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

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

  • 2. Bruzelius, M.
    et al.
    Iglesias, Maria Jesus
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Tregouet, D. A.
    Souto, J. C.
    Holmström, M.
    Frånberg, M.
    Strawbridge, R. J.
    Sabater-Lleal, M.
    Sennblad, B.
    Silveira, A.
    Soria, J. M.
    Morange, P. E.
    Butler, L.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hamsten, A.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Verema - an affinity proteomics study to identify and translate plasma biomarkers for venous thromboembolism2015Ingår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, s. 954-954Artikel i tidskrift (Refereegranskat)
  • 3.
    Byström, Sanna
    et al.
    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.
    Häggmark, Anna
    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.
    Drobin, Kim
    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.
    Fredolini, Claudia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. 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.
    et al.,
    Affinity Proteomic Profiling of Plasma, Cerebrospinal Fluid, and Brain Tissue within Multiple Sclerosis2014Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 13, nr 11, s. 4607-4619Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The brain is a vital organ and because it is well shielded from the outside environment, possibilities for noninvasive analysis are often limited. Instead, fluids taken from the spinal cord or circulatory system are preferred sources for the discovery of candidate markers within neurological diseases. In the context of multiple sclerosis (MS), we applied an affinity proteomic strategy and screened 22 plasma samples with 4595 antibodies (3450 genes) on bead arrays, then defined 375 antibodies (334 genes) for targeted analysis in a set of 172 samples and finally used 101 antibodies (43 genes) on 443 plasma as well as 573 cerebrospinal spinal fluid (CSF) samples. This revealed alteration of protein profiles in relation to MS subtypes for IRF8, IL7, METTL14, SLC30A7, and GAP43. Respective antibodies were subsequently used for immunofluorescence on human post-mortem brain tissue with MS pathology for expression and association analysis. There, antibodies for IRF8, IL7, and METTL14 stained neurons in proximity of lesions, which highlighted these candidate protein targets for further studies within MS and brain tissue. The affinity proteomic translation of profiles discovered by profiling human body fluids and tissue provides a powerful strategy to suggest additional candidates to studies of neurological disorders.

  • 4.
    Byström, Sanna
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Eklund, Martin
    Hong, Mun-Gwan
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Fredolini, Claudia
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Eriksson, Mikael
    Czene, Kamila
    Hall, Per
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Gabrielson, Marike
    Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density2018Ingår i: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 20, artikel-id 14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Mammographic breast density is one of the strongest risk factors for breast cancer, but molecular understanding of how breast density relates to cancer risk is less complete. Studies of proteins in blood plasma, possibly associated with mammographic density, are well-suited as these allow large-scale analyses and might shed light on the association between breast cancer and breast density. Methods: Plasma samples from 1329 women in the Swedish KARMA project, without prior history of breast cancer, were profiled with antibody suspension bead array (SBA) assays. Two sample sets comprising 729 and 600 women were screened by two different SBAs targeting a total number of 357 proteins. Protein targets were selected through searching the literature, for either being related to breast cancer or for being linked to the extracellular matrix. Association between proteins and absolute area-based breast density (AD) was assessed by quantile regression, adjusting for age and body mass index (BMI). Results: Plasma profiling revealed linear association between 20 proteins and AD, concordant in the two sets of samples (p < 0.05). Plasma levels of seven proteins were positively associated and 13 proteins negatively associated with AD. For eleven of these proteins evidence for gene expression in breast tissue existed. Among these, ABCC11, TNFRSF10D, F11R and ERRF were positively associated with AD, and SHC1, CFLAR, ACOX2, ITGB6, RASSF1, FANCD2 and IRX5 were negatively associated with AD. Conclusions: Screening proteins in plasma indicates associations between breast density and processes of tissue homeostasis, DNA repair, cancer development and/or progression in breast cancer. Further validation and follow-up studies of the shortlisted protein candidates in independent cohorts will be needed to infer their role in breast density and its progression in premenopausal and postmenopausal women.

  • 5.
    Byström, Sanna
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Eklund, Martin
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Hong, Mun-Gwan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Fredolini, Claudia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Eriksson, Mikael
    Czene, Kamila
    Hall, Per
    Schwenk, Jochen. M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Gabrielson, Marike
    Affinity proteomic profiling of plasma for proteins associated to mammographic breast densityManuskript (preprint) (Övrigt vetenskapligt)
  • 6. Dawed, A. Y.
    et al.
    Mari, A.
    McDonald, T. J.
    Hong, Mun-Gwan
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sharma, S.
    Robertson, N. R.
    Mahajan, A.
    Walker, M.
    Gough, S.
    Zhou, K.
    Forgie, I.
    Ruetten, H.
    Jones, A. G.
    Pearson, E. R.
    GLP-1 receptor variants markedly differentiate glycaemic response to GLP-1 receptor agonists: a DIRECT study2017Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, s. S393-S393Artikel i tidskrift (Refereegranskat)
  • 7.
    Dawed, A. Y.
    et al.
    Univ Dundee, Mol & Clin Med, Dundee, Scotland..
    Mari, A.
    CNR, Inst Neurosci, Padua, Italy..
    McDonald, T. J.
    Royal Devon & Exeter Hosp, NIHR Exeter Clin Res Facil, Exeter, Devon, England..
    Hong, Mun-Gwan
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Sharma, S.
    Helmholtz Zentrum Muenchen, Inst Epidemiol 2, Res Unit Mol Epidemiol, Munich, Germany..
    Robertson, N. R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Mahajan, A.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Walker, M.
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Gough, S.
    NIHR Oxford Biomed Res Ctr, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Zhou, K.
    Univ Dundee, Mol & Clin Med, Dundee, Scotland..
    Forgie, I
    Univ Dundee, Mol & Clin Med, Dundee, Scotland..
    Ruetten, H.
    Sanofi Aventis Deutschland GmbH, TMED, Frankfurt, Germany..
    Jones, A. G.
    Royal Devon & Exeter Hosp, NIHR Exeter Clin Res Facil, Exeter, Devon, England..
    Pearson, E. R.
    Univ Dundee, Mol & Clin Med, Dundee, Scotland..
    GLP-1 RECEPTOR VARIANTS MARKEDLY DIFFERENTIATE GLYCAEMIC RESPONSE TO GLP-1 RECEPTOR AGONISTS: A DIRECT STUDY2018Ingår i: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 123, s. 13-14Artikel i tidskrift (Övrigt vetenskapligt)
  • 8.
    Drobin, Kimi
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Assadi, Ghazaleh
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden..
    Hong, Mun-Gwan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Anggraeni Andersson, Margaretha
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Fredolini, Claudia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab. Royal Inst Technol, KTH, Sch Biotechnol, Affin Prote,SciLifeLab, Stockholm, Sweden..
    Forsström, Björn
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Reznichenko, Anna
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden..
    Akhter, Tahmina
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden..
    Ek, Weronica E.
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.;Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Bonfiglio, Ferdinando
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.;Biodonostia Hlth Res Inst, Dept Gastrointestinal & Liver Dis, San Sebastian, Spain..
    Hansen, Mark Berner
    AstraZeneca R&D, Innovat & Global Med, Molndal, Sweden.;Univ Copenhagen, Bispebjerg Hosp, Ctr Digest Dis, Copenhagen, Denmark..
    Sandberg, Kristian
    Uppsala Univ, Sci Life Lab, Drug Discovery & Dev Platform, Uppsala, Sweden.;Uppsala Univ, Uppsala Biomed Ctr, Dept Med Chem, Organ Pharmaceut Chem, Uppsala, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Greco, Dario
    Univ Helsinki, Inst Biotechnol, Helsinki, Finland..
    Repsilber, Dirk
    Orebro Univ, Sch Med Sci, Orebro, Sweden..
    Schwenk, Jochen M.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    D'Amato, Mauro
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.;BioDonostia Hlth Res Inst, San Sebastian, Spain.;Ikerbasque, Basque Fdn Sci, Bilbao, Spain..
    Halfvarson, Jonas
    Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, SE-70182 Orebro, Sweden..
    Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci2019Ingår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, nr 2, s. 306-316Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential. Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohns disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping. By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity. Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.

  • 9.
    Fredolini, Claudia
    et al.
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Byström, Sanna
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Pin, Elisa
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Edfors, Fredrik
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Tamburro, Davide
    Iglesias, Maria Jesus
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Häggmark, Anna
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Immunocapture strategies in translational proteomics2016Ingår i: Expert Review of Proteomics, ISSN 1478-9450, E-ISSN 1744-8387, Vol. 13, nr 1, s. 83-98Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Aiming at clinical studies of human diseases, antibody-assisted assays have been applied to biomarker discovery and toward a streamlined translation from patient profiling to assays supporting personalized treatments. In recent years, integrated strategies to couple and combine antibodies with mass spectrometry-based proteomic efforts have emerged, allowing for novel possibilities in basic and clinical research. Described in this review are some of the field's current and emerging immunocapture approaches from an affinity proteomics perspective. Discussed are some of their advantages, pitfalls and opportunities for the next phase in clinical and translational proteomics.

  • 10.
    Hong, Mun-Gwan
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Lee, Woojoo
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Pawitan, Yudi
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Multidimensional Normalization to Minimize Plate Effects of Suspension Bead Array Data2016Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 15, nr 10, s. 3473-3480Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Enhanced by the growing number of biobanks, biomarker studies can now be performed with reasonable statistical power by using large sets of samples. Antibody-based proteomics by means of suspension bead arrays offers one attractive approach to analyze serum, plasma, or CSF samples for such studies in microtiter plates. To expand measurements beyond single batches, with either 96 or 384 samples per plate, suitable normalization methods are required to minimize the variation between plates. Here we propose two normalization approaches utilizing MA coordinates. The multidimensional MA (multi-MA) and MA-loess both consider all samples of a microtiter plate per suspension bead array assay and thus do not require any external reference samples. We demonstrate the performance of the two MA normalization methods with data obtained from the analysis of 384 samples including both serum and plasma. Samples were randomized across 96-well sample plates, processed, and analyzed in assay plates, respectively. Using principal component analysis (PCA), we could show that plate-wise clusters found in the first two components were eliminated by multi-MA normalization as compared with other normalization methods. Furthermore, we studied the correlation profiles between random pairs of antibodies and found that both MA normalization methods substantially reduced the inflated correlation introduced by plate effects. Normalization approaches using multi-MA and MA-loess minimized batch effects arising from the analysis of several assay plates with antibody suspension bead arrays. In a simulated biomarker study, multi-MA restored associations lost due to plate effects. Our normalization approaches, which are available as R package MDimNornin, could also be useful in studies using other types of high-throughput assay data.

  • 11.
    Häggmark, Anna
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mikus, Maria
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mohsenchian, Atefeh
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Forsström, Björn
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Gajewska, Beata
    Baranczyk-Kuzma, Anna
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Kuzma-Kozakiewicz, Magdalena
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Plasma profiling revelas three proteins associated to amyotrophic lateral sclerosis2014Ingår i: Annals of Clinical and Translational Neurology, ISSN 2328-9503, Vol. 1, nr 8, s. 544-553Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

  • 12.
    Iglesias, Maria Jesus
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Bruzelius, M.
    Hong, M-Gwan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Tregouet, D. A.
    Perisic, L.
    Frånberg, M.
    Parini, P.
    Ganna, A.
    Ingelsson, E.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hedin, U.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Silveira, A.
    Morange, P. E.
    Hamsten, A.
    Schwenk, JM, Jochen
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    An affinity proteomics study for plasma biomarker candidates of cardiovascular disease in venous thromboembolism2015Ingår i: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, s. 956-956Artikel i tidskrift (Refereegranskat)
  • 13. Matic, L. P.
    et al.
    Iglesias, Maria Jesus
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Vesterlund, M.
    Lengquist, M.
    Hong, Mun-Gwan
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Saieed, S.
    Sanchez-Rivera, Laura
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Berg, M.
    Razuvaev, A.
    Kronqvist, M.
    Lund, K.
    Caidahl, K.
    Gillgren, P.
    Pontén, F.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Hansson, G. K.
    Paulsson-Berne, G.
    Fagman, E.
    Roy, J.
    Hultgren, R.
    Bergström, G.
    Lehtiö, J.
    Odeberg, Jacob
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Hedin, U.
    Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage2018Ingår i: JACC: Basic to Translational Science, ISSN 2452-302X, Vol. 3, nr 4, s. 464-480Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 14.
    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.

  • 15.
    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.

  • 16.
    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.

  • 17.
    Thomas, Cecilia Engel
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Häussler, Ragna S.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics.
    Raverdy, V.
    Ctr Hosp Reg Univ Lille 2, Lille, France..
    Dale, Matilda
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Vinuela, A.
    Univ Geneva, Dept Genet Med & Dev, Sch Med, Geneva, Switzerland..
    Canouil, M.
    Univ Lille, CNRS, Inst Pasteur Lille, Lille, France..
    Dermitzakis, E. T.
    Univ Geneva, Dept Genet Med & Dev, Sch Med, Geneva, Switzerland..
    Froguel, P.
    Univ Lille, CNRS, Inst Pasteur Lille, Lille, France..
    Brunak, S.
    Tech Univ Denmark, Dept Bio & Hlth Informat, Lyngby, Denmark..
    Pattou, F.
    Ctr Hosp Reg Univ Lille 2, Lille, France..
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics.
    Individual effects of gastric bypass surgery on longitudinal blood protein profiles: an IMI DIRECT study2019Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, s. S271-S271Artikel i tidskrift (Övrigt vetenskapligt)
  • 18. Wilman, H. R.
    et al.
    Parisinos, C. A.
    Atabaki-Pasdar, N.
    Kelly, M.
    Thomas, E. L.
    Neubauer, S.
    Jennison, C.
    Ehrhardt, B.
    Baum, P.
    Schoelsch, C.
    Freijer, J.
    Grempler, R.
    Graefe-Mody, U.
    Hennige, A.
    Dings, C.
    Lehr, T.
    Scherer, N.
    Sihinecich, I.
    Pattou, F.
    Raverdi, V.
    Caiazzo, R.
    Torres, F.
    Verkindt, H.
    Mari, A.
    Tura, A.
    Giorgino, T.
    Bizzotto,
    Froguel, P.
    Bonneford, A.
    Canouil, M.
    Dhennin, V.
    Brorsson, C.
    Brunak, S.
    De Masi, F.
    Gudmundsdóttir, V.
    Pedersen, H.
    Banasik, K.
    Thomas, C.
    Sackett, P.
    Staerfeldt, H. -H
    Lundgaard, A.
    Nilsson, B.
    Nielsen, A.
    Mazzoni, G.
    Karaderi, T.
    Rasmussen, S.
    Johansen, J.
    Allesøe, R.
    Fritsche, A.
    Thorand, B.
    Adamski, J.
    Grallert, H.
    Haid, M.
    Sharma, S.
    Troll, M.
    Adam, J.
    Ferrer, J.
    Eriksen, H.
    Frost, G.
    Häussler, Ragna S.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    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.
    Uhlén, Mathias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nicolay, C.
    Pavo, I.
    Steckel-Hamann, B.
    Thomas, M.
    Adragni, K.
    Wu, H.
    Hart, L.
    Roderick, S.
    van Leeuwen, N.
    Dekkers, K.
    Frau, F.
    Gassenhuber, J.
    Jablonka, B.
    Musholt, P.
    Ruetten, H.
    Tillner, J.
    Baltauss, T.
    Bernard Poenaru, O.
    de Preville, N.
    Rodriquez, M.
    Arumugam, M.
    Allin, K.
    Engelbrechtsen, L.
    Hansen, T.
    Forman, A.
    Jonsson, A.
    Pedersen, O.
    Dutta, A.
    Vogt, J.
    Vestergaard, H.
    Laakso, M.
    Kokkola, T.
    Kuulasmaa, T.
    Franks, P.
    Giordano, N.
    Pomares-Millan, H.
    Fitipaldi, H.
    Mutie, P.
    Klintenberg, M.
    Bergstrom, M.
    Groop, L.
    Ridderstrale, M.
    Atabaki Pasdar, N.
    Deshmukh, H.
    Heggie, A.
    Wake, D.
    McEvoy, D.
    McVittie, I.
    Walker, M.
    Hattersley, A.
    Hill, A.
    Jones, A.
    McDonald, T.
    Perry, M.
    Nice, R.
    Hudson, M.
    Thorne, C.
    Dermitzakis, E.
    Viñuela, A.
    Cabrelli, L.
    Loftus, H.
    Dawed, A.
    Donnelly, L.
    Forgie, I.
    Pearson, E.
    Palmer, C.
    Brown, A.
    Koivula, R.
    Wesolowska-Andersen, A.
    Abdalla, M.
    McRobert, N.
    Fernandez, J.
    Jiao, Y.
    Robertson, N.
    Gough, S.
    Kaye, J.
    Mourby, M.
    Mahajan, A.
    McCarthy, M.
    Shah, N.
    Teare, H.
    Holl, R.
    Koopman, A.
    Rutters, F.
    Beulens, J.
    Groeneveld, L.
    Bell, J.
    Thomas, L.
    Whitcher, B.
    Hingorani, A. D.
    Patel, R. S.
    Hemingway, H.
    Franks, P. W.
    Bell, J. D.
    Banerjee, R.
    Yaghootkar, H.
    Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration2019Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 71, nr 3, s. 594-602Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background &amp; Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p &lt;5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.

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