| 1. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 2. |
- Bensberg, Maike, et al.
(författare)
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TET2 as a tumor suppressor and therapeutic target in T-cell acute lymphoblastic leukemia
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:34
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Tidskriftsartikel (refereegranskat)abstract
- Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is an aggres-sive malignancy resulting from overproduction of immature T-cells in the thymus and is typified by widespread alterations in DNA methyl-ation. As survival rates for relapsed T-ALL remain dismal (10 to 25%), development of targeted therapies to prevent relapse is key to improv-ing prognosis. Whereas mutations in the DNA demethylating enzyme TET2 are frequent in adult T-cell malignancies, TET2 mutations in T-ALL are rare. Here, we analyzed RNA-sequencing data of 321 primary T-ALLs, 20 T-ALL cell lines, and 25 normal human tissues, revealing that TET2 is transcriptionally repressed or silenced in 71% and 17% of T-ALL, respec-tively. Furthermore, we show that TET2 silencing is often associated with hypermethylation of the TET2 promoter in primary T-ALL. Impor-tantly, treatment with the DNA demethylating agent, 5-azacytidine (5-aza), was significantly more toxic to TET2-silenced T-ALL cells and resulted in stable re-expression of the TET2 gene. Additionally, 5-aza led to up-regulation of methylated genes and human endogenous ret-roviruses (HERVs), which was further enhanced by the addition of phys-iological levels of vitamin C, a potent enhancer of TET activity. Together, our results clearly identify 5-aza as a potential targeted therapy for TET2-silenced T-ALL.
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| 3. |
- De Palma, Adriana, et al.
(författare)
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Predicting bee community responses to land-use changes : effects of geographic and taxonomic biases
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises.
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| 4. |
- Doumpas, Nikolaos, et al.
(författare)
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TCF/LEF dependent and independent transcriptional regulation of Wnt/beta-catenin target genes
- 2019
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Ingår i: EMBO Journal. - : WILEY. - 0261-4189 .- 1460-2075. ; 38:2
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Tidskriftsartikel (refereegranskat)abstract
- During canonical Wnt signalling, the activity of nuclear beta-catenin is largely mediated by the TCF/LEF family of transcription factors. To challenge this view, we used the CRISPR/Cas9 genome editing approach to generate HEK 293T cell clones lacking all four TCF/LEF genes. By performing unbiased whole transcriptome sequencing analysis, we found that a subset of beta-catenin transcriptional targets did not require TCF/LEF factors for their regulation. Consistent with this finding, we observed in a genome-wide analysis that beta-catenin occupied specific genomic regions in the absence of TCF/LEF. Finally, we revealed the existence of a transcriptional activity of beta-catenin that specifically appears when TCF/LEF factors are absent, and refer to this as beta-catenin-GHOST response. Collectively, this study uncovers a previously neglected modus operandi of beta-catenin that bypasses the TCF/LEF transcription factors.
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| 5. |
- Douvlataniotis, Karolos, et al.
(författare)
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No evidence for DNA N-6-methyladenine in mammals
- 2020
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Ingår i: Science Advances. - Washington, DC, United States : American Association for the Advancement of Science (A A A S). - 2375-2548. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- N-6-methyladenine (6mdA) is a widespread DNA modification in bacteria. More recently, 6mdA has also been characterized in mammalian DNA. However, measurements of 6mdA abundance and profiles are often very dissimilar between studies, even when performed on DNA from identical mammalian cell types. Using comprehensive bioinformatics analyses of published data and novel experimental approaches, we reveal that efforts to assay 6mdA in mammals have been severely compromised by bacterial contamination, RNA contamination, technological limitations, and antibody nonspecificity. These complications render 6mdA an exceptionally problematic DNA modification to study and have resulted in erroneous detection of 6mdA in several mammalian systems. Together, our results strongly imply that the evidence published to date is not sufficient to support the presence of 6mdA in mammals.
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| 6. |
- Gawel, Danuta, et al.
(författare)
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A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
- 2019
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs. Methods: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs. Results: We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model. Conclusions: Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.
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| 7. |
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| 8. |
- Gustafsson, Mika, et al.
(författare)
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A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases
- 2015
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 7:313
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Tidskriftsartikel (refereegranskat)abstract
- Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.
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| 9. |
- Henriksson, Pontus, et al.
(författare)
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DNA methylation in infants with low and high body fatness
- 2020
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Ingår i: BMC Genomics. - : BioMed Central. - 1471-2164. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBirth weight is determined by the interplay between infant genetics and the intrauterine environment and is associated with several health outcomes in later life. Many studies have reported an association between birth weight and DNA methylation in infants and suggest that altered epigenetics may underlie birthweight-associated health outcomes. However, birth weight is a relatively nonspecific measure of fetal growth and consists of fat mass and fat-free mass which may have different effects on health outcomes which motivates studies of infant body composition and DNA methylation. Here, we combined genome-wide DNA methylation profiling of buccal cells from 47 full-term one-week old infants with accurate measurements of infant fat mass and fat-free mass using air-displacement plethysmography.ResultsNo significant association was found between DNA methylation in infant buccal cells and infant body composition. Moreover, no association between infant DNA methylation and parental body composition or indicators of maternal glucose metabolism were found.ConclusionsDespite accurate measures of body composition, we did not identify any associations between infant body fatness and DNA methylation. These results are consistent with recent studies that generally have identified only weak associations between DNA methylation and birthweight. Although our results should be confirmed by additional larger studies, our findings may suggest that differences in DNA methylation between individuals with low and high body fatness may be established later in childhood.
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| 10. |
- Lentini, Antonio, et al.
(författare)
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A reassessment of DNA-immunoprecipitation-based genomic profiling
- 2018
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Ingår i: Nature Methods. - : NATURE PUBLISHING GROUP. - 1548-7091 .- 1548-7105. ; 15:7, s. 499-
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Tidskriftsartikel (refereegranskat)abstract
- DNA immunoprecipitation followed by sequencing (DIP-seq) is a common enrichment method for profiling DNA modifications in mammalian genomes. However, the results of independent DIP-seq studies often show considerable variation between profiles of the same genome and between profiles obtained by alternative methods. Here we show that these differences are primarily due to the intrinsic affinity of IgG for short unmodified DNA repeats. This pervasive experimental error accounts for 50-99% of regions identified as enriched for DNA modifications in DIP-seq data. Correction of this error profoundly altered DNA-modification profiles for numerous cell types, including mouse embryonic stem cells, and subsequently revealed novel associations among DNA modifications, chromatin modifications and biological processes. We conclude that both matched input and IgG controls are essential in order for the results of DIP-based assays to be interpreted correctly, and that complementary, non-antibody-based techniques should be used to validate DIP-based findings to avoid further misinterpretation of genome-wide profiling data.
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| 11. |
- Lentini, Antonio, et al.
(författare)
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Analyzing DNA-Immunoprecipitation Sequencing Data
- 2021
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Ingår i: DNA Modifications. - New York, NY : Humana Press. - 9781071608753 - 9781071608760 ; 2198, s. 431-439
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Bokkapitel (refereegranskat)abstract
- Genome-wide profiling of DNA modifications has advanced our understanding of epigenetics in mammalian biology. Whereas several different methods for profiling DNA modifications have been developed over the last decade, DNA-immunoprecipitation coupled with high-throughput sequencing (DIP-seq) has proven a particularly adaptable and cost-effective approach. DIP-seq was especially valuable in initial studies of the more recently discovered DNA modifications, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine. As an enrichment-based profiling method, analysis of DIP-seq data poses several unique, and often unappreciated bioinformatics challenges, which if unmet, can profoundly affect the results and conclusions drawn from the data. Here, we outline key considerations in both the design of DIP-seq assays and analysis of DIP-seq data to ensure the accuracy and reproducibility of DIP-seq based studies.
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| 12. |
- Lentini, Antonio, 1990-
(författare)
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Dynamic regulation of DNA methylation in human T-cell biology
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- T helper cells play a central role in orchestrating immune responses in humans. Upon encountering a foreign antigen, T helper cells are activated followed by a differentiation process where the cells are specialised to help combating the infection. Dysregulation of T helper cell activation, differentiation and function has been implicated in numerous diseases, including autoimmunity and cancer. Whereas gene-regulatory networks help drive T-cell differentiation, acquisition of stable cell states require heritable epigenetic signals, such as DNA methylation. Indeed, the establishment of DNA methylation patterns is a key part of appropriate T-cell differentiation but how this is regulated over time remains unknown. Methylation can be directly attached to cytosine residues in DNA to form 5-methylcytosine (5mC) but the removal of DNA methylation requires multiple enzymatic reactions, commonly initiated by the conversion into 5-hydroxymethylcytosine (5hmC), thus creating a highly complex regulatory system. This thesis aimed to investigate how DNA methylation is dynamically regulated during T-cell differentiation.To this end, we employed large-scale profiling techniques combining gene expression as well as genome-wide 5mC and 5hmC measurements to construct a time-series model of epigenetic regulation of differentiation. This revealed that early T-cell activation was accompanied by extensive genome-wide deposition of 5hmC which resulted in demethylation upon proliferation. Early DNA methylation remodelling through 5hmC was not only indicative of demethylation events during T-cell differentiation but also marked changes persisting longterm in memory T-cell subsets. These results suggest that priming of epigenetic landscapes in T-cells is initiated during early activation events, preceding any establishment of a stable lineage, which are then maintained throughout the cells lifespan. The regions undergoing remodelling were also highly enriched for genetic variants in autoimmune diseases which we show to be functional through disruption of protein binding. These variants could potentially disrupt gene-regulatory networks and the establishment of epigenetic priming, highlighting the complex interplay between genetic and epigenetic layers. In the course of this work, we discovered that a commonly used technique to study genome-wide DNA modifications, DNA immunoprecipitation (DIP)-seq, had a false discovery rate between 50-99% depending on the modification and cell type being assayed. This represented inherent technical errors related to the use of antibodies resulting in off-target binding of repetitive sequences lacking any DNA modifications. These sequences are common in mammalian genomes making robust detection of rare DNA modifications very difficult due to the high background signals. However, offtarget binding could easily be controlled for using a non-specific antibody control which greatly improved data quality and biological insight of the data. Although future studies are advised to use alternative methods where available, error correction is an acceptable alternative which will help fuel new discoveries through the removal of extensive background signals.Taken together, this thesis shows how integrative use of high-resolution epigenomic data can be used to study complex biological systems over time as well as how these techniques can be systematically characterised to identify and correct errors resulting in improved detection.
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| 13. |
- Lentini, Antonio, et al.
(författare)
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Mapping DNA Methylation in Mammals: The State of the Art
- 2021
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Ingår i: DNA Modifications. - New York, NY : Humana Press. - 9781071608753 - 9781071608760 ; 2198, s. 37-50
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Bokkapitel (refereegranskat)abstract
- A complete understanding of the dynamics and function of cytosine modifications in mammalian biology is lacking. Central to achieving this understanding is the availability of techniques that permit sensitive and specific genome-wide mapping of DNA modifications in mammalian DNA. The last decade has seen the development of a vast arsenal of novel profiling approaches enabling epigeneticists to tackle research questions that were previously out of reach. Here, we review the techniques currently available for profiling DNA modifications in mammals, discuss their strengths and weaknesses, and speculate on the future direction of DNA modification profiling technologies.
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| 14. |
- Marias, Giannis, et al.
(författare)
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Security and privacy issues for the network of the future
- 2012
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Ingår i: Security and Communication Networks. - : Wiley Blackwell. - 1939-0114 .- 1939-0122. ; 5:9, s. 987-1005
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Forskningsöversikt (refereegranskat)abstract
- The vision towards the Network of the Future cannot be separated from the fact that today's networks, and networking services are subject to sophisticated and very effective attacks. When these attacks first appeared, spoofing and distributed denial-of-service attacks were treated as apocalypse for networking. Now, they are considered moderate damage, whereas more sophisticated and inconspicuous attacks, such as botnets activities, might have greater and far reaching impact. As the Internet is expanding to mobile phones and smart dust and as its social coverage is liberalized towards the realization of ubiquitous computing (with communication), the concerns on security and privacy have become deeper and the problems more challenging than ever. Re-designing the Internet as the Network of the Future is self-motivating for researchers, and security and privacy cannot be provided again as separate, external, add-on, solutions. In this paper, we discuss the security and privacy challenges of the Network of the Future and try to delimit the solutions space on the basis of emerging techniques. We also review methods that help the quantification of security and privacy in an effort to provide a more systematic and quantitative treatment of the area in the future.
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| 15. |
- Mattson, Lina, et al.
(författare)
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Potential Involvement of Type I Interferon Signaling in Immunotherapy in Seasonal Allergic Rhinitis
- 2016
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Ingår i: Journal of Immunology Research. - : HINDAWI PUBLISHING CORP. - 2314-8861 .- 2314-7156.
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Tidskriftsartikel (refereegranskat)abstract
- Specific immunotherapy (SIT) reverses the symptoms of seasonal allergic rhinitis (SAR) in most patients. Recent studies report type I interferons shifting the balance between type I T helper cell (Th1) and type II T helper cells (Th2) towards Th2 dominance by inhibiting the differentiation of naive Tcells into Th1 cells. As SIT is thought to cause a shift towardsTh1 dominance, we hypothesized that SIT would alter interferon type I signaling. To test this, allergen and diluent challenged CD4(+) T cells from healthy controls and patients from different time points were analyzed. The initial experiments focused on signature genes of the pathway and found complex changes following immunotherapy, which were consistent with our hypothesis. As interferon signaling involves multiple genes, expression profiling studies were performed, showing altered expression of the pathway. These findings require validation in a larger group of patients in further studies.
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| 16. |
- Meehan, Richard R., et al.
(författare)
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DNA methylation as a genomic marker of exposure to chemical and environmental agents
- 2018
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Ingår i: Current opinion in chemical biology. - : ELSEVIER SCI LTD. - 1367-5931 .- 1879-0402. ; 45, s. 48-56
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Forskningsöversikt (refereegranskat)abstract
- Recent progress in interpreting comprehensive genetic and epigenetic profiles for human cellular states has contributed new insights into the developmental origins of disease, elucidated novel signalling pathways and enhanced drug discovery programs. A similar comprehensive approach to decoding the epigenetic readouts from chemical challenges in vivo would yield new paradigms for monitoring and assessing environmental exposure in model systems and humans.
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| 17. |
- Nestor, Colm, et al.
(författare)
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5-Hydroxymethylcytosine Remodeling Precedes Lineage Specification during Differentiation of Human CD4(+) T Cells
- 2016
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Ingår i: Cell Reports. - : CELL PRESS. - 2211-1247. ; 16:2, s. 559-570
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Tidskriftsartikel (refereegranskat)abstract
- 5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by the TET family of enzymes as part of a recently discovered active DNA de-methylation pathway. 5hmC plays important roles in regulation of gene expression and differentiation and has been implicated in T cell malignancies and autoimmunity. Here, we report early and widespread 5mC/5hmC remodeling during human CD4(+) T cell differentiation ex vivo at genes and cell-specific enhancers with known T cell function. We observe similar DNA de-methylation in CD4(+) memory T cells in vivo, indicating that early remodeling events persist long term in differentiated cells. Underscoring their important function, 5hmC loci were highly enriched for genetic variants associated with T cell diseases and T-cell-specific chromosomal interactions. Extensive functional validation of 22 risk variants revealed potentially pathogenic mechanisms in diabetes and multiple sclerosis. Our results support 5hmC-mediated DNA de-methylation as a key component of CD4(+) T cell biology in humans, with important implications for gene regulation and lineage commitment.
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| 18. |
- Nestor, Colm, et al.
(författare)
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DNA Methylation Changes Separate Allergic Patients from Healthy Controls and May Reflect Altered CD4⁺ T-Cell Population Structure
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Altered DNA methylation patterns in CD4+ T-cells indicate the importance of epigenetic mechanisms in inflammatory diseases. However, the identification of these alterations is complicated by the heterogeneity of most inflammatory diseases. Seasonal allergic rhinitis (SAR) is an optimal disease model for the study of DNA methylation because of its well-defined phenotype and etiology. We generated genome-wide DNA methylation (Npatients = 8, Ncontrols = 8) and gene expression (Npatients = 9, Ncontrols = 10) profiles of CD4+ T-cells from SAR patients and healthy controls using Illumina's HumanMethylation450 and HT-12 microarrays, respectively. DNA methylation profiles clearly and robustly distinguished SAR patients from controls, during and outside the pollen season. In agreement with previously published studies, gene expression profiles of the same samples failed to separate patients and controls. Separation by methylation (Npatients = 12, Ncontrols = 12), but not by gene expression (Npatients = 21, Ncontrols = 21) was also observed in an in vitro model system in which purified PBMCs from patients and healthy controls were challenged with allergen. We observed changes in the proportions of memory T-cell populations between patients (Npatients = 35) and controls (Ncontrols = 12), which could explain the observed difference in DNA methylation. Our data highlight the potential of epigenomics in the stratification of immune disease and represents the first successful molecular classification of SAR using CD4+ T cells.
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| 19. |
- Nestor, Colm E, et al.
(författare)
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Rapid reprogramming of epigenetic and transcriptional profiles in mammalian culture systems.
- 2015
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Ingår i: Genome Biology. - : BioMed Central. - 1465-6906 .- 1474-760X. ; 16, s. 11-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe DNA methylation profile of mammalian cell lines differs from the primary tissue from which they were derived, exhibiting increasing divergence from the in vivo methylation profile with extended time in culture. Few studies have directly examined the initial epigenetic and transcriptional consequences of adaptation of primary mammalian cells to culture, and the potential mechanisms through which this epigenetic dysregulation occurs is unknown.ResultsWe demonstrate that adaptation of mouse embryonic fibroblast, MEFS, to cell culture results in a rapid reprogramming of epigenetic and transcriptional states. We observed global 5-hydroxymethylcytosine (5hmC) erasure within three days of culture initiation. Loss of genic 5hmC was independent of global 5-methylcytosine (5mC) levels and could be partially rescued by addition of Vitamin C. Significantly, 5hmC loss was not linked to concomitant changes in transcription. Discrete promoter-specific gains of 5mC were also observed within seven days of culture initiation. Against this background of global 5hmC loss we identified a handful of developmentally important genes that maintained their 5hmC profile in culture, including the imprinted loci Gnas and H19. Similar outcomes were identified in the adaption of CD4+ T-cells to culture.ConclusionsWe report a dramatic and novel consequence of adaptation of mammalian cells to culture in which global loss of 5hmC occurs; suggesting rapid concomitant loss of methylcytosine dioxygenase activity. The observed epigenetic and transcriptional re-programming occurs much earlier than previously assumed, and has significant implications for the use of cell lines as faithful mimics of in vivo epigenetic and physiological processes.
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| 20. |
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