Change search
Link to record
Permanent link

Direct link
BETA
Publications (10 of 14) Show all publications
Thomas, C. E., Häussler, R. S., Hong, M.-G., Raverdy, V., Dale, M., Vinuela, A., . . . Schwenk, J. M. (2019). Individual effects of gastric bypass surgery on longitudinal blood protein profiles: an IMI DIRECT study. Paper presented at 55th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 16-20, 2019, Barcelona, SPAIN. Diabetologia, 62, S271-S271
Open this publication in new window or tab >>Individual effects of gastric bypass surgery on longitudinal blood protein profiles: an IMI DIRECT study
Show others...
2019 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, p. S271-S271Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
SPRINGER, 2019
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:kth:diva-261975 (URN)000485303802156 ()
Conference
55th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 16-20, 2019, Barcelona, SPAIN
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2019-10-14 Created: 2019-10-14 Last updated: 2019-10-14Bibliographically approved
Drobin, K., Assadi, G., Hong, M.-G., Anggraeni Andersson, M., Fredolini, C., Forsström, B., . . . Halfvarson, J. (2019). Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci. Inflammatory Bowel Diseases, 25(2), 306-316
Open this publication in new window or tab >>Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci
Show others...
2019 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 2, p. 306-316Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Oxford University Press, 2019
Keywords
inflammatory bowel disease, affinity proteomics, LACC1
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:kth:diva-249898 (URN)10.1093/ibd/izy326 (DOI)000462580900020 ()30358838 (PubMedID)2-s2.0-85059799081 (Scopus ID)
Note

QC 20190423

Available from: 2019-04-23 Created: 2019-04-23 Last updated: 2019-04-23Bibliographically approved
Uhlén, M., Karlsson, M. J., Hober, A., Svensson, A.-S., Scheffel, J., Kotol, D., . . . Sivertsson, Å. (2019). The human secretome. Science Signaling, 12(609), Article ID eaaz0274.
Open this publication in new window or tab >>The human secretome
Show others...
2019 (English)In: Science Signaling, ISSN 1945-0877, E-ISSN 1937-9145, Vol. 12, no 609, article id eaaz0274Article in journal (Refereed) Published
Abstract [en]

The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.

Place, publisher, year, edition, pages
NLM (Medline), 2019
National Category
Biochemistry and Molecular Biology Cell Biology
Identifiers
urn:nbn:se:kth:diva-265462 (URN)10.1126/scisignal.aaz0274 (DOI)000499099300003 ()31772123 (PubMedID)2-s2.0-85075677906 (Scopus ID)
Note

QC 20191218

Available from: 2019-12-18 Created: 2019-12-18 Last updated: 2020-01-10Bibliographically approved
Byström, S., Eklund, M., Hong, M.-G., Fredolini, C., Eriksson, M., Czene, K., . . . Gabrielson, M. (2018). Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density. Breast Cancer Research, 20, Article ID 14.
Open this publication in new window or tab >>Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density
Show others...
2018 (English)In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 20, article id 14Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2018
Keywords
Mammographic breast density, Plasma, Protein profiling, Suspension bead array, Affinity proteomics, KARMA cohort
National Category
Clinical Medicine
Identifiers
urn:nbn:se:kth:diva-223790 (URN)10.1186/s13058-018-0940-z (DOI)000425114200001 ()29444691 (PubMedID)2-s2.0-85042063089 (Scopus ID)
Funder
Swedish Research CouncilThe Kamprad Family FoundationKnut and Alice Wallenberg FoundationSwedish Cancer SocietyScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180307

Available from: 2018-03-07 Created: 2018-03-07 Last updated: 2018-03-07Bibliographically approved
Dawed, A. Y., Mari, A., McDonald, T. J., Hong, M.-G., Sharma, S., Robertson, N. R., . . . Pearson, E. R. (2018). GLP-1 RECEPTOR VARIANTS MARKEDLY DIFFERENTIATE GLYCAEMIC RESPONSE TO GLP-1 RECEPTOR AGONISTS: A DIRECT STUDY. Basic & Clinical Pharmacology & Toxicology, 123, 13-14
Open this publication in new window or tab >>GLP-1 RECEPTOR VARIANTS MARKEDLY DIFFERENTIATE GLYCAEMIC RESPONSE TO GLP-1 RECEPTOR AGONISTS: A DIRECT STUDY
Show others...
2018 (English)In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 123, p. 13-14Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2018
National Category
Medical Genetics
Identifiers
urn:nbn:se:kth:diva-231230 (URN)10.1111/bcpt.13020 (DOI)000434060000036 ()
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180628

Available from: 2018-06-28 Created: 2018-06-28 Last updated: 2018-06-28Bibliographically approved
Matic, L. P., Iglesias, M. J., Vesterlund, M., Lengquist, M., Hong, M.-G., Saieed, S., . . . Hedin, U. (2018). Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage. JACC: Basic to Translational Science, 3(4), 464-480
Open this publication in new window or tab >>Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage
Show others...
2018 (English)In: JACC: Basic to Translational Science, ISSN 2452-302X, Vol. 3, no 4, p. 464-480Article in journal (Refereed) Published
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.

Keywords
atherosclerosis, biomarkers, intraplaque hemorrhage, omics analyses, translational studies
National Category
Basic Medicine
Identifiers
urn:nbn:se:kth:diva-238051 (URN)10.1016/j.jacbts.2018.04.001 (DOI)2-s2.0-85053830575 (Scopus ID)
Note

Export Date: 30 October 2018; Article; Correspondence Address: Hedin, U.; Department of Molecular Medicine and Surgery, L8:03, Karolinska Institute, Sweden; email: Ulf.Hedin@ki.se

QC 20190115

Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2020-01-10Bibliographically approved
Dawed, A. Y., Mari, A., McDonald, T. J., Hong, M.-G., Sharma, S., Robertson, N. R., . . . Pearson, E. R. (2017). GLP-1 receptor variants markedly differentiate glycaemic response to GLP-1 receptor agonists: a DIRECT study. Paper presented at 53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL. Diabetologia, 60, S393-S393
Open this publication in new window or tab >>GLP-1 receptor variants markedly differentiate glycaemic response to GLP-1 receptor agonists: a DIRECT study
Show others...
2017 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S393-S393Article in journal (Refereed) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:kth:diva-216634 (URN)000408315002188 ()
Conference
53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL
Note

QC 20171101

Available from: 2017-11-01 Created: 2017-11-01 Last updated: 2017-11-01Bibliographically approved
Pin, E., Henjes, F., Hong, M.-G., Wiklund, F., Magnusson, P., Bjartell, A., . . . Schwenk, J. M. (2017). Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer. Journal of Proteome Research, 16(1), 204-216
Open this publication in new window or tab >>Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer
Show others...
2017 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 16, no 1, p. 204-216Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2017
Keywords
autoimmunity, prostate cancer, prostein, planar microarray, suspension bead array, profiling epitope mapping, Human Protein Atlas, antigen, peptide
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-201244 (URN)10.1021/acs.jproteome.6b00620 (DOI)000391782100019 ()2-s2.0-85017653060 (Scopus ID)
Note

QC 20170216

Available from: 2017-02-16 Created: 2017-02-16 Last updated: 2020-01-10Bibliographically approved
Fredolini, C., Byström, S., Pin, E., Edfors, F., Tamburro, D., Iglesias, M. J., . . . Schwenk, J. M. (2016). Immunocapture strategies in translational proteomics. Expert Review of Proteomics, 13(1), 83-98
Open this publication in new window or tab >>Immunocapture strategies in translational proteomics
Show others...
2016 (English)In: Expert Review of Proteomics, ISSN 1478-9450, E-ISSN 1744-8387, Vol. 13, no 1, p. 83-98Article, review/survey (Refereed) Published
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.

Place, publisher, year, edition, pages
Taylor & Francis, 2016
Keywords
Antibodies, immunocapture, mass spectrometry, protein enrichment, sandwich assays, SRM
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-180965 (URN)10.1586/14789450.2016.1111141 (DOI)000367351000001 ()26558424 (PubMedID)
Note

QC 20160128

Available from: 2016-01-28 Created: 2016-01-26 Last updated: 2020-01-10Bibliographically approved
Bruzelius, M., Iglesias, M. J., Hong, M.-G., Sanchez-Rivera, L., Gyorgy, B., Souto, J. C., . . . Odeberg, J. (2016). PDGFB, a new candidate plasma biomarker for venous thromboembolism: Results from the VEREMA affinity proteomics study. Blood, 128(23), e59-e66
Open this publication in new window or tab >>PDGFB, a new candidate plasma biomarker for venous thromboembolism: Results from the VEREMA affinity proteomics study
Show others...
2016 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 128, no 23, p. e59-e66Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
American Society of Hematology, 2016
National Category
Hematology
Identifiers
urn:nbn:se:kth:diva-207449 (URN)10.1182/blood-2016-05-711846 (DOI)000392652300001 ()2-s2.0-85015658471 (Scopus ID)
Note

QC 20170523

Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2020-01-10Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8603-8293

Search in DiVA

Show all publications