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- Bruzelius, Maria, et al.
(författare)
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PDGFB, a new candidate plasma biomarker for venous thromboembolism : results from the VEREMA affinity proteomics study
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:23, s. E59-E66
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Tidskriftsartikel (refereegranskat)abstract
- 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 beta (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 (rho similar to 0.30) with each other, they were independently associated with VTE risk in a joint model in FARIVE (VWF P < .001; PDGFB P = .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.
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2. |
- Ersmark, Erik, et al.
(författare)
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From the Past to the Present : Wolf Phylogeography and Demographic History Based on the Mitochondrial Control Region
- 2016
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Ingår i: Frontiers in Ecology and Evolution. - : FRONTIERS MEDIA SA. - 2296-701X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The global distribution of the gray wolf (Canis lupus) is a complex assembly consisting of a large number of populations and described subspecies. How these lineages are related to one another is still not fully resolved, largely due to the fact that large geographical regions remain poorly sampled both at the core and periphery of the species' range. Analyses of ancient wolves have also suffered from uneven sampling, but have shown indications of a major turnover at some point during the Pleistocene-Holocene boundary in northern North America. Here we analyze variation in the mitochondrial control region in 122 contemporary wolves from some of the less studied populations, as well as six samples from the previously unstudied Greenland subspecies (Canis I. orlon) and two Late Pleistocene samples from Siberia. Together with the publicly available control region sequences of both modern and ancient wolves, this study examines genetic diversity on a wide geographical and temporal scale that includes both Eurasia and North America. We identify 13 new haplotypes, of which the majority is found in northern and eastern Asia. The results show that the Greenland samples are all represented by one haplotype, previously identified in North American wolves, among which this population seems to trace its maternal lineage. The phylogeny and network analyses show a wide spatial distribution of several lineages, but also some clusters with more distinct geographical affiliation. In North America, we find support for an end-Pleistocene population bottleneck through coalescent simulations under an approximate Bayesian framework in contrast to previous studies that suggested an extinction-replacement event. However, we find no support for a similar bottleneck in Eurasia. Overall, this global analysis helps to clarify our understanding of the complex history for wolves in Eurasia and North America.
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4. |
- Fagerberg, Linn, et al.
(författare)
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Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
- 2014
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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5. |
- Fagerberg, Linn, et al.
(författare)
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Contribution of antibody-based protein profiling to the human chromosome-centric proteome project (C-HPP)
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:6, s. 2439-2448
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Tidskriftsartikel (refereegranskat)abstract
- 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).
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7. |
- Grapotte, Mathys, et al.
(författare)
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Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723.
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Tidskriftsartikel (refereegranskat)abstract
- Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
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8. |
- Grapotte, M, et al.
(författare)
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Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3297-
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Tidskriftsartikel (refereegranskat)abstract
- Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
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9. |
- Hillberg, Emil, et al.
(författare)
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Flexibility needs in the future power system
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Power system flexibility relates to the ability of the power system to manage changes. Solutions providing advances in flexibility are of utmost importance for the future power system. Development and deployment of innovative technologies, communication and monitoring possibilities, as well as increased interaction and information exchange, are enablers to provide holistic flexibility solutions. Furthermore, development of new methods for market design and analysis, as well as methods and procedures related to system planning and operation, will be required to utilise available flexibility to provide most value to society. However, flexibility is not a unified term and is lacking a commonly accepted definition. Several definitions of flexibility have been suggested, some of which restrict the definition of flexibility to relate to changes in supply and demand while others do not put this limitation. The flexibility term is used as an umbrella covering various needs and aspects in the power system. This situation makes it highly complex to discuss flexibility in the power system and craves for differentiation to enhance clarity. In this report, the solution has been to differentiate the flexibility term on needs, and to categorise flexibility needs in four categories: Flexibility for Power: - Need Description: Short term equilibrium between power supply and power demand, a system wide requirement for maintaining the frequency stability. - Main Rationale: Increased amount of intermittent, weather dependent, power supply in the generation mix. - Activation Timescale: Fractions of a second up to an hour. Flexibility for Energy: - Need Description: Medium to long term equilibrium between energy supply and energy demand, a system wide requirement for demand scenarios over time. - Main Rationale: Decreased amount of fuel storage-based energy supply in the generation mix. - Activation Timescale: Hours to several years. Flexibility for Transfer Capacity: - Need Description: Short to medium term ability to transfer power between supply and demand, where local or regional limitations may cause bottlenecks resulting in congestion costs. - Main Rationale: Increased utilisation levels, with increased peak demands and increased peak supply. - Activation Timescale: Minutes to several hours. Flexibility for Voltage: - Need Description: Short term ability to keep the bus voltages within predefined limits, a local and regional requirement. - Main Rationale: Increased amount of distributed power generation in the distribution systems, resulting in bi-directional power flows and increased variance of operating scenarios. - Activation Timescale: Seconds to tens of minutes.Here, flexibility needs are considered from over-all system perspectives (stability, frequency and energy supply) and from more local perspectives (transfer capacities, voltage and power quality). With flexibility support considered for both operation and planning of the power system, it is required in a timescale from fractions of a second (e.g. stability and frequency support) to minutes and hours (e.g. thermal loadings and generation dispatch) to months and years (e.g. planning for seasonal adequacy and planning of new investments).
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10. |
- 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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