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Publications (10 of 85) Show all publications
Uhlén, M., Zhang, C., Lee, S., Sjöstedt, E., Fagerberg, L., Bidkhori, G., . . . Ponten, F. (2017). A pathology atlas of the human cancer transcriptome. Science, 357(6352), 660-+.
Open this publication in new window or tab >>A pathology atlas of the human cancer transcriptome
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2017 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 357, no 6352, 660-+ p.Article in journal (Refereed) Published
Abstract [en]

Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE, 2017
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-214334 (URN)10.1126/science.aan2507 (DOI)000407793600028 ()2-s2.0-85028362951 (Scopus ID)
Note

QC 20170913

Available from: 2017-09-13 Created: 2017-09-13 Last updated: 2017-11-07Bibliographically approved
Omazic, B., Ayoglu, B., Löhr, M., Segersvärd, R., Verbeke, C., Magalhaes, I., . . . Ringden, O. (2017). A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients with Pancreatic Cancer. Journal of immunotherapy (1997), 40(4), 132-139.
Open this publication in new window or tab >>A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients with Pancreatic Cancer
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2017 (English)In: Journal of immunotherapy (1997), ISSN 1524-9557, E-ISSN 1537-4513, Vol. 40, no 4, 132-139 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Lippincott Williams and Wilkins, 2017
Keyword
HSCT, pancreatic adenocarcinoma, radical surgery
National Category
Cancer and Oncology Immunology
Identifiers
urn:nbn:se:kth:diva-207424 (URN)10.1097/CJI.0000000000000164 (DOI)000398850800003 ()2-s2.0-85016172220 (Scopus ID)
Note

QC 20170524

Available from: 2017-05-24 Created: 2017-05-24 Last updated: 2017-06-02Bibliographically approved
Thul, P. J., Åkesson, L., Wiking, M., Mahdessian, D., Geladaki, A., Ait Blal, H., . . . Lundberg, E. (2017). A subcellular map of the human proteome. Science, 356(6340), Article ID 820.
Open this publication in new window or tab >>A subcellular map of the human proteome
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2017 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 356, no 6340, 820Article in journal (Refereed) Published
Abstract [en]

Resolving the spatial distribution of the human proteome at a subcellular level can greatly increase our understanding of human biology and disease. Here we present a comprehensive image-based map of subcellular protein distribution, the Cell Atlas, built by integrating transcriptomics and antibody-based immunofluorescence microscopy with validation by mass spectrometry. Mapping the in situ localization of 12,003 human proteins at a single-cell level to 30 subcellular structures enabled the definition of the proteomes of 13 major organelles. Exploration of the proteomes revealed single-cell variations in abundance or spatial distribution and localization of about half of the proteins to multiple compartments. This subcellular map can be used to refine existing protein-protein interaction networks and provides an important resource to deconvolute the highly complex architecture of the human cell.

Place, publisher, year, edition, pages
American Association for the Advancement of Science, 2017
Keyword
antibody, proteome, biology, cells and cell components, disease incidence, image analysis, physiological response, protein, proteomics, spatial distribution, Article, cell organelle, cellular distribution, human, human cell, immunofluorescence microscopy, mass spectrometry, priority journal, protein analysis, protein localization, protein protein interaction, single cell analysis, transcriptomics
National Category
Cell Biology
Identifiers
urn:nbn:se:kth:diva-216588 (URN)10.1126/science.aal3321 (DOI)000401957900032 ()2-s2.0-85019201137 (Scopus ID)
Note

QC 20171208

Available from: 2017-12-08 Created: 2017-12-08 Last updated: 2017-12-08Bibliographically approved
Lourido, L., Ayoglu, B., Fernandez-Tajes, J., Oreiro, N., Henjes, F., Hellstroem, C., . . . Blanco, F. J. (2017). Discovery of circulating proteins associated to knee radiographic osteoarthritis. Scientific Reports, 7, Article ID 137.
Open this publication in new window or tab >>Discovery of circulating proteins associated to knee radiographic osteoarthritis
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 137Article in journal (Refereed) Published
Abstract [en]

Currently there are no sufficiently sensitive biomarkers able to reflect changes in joint remodelling during osteoarthritis (OA). In this work, we took an affinity proteomic approach to profile serum samples for proteins that could serve as indicators for the diagnosis of radiographic knee OA. Antibody suspension bead arrays were applied to analyze serum samples from patients with OA (n = 273), control subjects (n = 76) and patients with rheumatoid arthritis (RA, n = 244). For verification, a focused bead array was built and applied to an independent set of serum samples from patients with OA (n = 188), control individuals (n = 83) and RA (n = 168) patients. A linear regression analysis adjusting for sex, age and body mass index (BMI) revealed that three proteins were significantly elevated (P < 0.05) in serum from OA patients compared to controls: C3, ITIH1 and S100A6. A panel consisting of these three proteins had an area under the curve of 0.82 for the classification of OA and control samples. Moreover, C3 and ITIH1 levels were also found to be significantly elevated (P < 0.05) in OA patients compared to RA patients. Upon validation in additional study sets, the alterations of these three candidate serum biomarker proteins could support the diagnosis of radiographic knee OA.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:kth:diva-205464 (URN)10.1038/s41598-017-00195-8 (DOI)000396868900019 ()28273936 (PubMedID)
Available from: 2017-05-22 Created: 2017-05-22 Last updated: 2017-05-22Bibliographically 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
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2017 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 16, no 1, 204-216 p.Article 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
Keyword
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: 2017-11-29Bibliographically approved
Idborg, H., Zandian, A., Hellstrom, C., Mattsson, C., Fredolini, C., Uhlén, M., . . . Nilsson, P. (2017). PROTEIN PROFILING IN PLASMA REVEALS MOLECULAR SUBGROUPS IN SYSTEMIC LUPUS ERYTHEMATOSUS. Paper presented at 37th European Workshop on Rheumatology Research (EWRR), MAR 02-04, 2017, Athens, GREECE. Annals of the Rheumatic Diseases, 76, A52-A52.
Open this publication in new window or tab >>PROTEIN PROFILING IN PLASMA REVEALS MOLECULAR SUBGROUPS IN SYSTEMIC LUPUS ERYTHEMATOSUS
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2017 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, A52-A52 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2017
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:kth:diva-216642 (URN)10.1136/annrheumdis-2016-211052.1 (DOI)000411783100070 ()
Conference
37th European Workshop on Rheumatology Research (EWRR), MAR 02-04, 2017, Athens, GREECE
Note

QC 20171031

Available from: 2017-10-31 Created: 2017-10-31 Last updated: 2017-10-31Bibliographically approved
Schwenk, J. M., Omenn, G. S., Sun, Z., Campbell, D. S., Baker, M. S., Overall, C. M., . . . Deutsch, E. W. (2017). The Human Plasma Proteome Draft of 2017: Building on the Human Plasma PeptideAtlas from Mass Spectrometry and Complementary Assays. Journal of Proteome Research, 16(12), 4299-4310.
Open this publication in new window or tab >>The Human Plasma Proteome Draft of 2017: Building on the Human Plasma PeptideAtlas from Mass Spectrometry and Complementary Assays
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2017 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 16, no 12, 4299-4310 p.Article, review/survey (Refereed) Published
Abstract [en]

Human blood plasma provides a highly accessible window to the proteome of any individual in health and disease. Since its inception in 2002, the Human Proteome Organization's Human Plasma Proteome Project (HPPP) has been promoting advances in the study and understanding of the full protein complement of human plasma and on determining the abundance and modifications of its components. In 2017, we review the history of the HPPP and the advances of human plasma proteomics in general, including several recent achievements. We then present the latest 2017-04 build of Human Plasma PeptideAtlas, which yields ∼43 million peptide-spectrum matches and 122,730 distinct peptide sequences from 178 individual experiments at a 1% protein-level FDR globally across all experiments. Applying the latest Human Proteome Project Data Interpretation Guidelines, we catalog 3509 proteins that have at least two non-nested uniquely mapping peptides of nine amino acids or more and >1300 additional proteins with ambiguous evidence. We apply the same two-peptide guideline to historical PeptideAtlas builds going back to 2006 and examine the progress made in the past ten years in plasma proteome coverage. We also compare the distribution of proteins in historical PeptideAtlas builds in various RNA abundance and cellular localization categories. We then discuss advances in plasma proteomics based on targeted mass spectrometry as well as affinity assays, which during early 2017 target ∼2000 proteins. Finally, we describe considerations about sample handling and study design, concluding with an outlook for future advances in deciphering the human plasma proteome.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2017
Keyword
Human Proteome Project, mass spectrometry, plasma, proteomics
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-220373 (URN)10.1021/acs.jproteome.7b00467 (DOI)000417228900006 ()28938075 (PubMedID)2-s2.0-85037364446 (Scopus ID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut and Alice Wallenberg Foundation
Note

QC 20171219

Available from: 2017-12-19 Created: 2017-12-19 Last updated: 2018-01-03Bibliographically approved
Zandian, A., Forsström, B., Häggmark-Månberg, A., Schwenk, J. M., Uhlén, M., Nilsson, P. & Ayoglu, B. (2017). Whole-Proteome Peptide Microarrays for Profiling Autoantibody Repertoires within Multiple Sclerosis and Narcolepsy. Journal of Proteome Research, 16(3), 1300-1314.
Open this publication in new window or tab >>Whole-Proteome Peptide Microarrays for Profiling Autoantibody Repertoires within Multiple Sclerosis and Narcolepsy
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2017 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 16, no 3, 1300-1314 p.Article in journal (Refereed) Published
Abstract [en]

The underlying molecular mechanisms of autoimmune diseases are poorly understood. To unravel the autoimmune processes across diseases, comprehensive and unbiased analyses of proteins targets recognized by the adaptive immune system are needed. Here we present an approach starting from high-density peptide arrays to characterize autoantibody repertoires and to identify new autoantigens. A set of ten plasma and serum samples from subjects with multiple sclerosis, narcolepsy, and without any disease diagnosis were profiled on a peptide array representing the whole proteome, hosting 2.2 million 12-mer peptides with a six amino acid lateral shift. On the basis of the IgG reactivities found on these whole-proteome peptide micro arrays, a set of 23 samples was then studied on a targeted array with 174 000 12-mer peptides of single amino acid lateral shift. Finally, verification of IgG reactivities was conducted with a larger sample set (n = 448) using the bead-based peptide microarrays. The presented workflow employed three different peptide microarray formats to discover and resolve the epitopes of human autoantibodies and revealed two potentially new autoantigens: MAP3K7 in multiple sclerosis and NRXN1 in narcolepsy. The presented strategy provides insights into antibody repertoire reactivity at a peptide level and may accelerate the discovery and validation of autoantigens in human diseases.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2017
Keyword
peptide microarrays, autoantibody profiling, epitope mapping narcolepsy, multiple sclerosis
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-205512 (URN)10.1021/acs.jproteome.6b00916 (DOI)000395726200017 ()28121444 (PubMedID)2-s2.0-85014691057 (Scopus ID)
Funder
VINNOVAKnut and Alice Wallenberg Foundation
Note

QC 20170524

Available from: 2017-05-24 Created: 2017-05-24 Last updated: 2017-09-05Bibliographically approved
Ayoglu, B., Mitsios, N., Kockum, I., Khademi, M., Zandian, A., Sjoberg, R., . . . Nilsson, P. (2016). Anoctamin 2 identified as an autoimmune target in multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America, 113(8), 2188-2193.
Open this publication in new window or tab >>Anoctamin 2 identified as an autoimmune target in multiple sclerosis
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2016 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 8, 2188-2193 p.Article in journal (Refereed) Published
Abstract [en]

Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system and also is regarded as an autoimmune condition. However, the antigenic targets of the autoimmune response in MS have not yet been deciphered. In an effort to mine the autoantibody repertoire within MS, we profiled 2,169 plasma samples from MS cases and population-based controls using bead arrays built with 384 human protein fragments selected from an initial screening with 11,520 antigens. Our data revealed prominently increased autoantibody reactivity against the chloride-channel protein anoctamin 2 (ANO2) in MS cases compared with controls. This finding was corroborated in independent assays with alternative protein constructs and by epitope mapping with peptides covering the identified region of ANO2. Additionally, we found a strong interaction between the presence of ANO2 autoantibodies and the HLA complex MS-associated DRB1*15 allele, reinforcing a potential role for ANO2 autoreactivity in MS etiopathogenesis. Furthermore, immunofluorescence analysis in human MS brain tissue showed ANO2 expression as small cellular aggregates near and inside MS lesions. Thus this study represents one of the largest efforts to characterize the autoantibody repertoire within MS. The findings presented here demonstrate that an ANO2 autoimmune subphenotype may exist in MS and lay the groundwork for further studies focusing on the pathogenic role of ANO2 autoantibodies in MS.

Place, publisher, year, edition, pages
National Academy of Sciences of the USA, 2016
Keyword
multiple sclerosis, autoimmunity, autoantibodies, protein microarrays, affinity proteomics
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-183623 (URN)10.1073/pnas.1518553113 (DOI)000370620300067 ()26862169 (PubMedID)2-s2.0-84959220664 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationAFA InsuranceScience for Life Laboratory - a national resource center for high-throughput molecular bioscienceSwedish Research CouncilThe Swedish Brain Foundation
Note

QC 20160411

Available from: 2016-04-11 Created: 2016-03-18 Last updated: 2017-11-30Bibliographically approved
Remnestål, J., Just, D., Mitsios, N., Fredolini, C., Mulder, J., Schwenk, J. M., . . . Häggmark-Månberg, A. (2016). CSF profiling of the human brain enriched proteome reveals associations of neuromodulin and neurogranin to Alzheimer's disease. PROTEOMICS - Clinical Applications, 10(12), 1242-1253.
Open this publication in new window or tab >>CSF profiling of the human brain enriched proteome reveals associations of neuromodulin and neurogranin to Alzheimer's disease
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2016 (English)In: PROTEOMICS - Clinical Applications, ISSN 1862-8346, E-ISSN 1862-8354, Vol. 10, no 12, 1242-1253 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2016
Keyword
Alzheimer's disease, Cerebrospinal fluid, Neurogranin, Neuromodulin, Neuroproteomics
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-199507 (URN)10.1002/prca.201500150 (DOI)000389221400009 ()2-s2.0-84990913359 (Scopus ID)
Note

QC 20170117

Available from: 2017-01-17 Created: 2017-01-09 Last updated: 2017-11-29Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8141-8449

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