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  • 151. Nordström, H.
    et al.
    Falk, K. I.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Lundkvist, A.
    DNA Microarray Technique for Detection and Identification of Viruses Causing Encephalitis and Hemorrhagic Fever2009Ingår i: Detection of Highly Dangerous Pathogens: Microarray Methods for BSL 3 and BSL 4 Agents, John Wiley & Sons, 2009, s. 113-123Kapitel i bok, del av antologi (Refereegranskat)
  • 152. Notarnicola, A.
    et al.
    Hellstrom, C.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mattsson, C.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Andersson, E.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Idborg, H.
    Jemseby, E.
    Neiman, Maja
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Jakobsson, P-J
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundberg, I. E.
    NEW AUTOIMMUNE TARGETS IN IDIOPATHIC INFLAMMATORY MYOPATHIES - AN ANTIGEN BEAD ARRAY APPROACH2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 626-626Artikel i tidskrift (Övrigt vetenskapligt)
  • 153.
    Notarnicola, A.
    et al.
    Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Mattsson, C.
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Idborg, H.
    Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Hellström, Cecilia
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Jemseby, E.
    Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Jacobsson, P. -J
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Lundberg, I. E.
    Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    ANALYSIS OF THE AUTOANTIBODY REPERTOIRE IN IDIOPATHIC INFLAMMATORY MYOPATHIES USING ANTIGEN BEAD ARRAY2015Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 74, s. 174-174Artikel i tidskrift (Övrigt vetenskapligt)
  • 154.
    Olsson, T.
    et al.
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Huang, J.
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Hellström, Cecilia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Tengvall, K.
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Kammer, P.
    German Canc Res Ctr, Heidelberg, Germany..
    Bistrom, M.
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Bomfim, I. Lima
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Stridh, P.
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Butt, J.
    German Canc Res Ctr, Heidellberg, Germany..
    Nicole, B.
    German Canc Res Ctr, Heidelberg, Germany..
    Michel, A.
    German Canc Res Ctr, Heidelberg, Germany..
    Ayoglu, Burcu
    KTH, Centra, Science for Life Laboratory, SciLifeLab. Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Lundberg, K.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Lundberg, I.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Olafsson, S.
    deCode Genet, Reykavik, Iceland..
    Jonsdottir, I.
    deCode Genet, Reykavik, Iceland..
    Stefansson, K.
    deCode Genet, Reykavik, Iceland..
    Dilthey, A.
    Welcome Trust Ctr Human Genet, Oxford, England..
    Hillert, J.
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Alfredsson, L.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Sundstrom, P.
    Umea Univ, Pharmacol & Clin Neurosci, Umea, Sweden..
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Waterboer, T.
    German Canc Res Ctr, Heidelberg, Germany..
    Kockum, I.
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Molecular mimicry between the autoantigen Anoctamin 2 and Epstein Barr virus nuclear antigen 1 associates with increased risk for multiple sclerosis2018Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, s. 64-64Artikel i tidskrift (Övrigt vetenskapligt)
  • 155. Omazic, B.
    et al.
    Ayoglu, Burcu
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Löhr, M.
    Segersvärd, R.
    Verbeke, C.
    Magalhaes, I.
    Potacova, Z.
    Mattsson, J.
    Terman, A.
    Ghazi, S.
    Albiin, N.
    Kartalis, N.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Poiret, T.
    Zhenjiang, L.
    Heuchel, R.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Permert, J.
    Maeurer, M. J.
    Ringden, O.
    A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients with Pancreatic Cancer2017Ingår i: Journal of immunotherapy (1997), ISSN 1524-9557, E-ISSN 1537-4513, Vol. 40, nr 4, s. 132-139Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A∗01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT. Both TAAs were highly expressed in the original tumor tissue suggesting that HSCT promoted a clinically relevant, long-lasting cellular immune response. In contrast to untreated controls, who succumbed to progressive disease, both patients are tumor-free 9 years after diagnosis. Radical surgery combined with HSCT may cure pancreatic adenocarcinoma and change the cellular immune repertoire capable of responding to clinically and biologically relevant TAAs.

  • 156.
    O'Meara, Deirdre
    et al.
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Nilsson, Peter
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Nygren, Per-Åke
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Uhlen, Mathias
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Capture of single-stranded DNA assisted by oligonucleotide modules1998Ingår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 255, nr 2, s. 195-203Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Real-time biospecific interaction analysis was employed to monitor direct capture of a hepatitis C virus (HCV) derived polymerase chain reaction (PCR) product by nucleic acid hybridization. Different formats for hybridization were used to study the interaction between a single-stranded HCV PCR product and capture oligonucleotides immobilized on a sensor chip via streptavidin-biotin chemistry. By employing a prehybridization step in solution with nonbiotin oligonucleotides complementary to the single-stranded target and adjacent to the immobilized probe, a significant capture was achieved in comparison to the low capture efficiency obtained using single immobilized probes (9-36 mer). High capture efficiencies were also observed when shorter immobilized probes were used in combination with strings of adjacently positioned prehybridized probes (i.e., modules). Interestingly, the introduction of single nucleotide gaps between prehybridized and/or immobilized probes dramatically reduced the capture efficiency. These results suggest that flexible systems for capture could be designed from libraries of short oligonucleotides (9 mers) used in module fashion, taking advantage of stacking interactions between the oligonucleotides. The potential applications of such oligonucleotide-assisted capture systems are discussed.

  • 157.
    Paavilainen, Linda
    et al.
    Uppsala University.
    Wernerus, Henrik
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Uhlen, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Hober, Sophia
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Wester, Kenneth
    Uppsala University.
    Ponten, Fredrik
    Uppsala University.
    Evaluation of monospecific antibodies: A comparison study with commercial analogs using immunohistochemistry on tissue microarrays2008Ingår i: Applied immunohistochemistry & molecular morphology (Print), ISSN 1541-2016, E-ISSN 1533-4058, Vol. 16, nr 5, s. 493-502Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Generation of monospecific antibodies (msAbs) (multiepitope) through affinity purification of polyclonal jntiscra is I plausible strategy, for high-throughput production Of affinity reagents toward large sets of proteins. These antibodies are generated using readily accessible gene Sequence information from publicly available databases. The resulting antibodies have the potential to be used in a variety of assays. probing differentially presented and altered proteins with high sensitivity and specificity. In the present study, 48 msAbs were compared with corresponding commercial analogs. Immunohistochemical staining properties were evaluated on tissue microarrays. representing various normal human tissues from 144 different individuals. MaAbs showed similar immunostaining patterns as compared with corresponding commercial analogs in 44 Out of totally 48 (92%) antibody pairs analyzed. Although only few antibody pairs showed major discrepancies. minor dissimilarities were frequently seen. Our results suggest that msAbs are reliable and valuable tools in antibody-based proteomics. enabling analysis of protein expression patterns in cells and tissues, High-throughput strategies employing such antibodies provide a consistent approach in the exploration of the human proleome.

  • 158. Pang, S. T.
    et al.
    Weng, W. H.
    Flores-Morales, A.
    Johansson, B.
    Pourian, M. R.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Pousette, A.
    Larsson, C.
    Norstedt, G.
    Cytogenetic and expression profiles associated with transformation to androgen-resistant prostate cancer2006Ingår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 66, nr 2, s. 157-172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND. The mechanisms underlying the progression of prostate cancer to androgen-resistant cancer are still not fully understood. Here, we studied the genetic events associated with this transformation. METHODS. The androgen sensitive prostate cancer cells line LNCaP-FGC and its androgen resistant subline LNCaP-r were investigated using SKY, CGH, and cDNA microarray. RESULTS. Karyotypically, several additional chromosomal aberrations were seen in LNCaP-r as compared to the parental line. CGH also revealed unique net chromosomal alterations in LNCaP-r compared to LNCaP-FGC, including gain of 2p13-23, 2q21-32, and 13q and loss of 6p22-pter. cDNA microarray analysis identified several genes involved in DNA methylation, such as DNMT2, DNMT3a, and methyl-CpG binding domain protein 2 and 4 that were higher expressed in LNCaP-r. Interestingly, androgen responsiveness of LNCaP-r was restored after treated with DNA methyltransferase inhibitor. CONCLUSIONS. Our findings may serve as a basis for molecular dissection of the mechanisms involved in development of androgen resistant prostate cancer.

  • 159.
    Papiol, Sergi
    et al.
    Univ Munich, Inst Psychiat Phen & Genom, Med Ctr, Munich, Germany..
    Just, David
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Kannaiyan, Nirmal
    Univ Munich, Inst Psychiat Phen & Genom, Med Ctr, Munich, Germany.;Univ Munich, Med Ctr, Mol & Behav Neurobiol, Munich, Germany..
    Anderson-Schmidt, Heike
    Univ Med Ctr Goettingen, Gottingen, Germany..
    Budde, Monika
    Univ Munich, Inst Psychiat Phen & Genom, Med Ctr, Munich, Germany..
    Gade, Katrin
    Univ Munich, Inst Psychiat Phen & Genom, Med Ctr, Munich, Germany..
    Heilbronner, Urs
    Univ Munich, Inst Psychiat Phen & Genom, Med Ctr, Munich, Germany..
    Rossner, Moritz
    Univ Munich, Med Ctr, Mol & Behav Neurobiol, Munich, Germany..
    Nilsson, Peter
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schulze, Thomas
    Univ Munich, Inst Psychiat Phen & Genom, Med Ctr, Munich, Germany..
    HIGH-THROUGHPUT ANTIBODY-BASED PROFILING OF SERUM IN SCHIZOPHRENIA AND BIPOLAR DISORDER PATIENTS: AN INTEGRATIVE GENOMICS-PROTEOMICS PILOT STUDY2019Ingår i: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, s. S993-S994Artikel i tidskrift (Övrigt vetenskapligt)
  • 160.
    Pei, Zhichao
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemi.
    Yu, Hui
    KTH, Skolan för kemivetenskap (CHE), Kemi.
    Theurer, Matthias
    KTH, Skolan för kemivetenskap (CHE), Kemi.
    Waldén, Annelie
    KTH, Skolan för bioteknologi (BIO).
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO).
    Yan, Mingdi
    KTH, Skolan för kemivetenskap (CHE), Kemi.
    Ramström, Olof
    KTH, Skolan för kemivetenskap (CHE), Kemi.
    Photogenerated Carbohydrate Microarrays2007Ingår i: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 8, nr 2, s. 166-168Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chemical Equation Presented) Sugars in a row. A new strategy for carbohydrate microarrays based on photochemical ligation of perfluorophenylazide-derivatized carbohydrates to PEO surfaces is presented. It constitutes a controllable and robust method of array fabrication, on the carbohydrate chemistry and on the surface-chemistry levels, and the resulting carbohydrate arrays can be efficiently used to reveal the recognition patterns of carbohydrate-binding proteins.

  • 161.
    Perotin, Jeanne-Marie
    et al.
    Univ Southampton, NIHR Southampton Biomed Res Ctr, Clin & Expt Sci, Fac Med, Southampton, Hants, England..
    Mikus, Maria
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. Sci Life Lab, Stockholm, Sweden.;Royal Inst Technol, Stockholm, Sweden..
    Gozzard, Neil
    UCB, Slough, Berks, England..
    Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux2019Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 53, nr 6, artikel-id 1900453Artikel i tidskrift (Refereegranskat)
  • 162. Pershad, K.
    et al.
    Pavlovic, J. D.
    Gräslund, S.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Colwill, K.
    Karatt-Vellatt, A.
    Schofield, D. J.
    Dyson, M. R.
    Pawson, T.
    Kay, B. K.
    McCafferty, J.
    Generating a panel of highly specific antibodies to 20 human SH2 domains by phage display2010Ingår i: Protein Engineering Design & Selection, ISSN 1741-0126, E-ISSN 1741-0134, Vol. 23, nr 4, s. 279-288Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To demonstrate the utility of phage display in generating highly specific antibodies, affinity selections were conducted on 20 related Src Homology 2 (SH2) domains (ABL1, ABL2, BTK, BCAR3, CRK, FYN, GRB2, GRAP2, LYN, LCK, NCK1, PTPN11 C, PIK3R1 C, PLC gamma 1 C, RASA1 C, SHC1, SH2D1A, SYK N, VAV1 and the tandem domains of ZAP70). The domains were expressed in Escherichia coli, purified and used in affinity selection experiments. In total, 1292/3800 of the resultant antibodies were shown to bind the target antigen. Of the 695 further evaluated in specificity ELISAs against all 20 SH2 domains, 379 antibodies were identified with unique specificity (i.e. monospecific). Sequence analysis revealed that there were at least 150 different clones with 1-19 different antibodies/antigen. This includes antibodies that distinguish between ABL1 and ABL2, despite their 89% sequence identity. Specificity was confirmed for many on protein arrays fabricated with 432 different proteins. Thus, even though the SH2 domains share a common three-dimensional structure and 20-89% identity at the primary structure level, we were able to isolate antibodies with exquisite specificity within this family of structurally related domains.

  • 163. Persson, Björn
    et al.
    Stenhag, K
    Nilsson, Peter
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Larsson, A
    Uhlen, Mathias
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Nygren, Per-Åke
    KTH, Tidigare Institutioner                               , Bioteknologi.
    Analysis of oligonucleotide probe affinities using surface plasmon resonance: A means for mutational scanning1997Ingår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 246, nr 1, s. 34-44Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A novel strategy for real-time analysis of oligonucleotide probe hybridization based on detection by surface plasmon resonance is described. The design of the analysis, exploiting the rapid dissociation kinetics of short oligonucleotides from their hybridization templates, allows monitoring in genuine sensor mode of equilibrium hybridization responses, circumventing the need for regeneration between sample cycles. Applied to a model system comprising oligonucleotide probes and different immobilized hybridization targets the effects of temperature, probe length, and nucleotide substitutions in template were investigated. The procedure described was observed to have an efficient discriminatory power with respect to end-mismatch situations. Affinity determinations of octamer probes showed good correlation between calculated T-m-values and probe affinities. From affinity data collected at different temperatures thermodynamic parameters were determined, which correlated well with data obtained from theoretical calculations. The technique, modified to a simplified form, allowed detection of single nucleotide substitutions in a target template, suggesting that procedures for confirmatory DNA sequencing can be envisioned.

  • 164.
    Persson, Mats
    et al.
    Karolinska Inst, Solna, Sweden..
    Zandian, Arasch
    KTH.
    Wingard, Louise
    Karolinska Inst, Solna, Sweden..
    Nilsson, Hanna
    Karolinska Inst, Solna, Sweden..
    Sjostedt, Evelina
    Uppsala Univ, Uppsala, Sweden..
    Johansson, Daniel
    Karolinska Inst, Solna, Sweden..
    Just, David
    KTH.
    Hellström, Cecilia
    KTH.
    Uhlén, Mathias
    Schwenk, Jochen M.
    Häggmark-Månberg, Anna
    KTH.
    Norbeck, Oscar
    Karolinska Inst, Solna, Sweden..
    Owe-Larsson, Bjorn
    Karolinska Inst, Solna, Sweden..
    Nilsson, Peter
    KTH.
    Searching for Novel Autoantibodies with Clinical Relevance in Psychiatric Disorders2018Ingår i: Schizophrenia Bulletin, ISSN 0586-7614, E-ISSN 1745-1701, Vol. 44, s. S120-S121Artikel i tidskrift (Övrigt vetenskapligt)
  • 165.
    Pin, Elisa
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Henjes, Frauke
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Wiklund, Fredrik
    Magnusson, Patrik
    Bjartell, Anders
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer2017Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 16, nr 1, s. 204-216Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a demand for novel targets and approaches to diagnose and treat prostate cancer (PCA). In this context, serum and plasma samples from a total of 609 individuals from two independent patient cohorts were screened for IgG reactivity against a sum of 3833 human protein fragments. Starting from planar protein arrays with 3786 protein fragments to screen 80 patients with and without PCA diagnosis, 161 fragments (4%) were chosen for further analysis based on their reactivity profiles. Adding 71 antigens from literature, the selection of antigens was corroborated for their reactivity in a set of 550 samples using suspension bead arrays. The antigens prostein (SLC45A3), TATA-box binding protein (TBP), and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) showed higher reactivity in PCA patients with late disease compared with early disease. Because of its prostate tissue specificity, we focused on prostein and continued with mapping epitopes of the 66-mer protein fragment using patient samples. Using bead-based assays and 15-mer peptides, a minimal peptide epitope was identified and refined by alanine scanning to the KPxAPFP. Further sequence alignment of this motif revealed homology to transmembrane protein 79 (TMEM79) and TGF-beta-induced factor 2 (TGIF2), thus providing a reasoning for cross-reactivity found in females. A comprehensive workflow to discover and validate IgG reactivity against prostein and homologous targets in human serum and plasma was applied. This study provides useful information when searching for novel biomarkers or drug targets that are guided by the reactivity of the immune system against autoantigens.

  • 166. Ponten, Fredrik
    et al.
    Gry, Marcus
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Fagerberg, Linn
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Lundberg, Emma
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Asplund, Anna
    Berglund, Lisa
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Oksvold, Per
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Björling, Erik
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Hober, Sophia
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Kampf, Caroline
    Navani, Sanjay
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Ottosson, Jenny
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Persson, Anja
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Wernérus, Henrik
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Wester, Kenneth
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    A global view of protein expression in human cells, tissues, and organs2009Ingår i: Molecular Systems Biology, ISSN 1744-4292, E-ISSN 1744-4292, Vol. 5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Defining the protein profiles of tissues and organs is critical to understanding the unique characteristics of the various cell types in the human body. In this study, we report on an anatomically comprehensive analysis of 4842 protein profiles in 48 human tissues and 45 human cell lines. A detailed analysis of over 2 million manually annotated, high-resolution, immunohistochemistry- based images showed a high fraction (>65%) of expressed proteins in most cells and tissues, with very few proteins (<2%) detected in any single cell type. Similarly, confocal microscopy in three human cell lines detected expression of more than 70% of the analyzed proteins. Despite this ubiquitous expression, hierarchical clustering analysis, based on global protein expression patterns, shows that the analyzed cells can be still subdivided into groups according to the current concepts of histology and cellular differentiation. This study suggests that tissue specificity is achieved by precise regulation of protein levels in space and time, and that different tissues in the body acquire their unique characteristics by controlling not which proteins are expressed but how much of each is produced. Molecular Systems Biology 5: 337; published online 22 December 2009; doi:10.1038/msb.2009.93

  • 167.
    Pontén, Fredrik
    et al.
    Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University.
    Gry, Marcus
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Björling, Erik
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Berglund, Lisa
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Al-Khalili Szigyarto, Cristina
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Lundberg, Emma
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Andersson-Svahn, Helene
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Asplund, Anna
    Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University.
    Hober, Sophia
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Kampf, Caroline
    Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University.
    Nilsson, Kenneth
    Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Ottosson, Jenny
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Persson, Anja
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Wernérus, Henrik
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Wester, Kenneth
    Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Ubiquitous protein expression in human cells, tissues and organsManuskript (Övrigt vetenskapligt)
  • 168.
    Quintana, Maria del Pilar
    et al.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden..
    Ch'ng, Jun-Hong
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden.;Natl Univ Singapore, Dept Microbiol & Immunol, Singapore, Singapore..
    Moll, Kirsten
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden..
    Zandian, Arash
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Idris, Zulkarnain Md
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden.;Univ Kebangsaan, Malaysia Med Ctr, Fac Med, Dept Parasitol & Med Entomol, Kuala Lumpur, Malaysia..
    Saiwaew, Somporn
    Mahidol Univ, Fac Trop Med, Dept Clin Trop Med, Bangkok, Thailand..
    Qundos, Ulrika
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Wahlgren, Mats
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden..
    Antibodies in children with malaria to PfEMP1, RIFIN and SURFIN expressed at the Plasmodium falciparum parasitized red blood cell surface2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 3262Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Naturally acquired antibodies to proteins expressed on the Plasmodium falciparum parasitized red blood cell (pRBC) surface steer the course of a malaria infection by reducing sequestration and stimulating phagocytosis of pRBC. Here we have studied a selection of proteins representing three different parasite gene families employing a well-characterized parasite with a severe malaria phenotype (FCR3S1.2). The presence of naturally acquired antibodies, impact on rosetting rate, surface reactivity and opsonization for phagocytosis in relation to different blood groups of the ABO system were assessed in a set of sera from children with mild or complicated malaria from an endemic area. We show that the naturally acquired immune responses, developed during malaria natural infection, have limited access to the pRBCs inside a blood group A rosette. The data also indicate that SURFIN4.2 may have a function at the pRBC surface, particularly during rosette formation, this role however needs to be further validated. Our results also indicate epitopes differentially recognized by rosette-disrupting antibodies on a peptide array. Antibodies towards parasite-derived proteins such as PfEMP1, RIFIN and SURFIN in combination with host factors, essentially the ABO blood group of a malaria patient, are suggested to determine the outcome of a malaria infection.

  • 169.
    Quintana, Maria del Pilar
    et al.
    Karolinska Inst, Biomedicum, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden..
    Ch'ng, Jun-Hong
    Karolinska Inst, Biomedicum, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden.;Natl Univ Singapore, Dept Microbiol & Immunol, Singapore, Singapore..
    Zandian, Arash
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics.
    Imam, Maryam
    Karolinska Inst, Biomedicum, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden..
    Hultenby, Kjell
    Karolinska Inst, Dept Lab Med, Div Clin Res Ctr, Huddinge, Sweden..
    Theisen, Michael
    Statens Serum Inst, Dept Congenital Disorders, Copenhagen, Denmark.;Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Ctr Med Parasitol, Copenhagen, Denmark..
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics.
    Qundos, Ulrika
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics.
    Moll, Kirsten
    Karolinska Inst, Biomedicum, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden..
    Chan, Sherwin
    Karolinska Inst, Biomedicum, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden..
    Wahlgren, Mats
    Karolinska Inst, Biomedicum, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden..
    SURGE complex of Plasmodium falciparum in the rhoptry-neck (SURFIN4.2-RON4-GLURP) contributes to merozoite invasion2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 8, artikel-id e0201669Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Plasmodium falciparum invasion into red blood cells (RBCs) is a complex process engaging proteins on the merozoite surface and those contained and sequentially released from the apical organelles (micronemes and rhoptries). Fundamental to invasion is the formation of a moving junction (MJ), a region of close apposition of the merozoite and the RBC plasma membranes, through which the merozoite draws itself before settling into a newly formed parasitophorous vacuole (PV). SURFIN4.2 was identified at the surface of the parasitized RBCs (pRBCs) but was also found apically associated with the merozoite. Using antibodies against the N-terminus of the protein we show the presence of SURFIN4.2 in the neck of the rhoptries, its secretion into the PV and shedding into the culture supernatant upon schizont rupture. Using immunoprecipitation followed by mass spectrometry we describe here a novel protein complex we have named SURGE where SURFIN4.2 forms interacts with the rhoptry neck protein 4 (RON4) and the Glutamate Rich Protein (GLURP). The N-terminal cysteine-rich domain (CRD) of SURFIN4.2 mediates binding to the RBC membrane and its interaction with RON4 suggests its involvement in the contact between the merozoite apex and the RBC at the MJ. Supporting this suggestion, we also found that polyclonal antibodies to the extracellular domain (including the CRD) of SURFIN4.2 partially inhibit merozoite invasion. We propose that the formation of the SURGE complex participates in the establishment of parasite infection within the PV and the RBCs.

  • 170.
    Qundos, Ulrika
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Drobin, Kimi
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mattsson, Cecilia
    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.
    Sjöberg, Ronald
    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.
    Solomon, David
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    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.
    Michaelsson, Karl
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients2016Ingår i: PROTEOMICS - Clinical Applications, ISSN 1862-8346, E-ISSN 1862-8354, Vol. 10, nr 6, s. 681-690Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Affinity proteomic approaches by antibody bead arrays enable multiplexed analysis of proteins in body fluids. In the presented study, we investigated blood plasma within osteoporosis to discovery differential protein profiles and to propose novel biomarkers candidates for subsequent studies. Experimental design: Starting with 4608 antibodies and plasma samples from 22 women for an untargeted screening, a set of 72 proteins were suggested for further analysis. Complementing these with targets from literature and other studies, a targeted bead array of 180 antibodies was built to profile for 92 proteins in plasma samples of 180 women from two independent population-based studies. Results: Differential profiles between osteoporosis patients and matched controls were discovered for 12 proteins in at least one of the two study sets. Among these targets, the levels of autocrine motility factor receptor (AMFR) were concordantly lower in plasma of female osteoporosis patients. Subsequently, verification of anti-AMFR antibody selectivity was conducted using high-density peptide and protein arrays, and Western blotting. Conclusions and clinical relevance: Further validation in additional study sets will be needed to determine the clinical value of the observed decrease in AMFR plasma levels in osteoporosis patients, but AMFR may aid our understanding of disease mechanisms and could support existing tools for diagnosis and monitoring of patient mobility within osteoporosis.

  • 171.
    Qundos, Ulrika
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Tybring, Gunnel
    Divers, Mark
    Odeberg, Jacob
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    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.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Profiling post-centrifugation delay of serum and plasma with antibody bead arrays2013Ingår i: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 95, nr SI, s. 46-54Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several biobanking initiatives have emerged to create extensive collections of specimen for biomedical studies and various analytical platforms. An affinity proteomic analysis with antibody suspension bead arrays was conducted to investigate the influence of the pre-analytical time and temperature conditions on blood derived samples. Serum and EDTA plasma prepared from 16 individuals was centrifuged and aliquots were kept either at 4. °C or in ambient temperature for 1. h and up to 36. h prior to first storage. Multiplexed protein profiles of post-centrifugation delay were generated in 384 biotinylated samples using 373 antibodies that targeted 343 unique proteins. Very few profiles were observed as significantly altered by the studied temperature and time intervals. Single binder and sandwich assays revealed decreasing levels of caldesmon 1 (CALD1) related to EDTA standard tubes and prolonged post-centrifugation delay of 36. h. Indications from changes in CALD1 levels require further confirmation in independent material, but the current data suggests that samples should preferentially be frozen during the day of collection when to be profiled with antibody arrays selected for this study. Biological significance: Affinity-based profiling of serum and plasma by microarray assays can provide unique opportunities for the discovery of biomarkers. It is though often not known how differences in sample handling after collection influence the downstream analysis. By profiling three types of blood preparations for alterations in protein profiles with respect to time and temperature post centrifugation, we addressed an important component in the analysis and of such specimen. We believe that this analysis adds valuable information to be considered when biobanking blood derived samples.This article is part of a Special Issue entitled: Standardization and Quality Control in Proteomics.

  • 172.
    Qundos, Ulrika
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Johannesson, H.
    Fredolini, Claudia
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    O'Hurley, G.
    Branca, R.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Wiklund, F.
    Bjartell, A.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Analysis of plasma from prostate cancer patients links decreased carnosine dipeptidase 1 levels to lymph node metastasis2014Ingår i: Translational Proteomics, ISSN 2212-9634, Vol. 2, nr 1, s. 14-24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a need for a better differentiation of aggressive tumors in prostate cancer to design a tailored treatment for each patient, preferably by a minimally invasive analysis of blood samples. In a previous study, we discovered a decrease of plasma levels of carnosine dipeptidase 1 (CNDP1) in association with aggressive prostate cancer. Now this relation has been investigated and characterized further by generating several new antibodies for extended analysis of CNDP1 in plasma. Multi-antibody sandwich assays were developed and applied to 1214 samples from two Swedish cohorts that confirmed decreased levels of CNDP1 in plasma from patients with advanced disease. Therein, data from CNDP1 assays allowed a better differentiation between tumor N stages than clinical tPSA, but did not when classifying T or M stages. Further investigations can now elucidate mechanisms behind decreasing levels of CNDP1 in plasma and primary in regards to lymph node metastasis.

  • 173.
    Qundos, Ulrika
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Johannesson, Henrik
    Fredolini, Claudia
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    O´Hurley, Gillian
    Branca, Rui
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Wiklund, Fredrik
    Bjartell, Anders
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Plasma levels of carnosine dipeptidase 1 decrease in prostate cancer patients with lymph node metastasisManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    There is a need for a better differentiation of aggressive tumors in prostate cancer to design a tailored treatment for each patient, preferably by a minimally invasive analysis of blood samples. In a previous study, we discovered a decrease of plasma levels of carnosine dipeptidase 1 (CNDP1) in association with aggressive prostate cancer. Now this relation has been investigated and characterized further by generating several new antibodies for extended analysis of CNDP1 in plasma. Multi-antibody sandwich assays were developed and applied to 1,214 samples from two Swedish cohorts that confirmed decreased levels of CNDP1 in plasma for patients with advanced disease. Therein, CNDP1 assays revealed superior differentiation for tumor N stages than clinical tPSA. Further investigations can now elucidate mechanisms behind decreasing levels of CNDP1 in plasma and primary in regards to lymph node metastasis.

  • 174.
    Remnestål, Julia
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Just, David
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mitsios, Nicholas
    Fredolini, Claudia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mulder, Jan
    Schwenk, Jochen M.
    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.
    Kultima, Kim
    Ingelsson, Martin
    Kilander, Lena
    Lannfelt, Lars
    Svenningsson, Per
    Nellgard, Bengt
    Zetterberg, Henrik
    Blennow, Kaj
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Häggmark-Månberg, Anna
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    CSF profiling of the human brain enriched proteome reveals associations of neuromodulin and neurogranin to Alzheimer's disease2016Ingår i: PROTEOMICS - Clinical Applications, ISSN 1862-8346, E-ISSN 1862-8354, Vol. 10, nr 12, s. 1242-1253Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: This study is part of a larger effort aiming to expand the knowledge of brain-enriched proteins in human cerebrospinal fluid (CSF) and to provide novel insight into the relation between such proteins and different neurodegenerative diseases. Experimental design: Here 280 brain-enriched proteins in CSF from patients with Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are profiled. In total, 441 human samples of ventricular CSF collected post mortem and lumbar CSF collected ante mortem are analyzed using 376 antibodies in a suspension bead array setup, utilizing a direct labelling approach. Results: Among several proteins displaying differentiated profiles between sample groups, we focus here on two synaptic proteins, neuromodulin (GAP43) and neurogranin (NRGN). They are both found at elevated levels in CSF from AD patients in two independent cohorts, providing disease-associated profiles in addition to verifying and strengthening previously observed patterns. Increased levels are also observed for patients for whom the AD diagnosis was not established at the time of sampling. Conclusions and clinical relevance: These findings indicate that analyzing the brain-enriched proteins in CSF is of particular interest to increase the understanding of the CSF proteome and its relation to neurodegenerative disorders. In addition, this study lends support to the notion that measurements of these synaptic proteins could potentially be of great relevance in future diagnostic tests for AD.

  • 175.
    Reuterswärd, Philippa
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Bergström, Sofia
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Orikiiriza, Judy
    Makerere Univ, Coll Hlth Sci, Infect Dis Inst, Kampala, Uganda..
    Lindquist, Elisabeth
    Umeå Univ, Dept Mol Biol, Umeå, Sweden..
    Bergström, Sven
    Umeå Univ, Dept Mol Biol, Umeå, Sweden..
    Svahn Andersson, Helene
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ayoglu, Burcu
    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.
    Wahlgren, Mats
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
    Normark, Johan
    Umeå Univ, Dept Mol Biol, Umeå, Sweden..
    Ribacke, Ulf
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Levels of human proteins in plasma associated with acute paediatric malaria2018Ingår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 17, artikel-id 426Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The intimate interaction between the pathophysiology of the human host and the biology of the Plasmodium falciparum parasite results in a wide spectrum of disease outcomes in malaria. Development of severe disease is associated with a progressively augmented imbalance in pro- and anti-inflammatory responses to high parasite loads and sequestration of parasitized erythrocytes. Although these phenomena collectively constitute common denominators for the wide variety of discrete severe malaria manifestations, the mechanistic rationales behind discrepancies in outcome are poorly understood. Exploration of the human pathophysiological response by variations in protein profiles in plasma presents an excellent opportunity to increase the understanding. This is ultimately required for better prediction, prevention and treatment of malaria, which is essential for ongoing elimination and eradication efforts. Results: An affinity proteomics approach was used to analyse 541 paediatric plasma samples collected from community controls and patients with mild or severe malaria in Rwanda. Protein profiles were generated with an antibody-based suspension bead array containing 255 antibodies targetting 115 human proteins. Here, 57 proteins were identified with significantly altered levels (adjusted p-values<0.001) in patients with malaria compared to controls. From these, the 27 most significant proteins (adjusted p-values<10(-14)) were selected for a stringent analysis approach. Here, 24 proteins showed elevated levels in malaria patients and included proteins involved in acute inflammatory response as well as cell adhesion. The remaining three proteins, also implicated in immune regulation and cellular adhesivity, displayed lower abundance in malaria patients. In addition, 37 proteins (adjusted p-values<0.05) were identified with increased levels in patients with severe compared to mild malaria. This set includes, proteins involved in tissue remodelling and erythrocyte membrane proteins. Collectively, this approach has been successfully used to identify proteins both with known and unknown association with different stages of malaria. Conclusion: In this study, a high-throughput affinity proteomics approach was used to find protein profiles in plasma linked to P. falciparum infection and malaria disease progression. The proteins presented herein are mainly involved in inflammatory response, cellular adhesion and as constituents of erythrocyte membrane. These findings have a great potential to provide increased conceptual understanding of host-parasite interaction and malaria pathogenesis.

  • 176.
    Reuterswärd, Philippa
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Sofia, Bergström
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Orikiiriza, Judy
    Lindquist, Elisabeth
    Bergström, Sven
    Andersson Svahn, Helene
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Ayoglu, Burcu
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Uhlén, Mathias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Wahlgren, Mats
    Normark, Johan
    Ribacke, Ulf
    Nilsson, Peter
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Levels of human proteins in plasma as indicators for acute severe pediatric malariaManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background

    Existing low resource diagnostics for malaria infection suffer from sensitivity and specificity issues while lacking sufficient prognostic value. Identifying human host proteins could improve the possibilities to predict the risk of development of acute severe malaria. This will possible enable improved treatment and thereby lead to a decrease in mortality of malaria infected children. Furthermore, discovering host proteins with altered levels during active infection could generate leads to better understand host-parasite interaction.

    Results

    Here, we have analyzed a total of 541 pediatric plasma samples that were collected from community controls and individuals with mild or severe malaria in Rwanda. Protein profiles of these plasma samples were generated with an antibody-based suspension bead array containing 255 antibodies targeting 115 human proteins. We present 22 proteins with a strong discriminatory capacity (adjusted p-values below 10-19) for separating malaria cases from community controls. This panel of proteins contains among others acute phase proteins and proteins connected to cell adhesion and migration. Among these, three proteins showed lower plasma levels in the group of malaria-infected individuals compared to the control group. One of these proteins is the anti-adhesive secreted protein acidic and cysteine rich (SPARC) with possible connections to parasite cytoadhesion. A multi-protein panel of six proteins, including SPARC, could differentiate between controls and malaria cases with an AUC of 0.98. Furthermore, a panel of 37 proteins, including proteins associated to erythrocyte membranes, was identified as candidates for separation of mild and severe malaria patients (adjusted pvalues below 0.05).

    Conclusion

    The herein identified set of human proteins has a significant discriminatory capacity between community controls and malaria cases. We also present proteins offering the possibility to enable stratification and risk prediction for the development of severe malaria. This constitutes an important set that could enable enhanced understanding and thereby also possibilities for better treatment of acute severe pediatric malaria.

     

  • 177. Ribacke, Ulf
    et al.
    Mok, Bobo W.
    Wirta, Valtteri
    Normark, Johan
    Lundeberg, Joakim
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Kironde, Fred
    Egwang, Thomas G.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Wahlgren, Mats
    Genome wide gene amplifications and deletions in Plasmodium falciparum2007Ingår i: Molecular and biochemical parasitology (Print), ISSN 0166-6851, E-ISSN 1872-9428, Vol. 155, nr 1, s. 33-44Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The extent to which duplications and deletions occur in the Plasmodium falciparum genome, outside of the subtelomeres, and their contribution to the virulence of the malaria parasite is not known. Here we show the presence of multiple genome wide copy number polymorphisms (CNPs) covering 82 genes, the most extensive spanning a cumulative size of 110 kilobases. CNPs were identified in both laboratory strains and fresh clinical isolates using a 70-mer oligonucleotide microarray in conjunction with fluorescent in situ hybridizations and real-time quantitative PCR. The CNPs were found on all chromosomes except on chromosomes 6 and 8 and involved a total of 50 genes with increased copy numbers and 32 genes with decreased copy numbers relative to the 3D7 parasite. The genes, amplified in up to six copies, encode molecules involved in cell cycle regulation. cell division, drug resistance, erythrocyte invasion, sexual differentiation and unknown functions. These together with previous findings, suggest that the malaria parasite employs gene duplications and deletions as general strategies to enhance its survival and spread. Further analysis of the impact of discovered genetic differences and the underlying mechanisms is likely to generate a better understanding of the biology and the virulence of the malaria parasite.

  • 178.
    Rimini, Rebecca
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Sundberg, Marten
    Sjöberg, Ronald
    Klevebring, Daniel
    Gry, Marcus
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Validation of serum protein profiles by a dual antibody array approach2009Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In recent years, affinity-based technologies have become important tools for serum profiling to uncover protein expression patterns linked to disease state or therapeutic effects. In this study, we describe a path towards the production of an antibody microarray to allow protein profiling of biotinylated human serum samples with reproducible sensitivity in the picomolar range. With the availability of growing numbers of affinity reagents, protein profiles are to be validated in efficient manners and we describe a cross-platform strategy based on data concordance with a suspension bead array to interrogate the identical set of antibodies with the same cohort of serum samples. Comparative analysis enabled to screen for high-performing antibodies, which were displaying consistent results across the two platforms and targeting known serum components. Moreover, data processing methods such as sample referencing and normalization were evaluated for their effects on inter-platform agreement. Our work suggests that mutual validation of protein expression profiles using alternative microarray platforms holds great potential in becoming an important and valuable component in affinity-based high-throughput proteomic screenings as it allows to narrow down the number of discovered targets prior to orthogonal, uniplexed validation approaches.

  • 179. Ruiz-Riquelme, A.
    et al.
    Sánchez-Iglesias, S.
    Rábano, A.
    Guillén-Navarro, E.
    Domingo-Jiménez, R.
    Ramos, A.
    Rosa, I.
    Senra, A.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    García, Á.
    Araújo-Vilar, D.
    University of Santiago de Compostela-IDIS, Spain.
    Requena, J. R.
    University of Santiago de Compostela-IDIS, Spain.
    Larger aggregates of mutant seipin in Celia's Encephalopathy, a new protein misfolding neurodegenerative disease2015Ingår i: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 83, s. 44-53, artikel-id 3572Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Celia's Encephalopathy (MIM #. 615924) is a recently discovered fatal neurodegenerative syndrome associated with a new BSCL2 mutation (c.985C>T) that results in an aberrant isoform of seipin (Celia seipin). This mutation is lethal in both homozygosity and compounded heterozygosity with a lipodystrophic BSCL2 mutation, resulting in a progressive encephalopathy with fatal outcomes at ages 6-8. Strikingly, heterozygous carriers are asymptomatic, conflicting with the gain of toxic function attributed to this mutation. Here we report new key insights about the molecular pathogenic mechanism of this new syndrome. Intranuclear inclusions containing mutant seipin were found in brain tissue from a homozygous patient suggesting a pathogenic mechanism similar to other neurodegenerative diseases featuring brain accumulation of aggregated, misfolded proteins. Sucrose gradient distribution showed that mutant seipin forms much larger aggregates as compared with wild type (wt) seipin, indicating an impaired oligomerization. On the other hand, the interaction between wt and Celia seipin confirmed by coimmunoprecipitation (CoIP) assays, together with the identification of mixed oligomers in sucrose gradient fractionation experiments can explain the lack of symptoms in heterozygous carriers. We propose that the increased aggregation and subsequent impaired oligomerization of Celia seipin leads to cell death. In heterozygous carriers, wt seipin might prevent the damage caused by mutant seipin through its sequestration into harmless mixed oligomers.

  • 180.
    Russom, Aman
    et al.
    KTH, Tidigare Institutioner, Signaler, sensorer och system.
    Ahmadian, Afshin
    KTH, Tidigare Institutioner, Bioteknologi.
    Andersson, Helene
    KTH, Tidigare Institutioner, Signaler, sensorer och system.
    Nilsson, Peter
    KTH, Tidigare Institutioner, Bioteknologi.
    Stemme, Göran
    KTH, Tidigare Institutioner, Signaler, sensorer och system.
    Single-nucleotide polymorphism analysis by allele-specific extension of fluorescently labeled nucleotides in a microfluidic flow-through device2003Ingår i: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 24, nr 1-2, s. 158-161Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We describe a microfluidic approach for allele-specific extension of fluorescently labeled nucleotides for scoring of single-nucleotide polymorphism (SNP). The method takes advantage of the fact that the reaction kinetics differs between matched and mismatched configurations of allele-specific primers hybridized to DNA template. A microfluidic flow-through device for biochemical reactions on beads was used to take advantage of the reaction kinetics to increase the sequence specificity of the DNA polymerase, discriminating mismatched configurations from matched. The volume of the reaction chamber was 12.5 nL. All three possible variants of an SNP site at codon 72 of the p53 gene were scored using our approach. This work demonstrates the possibility of scoring SNP by allele-specific extension of fluorescently labeled nucleotides in a microfluidic flow-through device, The sensitive detection system and easy microfabrication of the microfluidic device enable further miniaturization and production of an array format of microfluidic devices for high-throughput SNP analysis.

  • 181.
    Schofield, James P. R.
    et al.
    Ctr Prote Res, Biol Sci, Southampton, Hants, England.;NIHR Southampton Biomed Res Ctr, Clin & Expt Sci, Fac Med, Southampton, Hants, England.;Univ Southampton, Inst Life Sci, Ctr Prote Res, Southampton, Hants, England..
    Mikus, Maria
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics.
    Sigmund, Ralf
    BI, Res Methodol & Biostat, Ingelheim, Germany..
    Stratification of asthma phenotypes by airway proteomic signatures2019Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 144, nr 1, s. 70-82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.

  • 182. Schrader, J.
    et al.
    Moyle, R.
    Bhalerao, R.
    Hertzberg, M.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner, Bioteknologi.
    Nilsson, Peter
    KTH, Tidigare Institutioner, Bioteknologi.
    Bhalerao, R. P.
    Cambial meristem dormancy in trees involves extensive remodelling of the transcriptome2004Ingår i: The Plant Journal, ISSN 0960-7412, E-ISSN 1365-313X, Vol. 40, nr 2, s. 173-187Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The establishment of the dormant state in meristems involves considerable physiological and metabolic alterations necessary for surviving unfavourable growth conditions. However, a global molecular analysis of dormancy in meristems has been hampered by the difficulty in isolating meristem cells. We used cryosectioning to isolate purified cambial meristem cells from the woody plant Populus tremula during active growth and dormancy. These samples were used to generate meristem-specific cDNA libraries and for cDNA microarray experiments to define the global transcriptional changes underlying cambial dormancy. The results indicate a significant reduction in the complexity of the cambial transcriptome in the dormant state. Although cell division is terminated in the dormant cambium, the cell cycle machinery appears to be maintained in a skeletal state as suggested by the continued presence of transcripts for several cell cycle regulators. The downregulation of PttPIN1 and PttPIN2 transcripts explains the reduced basipetal polar auxin transport during dormancy. The induction of a member of the SINA family of ubiquitin ligases implicated in auxin signalling indicates a potential mechanism for modulation of auxin sensitivity during cambial dormancy. The metabolic alterations during dormancy are mirrored in the induction of genes involved in starch breakdown and the glyoxysomal cycle. Interestingly, the induction of RGA1 like gene suggests modification of gibberellin signalling in cambial dormancy. The induction of genes such as poplar orthologues of FIE and HAP2 indicates a potential role for these global regulators of transcription in orchestrating extensive changes in gene expression during dormancy.

  • 183. Schrader, J.
    et al.
    Nilsson, J.
    Mellerowicz, E.
    Berglund, A.
    Nilsson, Peter
    KTH, Tidigare Institutioner, Bioteknologi.
    Hertzberg, M.
    Sandberg, G.
    A high-resolution transcript profile across the wood-forming meristem of poplar identifies potential regulators of cambial stem cell identity2004Ingår i: The Plant Cell, ISSN 1040-4651, E-ISSN 1532-298X, Vol. 16, nr 9, s. 2278-2292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Plant growth is the result of cell proliferation in meristems, which requires a careful balance between the formation of new tissue and the maintenance of a set of undifferentiated stem cells. Recent studies have provided important information on several genetic networks responsible for stem cell maintenance and regulation of cell differentiation in the apical meristems of shoots and roots. Nothing, however, is known about the regulatory networks in secondary meristems like the vascular cambium of trees. We have made use of the large size and highly regular layered organization of the cambial meristem to create a high-resolution transcriptional map covering 220 mum of the cambial region of aspen (Populus tremula). Clusters of differentially expressed genes revealed substantial differences in the transcriptomes of the six anatomically homogenous cell layers in the meristem zone. Based on transcriptional and anatomical data, we present a model for the position of the stem cells and the proliferating mother cells in the cambial zone. We also provide sets of marker genes for different stages of xylem and phloem differentiation and identify potential regulators of cambial meristem activity. Interestingly, analysis of known regulators of apical meristem development indicates substantial similarity in regulatory networks between primary and secondary meristems.

  • 184. Schroetter, Andreas
    et al.
    Park, Young Mok
    Marcus, Katrin
    Martins-de-Souza, Daniel
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    El Magraoui, Fouzi
    Meyer, Helmut E.
    Grinberg, Lea T.
    Key players in neurodegenerative disorders in focus - New insights into the proteomic profile of Alzheimer's disease, schizophrenia, ALS, and multiple sclerosis24th HUPO BPP Workshop: September 29, 2015, Vancouver, Canada2016Ingår i: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 16, nr 7, s. 1047-1050Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The HUPO Brain Proteome Project (HUPO BPP) held its 24th workshop in Vancouver, Canada, September 29, 2015. The focus of the autumn workshop was on new insights into the proteomic profile of Alzheimer's disease, schizophrenia, ALS and multiple sclerosis.

  • 185.
    Schwenk, Jochen M.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Gry, Marcus
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Rimini, Rebecca
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Antibody suspension bead arrays within serum proteomics2008Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 7, nr 8, s. 3168-3179Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antibody microarrays offer a powerful tool to screen for target proteins in complex samples. Here, we describe an approach for systematic analysis of serum, based on antibodies and using color-coded beads for the creation of antibody arrays in suspension. This method, adapted from planar antibody arrays, offers a fast, flexible, and multiplexed procedure to screen larger numbers of serum samples, and no purification steps are required to remove excess labeling substance. The assay system detected proteins down to lower picomolar levels with dynamic ranges over 3 orders of magnitude. The feasibility of this workflow was shown in a study with more than 200 clinical serum samples tested for 20 serum proteins.

  • 186.
    Schwenk, Jochen M.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Igel, Ulrika
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Kato, Bernet S.
    Nicholson, George
    Karpe, Fredrik
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Comparative protein profiling of serum and plasma using an antibody suspension bead array approach2010Ingår i: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 10, nr 3, s. 532-540Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the pursuit towards a systematic analysis of human diseases, array-based approaches within antibody proteomics offer high-throughput strategies to discover protein biomarkers in serum and plasma. To investigate the influence of sample preparation on such discovery attempts, we report on a systematic effort to compare serum and plasma protein profiles determined with an antibody suspension bead array. The intensity levels were used to define protein profiles and no significant differences between serum and plasma were observed for 79% of the 174 antibodies (targeting 156 proteins). By excluding 36 antibodies giving rise to differential intensity levels, cluster analysis revealed donor-specific rather than preparation-dependent grouping. With a cohort from a clinically relevant medical condition, the metabolic syndrome, the influence of the sample type on a multiplexed biomarker discovery approach was further investigated. Independent comparisons of protein profiles in serum and plasma revealed an antibody targeting ADAMTSL-4, a protein that would qualify to be studied further in association with the condition. In general, the preparation type had an impact on the results of the applied antibody suspension bead array, and while the technical variability was equal, plasma offered a greater biological variability and allowed to give rise to more discoveries than serum.

  • 187.
    Schwenk, Jochen M.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Igel, Ulrika
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Neiman, Maja
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Langen, Hanno
    Becker, Charlotte
    Bjartell, Anders
    Ponten, Fredrik
    Wiklund, Fredrik
    Gronberg, Henrik
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Toward Next Generation Plasma Profiling via Heat-induced Epitope Retrieval and Array-based Assays2010Ingår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 9, nr 11, s. 2497-2507Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a need for high throughput methods for screening patient samples in the quest for potential biomarkers for diagnostics and patient care. Here, we used a combination of undirected target selection, antibody suspension bead arrays, and heat-induced epitope retrieval to allow for protein profiling of human plasma in a novel and systematic manner. Several antibodies were found to reveal altered protein profiles upon epitope retrieval at elevated temperatures with limits of detection improving into lower ng/ml ranges. In a study based on prostate cancer patients, several proteins with differential profiles were discovered and subsequently validated in an independent cohort. For one of the potential biomarkers, the human carnosine dipeptidase 1 protein (CNDP1), the differences were determined to be related to the glycosylation status of the targeted protein. The study shows a path of pursuit for large scale screening of biobank repositories in a flexible and proteome-wide fashion by utilizing heat-induced epitope retrieval and using an antibody suspension bead array format. Molecular & Cellular Proteomics 9:2497-2507, 2010.

  • 188.
    Schwenk, Jochen M.
    et al.
    KTH, Skolan för bioteknologi (BIO).
    Lindberg, Johan
    Sundberg, Mårten
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Determination of binding specificities in highly multiplexed bead-based assays for antibody proteomics2007Ingår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 6, nr 1, s. 125-132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One of the major challenges of antibody-based proteomics is the quality assurance of the generated antibodies to ensure specificity to the target protein. Here we describe a single tube multiplex approach to simultaneously analyze the binding of antibodies to a large number of different antigens. This bead-based assay utilizes the full multiplexing capacity theoretically offered by the Luminex suspension array technology. A protocol for an increased coupling throughput for the immobilization of antigens was developed and used to set up complex and stabile 100-plex bead mixtures. The possibility of using a two-dimensional multiplexing, in terms of high numbers of both analytes and samples or as in this case antigens and antibodies, enables the specificity of 96 antibodies versus 100 different antigens to be determined in 2 h. This high throughput analysis will potentially have great impact on the possibility for the utilization of different antibody proteomics approaches where the quality assessment of antibodies is of the utmost importance.

  • 189.
    Schwenk, Jochen M.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Antibody suspension bead arrays2011Ingår i: Methods in molecular biology (Clifton, N.J.), ISSN 1940-6029, Vol. 723, s. 29-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alongside the increasing availability of affinity reagents, antibody microarrays have been developed to become a powerful tool to screen for target proteins in complex samples. Besides multiplexed sandwich immunoassays, the application of directly applying labeled sample onto arrays with immobilized capture reagents offers an approach to facilitate a systematic, high-throughput analysis of body fluids such as serum or plasma. An alternative to commonly used planar arrays has become available in form of a system based on color-coded beads for the creation of antibody arrays in suspension. The assay procedure offers an uncomplicated option to screen larger numbers of serum or plasma samples with variable sets of capture reagents. In addition, the established procedure of whole sample biotinylation circumvents the purification steps, which are generally required to remove excess labeling substance. We have shown that this assay system allows detecting proteins down into lower pico-molar and higher picogram per milliliter levels with dynamic ranges over three orders of magnitude. Presently, this workflow enables the profiling of 384 clinical samples for up to 100 proteins per assay.

  • 190.
    Schwenk, Jochen M
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Assessment of antibody specificity using suspension bead arrays.2011Ingår i: Vol. 785, nr Pt. 2, s. 183-189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    With the increasing collection of affinity reagents, their validation in terms of functionality and binding specificity becomes a challenge. To match this growing need, miniaturized and parallelized platforms have become available to corroborate the applicability for a broad range of binder scaffolds. Among the -commonly used systems, planar microarrays have been a platform of choice for a long time but alternative systems are emerging, of which one is based on color-coded beads for the creation of arrays in suspension. The latter systems offer to perform a two-dimensional multiplexing by now analyzing up to 384 samples against up to 500 analytes in a single experiment. While the analyte parameter is flexible in terms of its composition, an extended screening can be facilitated without the need to set up a microarray production facility.

  • 191. Sierra-Sanchez, Alvaro
    et al.
    Garrido-Martin, Diego
    Lourido, Lucia
    Gonzalez-Gonzalez, Maria
    Diez, Paula
    Ruiz-Romero, Cristina
    Sjöberg, Ronald
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Droste, Conrad
    De Las Rivas, Javier
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Blanco, Francisco
    Fuentes, Manuel
    Screening and Validation of Novel Biomarkers in Osteoarticular Pathologies by Comprehensive Combination of Protein Array Technologies2017Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 16, nr 5, s. 1890-1899Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Osteoarthritis (OA) is one of the most prevalent articular diseases. The identification of proteins closely associated with the diagnosis, progression, prognosis, and treatment response is dramatically required for this pathology. In this work, differential serum protein profiles have been identified in OA and rheumatoid arthritis (RA) by antibody arrays containing 151 antibodies against 121 antigens in a cohort of 36 samples. Then the identified differential serum protein profiles have been validated in a larger cohort of 282 samples. The overall immunoreactivity is higher in the pathological situations in comparison with the controls. Several proteins have been identified as biomarker candidates for OA and RA. Most of these biomarker candidates are proteins related to inflammatory response, lipid metabolism, or bone and extracellular matrix formation, degradation, or remodeling.

  • 192. Sievertzon, M.
    et al.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Lundeberg, Joakim
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Improving reliability and performance of DNA microarrays2006Ingår i: Expert Review of Molecular Diagnostics, ISSN 1473-7159, Vol. 6, nr 3, s. 481-492Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    A great many platforms and versions of the microarray technology, with different characteristics and applications, have been developed. This review will describe some key issues in reliability and performance with the two most commonly used platforms for gene expression analysis, in situ-synthesized oligonucleotide microarrays or GeneChip((R)) and spotted microarrays. Some recent advances and new applications within the field will be mentioned briefly.

  • 193.
    Sievertzon, Maria
    et al.
    KTH, Tidigare Institutioner, Bioteknologi.
    Agaton, Charlotta
    KTH, Tidigare Institutioner, Bioteknologi.
    Nilsson, Peter
    KTH, Tidigare Institutioner, Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner, Bioteknologi.
    Amplification of mRNA populations by a cDNA tag strategy2004Ingår i: BioTechniques, ISSN 0736-6205, Vol. 36, nr 2, s. 253-259Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Here we describe an amplification method for global transcript analysis. The strategy relies on amplification of cDNA tags (signature tags) achieved by random fragmentation of the cDNAs to short tags of similar length, isolation of the 3' ends and then PCR amplification of the 3'-end signature tag population. This method minimizes biased amplification that may occur during parallel amplification of long and short templates. The amplified tags can be either cloned and sequenced or labeled and hybridized to DNA arrays to identify the expressed transcripts. To verify that the relative levels between transcripts in different mRNA/cDNA populations are maintained during the amplification protocol, we have used the Affymetrix oligonucleotide platform and real-time PCR.

  • 194. Sjodin, Andreas
    et al.
    Bylesjo, Max
    Skogstrom, Oskar
    Eriksson, Daniel
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Ryden, Patrik
    Jansson, Stefan
    Karlsson, Jan
    UPSC-BASE - Populus transcriptomics online2006Ingår i: The Plant Journal, ISSN 0960-7412, E-ISSN 1365-313X, Vol. 48, nr 5, s. 806-817Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The increasing accessibility and use of microarrays in transcriptomics has accentuated the need for purpose-designed storage and analysis tools. Here we present UPSC-BASE, a database for analysis and storage of Populus DNA microarray data. A microarray analysis pipeline has also been established to allow consistent and efficient analysis (from small to large scale) of samples in various experimental designs. A range of optimized experimental protocols is provided for each step in generating the data. Within UPSC-BASE, researchers can perform standard and advanced microarray analysis procedures in a user-friendly environment. Background corrections, normalizations, quality-control tools, visualizations, hypothesis tests and export tools are provided without requirements for expert-level knowledge. Although the database has been developed primarily for handling Populus DNA microarrays, most of the tools are generic and can be used for other types of microarray. UPSC-BASE is also a repository of Populus microarray information, providing data from 21 experiments on a total of 407 microarray hybridizations in the public domain of the database. There are also an additional 10 experiments containing 347 hybridizations, where the automatically analysed data are searchable.

  • 195.
    Sjöberg, Ronald
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Andersson, Eni
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hellström, Cecilia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mattsson, Cecilia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ayoglu, Burcu
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    High-density antigen microarrays for the assessment of antibody selectivity and off-target binding2018Ingår i: Epitope Mapping Protocols, Humana Press Inc. , 2018, s. 231-238Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    With the increasing availability of collections of antibodies, their evaluation in terms of binding selectivity becomes an important but challenging task. Planar antigen microarrays are very suitable tools to address this task and provide a powerful proteomics platform for the characterization of the binding selectivity of antibodies toward thousands of antigens in parallel. In this chapter, we describe our in-house developed procedures for the generation of high-density planar antigen microarrays with over 21,000 features. We also provide the details of the assay protocol, which we routinely use for the assessment of binding selectivity of the polyclonal antibodies generated within the Human Protein Atlas. © Springer Science+Business Media, LLC, part of Springer Nature 2018.

  • 196.
    Sjöberg, Ronald
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hammarström, L.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Biosensor based protein profiling on reverse phase serum microarray2012Ingår i: Journal of Proteomics & Bioinformatics, ISSN 0974-276X, E-ISSN 0974-276X, Vol. 5, nr 8, s. 185-189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The reverse phase serum microarray format enables multi-parallel and simultaneous analysis of literally thousands of samples, a feature which is of uttermost importance for protein profiling of clinical samples. We have here screened 2400 serum samples for their potential IgA deficiency by using a fluorescence based reverse phase serum microarray platform and a biosensor based label-free microarray platform for verification and also compared our microarray-results to clinical routine ELISA. We have been able to identify possible IgA-deficiencies and to show the suitability of our microarray-platforms for large-scale screening of clinical serum samples. The two microarray methods show reproducibility and correlation towards each other and low variation between replicates within each platform. Both of the microarray platforms show less agreement towards ELISA. The fluorescence based microarray method has been shown to be applicable for large-scale screening of clinically important serum samples for detection of possibly IgA-deficient patients. Furthermore, it was found that the microarray based biosensor method could be used for determining the relative differences in concentration of IgA between the samples.

  • 197.
    Sjöberg, Ronald
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mattsson, Cecilia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Andersson, Eni
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hellström, Cecilia
    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.
    Ayoglu, Burcu
    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.
    Exploration of high-density protein microarrays for antibody validation and autoimmunity profiling2016Ingår i: New Biotechnology, ISSN 1871-6784, E-ISSN 1876-4347, Vol. 33, nr 5, s. 582-592Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High-density protein microarrays of recombinant human protein fragments, representing 12,412 unique Ensembl Gene IDs, have here been produced and explored. These protein microarrays were used to analyse antibody off-target interactions, as well as for profiling the human autoantibody repertoire in plasma against the antigens represented by the protein fragments. Affinity-purified polyclonal antibodies produced within the Human Protein Atlas (HPA) were analysed on microarrays of three different sizes, ranging from 384 antigens to 21,120 antigens, for evaluation of the antibody validation criteria in the HPA. Plasma samples from secondary progressive multiple sclerosis patients were also screened in order to explore the feasibility of these arrays for broad-scale profiling of autoantibody reactivity. Furthermore, analysis on these near proteome-wide microarrays was complemented with analysis on HuProt (TM) Human Proteome protein microarrays. The HPA recombinant protein microarray with 21,120 antigens and the HuProt (TM) Human Proteome protein microarray are currently the largest protein microarray platforms available to date. The results on these arrays show that the Human Protein Atlas antibodies have few off-target interactions if the antibody validation criteria are kept stringent and demonstrate that the HPA-produced high-density recombinant protein fragment microarrays allow for a high-throughput analysis of plasma for identification of possible autoantibody targets in the context of various autoimmune conditions.

  • 198.
    Sjöberg, Ronald
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Mattsson, Cecilia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Andersson, Eni
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Hellström, Cecilia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Zhu, Heng
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Ayoglu, Brucu
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Exploration of high-density protein microarrays for antibody validation and autoimmunity profilingManuskript (preprint) (Övrigt vetenskapligt)
  • 199.
    Sjöberg, Ronald
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Sundberg, Mårten
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Gundberg, Anna
    KTH, Skolan för bioteknologi (BIO).
    Sivertsson, Åsa
    KTH, Skolan för bioteknologi (BIO).
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO).
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101).
    Validation of affinity reagents using antigen microarrays2011Ingår i: New Biotechnology, ISSN 1871-6784, E-ISSN 1876-4347, Vol. 29, nr 5, s. 555-563Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a need for standardised validation of affinity reagents to determine their binding selectivity and specificity. This is of particular importance for systematic efforts that aim to cover the human proteome with different types of binding reagents. One such international program is the SH2-consortium, which was formed to generate a complete set of renewable affinity reagents to the SH2-domain containing human proteins. Here, we describe a microarray strategy to validate various affinity reagents, such as recombinant single-chain antibodies, mouse monoclonal antibodies and antigen-purified polyclonal antibodies using a highly multiplexed approach. An SH2-specific antigen microarray was designed and generated, containing more than 6000 spots displayed by 14 identical subarrays each with 406 antigens, where 105 of them represented SH2-domain containing proteins. Approximately 400 different affinity reagents of various types were analysed on these antigen microarrays carrying antigens of different types. The microarrays revealed not only very detailed specificity profiles for all the binders, but also showed that overlapping target sequences of spotted antigens were detected by off-target interactions. The presented study illustrates the feasibility of using antigen microarrays for integrative, high-throughput validation of various types of binders and antigens.

  • 200. Sjöstedt, Evelina
    et al.
    Fagerberg, Linn
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Hallström, Björn M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Häggmark, Anna
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Mitsios, Nicholas
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Pontén, Fredrik
    Hökfelt, Tomas
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Mulder, Jan
    Defining the Human Brain Proteome Using Transcriptomics and Antibody-Based Profiling with a Focus on the Cerebral Cortex2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 6, artikel-id UNSP e0130028Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The mammalian brain is a complex organ composed of many specialized cells, harboring sets of both common, widely distributed, as well as specialized and discretely localized proteins. Here we focus on the human brain, utilizing transcriptomics and public available Human Protein Atlas (HPA) data to analyze brain-enriched (frontal cortex) polyadenylated messenger RNA and long non-coding RNA and generate a genome-wide draft of global and cellular expression patterns of the brain. Based on transcriptomics analysis of altogether 27 tissues, we have estimated that approximately 3% (n=571) of all protein coding genes and 13% (n=87) of the long non-coding genes expressed in the human brain are enriched, having at least five times higher expression levels in brain as compared to any of the other analyzed peripheral tissues. Based on gene ontology analysis and detailed annotation using antibody-based tissue micro array analysis of the corresponding proteins, we found the majority of brain-enriched protein coding genes to be expressed in astrocytes, oligodendrocytes or in neurons with molecular properties linked to synaptic transmission and brain development. Detailed analysis of the transcripts and the genetic landscape of brainenriched coding and non-coding genes revealed brain-enriched splice variants. Several clusters of neighboring brain-enriched genes were also identified, suggesting regulation of gene expression on the chromatin level. This multi-angle approach uncovered the brainenriched transcriptome and linked genes to cell types and functions, providing novel insights into the molecular foundation of this highly specialized organ.

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