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Publications (10 of 19) Show all publications
Uhlén, M., Karlsson, M., Zhong, W., Abdellah, T., Pou, C., Mikes, J., . . . Brodin, P. (2019). A genome-wide transcriptomic analysis of protein-coding genes in human blood cells. Science, 366(6472), 1471-+, Article ID eaax9198.
Open this publication in new window or tab >>A genome-wide transcriptomic analysis of protein-coding genes in human blood cells
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2019 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 366, no 6472, p. 1471-+, article id eaax9198Article in journal (Refereed) Published
Abstract [en]

Blood is the predominant source for molecular analyses in humans, both in clinical and research settings. It is the target for many therapeutic strategies, emphasizing the need for comprehensive molecular maps of the cells constituting human blood. In this study, we performed a genome-wide transcriptomic analysis of protein-coding genes in sorted blood immune cell populations to characterize the expression levels of each individual gene across the blood cell types. All data are presented in an interactive, open-access Blood Atlas as part of the Human Protein Atlas and are integrated with expression profiles across all major tissues to provide spatial classification of all protein-coding genes. This allows for a genome-wide exploration of the expression profiles across human immune cell populations and all major human tissues and organs.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE, 2019
National Category
Genetics
Identifiers
urn:nbn:se:kth:diva-266527 (URN)10.1126/science.aax9198 (DOI)000503861000045 ()31857451 (PubMedID)
Note

QC 20200205

Available from: 2020-02-05 Created: 2020-02-05 Last updated: 2020-02-05Bibliographically approved
Pineau, C., Hikmet, F., Zhang, C., Oksvold, P., Chen, S., Fagerberg, L., . . . Lindskog, C. (2019). Cell Type-Specific Expression of Testis Elevated Genes Based on Transcriptomics and Antibody-Based Proteomics. Journal of Proteome Research, 18(12), 4215-4230
Open this publication in new window or tab >>Cell Type-Specific Expression of Testis Elevated Genes Based on Transcriptomics and Antibody-Based Proteomics
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2019 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 18, no 12, p. 4215-4230Article in journal (Refereed) Published
Abstract [en]

One of the most complex organs in the human body is the testis, where spermatogenesis takes place. This physiological process involves thousands of genes and proteins that are activated and repressed, making testis the organ with the highest number of tissue-specific genes. However, the function of a large proportion of the corresponding proteins remains unknown and testis harbors many missing proteins (MPs), defined as products of protein-coding genes that lack experimental mass spectrometry evidence. Here, an integrated omics approach was used for exploring the cell type-specific protein expression of genes with an elevated expression in testis. By combining genome-wide transcriptomics analysis with immunohistochemistry, more than 500 proteins with distinct testicular protein expression patterns were identified, and these were selected for in-depth characterization of their in situ expression in eight different testicular cell types. The cell type-specific protein expression patterns allowed us to identify six distinct clusters of expression at different stages of spermatogenesis. The analysis highlighted numerous poorly characterized proteins in each of these clusters whose expression overlapped with that of known proteins involved in spermatogenesis, including 88 proteins with an unknown function and 60 proteins that previously have been classified as MPs. Furthermore, we were able to characterize the in situ distribution of several proteins that previously lacked spatial information and cell type-specific expression within the testis. The testis elevated expression levels both at the RNA and protein levels suggest that these proteins are related to testis-specific functions. In summary, the study demonstrates the power of combining genome-wide transcriptomics analysis with antibody-based protein profiling to explore the cell type-specific expression of both well-known proteins and MPs. The analyzed proteins constitute important targets for further testis-specific research in male reproductive disorders.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019
Keywords
antibody-based proteomics, immunohistochemistry, missing proteins, protein evidence, reproduction, spermatogenesis, testis, transcriptomics
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-263250 (URN)10.1021/acs.jproteome.9b00351 (DOI)000502164100015 ()31429579 (PubMedID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20191106

Available from: 2019-11-06 Created: 2019-11-06 Last updated: 2020-01-10Bibliographically approved
Sjöstedt, E., Sivertsson, Å., Norradin, F. H., Katona, B., Näsström, Å., Vuu, J., . . . Lindskog, C. (2018). Integration of Transcriptomics and Antibody-Based Proteomics for Exploration of Proteins Expressed in Specialized Tissues. Journal of Proteome Research, 17(12), 4127-4137
Open this publication in new window or tab >>Integration of Transcriptomics and Antibody-Based Proteomics for Exploration of Proteins Expressed in Specialized Tissues
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2018 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 17, no 12, p. 4127-4137Article in journal (Refereed) Published
Abstract [en]

A large portion of human proteins are referred to as missing proteins, defined as protein-coding genes that lack experimental data on the protein level due to factors such as temporal expression, expression in tissues that are difficult to sample, or they actually do not encode functional proteins. In the present investigation, an integrated omics approach was used for identification and exploration of missing proteins. Transcriptomics data from three different sourcesthe Human Protein Atlas (HPA), the GTEx consortium, and the FANTOM5 consortiumwere used as a starting point to identify genes selectively expressed in specialized tissues. Complementing the analysis with profiling on more specific tissues based on immunohistochemistry allowed for further exploration of cell-type-specific expression patterns. More detailed tissue profiling was performed for >300 genes on complementing tissues. The analysis identified tissue-specific expression of nine proteins previously listed as missing proteins (POU4F1, FRMD1, ARHGEF33, GABRG1, KRTAP2-1, BHLHE22, SPRR4, AVPR1B, and DCLK3), as well as numerous proteins with evidence of existence on the protein level that previously lacked information on spatial resolution and cell-type- specific expression pattern. We here present a comprehensive strategy for identification of missing proteins by combining transcriptomics with antibody-based proteomics. The analyzed proteins provide interesting targets for organ-specific research in health and disease.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
Keywords
missing proteins, transcriptomics, proteomics, protein localization, immunohistochemistry, antibodies, tissue profiling
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Biological Sciences
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-236474 (URN)10.1021/acs.jproteome.8b00406 (DOI)000452930000010 ()30272454 (PubMedID)2-s2.0-85055105364 (Scopus ID)
Note

QC 20181018

Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2020-01-10Bibliographically 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, article id 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
Keywords
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: 2020-01-10Bibliographically approved
Uhlén, M., Fagerberg, L., Hallström, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., . . . Pontén, F. (2015). Tissue-based map of the human proteome. Science, 347(6220), 1260419
Open this publication in new window or tab >>Tissue-based map of the human proteome
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2015 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 347, no 6220, p. 1260419-Article in journal (Refereed) Published
Abstract [en]

Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.

Keywords
isoprotein, membrane protein, protein, proteome, tumor protein
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-160035 (URN)10.1126/science.1260419 (DOI)000348225800036 ()25613900 (PubMedID)2-s2.0-84925582323 (Scopus ID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut and Alice Wallenberg Foundation
Note

QC 20150216

Available from: 2015-02-13 Created: 2015-02-13 Last updated: 2020-01-10Bibliographically approved
Fagerberg, L., Hallström, B. M., Oksvold, P., Kampf, C., Djureinovic, D., Odeberg, J., . . . Uhlén, M. (2014). Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Molecular & Cellular Proteomics, 13(2), 397-406
Open this publication in new window or tab >>Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
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2014 (English)In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 13, no 2, p. 397-406Article in journal (Refereed) Published
Abstract [en]

Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.

Keywords
article, gene expression, human, human tissue, immunohistochemistry, priority journal, protein analysis, protein expression, proteomics, spermatogenesis, transcriptomics
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-142992 (URN)10.1074/mcp.M113.035600 (DOI)000331369000002 ()24309898 (PubMedID)2-s2.0-84893276590 (Scopus ID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut and Alice Wallenberg FoundationEU, FP7, Seventh Framework Programme, HEALTH-F4-2008-201648/PROSPECTS
Note

QC 20140314

Available from: 2014-03-14 Created: 2014-03-14 Last updated: 2020-01-10Bibliographically approved
Stadler, C., Fagerberg, L., Sivertsson, Å., Oksvold, P., Zwahlen, M., Hallström, B. M., . . . Uhlén, M. (2014). RNA- and Antibody-Based Profiling of the Human Proteome with Focus on Chromosome 19. Journal of Proteome Research, 13(4), 2019-2027
Open this publication in new window or tab >>RNA- and Antibody-Based Profiling of the Human Proteome with Focus on Chromosome 19
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2014 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 13, no 4, p. 2019-2027Article in journal (Refereed) Published
Abstract [en]

An important part of the Human Proteome Project is to characterize the protein complement of the genome with antibody-based profiling. Within the framework of this effort, a new version 12 of the Human Protein Atlas (www.proteinatlas.org) has been launched, including transcriptomics data for 27 tissues and 44 cell lines to complement the protein expression data from antibody-based profiling. Besides the extensive addition of transcriptomics data, the Human Protein Atlas now contains antibody-based protein profiles for 82% of the 20 329 putative protein-coding genes. The comprehensive data resulting from RNA-seq analysis and antibody-based profiling performed within the Human Protein Atlas as well as information from UniProt were used to generate evidence summary scores for each of the 20 329 genes, of which 94% now have experimental evidence at least at transcript level. The evidence scores for all individual genes are displayed with regards to both RNA- and antibody-based protein profiles, including chromosome-centric visualizations. An analysis of the human chromosome 19 shows that similar to 43% of the genes are expressed at the transcript level in all 27 tissues analyzed, suggesting a "house-keeping" function, while 12% of the genes show a more tissue-specific pattern with enriched expression in one of the analyzed tissues only.

Keywords
antibodies, Human Proteome Project, Human Protein Atlas, immunohistochemistry, immunofluorescence, RNA deep sequencing, tissue profiling, transcriptomics, chromosome 19
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-145089 (URN)10.1021/pr401156g (DOI)000334016400022 ()2-s2.0-84898766939 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationEU, FP7, Seventh Framework ProgrammeScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20140508

Available from: 2014-05-08 Created: 2014-05-08 Last updated: 2020-01-10Bibliographically approved
Fagerberg, L., Oksvold, P., Skogs, M., Älgenäs, C., Lundberg, E., Pontén, F., . . . Uhlén, M. (2013). Contribution of antibody-based protein profiling to the human chromosome-centric proteome project (C-HPP). Journal of Proteome Research, 12(6), 2439-2448
Open this publication in new window or tab >>Contribution of antibody-based protein profiling to the human chromosome-centric proteome project (C-HPP)
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2013 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 12, no 6, p. 2439-2448Article in journal (Refereed) Published
Abstract [en]

A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease. Here, we report on the protein evidence for all genes predicted from the genome sequence based on manual annotation from literature (UniProt), antibody-based profiling in cells, tissues and organs and analysis of the transcript profiles using next generation sequencing in human cell lines of different origins. We estimate that there is good evidence for protein existence for 69% (n = 13985) of the human protein-coding genes, while 23% have only evidence on the RNA level and 7% still lack experimental evidence. Analysis of the expression patterns shows few tissue-specific proteins and approximately half of the genes expressed in all the analyzed cells. The status for each gene with regards to protein evidence is visualized in a chromosome-centric manner as part of a new version of the Human Protein Atlas (www.proteinatlas.org).

Keywords
Antibody-based protein profiling, C-HPP
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-134163 (URN)10.1021/pr300924j (DOI)000320298600010 ()23276153 (PubMedID)2-s2.0-84879327718 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationEU, FP7, Seventh Framework ProgrammeScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20131120

Available from: 2013-11-20 Created: 2013-11-18 Last updated: 2020-01-10Bibliographically approved
Kampf, C., Bergman, J., Oksvold, P., Asplund, A., Navani, S., Wiking, M., . . . Pontén, F. (2012). A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas. BMC Medicine, 10, 103
Open this publication in new window or tab >>A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas
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2012 (English)In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 10, p. 103-Article in journal (Refereed) Published
Abstract [en]

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

Keywords
Antibody-based proteomics, cancer biomarkers, tissue and cell dictionary, immunohistochemistry, protein expression, histology, pathology
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-110082 (URN)10.1186/1741-7015-10-103 (DOI)000312389800001 ()2-s2.0-84866045885 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20130110

Available from: 2013-01-10 Created: 2013-01-10 Last updated: 2020-01-10Bibliographically approved
Uhlén, M., Oksvold, P., Älgenäs, C., Hamsten, C., Fagerberg, L., Klevebring, D., . . . Sivertsson, Å. (2012). Antibody-based Protein Profiling of the Human Chromosome 21. Molecular & Cellular Proteomics, 11(3)
Open this publication in new window or tab >>Antibody-based Protein Profiling of the Human Chromosome 21
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2012 (English)In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 11, no 3Article in journal (Refereed) Published
Abstract [en]

A Human Proteome Project has been proposed to create a knowledgebased resource based on a systematical mapping of all human proteins, chromosome by chromosome, in a gene-centric manner. With this background, we here describe the systematic analysis of chromosome 21 using an antibody-based approach for protein profiling using both confocal microscopy and immunohistochemistry, complemented with transcript profiling using next generation sequencing data. We also describe a new approach for protein isoform analysis using a combination of antibody-based probing and isoelectric focusing. The analysis has identified several genes on chromosome 21 with no previous evidence on the protein level and the isoform analysis indicates that a large fraction of human proteins have multiple isoforms. A chromosome-wide matrix is presented with status for all chromosome 21 genes regarding subcellular localization, tissue distribution and molecular characterization of the corresponding proteins. The path to generate a chromosome-specific resource, including integrated data from complementary assay platforms, such as mass spectrometry and gene tagging analysis, is discussed.

National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-51404 (URN)10.1074/mcp.M111.013458 (DOI)000301296900011 ()22042635 (PubMedID)2-s2.0-84857963287 (Scopus ID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut and Alice Wallenberg Foundation
Note
QS 20111212Available from: 2011-12-12 Created: 2011-12-12 Last updated: 2020-01-10Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3014-5502

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