| 1. |
- Thul, Peter J., et al.
(författare)
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A subcellular map of the human proteome
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 356:6340
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
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| 3. |
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| 4. |
- Karlsson, Max, et al.
(författare)
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Genome-wide single cell annotation of the human protein-coding genes
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- An important quest for the life science community is to deliver a complete annotation of the human building-blocks of life, the genes and the proteins. Here, we report on a genome-wide effort to annotate all protein-coding genes based on single cell transcriptomics data representing all major tissues and organs in the human body, integrated with data from bulk transcriptomics and antibody-based tissue profiling. Altogether, 25 tissues have been analyzed with single cell transcriptomics resulting in genome-wide expression in 444 single cell types using a strategy involving pooling data from individual cells to obtain genome-wide expression profiles of individual cell type. We introduce a new genome-wide classification tool based on clustering of similar expression profiles across single cell types, which can be visualized using dimensional reduction maps (UMAP). The clustering classification is integrated with a new “tau” score classification for all protein-coding genes, resulting in a measure of single cell specificity across all cell types for all individual genes. The analysis has allowed us to annotate all human protein-coding genes with regards to function and spatial distribution across individual cell types across all major tissues and organs in the human body. A new version of the open access Human Protein Atlas (www.proteinatlas.org) has been launched to enable researchers to explore the new genome-wide annotation on an individual gene level.
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| 5. |
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| 6. |
- Mahdessian, Diana, et al.
(författare)
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Profiling the human cytoplasmic proteome.
- 2016
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Ingår i: Molecular Biology of the Cell. - : AMER SOC CELL BIOLOGY. - 1059-1524 .- 1939-4586. ; 27
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Munster, Vincent J, et al.
(författare)
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Mallards and highly pathogenic avian influenza ancestral viruses, northern Europe
- 2005
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Ingår i: Emerging Infectious Diseases. - Atlanta : Center of disease control. - 1080-6040 .- 1080-6059. ; 11:10, s. 1545-1551
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Tidskriftsartikel (refereegranskat)abstract
- Outbreaks of highly pathogenic avian influenza (HPAI), which originate in poultry upon transmission of low pathogenic viruses from wild birds, have occurred relatively frequently in the last decade. During our ongoing surveillance studies in wild birds, we isolated several influenza A viruses of hemagglutinin subtype H5 and H7 that contain various neuraminidase subtypes. For each of the recorded H5 and H7 HPAI outbreaks in Europe since 1997, our collection contained closely related virus isolates recovered from wild birds, as determined by sequencing and phylogenetic analyses of the hemagglutinin gene and antigenic characterization of the hemagglutinin glycoprotein. The minor genetic and antigenic diversity between the viruses recovered from wild birds and those causing HPAI outbreaks indicates that influenza A virus surveillance studies in wild birds can help generate prototypic vaccine candidates and design and evaluate diagnostic tests, before outbreaks occur in animals and humans.
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| 8. |
- Munster, Vincent J., et al.
(författare)
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Spatial, temporal, and species variation in prevalence of influenza A viruses in wild migratory birds
- 2007
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 3:5, s. 630-638
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Tidskriftsartikel (refereegranskat)abstract
- Although extensive data exist on avian influenza in wild birds in North America, limited information is available from elsewhere, including Europe. Here, molecular diagnostic tools were employed for high-throughput surveillance of migratory birds, as an alternative to classical labor-intensive methods of virus isolation in eggs. This study included 36,809 samples from 323 bird species belonging to 18 orders, of which only 25 species of three orders were positive for influenza A virus. Information on species, locations, and timing is provided for all samples tested. Seven previously unknown host species for avian influenza virus were identified: barnacle goose, bean goose, brent goose, pink-footed goose, bewick's swan, common gull, and guillemot. Dabbling ducks were more frequently infected than other ducks and Anseriformes; this distinction was probably related to bird behavior rather than population sizes. Waders did not appear to play a role in the epidemiology of avian influenza in Europe, in contrast to the Americas. The high virus prevalence in ducks in Europe in spring as compared with North America could explain the differences in virus–host ecology between these continents. Most influenza A virus subtypes were detected in ducks, but H13 and H16 subtypes were detected primarily in gulls. Viruses of subtype H6 were more promiscuous in host range than other subtypes. Temporal and spatial variation in influenza virus prevalence in wild birds was observed, with influenza A virus prevalence varying by sampling location; this is probably related to migration patterns from northeast to southwest and a higher prevalence farther north along the flyways. We discuss the ecology and epidemiology of avian influenza A virus in wild birds in relation to host ecology and compare our results with published studies. These data are useful for designing new surveillance programs and are particularly relevant due to increased interest in avian influenza in wild birds.
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| 9. |
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| 10. |
- Skogs, Marie, et al.
(författare)
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Antibody Validation in Bioimaging Applications Based on Endogenous Expression of Tagged Proteins
- 2017
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 16:1, s. 147-155
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Tidskriftsartikel (refereegranskat)abstract
- Antibodies are indispensible research tools, yet the scientific community has not adopted standardized procedures to validate their specificity. Here we present a strategy to systematically validate antibodies for immunofluorescence (IF) applications using gene tagging. We have assessed the on- and off-target binding capabilities of 197 antibodies using 108 cell lines expressing EGFP-tagged target proteins at endogenous levels. Furthermore, we assessed batch-to-batch effects for 35 target proteins, showing that both the on- and off-target binding patterns vary significantly between antibody batches and that the proposed strategy serves as a reliable procedure for ensuring reproducibility upon production of new antibody batches. In summary, we present a systematic scheme for antibody validation in IF applications using endogenous expression of tagged proteins. This is an important step toward a reproducible approach for context- and application-specific antibody validation and improved reliability of antibody-based experiments and research data.
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| 11. |
- Sullivan, Devin P., et al.
(författare)
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Deep learning is combined with massive-scale citizen science to improve large-scale image classification
- 2018
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Ingår i: Nature Biotechnology. - : NATURE PUBLISHING GROUP. - 1087-0156 .- 1546-1696. ; 36:9, s. 820-
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Tidskriftsartikel (refereegranskat)abstract
- Pattern recognition and classification of images are key challenges throughout the life sciences. We combined two approaches for large-scale classification of fluorescence microscopy images. First, using the publicly available data set from the Cell Atlas of the Human Protein Atlas (HPA), we integrated an image-classification task into a mainstream video game (EVE Online) as a mini-game, named Project Discovery. Participation by 322,006 gamers over 1 year provided nearly 33 million classifications of subcellular localization patterns, including patterns that were not previously annotated by the HPA. Second, we used deep learning to build an automated Localization Cellular Annotation Tool (Loc-CAT). This tool classifies proteins into 29 subcellular localization patterns and can deal efficiently with multi-localization proteins, performing robustly across different cell types. Combining the annotations of gamers and deep learning, we applied transfer learning to create a boosted learner that can characterize subcellular protein distribution with F1 score of 0.72. We found that engaging players of commercial computer games provided data that augmented deep learning and enabled scalable and readily improved image classification.
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| 12. |
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| 13. |
- Thul, Peter, et al.
(författare)
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Exploring the Proteome of Multilocalizing Proteins
- 2017
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Ingår i: Molecular Biology of the Cell. - : American Society for Cell Biology. - 1059-1524 .- 1939-4586. ; 28
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 14. |
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| 15. |
- Thul, Peter, et al.
(författare)
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Multilocalizing Human Proteins
- 2018
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Ingår i: Molecular Biology of the Cell. - : AMER SOC CELL BIOLOGY. - 1059-1524 .- 1939-4586. ; 29:26
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 16. |
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| 17. |
- Verhagen, Josanne H., et al.
(författare)
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Avian influenza a virus in wild birds in highly urbanized areas.
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Avian influenza virus (AIV) surveillance studies in wild birds are usually conducted in rural areas and nature reserves. Less is known of avian influenza virus prevalence in wild birds located in densely populated urban areas, while these birds are more likely to be in close contact with humans. Influenza virus prevalence was investigated in 6059 wild birds sampled in cities in the Netherlands between 2006 and 2009, and compared with parallel AIV surveillance data from low urbanized areas in the Netherlands. Viral prevalence varied with the level of urbanization, with highest prevalence in low urbanized areas. Within cities virus was detected in 0.5% of birds, while seroprevalence exceeded 50%. Ring recoveries of urban wild birds sampled for virus detection demonstrated that most birds were sighted within the same city, while few were sighted in other cities or migrated up to 2659 km away from the sample location in the Netherlands. Here we show that urban birds were infected with AIVs and that urban birds were not separated completely from populations of long-distance migrants. The latter suggests that wild birds in cities may play a role in the introduction of AIVs into cities. Thus, urban bird populations should not be excluded as a human-animal interface for influenza viruses.
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| 18. |
- Verhagen, Josanne H., et al.
(författare)
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Discordant detection of avian influenza virus subtypes in time and space between poultry and wild birds : Towards improvement of surveillance programs
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Avian influenza viruses from wild birds can cause outbreaks in poultry, and occasionally infect humans upon exposure to infected poultry. Identification and characterization of viral reservoirs and transmission routes is important to develop strategies that prevent infection of poultry, and subsequently virus transmission between poultry holdings and to humans. Based on spatial, temporal and phylogenetic analyses of data generated as part of intense and large-scale influenza surveillance programs in wild birds and poultry in the Netherlands from 2006 to 2011, we demonstrate that LPAIV subtype distribution differed between wild birds and poultry, suggestive of host-range restrictions. LPAIV isolated from Dutch poultry were genetically most closely related to LPAIV isolated from wild birds in the Netherlands or occasionally elsewhere in Western Europe. However, a relatively long time interval was observed between the isolations of related viruses from wild birds and poultry. Spatial analyses provided evidence for mallards (Anas platyrhynchos) being more abundant near primary infected poultry farms. Detailed year-round investigation of virus prevalence and wild bird species distribution and behavior near poultry farms should be used to improve risk assessment in relation to avian influenza virus introduction and retarget avian influenza surveillance programs.
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| 19. |
- Wiking, Mikaela, et al.
(författare)
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Drafting the intermediate filament proteome
- 2016
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Ingår i: Molecular Biology of the Cell. - : American society of cell biology. - 1059-1524 .- 1939-4586. ; 27
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Tidskriftsartikel (refereegranskat)
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| 20. |
- Wiking, Mikaela, et al.
(författare)
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The Subcellular Protein Atlas
- 2014
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Ingår i: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 25
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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