering of similar expression profiles across single cell types, which can be visualized using dimensional reduction maps (UMAP). The clustering classification is integrated with a new “tau” score classification for all protein-coding genes, resulting in a measure of single cell specificity across all cell types for all individual genes. The analysis has allowed us to annotate all human protein-coding genes with regards to function and spatial distribution across individual cell types across all major tissues and organs in the human body. A new version of the open access Human Protein Atlas (www.proteinatlas.org) has been launched to enable researchers to explore the new genome-wide annotation on an individual gene level.

3456789 251 - 300 av 697
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf