141 results on '"Beck, Stephan"'
Search Results
2. Genome-wide methylation profiling identifies novel methylated genes in neuroblastoma tumors.
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Olsson, Maja, Beck, Stephan, Kogner, Per, Martinsson, Tommy, and Carén, Helena
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- 2016
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3. Probe Lasso: A novel method to rope in differentially methylated regions with 450K DNA methylation data.
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Butcher, Lee M. and Beck, Stephan
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DNA methylation , *METHYLCYTOSINE , *DNA methyltransferases , *DATA analysis , *METHYLATION - Abstract
The speed and resolution at which we can scour the genome for DNA methylation changes has improved immeasurably in the last 10 years and the advent of the Illumina 450K BeadChip has made epigenome-wide association studies (EWAS) a reality. The resulting datasets are conveniently formatted to allow easy alignment of significant hits to genes and genetic features, however; methods that parse significant hits into discreet differentially methylated regions (DMRs) remain a challenge to implement. In this paper we present details of a novel DMR caller, the Probe Lasso: a flexible window based approach that gathers neighbouring significant-signals to define clear DMR boundaries for subsequent in-depth analysis. The method is implemented in the R package ChAMP (Morris et al., 2014) and returns sets of DMRs according to user-tuned levels of probe filtering (e.g., inclusion of sex chromosomes, polymorphisms) and probe-lasso size distribution. Using a sub-sample of colon cancer- and healthy colon-samples from TCGA we show that Probe Lasso shifts DMR calling away from just probe-dense regions, and calls a range of DMR sizes ranging from tens-of-bases to tens-of-kilobases in scale. Moreover, using TCGA data we show that Probe Lasso leverages more information from the array and highlights a potential role of hypomethylated transcription factor binding motifs not discoverable using a basic, fixed-window approach. [ABSTRACT FROM AUTHOR]
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- 2015
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4. Analysis pipelines and packages for Infinium HumanMethylation450 BeadChip (450k) data.
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Morris, Tiffany J. and Beck, Stephan
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PIPELINE contractors , *HYDRAULIC structures , *DATA analysis , *DEOXYRIBOSE , *NUCLEIC acids - Abstract
The Illumina HumanMethylation450 BeadChip has become a popular platform for interrogating DNA methylation in epigenome-wide association studies (EWAS) and related projects as well as resource efforts such as the International Cancer Genome Consortium (ICGC) and the International Human Epigenome Consortium (IHEC). This has resulted in an exponential increase of 450k data in recent years and triggered the development of numerous integrated analysis pipelines and stand-alone packages. This review will introduce and discuss the currently most popular pipelines and packages and is particularly aimed at new 450k users. [ABSTRACT FROM AUTHOR]
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- 2015
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5. Topography and edge effects are more important than elevation as drivers of vegetation patterns in a neotropical montane forest.
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Lippok, Denis, Beck, Stephan G., Renison, Daniel, Hensen, Isabell, Apaza, Amira E., Schleuning, Matthias, and Nakashizuka, Tohru
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VEGETATION patterns , *PLANT species diversity , *WOODY plants , *MICROCLIMATOLOGY , *ECOLOGICAL niche - Abstract
Aims The high plant species diversity of tropical mountain forests is coupled with high habitat heterogeneity along gradients in elevation and topography. We quantified the effects of elevation, topography and forest edge on habitat conditions and woody plant diversity of tropical montane forest fragments. Location Tropical montane forest fragments, ' Yungas', Bolivia. Methods We measured microclimate and sampled soil properties and woody vegetation at forest edges and in the forest interior on ridges and in gorges along an elevational gradient of 600 m. We analysed effects of elevation, topography and forest edge on habitat conditions (i.e. microclimate, soil properties and forest structure), species richness, evenness and composition with linear mixed effects models and detrended correspondence analysis ( DCA). Results Changes in habitat conditions were weaker along the elevational gradient than between forest interior and forest edge and between different topographies. Species richness was not affected by any gradient, while species evenness was reduced at forest edges. All three gradients affected species composition, while effects of topography and forest edge were stronger than that of elevation. Conclusions In general, effects of the 600-m elevational gradient were weak compared to effects of forest edge and topography. Edge effects shifted species composition towards pioneer species, while topographical heterogeneity is particularly important for generating high diversity in montane forests. These results underscore that edge effects have severe consequences in montane forest remnants and that small-scale variation between topographical microhabitats should be considered in studies that predict monotonous upslope migrations of plant species in tropical montane forests due to global warming. [ABSTRACT FROM AUTHOR]
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- 2014
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6. A Blueprint for an International Cancer Epigenome Consortium. A Report from the AACR Cancer Epigenome Task Force.
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Beck, Stephan, Bernstein, Bradley E., Campbell, Robert M., Costello, Joseph F., Dhanak, Dashyant, Ecker, Joseph R., Greally, John M., Issa, Jean-Pierre, Laird, Peter W., Polyak, Kornelia, Tycko, Benjamin, and Jones, Peter A.
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CANCER research , *GENE mapping , *TASK forces , *CANCER genetics , *CANCER genes , *INTERNATIONAL cooperation - Abstract
The article discusses a report on mapping human cancer epigenomes from the American Association for Cancer Research (AACR) Cancer Epigenome Task Force. The task force has recommended the establishment of the International Cancer Epigenome Project (ICEP) to make this task possible. The challenges of this mapping are suggested, such as the challenge of cell purification. The requirements of the proposed ICEP are also detailed.
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- 2012
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7. The epigenomic interface between genome and environment in common complex diseases.
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Bell, Christopher G. and Beck, Stephan
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MEDICAL genetics , *GENOMICS , *METHYLATION , *ETIOLOGY of diseases , *DNA - Abstract
The epigenome plays the pivotal role as interface between genome and environment. True genome-wide assessments of epigenetic marks, such as DNA methylation (methylomes) or chromatin modifications (chromatinomes), are now possible, either through high-throughput arrays or increasingly by second-generation DNA sequencing methods. The ability to collect these data at this level of resolution enables us to begin to be able to propose detailed questions, and interrogate this information, with regards to changes that occur due to development, lineage and tissue-specificity, and significantly those caused by environmental influence, such as ageing, stress, diet, hormones or toxins. Common complex traits are under variable levels of genetic influence and additionally epigenetic effect. The detection of pathological epigenetic alterations will reveal additional insights into their aetiology and how possible environmental modulation of this mechanism may occur. Due to the reversibility of these marks, the potential for sequence-specific targeted therapeutics exists. This review surveys recent epigenomic advances and their current and prospective application to the study of common diseases. [ABSTRACT FROM AUTHOR]
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- 2010
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8. AutoMeDIP-seq: A high-throughput, whole genome, DNA methylation assay
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Butcher, Lee M. and Beck, Stephan
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METHYLATION , *NUCLEOTIDE sequence , *PHENOTYPIC plasticity , *MICROBIOLOGICAL assay , *HUMAN genome , *EPIGENESIS - Abstract
Abstract: DNA methylation is an epigenetic mark linking DNA sequence and transcription regulation, and therefore plays an important role in phenotypic plasticity. The ideal whole genome methylation (methylome) assay should be accurate, affordable, high-throughput and agnostic with respect to genomic features. To this end, the methylated DNA immunoprecipitation (MeDIP) assay provides a good balance of these criteria. In this Methods paper, we present AutoMeDIP-seq, a technique that combines an automated MeDIP protocol with library preparation steps for subsequent second-generation sequencing. We assessed recovery of DNA sequences covering a range of CpG densities using in vitro methylated λ-DNA fragments (and their unmethylated counterparts) spiked-in against a background of human genomic DNA. We show that AutoMeDIP is more reliable than manual protocols, shows a linear recovery profile of fragments related to CpG density (R 2 =0.86), and that it is highly specific (>99%). AutoMeDIP-seq offers a competitive approach to high-throughput methylome analysis of medium to large cohorts. [ABSTRACT FROM AUTHOR]
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- 2010
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9. The methylome: approaches for global DNA methylation profiling
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Beck, Stephan and Rakyan, Vardhman K.
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METHYLATION , *DNA , *GENOMES , *HEALTH , *DISEASES - Abstract
DNA methylation plays a critical role in genome function both in health and disease. Almost 60 years after the discovery of 5-methyl cytosine and ∼25 years since the discovery that altered DNA methylation plays a role in disease, the first high-resolution DNA methylation profile (or methylome) of any genome –Arabidopsis thaliana – was determined. Although only ∼20% of the typical size of mammalian genomes, this milestone demonstrated that the methylomes of the human and similarly large genomes are now within reach. Here, we review current and emerging technologies that hold promise to deliver the first mammalian methylome and to facilitate comprehensive profiling of essentially any cell type in the context of development, disease and the environment. [Copyright &y& Elsevier]
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- 2008
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10. Evolutionary vignettes of natural killer cell receptors
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Sambrook, Jennifer G and Beck, Stephan
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IMMUNE system , *KILLER cells , *CELL receptors , *BIOLOGICAL evolution - Abstract
The discovery of novel immune receptors has led to a recent renaissance of research into the innate immune system, following decades of intense research of the adaptive immune system. Of particular interest has been the discovery of the natural killer (NK) cell receptors which, depending on type, interact with classical or non-classical MHC class I antigens of the adaptive immune system, thus functioning at the interface of innate and adaptive immunity. Here, we review recent progress with respect to two such families of NK receptors, the killer immunoglobulin-like receptors (KIRs) and the killer cell lectin-like receptors (KLRs), and attempt to trace their evolution across vertebrates. [Copyright &y& Elsevier]
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- 2007
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11. Epigenetic variation and inheritance in mammals
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Rakyan, Vardhman K and Beck, Stephan
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EPIGENESIS , *MAMMALS , *ECOLOGICAL heterogeneity , *PHENOTYPES , *GENOTYPE-environment interaction , *NUCLEOTIDE sequence - Abstract
What determines phenotype is one of the most fundamental questions in biology. Historically, the search for answers had focused on genetic or environmental variants, but recent studies in epigenetics have revealed a third mechanism that can influence phenotypic outcomes, even in the absence of genetic or environmental heterogeneity. Even more surprisingly, some epigenetic variants, or epialleles, can be inherited by the offspring, indicating the existence of a mechanism for biological heredity that is not based on DNA sequence. Recent work from mouse models, human monozygotic twin studies, and large-scale epigenetic profiling suggests that epigenetically determined phenotypes and epigenetic inheritance are more common than previously appreciated. [Copyright &y& Elsevier]
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- 2006
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12. THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX: Lessons from the DNA Sequence.
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Beck, Stephan and Trowsdale, John
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NUCLEOTIDE sequence , *MAJOR histocompatibility complex , *IMMUNE system , *GENETIC polymorphisms - Abstract
Discusses the DNA sequence of a human major histocompatibility complex. Cluster of immune system genes; Information on polymorphism; Sequences of complete haplotypes.
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- 2000
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13. Advances in epigenome-wide association studies for common diseases.
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Paul, Dirk S. and Beck, Stephan
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DISEASE research , *FUTURES studies , *BIOMARKERS , *EPIGENETICS , *DNA methylation - Abstract
Epigenome-wide association studies (EWASs) provide a systematic approach to uncovering epigenetic variants underlying common diseases. Discoveries have shed light on novel molecular mechanisms of disease and enabled the application of epigenetic variants as biomarkers. Here, we highlight the recent advances in this emerging line of research and discuss key challenges for current and future studies. [ABSTRACT FROM AUTHOR]
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- 2014
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14. An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo.
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Lujan, Celia, Tyler, Eleanor Jane, Ecker, Simone, Webster, Amy Philomena, Stead, Eleanor Rachel, Martinez-Miguel, Victoria Eugenia, Milligan, Deborah, Garbe, James Charles, Stampfer, Martha Ruskin, Beck, Stephan, Lowe, Robert, Bishop, Cleo Lucinda, and Bjedov, Ivana
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LONGEVITY , *PRIMARY cell culture , *HUMAN cell culture , *DRUG discovery , *RAPAMYCIN , *CELLULAR aging , *DRUG bioavailability - Abstract
Background: Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan. Methods: Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture. Results: We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo. Conclusions: Our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Sequence organisation of the class II region of the human MHC.
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Beck, Stephan and Trowsdale, John
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MAJOR histocompatibility complex , *GENES - Abstract
We present the genomic organisation of the extended class II region of the human MHC. This initial sequence, which is nearing completion, spans about 1.2 Mbp and is at present a composite of more than one haplotype. The sequencing of single haplotypes is planned for the future. The current sequence encompasses all of the known class II genes at the DP, DO, DM, DQ and DR loci as well as the transporter associated with antigen processing (TAP)/low molecular weight protein (LMP) antigen processing genes and the Tapasin locus, at the extended centromeric end. INSET: Feature map of the MHC class II region. [ABSTRACT FROM AUTHOR]
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- 1999
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16. Diversity in EWAS: current state, challenges, and solutions.
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Breeze, Charles E., Wong, Jason Y. Y., Beck, Stephan, Berndt, Sonja I., and Franceschini, Nora
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COMMUNITY involvement , *DNA methylation - Abstract
Here, we report a lack of diversity in epigenome-wide association studies (EWAS) and DNA methylation (DNAm) data, discuss current challenges, and propose solutions for EWAS and DNAm research in diverse populations. The strategies we propose include fostering community involvement, new data generation, and cost-effective approaches such as locus-specific analysis and ancestry variable region analysis. [ABSTRACT FROM AUTHOR]
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- 2022
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17. Taking the measure of the methylome.
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Beck, Stephan
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METHYLATION , *GENETIC research , *GENOMES , *COMPARATIVE studies - Abstract
This article discusses two studies that compare the performance of commonly-used techniques for DNA methylation analysis in terms of cost, resolution, genome coverage and accuracy. The studies tested a total of six methods, of which five are sequencing-based and one is array-based. Both studies assessed accuracy by comparing data sets between methods and find agreement between different methods for measuring genomic methylation. The challenges for future related research are explored.
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- 2010
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18. Getting up close and personal with UK genomics and beyond.
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Beck, Stephan
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COLLEGE teachers , *GENETIC research , *GENOMICS , *MEDICAL genetics , *ETHICS - Abstract
Stephan Beck discusses recent developments in sharing personal genomes as part of the Personal Genome Project in the UK and globally, and how these efforts are advancing research. [ABSTRACT FROM AUTHOR]
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- 2018
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19. Epigenetic Noise Fuels Cancer Evolution.
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Swanton, Charles and Beck, Stephan
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EPIGENETICS , *CANCER genetics , *GENOMES , *GENETIC mutation , *HUMAN genetic variation , *DNA methylation - Abstract
Cancer is a disease of the genome and the epigenome. Previous studies have shown that genomic changes such as mutations, copy number variation, and genomic rearrangements drive cancer evolution. In this issue of Cancer Cell , Landau and colleagues add epigenomic changes, specifically locally disordered DNA methylation, to cancer’s evolutionary trajectory. [ABSTRACT FROM AUTHOR]
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- 2014
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20. A–Z of methylome analysis
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Beck, Stephan
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- 2010
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21. Dr Nat Bumstead: Pioneer Researcher in Mapping the Chicken Genome.
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Beck, Stephan
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GENETICISTS , *BIOLOGISTS , *MICROBIOLOGISTS , *GENOMES , *CHICKENS - Abstract
Profiles Nat Bumstead who both laid the foundations and played a major influential role in establishing worldwide research on the genome of the chicken. Leading geneticist and accomplished researcher at the British Institute for Animal Health; Educational and family background; Career background; Love for sports, especially racket sports and rugby.
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- 2004
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22. Strategies of diaspore dispersal investment in Compositae: the case of the Andean highlands.
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Tovar, Carolina, Hudson, Lucia, Cuesta, Francisco, Meneses, Rosa Isela, Muriel, Priscilla, Hidalgo, Oriane, Palazzesi, Luis, Ballesteros, Carlos Suarez, Hunt, Eleanor Hammond, Diazgranados, Mauricio, Hind, D J Nicholas, Forest, Félix, Halloy, Stephan, Aguirre, Nikolay, Baker, William J, Beck, Stephan, Carilla, Julieta, Eguiguren, Paúl, Françoso, Elaine, and Gámez, Luis E
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FRAGMENTED landscapes , *BIOTIC communities , *SPECIES distribution , *UPLANDS , *MOUNTAIN ecology - Abstract
Background and Aims Understanding diaspore morphology and how much a species invests on dispersal appendages is key for improving our knowledge of dispersal in fragmented habitats. We investigate diaspore morphological traits in high-Andean Compositae and their main abiotic and biotic drivers and test whether they play a role in species distribution patterns across the naturally fragmented high-Andean grasslands. Methods We collected diaspore trait data for 125 Compositae species across 47 tropical high-Andean summits, focusing on achene length and pappus-to-achene length ratio, with the latter as a proxy of dispersal investment. We analysed the role of abiotic (temperature, elevation and latitude) and biotic factors (phylogenetic signal and differences between tribes) on diaspore traits and whether they are related to distribution patterns across the Andes, using phylogenomics, distribution modelling and community ecology analyses. Key Results Seventy-five percent of the studied species show small achenes (length <3.3 mm) and 67% have high dispersal investment (pappus length at least two times the achene length). Dispersal investment increases with elevation, possibly to compensate for lower air density, and achene length increases towards the equator, where non-seasonal climate prevails. Diaspore traits show significant phylogenetic signal, and higher dispersal investment is observed in Gnaphalieae, Astereae and Senecioneae, which together represent 72% of our species. High-Andean-restricted species found across the tropical Andes have, on average, the pappus four times longer than the achene, a significantly higher dispersal investment than species present only in the northern Andes or only in the central Andes. Conclusions Small achenes and high diaspore dispersal investment dominate among high-Andean Compositae, traits typical of mostly three tribes of African origin; but traits are also correlated with the environmental gradients within the high-Andean grasslands. Our results also suggest that diaspore dispersal investment is likely to shape species distribution patterns in naturally fragmented habitats. [ABSTRACT FROM AUTHOR]
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- 2023
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23. Individualized dynamic methylation-based analysis of cell-free DNA in postoperative monitoring of lung cancer.
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Chen, Kezhong, Kang, Guannan, Zhang, Zhihong, Lizaso, Analyn, Beck, Stephan, Lyskjær, Iben, Chervova, Olga, Li, Bingsi, Shen, Haifeng, Wang, Chenyang, Li, Bing, Zhao, Heng, Li, Xi, Yang, Fan, Kanu, Nnennaya, and Wang, Jun
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CELL-free DNA , *DNA analysis , *LUNG cancer , *SOMATIC mutation , *CIRCULATING tumor DNA - Abstract
Background: The feasibility of DNA methylation-based assays in detecting minimal residual disease (MRD) and postoperative monitoring remains unestablished. We aim to investigate the dynamic characteristics of cancer-related methylation signals and the feasibility of methylation-based MRD detection in surgical lung cancer patients. Methods: Matched tumor, tumor-adjacent tissues, and longitudinal blood samples from a cohort (MEDAL) were analyzed by ultra-deep targeted sequencing and bisulfite sequencing. A tumor-informed methylation-based MRD (timMRD) was employed to evaluate the methylation status of each blood sample. Survival analysis was performed in the MEDAL cohort (n = 195) and validated in an independent cohort (DYNAMIC, n = 36). Results: Tumor-informed methylation status enabled an accurate recurrence risk assessment better than the tumor-naïve methylation approach. Baseline timMRD-scores were positively correlated with tumor burden, invasiveness, and the existence and abundance of somatic mutations. Patients with higher timMRD-scores at postoperative time-points demonstrated significantly shorter disease-free survival in the MEDAL cohort (HR: 3.08, 95% CI: 1.48–6.42; P = 0.002) and the independent DYNAMIC cohort (HR: 2.80, 95% CI: 0.96–8.20; P = 0.041). Multivariable regression analysis identified postoperative timMRD-score as an independent prognostic factor for lung cancer. Compared to tumor-informed somatic mutation status, timMRD-scores yielded better performance in identifying the relapsed patients during postoperative follow-up, including subgroups with lower tumor burden like stage I, and was more accurate among relapsed patients with baseline ctDNA-negative status. Comparing to the average lead time of ctDNA mutation, timMRD-score yielded a negative predictive value of 97.2% at 120 days prior to relapse. Conclusions: The dynamic methylation-based analysis of peripheral blood provides a promising strategy for postoperative cancer surveillance. Trial registration: This study (MEDAL, MEthylation based Dynamic Analysis for Lung cancer) was registered on ClinicalTrials.gov on 08/05/2018 (NCT03634826). https://clinicaltrials.gov/ct2/show/NCT03634826. [ABSTRACT FROM AUTHOR]
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- 2023
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24. An integrated assessment of the vascular plant species of the Americas.
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Ulloa Ulloa, Carmen, Acevedo-Rodríguez, Pedro, Beck, Stephan, Belgrano, Manuel J., Bernal, Rodrigo, Berry, Paul E., Brako, Lois, Celis, Marcela, Davidse, Gerrit, Forzza, Rafaela C., Robbert Gradstein, S., Hokche, Omaira, León, Blanca, León-Yánez, Susana, Magill, Robert E., Neill, David A., Nee, Michael, Raven, Peter H., Stimmel, Heather, and Strong, Mark T.
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VASCULAR plants , *PLANT species , *CULTIVARS , *PLANT classification , *BOTANY - Abstract
The cataloging of the vascular plants of the Americas has a centuries-long history, but it is only in recent decades that an overview of the entire flora has become possible.We present an integrated assessment of all known native species of vascular plants in the Americas. Twelve regional and national checklists, prepared over the past 25 years and including two large ongoing flora projects, were merged into a single list. Our publicly searchable checklist includes 124,993 species, 6227 genera, and 355 families, which correspond to 33% of the 383,671 vascular plant species known worldwide. In the past 25 years, the rate at which new species descriptions are added has averaged 744 annually for the Americas, and we can expect the total to reach about 150,000. [ABSTRACT FROM AUTHOR]
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- 2017
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25. Virtual Valcamonica: Collaborative Exploration of Prehistoric Petroglyphs and Their Surrounding Environment in Multi-User Virtual Reality.
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Kulik, Alexander, Kunert, André, Beck, Stephan, Matthes, Carl-Feofan, Schollmeyer, Andre, Kreskowski, Adrian, Fröhlich, Bernd, Cobb, Sue, and D'Cruz, Mirabelle
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VIRTUAL reality , *CULTURAL property , *COLLECTIVE action , *ARCHAEOLOGISTS , *BIG data - Abstract
In this article, we present a novel, multi-user, virtual reality environment for the interactive, collaborative 3D analysis of large 3D scans and the technical advancements that were necessary to build it: a multi-view rendering system for large 3D point clouds, a suitable display infrastructure, and a suite of collaborative 3D interaction techniques. The cultural heritage site of Valcamonica in Italy with its large collection of prehistoric rock-art served as an exemplary use case for evaluation. The results show that our output-sensitive level-of-detail rendering system is capable of visualizing a 3D dataset with an aggregate size of more than 14 billion points at interactive frame rates. The system design in this exemplar application results from close exchange with a small group of potential users: archaeologists with expertise in rockart. The system allows them to explore the prehistoric art and its spatial context with highly realistic appearance. A set of dedicated interaction techniques was developed to facilitate collaborative visual analysis. A multi-display workspace supports the immediate comparison of geographically distributed artifacts. An expert review of the final demonstrator confirmed the potential for added value in rock-art research and the usability of our collaborative interaction techniques. [ABSTRACT FROM AUTHOR]
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- 2017
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26. Validation of the MethylationEPIC BeadChip for fresh-frozen and formalin-fixed paraffin-embedded tumours.
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Kling, Teresia, Wenger, Anna, Beck, Stephan, and Carén, Helena
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DNA methylation , *EPIGENETICS , *GENE expression - Abstract
DNA methylation is the most studied epigenetic modification due to its role in regulating gene expression, and its involvement in the pathogenesis of cancer and several diseases upon aberrations in methylation. The method of choice to evaluate genome-wide methylation has been the Illumina HumanMethylation450 BeadChip (450K), but it was recently replaced with the MethylationEPIC BeadChip (EPIC). We therefore sought to validate the EPIC array in comparison to the 450K array for both fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) tumours. We also performed analysis on the EPIC array with paired FF and FFPE samples to adapt to a clinical setting where FFPE is routinely used. Further, we compared two restoration methods, REPLI-g and Infinium, for FFPE-derived DNA on the EPIC array. The Pearson correlation of ß values for common probes on the 450K and EPIC array was high for both FF (mean: 0.992) and FFPE (mean: 0.984) samples. The ß values generated from the EPIC array for FFPE samples correlated well with the paired FF tumours, but varied between 0.901 and 0.987. We did note that sample pairs with lower correlation had less bimodal density distributions of ß values and displayed higher noise in the copy number alteration plots (generated from the methylation array data) in the FFPE sample. Both REPLI-g and the Infinium restoration for FFPE samples performed well on the EPIC array and generated equivalent correlation scores to the paired FF sample. [ABSTRACT FROM AUTHOR]
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- 2017
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27. Evaluation of Epigenetic Age Acceleration Scores and Their Associations with CVD-Related Phenotypes in a Population Cohort.
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Chervova, Olga, Chernysheva, Elizabeth, Panteleeva, Kseniia, Widayati, Tyas Arum, Hrbkova, Natalie, Schneider, Jadesada, Maximov, Vladimir, Ryabikov, Andrew, Tillmann, Taavi, Pikhart, Hynek, Bobak, Martin, Voloshin, Vitaly, Malyutina, Sofia, and Beck, Stephan
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PHENOTYPES , *AGE , *EPIGENETICS , *CORONARY disease , *ATHEROSCLEROTIC plaque - Abstract
Simple Summary: We consider a subset (n = 306) of an Eastern European ageing population cohort which was followed up for 15 years. Using blood DNA methylation data, we calculated nine epigenetic age acceleration scores, which are defined as deviations of epigenetic age from chronological age. We then evaluated how those scores are associated with available phenotypic data. This was implemented by splitting the phenotypic data into groups with positive and negative epigenetic age acceleration, and evaluating the difference between those groups. We observed strong association between all the considered epigenetic age acceleration and sex, suggesting that any analysis of these scores should be adjusted for sex. Moreover, even after adjusting for sex, the associations between the scores and considered phenotypes remain sex-specific. The only two associations that persisted through the entire dataset and both male and female subsets are incident coronary heart disease and smoking status. The observed associations of the various epigenetic age acceleration scores with both individual and groups of phenotypes suggest that these scores are sensitive to various cardiometabolic parameters, which might indicate their prognostic potential for related disorders. We evaluated associations between nine epigenetic age acceleration (EAA) scores and 18 cardiometabolic phenotypes using an Eastern European ageing population cohort richly annotated for a diverse set of phenotypes (subsample, n = 306; aged 45–69 years). This was implemented by splitting the data into groups with positive and negative EAAs. We observed strong association between all EAA scores and sex, suggesting that any analysis of EAAs should be adjusted by sex. We found that some sex-adjusted EAA scores were significantly associated with several phenotypes such as blood levels of gamma-glutamyl transferase and low-density lipoprotein, smoking status, annual alcohol consumption, multiple carotid plaques, and incident coronary heart disease status (not necessarily the same phenotypes for different EAAs). We demonstrated that even after adjusting EAAs for sex, EAA–phenotype associations remain sex-specific, which should be taken into account in any downstream analysis involving EAAs. The obtained results suggest that in some EAA–phenotype associations, negative EAA scores (i.e., epigenetic age below chronological age) indicated more harmful phenotype values, which is counterintuitive. Among all considered epigenetic clocks, GrimAge was significantly associated with more phenotypes than any other EA scores in this Russian sample. [ABSTRACT FROM AUTHOR]
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- 2023
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28. Epigenetics—The missing link between genetics, disease and the environment
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Beck, Stephan
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- 2006
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29. Comparison and imputation-aided integration of five commercial platforms for targeted DNA methylome analysis.
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Tanić, Miljana, Moghul, Ismail, Rodney, Simon, Dhami, Pawan, Vaikkinen, Heli, Ambrose, John, Barrett, James, Feber, Andrew, and Beck, Stephan
- Abstract
Targeted bisulfite sequencing (TBS) has become the method of choice for the cost-effective, targeted analysis of the human methylome at base-pair resolution. In this study, we benchmarked five commercially available TBS platforms—three hybridization capture-based (Agilent, Roche and Illumina) and two reduced-representation-based (Diagenode and NuGen)—across 11 samples. Two samples were also compared with whole-genome DNA methylation sequencing with the Illumina and Oxford Nanopore platforms. We assessed workflow complexity, on/off-target performance, coverage, accuracy and reproducibility. Although all platforms produced robust and reproducible data, major differences in the number and identity of the CpG sites covered make it difficult to compare datasets generated on different platforms. To overcome this limitation, we applied imputation and show that it improves interoperability from an average of 10.35% (0.8 million) to 97% (7.6 million) common CpG sites. Our study provides guidance on which TBS platform to use for different methylome features and offers an imputation-based harmonization solution that allows comparative, integrative analysis. Differences in CpG coverage of targeted bisulfite sequencing methods can be overcome using imputation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
30. From genomics to epigenomics: a loftier view of life.
- Author
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Beck, Stephan, Olek, Alexander, and Walter, Jörn
- Subjects
- *
GENOMICS , *EPIGENESIS , *MAJOR histocompatibility complex - Abstract
Focuses on complex systems of cells and organisms associated with the study of genomics. Definition of epigenesis given by biotechnologist R.C. Strohmann; Comparative analysis of epigenomic information from different organisms; Identification and analysis of epigenomic loci in the major histocompatibility complex.
- Published
- 1999
- Full Text
- View/download PDF
31. Researcher perspectives on ethics considerations in epigenetics: an international survey.
- Author
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Dupras, Charles, Knoppers, Terese, Palmour, Nicole, Beauchamp, Elisabeth, Liosi, Stamatina, Siebert, Reiner, Berner, Alison May, Beck, Stephan, Charest, Ian, and Joly, Yann
- Subjects
- *
SCIENCE in literature , *SCIENTIFIC literature , *EPIGENETICS , *ETHICS , *SOCIAL scientists , *PRIONS , *CHROMATIN , *RNA splicing - Abstract
Over the past decade, bioethicists, legal scholars and social scientists have started to investigate the potential implications of epigenetic research and technologies on medicine and society. There is growing literature discussing the most promising opportunities, as well as arising ethical, legal and social issues (ELSI). This paper explores the views of epigenetic researchers about some of these discussions. From January to March 2020, we conducted an online survey of 189 epigenetic researchers working in 31 countries. We questioned them about the scope of their field, opportunities in different areas of specialization, and ELSI in the conduct of research and knowledge translation. We also assessed their level of concern regarding four emerging non-medical applications of epigenetic testing—i.e., in life insurance, forensics, immigration and direct-to-consumer testing. Although there was strong agreement on DNA methylation, histone modifications, 3D structure of chromatin and nucleosomes being integral elements of the field, there was considerable disagreement on transcription factors, RNA interference, RNA splicing and prions. The most prevalent ELSI experienced or witnessed by respondents were in obtaining timely access to epigenetic data in existing databases, and in the communication of epigenetic findings by the media. They expressed high levels of concern regarding non-medical applications of epigenetics, echoing cautionary appraisals in the social sciences and humanities literature. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
32. Functional importance of avian seed dispersers changes in response to human-induced forest edges in tropical seed-dispersal networks.
- Author
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Saavedra, Francisco, Hensen, Isabell, Beck, Stephan, Böhning-Gaese, Katrin, Lippok, Denis, Töpfer, Till, and Schleuning, Matthias
- Subjects
- *
SEED dispersal by birds , *FRUGIVORES , *MOUNTAIN forests , *ANIMAL morphology , *TRANSPLANTING (Plant culture) , *SEEDLINGS , *ANIMAL-plant relationships - Abstract
Although seed-dispersal networks are increasingly used to infer the functioning of ecosystems, few studies have investigated the link between the properties of these networks and the ecosystem function of seed dispersal by animals. We investigate how frugivore communities and seed dispersal change with habitat disturbance and test whether relationships between morphological traits and functional roles of seed dispersers change in response to human-induced forest edges. We recorded interaction frequencies between fleshy fruited plants and frugivorous bird species in tropical montane forests in the Bolivian Andes and recorded functional bird traits (body mass, gape width and wing tip length) associated with quantitative (seed-removal rate) and qualitative (seed-deposition pattern) components of seed-dispersal effectiveness. We found that the abundance and richness of frugivorous birds were higher at forest edges. More fruits were removed and dispersed seeds were less clustered at edges than in the interior. Additionally, functional and interaction diversity were higher at edges than in the interior, but functional and interaction evenness did not differ. Interaction strength of bird species increased with body mass, gape width and wing tip length in the forest interior, but was not related to bird morphologies at forest edges. Our study suggests that increases in functional and interaction diversity and an even distribution of interaction strength across bird morphologies lead to enhanced quantity and tentatively enhanced quality of seed dispersal. It also suggests that the effects of species traits on ecosystem functions can vary along small-scale gradients of human disturbance. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
33. Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA.
- Author
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Lyskjær, Iben, Kara, Neesha, De Noon, Solange, Davies, Christopher, Rocha, Ana Maia, Strobl, Anna-Christina, Usher, Inga, Gerrand, Craig, Strauss, Sandra J., Schrimpf, Daniel, von Deimling, Andreas, Beck, Stephan, and Flanagan, Adrienne M.
- Subjects
- *
OSTEOSARCOMA , *BLOOD plasma , *PREOPERATIVE period , *CANCER relapse , *DNA methylation , *POSTOPERATIVE period , *DESCRIPTIVE statistics , *SURVIVAL analysis (Biometry) , *TUMOR markers , *EXTRACELLULAR space , *POLYMERASE chain reaction , *NUCLEIC acids , *BLOOD - Abstract
Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents. Circulating free (cfDNA) and circulating tumour DNA (ctDNA) are promising biomarkers for disease surveillance and prognostication in several cancer types; however, few such studies are reported for OS. The purpose of this study was to discover and validate methylation-based biomarkers to detect plasma ctDNA in patients with OS and explore their utility as prognostic markers. Candidate CpG markers were selected through analysis of methylation array data for OS, non-OS tumours and germline samples. Candidates were validated in two independent OS datasets (n = 162, n = 107) and the four top-performing markers were selected. Methylation-specific digital droplet PCR (ddPCR) assays were designed and experimentally validated in OS tumour samples (n = 20) and control plasma samples. Finally, ddPCR assays were applied to pre-operative plasma and where available post-operative plasma from 72 patients with OS, and findings correlated with outcome. Custom ddPCR assays detected ctDNA in 69% and 40% of pre-operative plasma samples (n = 72), based on thresholds of one or two positive markers respectively. ctDNA was detected in 5/17 (29%) post-operative plasma samples from patients, which in four cases were associated with or preceded disease relapse. Both pre-operative cfDNA levels and ctDNA detection independently correlated with overall survival (p = 0.0015 and p = 0.0096, respectively). Our findings illustrate the potential of mutation-independent methylation-based ctDNA assays for OS. This study lays the foundation for multi-institutional collaborative studies to explore the utility of plasma-derived biomarkers in the management of OS. • Pre-operative circulating tumour DNA (ctDNA) levels indicate poorer prognosis. • Total levels of circulating free DNA at diagnosis correlates with overall survival. • ctDNA detection after surgery points to residual disease. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
34. Functional interpretation of non-coding sequence variation: Concepts and challenges.
- Author
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Paul, Dirk S., Soranzo, Nicole, and Beck, Stephan
- Subjects
- *
NON-coding DNA , *NUCLEOTIDE sequence , *CANCER genetics , *GENETICS of diabetes , *MEDICAL genetics , *MEDICAL genomics - Abstract
Understanding the functional mechanisms underlying genetic signals associated with complex traits and common diseases, such as cancer, diabetes and Alzheimer's disease, is a formidable challenge. Many genetic signals discovered through genome-wide association studies map to non-protein coding sequences, where their molecular consequences are difficult to evaluate. This article summarizes concepts for the systematic interpretation of non-coding genetic signals using genome annotation data sets in different cellular systems. We outline strategies for the global analysis of multiple association intervals and the in-depth molecular investigation of individual intervals. We highlight experimental techniques to validate candidate (potential causal) regulatory variants, with a focus on novel genome-editing techniques including CRISPR/Cas9. These approaches are also applicable to low-frequency and rare variants, which have become increasingly important in genomic studies of complex traits and diseases. There is a pressing need to translate genetic signals into biological mechanisms, leading to prognostic, diagnostic and therapeutic advances. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
35. Novel epigenetic network biomarkers for early detection of esophageal cancer.
- Author
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Maity, Alok K., Stone, Timothy C., Ward, Vanessa, Webster, Amy P., Yang, Zhen, Hogan, Aine, McBain, Hazel, Duku, Margaraet, Ho, Kai Man Alexander, Wolfson, Paul, Graham, David G., Beck, Stephan, Teschendorff, Andrew E., and Lovat, Laurence B.
- Subjects
- *
EARLY detection of cancer , *BARRETT'S esophagus , *EPIGENOMICS , *GENETIC regulation , *BIOMARKERS , *DNA methylation - Abstract
Background: Early detection of esophageal cancer is critical to improve survival. Whilst studies have identified biomarkers, their interpretation and validity is often confounded by cell-type heterogeneity. Results: Here we applied systems-epigenomic and cell-type deconvolution algorithms to a discovery set encompassing RNA-Seq and DNA methylation data from esophageal adenocarcinoma (EAC) patients and matched normal-adjacent tissue, in order to identify robust biomarkers, free from the confounding effect posed by cell-type heterogeneity. We identify 12 gene-modules that are epigenetically deregulated in EAC, and are able to validate all 12 modules in 4 independent EAC cohorts. We demonstrate that the epigenetic deregulation is present in the epithelial compartment of EAC-tissue. Using single-cell RNA-Seq data we show that one of these modules, a proto-cadherin module centered around CTNND2, is inactivated in Barrett's Esophagus, a precursor lesion to EAC. By measuring DNA methylation in saliva from EAC cases and controls, we identify a chemokine module centered around CCL20, whose methylation patterns in saliva correlate with EAC status. Conclusions: Given our observations that a CCL20 chemokine network is overactivated in EAC tissue and saliva from EAC patients, and that in independent studies CCL20 has been found to be overactivated in EAC tissue infected with the bacterium F. nucleatum, a bacterium that normally inhabits the oral cavity, our results highlight the possibility of using DNAm measurements in saliva as a proxy for changes occurring in the esophageal epithelium. Both the CTNND2/CCL20 modules represent novel promising network biomarkers for EAC that merit further investigation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
36. The good, the bad and the ugly: Epigenetic mechanisms in glioblastoma.
- Author
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Carén, Helena, Pollard, Steven M., and Beck, Stephan
- Subjects
- *
EPIGENETICS , *GLIOBLASTOMA multiforme , *GENE expression , *GENE mapping , *CELL growth , *DEHYDROGENASE genetics , *MOLECULAR biology - Abstract
Abstract: Cell type-specific patterns of gene expression reflect epigenetic changes imposed through a particular developmental lineage as well as those triggered by environmental cues within adult tissues. There is great interest in elucidating the molecular basis and functional importance of epigenetic mechanisms in both normal physiology and disease – particularly in cancer, where abnormal ‘-omic’ states are often observed. In this article we review recent progress in studies of epigenetic mechanisms in the most common primary adult brain cancer, glioblastoma multiforme. Three distinct areas are discussed. First, the evidence in support of ongoing ‘normal’ epigenetic processes associated with differentiation – as predicted by ‘cancer stem cell’ models of the disease. Second, identification of site-specific and global epigenetic abnormalities. Third, genetic disruptions directly within the core epigenetic machinery, exemplified by the recently identified mutations within isocitrate dehydrogenase genes IDH1/2 and variant histone genes H3.3/H3F3A. These constitute the ‘good, the bad and the ugly’ of epigenetic mechanisms in cancer. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
37. Human-Induced Disturbance Alters Pollinator Communities in Tropical Mountain Forests.
- Author
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Kambach, Stephan, Guerra, Fernando, Beck, Stephan G., Hensen, Isabell, and Schleuning, Matthias
- Subjects
- *
FOREST ecology , *POLLINATORS , *ANTHROPOGENIC effects on nature , *DEFORESTATION , *FOREST fire prevention & control - Abstract
Mountain forest ecosystems in the Andes are threatened by deforestation. Increasing fire frequencies lead to fire-degraded habitats that are often characterized by a persistent fern-dominated vegetation. Little is known about the consequences of these drastic changes in habitat conditions for pollinator communities. In a rapid diversity assessment, we collected individuals of two major groups of insect pollinators (bees and butterflies/moths) with pan traps and compared pollinator diversities in a spatial block design between forest interior, forest edge and adjacent fire-degraded habitats at eight sites in the Bolivian Andes. We found that bee species richness and abundance were significantly higher in fire-degraded habitats than in forest habitats, whereas species richness and abundance of butterflies/moths increased towards the forests interior. Species turnover between forest and fire-degraded habitats was very high for both pollinator groups and was reflected by an increase in the body size of bee species and a decrease in the body size of butterfly/moth species in fire-degraded habitats. We conclude that deforestation by frequent fires has profound impacts on the diversity and composition of pollinator communities. Our tentative findings suggest shifts towards bee-dominated pollinator communities in fire-degraded habitats that may have important feedbacks on the regenerating communities of insect-pollinated plant species. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
38. A shared-scene-graph image-warping architecture for VR: Low latency versus image quality
- Author
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Smit, Ferdi, van Liere, Robert, Beck, Stephan, and Froehlich, Bernd
- Subjects
- *
COMPUTER graphics , *IMAGE quality in imaging systems , *COMPUTER architecture , *VIRTUAL reality , *COMPUTER engineering , *ENGINEERING design , *SMOOTHING (Numerical analysis) - Abstract
Abstract: Designing low end-to-end latency system architectures for virtual reality is still an open and challenging problem. We describe the design, implementation and evaluation of a client–server depth-image warping architecture that updates and displays the scene graph at the refresh rate of the display. Our approach works for scenes consisting of dynamic and interactive objects. The end-to-end latency is minimized as well as smooth object motion generated. However, this comes at the expense of image quality inherent to warping techniques. To improve image quality, we present a novel way of detecting and resolving occlusion errors due to warping. Furthermore, we investigate the use of asynchronous data transfers to increase the architecture''s performance in a multi-GPU setting. Besides polygonal rendering, we also apply image-warping techniques to iso-surface rendering. Finally, we evaluate the architecture and its design trade-offs by comparing latency and image quality to a conventional rendering system. Our experience with the system confirms that the approach facilitates common interaction tasks such as navigation and object manipulation. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
39. High levels of genetic variation at MHC class II DBB loci in the tammar wallaby ( Macropus eugenii).
- Author
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Yuanyuan Cheng, Siddle, Hannah V., Beck, Stephan, Eldridge, Mark D. B., and Belov, Katherine
- Subjects
- *
MAJOR histocompatibility complex , *IR genes , *MARSUPIALS , *MACROPUS eugenii , *WALLABIES , *ANIMAL genetics - Abstract
High levels of MHC diversity are crucial for immunological fitness of populations, with island populations particularly susceptible to loss of genetic diversity. In this study, the level of MHC class II DBB diversity was examined in tammar wallabies ( Macropus eugenii) from Kangaroo Island by genotyping class II-linked microsatellite loci and sequencing of DBB genes. Here we show that the tammar wallaby has at least four expressed MHC class II DBB loci and extensive genetic variation in the peptide-binding region of the DBB genes. These results contradict early studies which suggested that wallabies lacked MHC class II diversity and demonstrate that, in spite of the long-term isolation on an offshore island, this population of wallabies has a high level of DBB diversity. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
40. Inflammatory signalling as mediator of epigenetic modulation in tissue-specific chronic inflammation
- Author
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Bäckdahl, Liselotte, Bushell, Andrew, and Beck, Stephan
- Subjects
- *
CHRONIC diseases , *INFLAMMATION , *TISSUE-specific antigens , *EPIGENESIS , *HISTONE deacetylase , *DNA , *METHYLATION - Abstract
Abstract: Recent successes of therapeutic intervention in chronic inflammatory diseases using epigenetic modifiers such as histone deacetylase inhibitors and inhibitors of DNA methylation suggest that epigenetic reprogramming plays a role in the aetiology of these diseases. The epigenetic signature of a given immune cell is reflected in the history of modifications from different signals the cell has been subjected to during differentiation. Like other cells, differentiating immune cells are dependent on a complex combination of inter- and intracell signalling as well as transcription machineries to modulate their epigenomes in order to mediate differentiation. Despite extensive research into these processes, the link between cellular signalling and epigenetic modulation remains poorly understood. Here, we review recent progress and discuss key factors driving epigenetic modulation in chronic inflammation. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
41. EpiDISH web server: Epigenetic Dissection of Intra-Sample-Heterogeneity with online GUI.
- Author
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Zheng, Shijie C, Breeze, Charles E, Beck, Stephan, Dong, Danyue, Zhu, Tianyu, Ma, Liangxiao, Ye, Wei, Zhang, Guoqing, and Teschendorff, Andrew E
- Subjects
- *
INTERNET servers , *WEB-based user interfaces , *EPIGENETICS , *UPLOADING of data , *PLANT genetics , *DECONVOLUTION (Mathematics) - Abstract
Summary It is well recognized that cell-type heterogeneity hampers the interpretation of Epigenome-Wide Association Studies (EWAS). Many tools have emerged to address this issue, including several R/Bioconductor packages that infer cell-type composition. Here we present a web application for cell-type deconvolution, which offers the functionality of our EpiDISH Bioconductor/R package in a user-friendly GUI environment. Users can upload their data to infer cell-type composition and differentially methylated cytosines in individual cell-types for a range of different tissues. Availability and implementation EpiDISH web server is implemented with Shiny in R, and is freely available at https://www.biosino.org/EpiDISH/. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
42. A New Puya from the Upper Cloud Forest Limit in Bolivia.
- Author
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Vásquez Ch., Roberto, Ibisch, Pierre L., and Beck, Stephan G.
- Subjects
- *
PARAMO plants , *PLANTS , *PLANT species , *CLOUD forests - Abstract
Describes the Puya pizarroana plant from Páramo vegetation at the Bolivian cloud forest-limit. Comparison of P. pizarroana with P. brittoniana; Etymology of P. pizorroana; Observations; Habitat.
- Published
- 2003
43. Recruitment of Heterogeneous Nuclear Ribonucleoprotein A1 in Vivo to the LMP/TAP Region of the Major Histocompatibility Complex.
- Author
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Donev, Rossen, Horton, Roger, Beck, Stephan, Doneva, Teodora, Vatcheva, Radost, Bowen, W. Richard, and Sheer, Denise
- Subjects
- *
MAJOR histocompatibility complex , *NUCLEAR matrix - Abstract
Examines the role of nuclear matrix attachment regions (MAR) adjacent to the LMP/TAP gene cluster in class II region of the human major histocompatibility complex (MHC). Experimental procedures; Involvement in transcription regulation; Sequences containing the matrix recognition signature.
- Published
- 2003
- Full Text
- View/download PDF
44. Plant Research Excerpt: Revised Species Delimitation in the Giant Waterlily Genus Victoria (Nymphaeaceae) Con?rms a New Species and Has Implications for Its Conservation.
- Author
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Smith, Lucy T., Magdalena, Carlos, Przelomska, Natalia A. S., Pérez-Escobar, Oscar A., Melgar-Gómez, Darío G., Beck, Stephan, Negrão, Raquel, Mian, Sahr, Leitch, Ilia J., Dodsworth, Steven, Maurin, Olivier, Ribero-Guardia, Gaston, Salazar, César D., Gutierrez-Sibauty, Gloria, Antonelli, Alexandre, and Monro, Alexandre K.
- Subjects
- *
BOTANICAL gardens , *PHYLOGEOGRAPHY , *WATER lilies , *SPECIES , *ENDANGERED species , *WATER gardens - Published
- 2022
45. "Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology.".
- Author
-
Dritsoula, Athina, Kislikova, Maria, Oomatia, Amin, Webster, Amy P., Beck, Stephan, Ponticos, Markella, Lindsey, Ben, Norman, Jill, Wheeler, David C., Oates, Thomas, and Caplin, Ben
- Published
- 2021
- Full Text
- View/download PDF
46. Brave new epigenomes: the dawn of epigenetic engineering.
- Author
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Köferle, Anna, Stricker, Stefan H., and Beck, Stephan
- Subjects
- *
SEXISM in engineering , *ENGINEERING services , *CYTOLOGICAL research , *PHENOTYPIC plasticity , *MOLECULAR structure of chromatin - Abstract
New methods for epigenome editing now make it possible to manipulate the epigenome in living cells with unprecedented specificity and efficiency. These ground-breaking approaches are beginning to yield novel insights into the function of individual chromatin marks in the context of cellular phenotype. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
47. Brave new epigenomes: the dawn of epigenetic engineering.
- Author
-
KÕeferle, Anna, Stricker, Stefan H., and Beck, Stephan
- Subjects
- *
EPIGENETICS , *GENOME editing , *GENOMES , *CHROMATIN , *ZINC-finger proteins , *DNA-binding proteins - Abstract
New methods for epigenome editing now make it possible to manipulate the epigenome in living cells with unprecedented specificity and efficiency. These ground-breaking approaches are beginning to yield novel insights into the function of individual chromatin marks in the context of cellular phenotype. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
48. Plant dispersal strategies of high tropical alpine communities across the Andes.
- Author
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Tovar, Carolina, Melcher, Inga, Kusumoto, Buntarou, Cuesta, Francisco, Cleef, Antoine, Meneses, Rosa Isela, Halloy, Stephan, Llambí, Luis Daniel, Beck, Stephan, Muriel, Priscilla, Jaramillo, Ricardo, Jácome, Jorge, Carilla, Julieta, and Dalling, James
- Subjects
- *
PLANT dispersal , *MOUNTAIN ecology , *STRUCTURAL equation modeling , *PLANT communities , *MOUNTAIN plants - Abstract
Dispersal is a key ecological process that influences plant community assembly. Therefore, understanding whether dispersal strategies are associated with climate is of utmost importance, particularly in areas greatly exposed to climate change. We examined alpine plant communities located in the mountain summits of the tropical Andes across a 4,000‐km latitudinal gradient. We investigated species dispersal strategies and tested their association with climatic conditions and their evolutionary history.We used dispersal‐related traits (dispersal mode and growth form) to characterize dispersal strategies for 486 species recorded on 49 mountain summits. Then we analysed the phylogenetic signal of traits and investigated the association between dispersal traits, phylogeny, climate and space using structural equation modelling and fourth‐corner analysis together with RLQ ordination.A median of 36% species in the communities was anemochorous (wind‐dispersed) and herbaceous. This dispersal strategy was followed by the barochory‐herb combination (herbaceous with unspecialized seeds, dispersed by gravity) with a median of 26.3% species in the communities. The latter strategy was common among species with distributions restricted to alpine environments.While trait states were phylogenetically conserved, they were significantly associated with a temperature gradient. Low minimum air temperatures, found at higher latitudes/elevations, were correlated with the prevalence of barochory and the herb growth form, traits that are common among Caryophyllales, Brassicaceae and Poaceae. Milder temperatures, found at lower latitudes/elevations, were associated with endozoochorous, shrub species mostly from the Ericaceae family. Anemochorous species were found all along the temperature gradient, possibly due to the success of anemochorous Compositae species in alpine regions. We also found that trait state dominance was more associated with the climatic conditions of the summit than with community phylogenetic structure. Although the evolutionary history of the tropical Andean flora has also shaped dispersal strategies, our results suggest that the environment had a more predominant role.Synthesis. We showed that dispersal‐related traits are strongly associated with a gradient of minimum air temperatures in the Andes. Global warming may weaken this key filter at tropical alpine summits, potentially altering community dispersal strategies in this region and thus, plant community structure and composition. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
49. Thermal niche traits of high alpine plant species and communities across the tropical Andes and their vulnerability to global warming.
- Author
-
Cuesta, Francisco, Tovar, Carolina, Llambí, Luis D., Gosling, William D., Halloy, Stephan, Carilla, Julieta, Muriel, Priscilla, Meneses, Rosa I., Beck, Stephan, Ulloa Ulloa, Carmen, Yager, Karina, Aguirre, Nikolay, Viñas, Paul, Jácome, Jorge, Suárez‐Duque, David, Buytaert, Wouter, and Pauli, Harald
- Subjects
- *
PLANT species , *MOUNTAIN ecology , *MOUNTAIN plants , *PLANT communities , *SEASONAL temperature variations , *GLOBAL warming , *BIOGEOGRAPHY , *ECOLOGICAL niche , *ALPINE regions - Abstract
Aim: The climate variability hypothesis (CVH) predicts that locations with reduced seasonal temperature variation select for species with narrower thermal ranges. Here we (a) test the CVH by assessing the effect of latitude and elevation on the thermal ranges of Andean vascular plant species and communities, and (b) assess tropical alpine plants vulnerability to warming based on their thermal traits. Location: High tropical Andes. Taxon: Vascular plants. Methods: Temperature data for 505 vascular plant species from alpine communities on 49 summits, were extracted from 29,627 georeferenced occurrences. Species thermal niche traits (TNTs) were estimated using bootstrapping for: minimum temperature, optimum (mean) temperature and breadth (maximum‐minimum). Plant community‐weighted scores were estimated using the TNTs of their constituent species. CVH was tested for species, biogeographical species groups and communities. Vulnerability to global warming was assessed for species, biogeographical species groups and communities. Results: Species restricted to the equator showed narrower thermal niche breadth than species whose ranges stretch far from the equator, however, no difference in niche breadth was found across summits' elevation. Biogeographical species groups distributed close to the equator and restricted to alpine regions showed narrower niche breadth than those with broader ranges. Community‐weighted scores of thermal niche breadth were positively related to distance from equator but not to elevation. Based on their TNTs, species restricted to equatorial latitudes and plant communities dominated by these species were identified as the most vulnerable to the projected 1.5°C warming, due to a potentially higher risk of losing thermal niche space. Main conclusions: Our study confirms that the CVH applies to high tropical Andean plant species and communities, where latitude has a strong effect on the thermal niche breadth. TNTs are identified as suitable indicators of species' vulnerability to warming and are suggested to be included in long‐term biodiversity monitoring in the Andes. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
50. Epigenome-Wide Association Study of Incident Type 2 Diabetes in a British Population: EPIC-Norfolk Study.
- Author
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Cardona, Alexia, Day, Felix R., Perry, John R. B., Loh, Marie, Chu, Audrey Y., Lehne, Benjamin, Paul, Dirk S., Lotta, Luca A., Stewart, Isobel D., Kerrison, Nicola D., Scott, Robert A., Khaw, Kay-Tee, Forouhi, Nita G., Langenberg, Claudia, Liu, Chunyu, Mendelson, Michael M., Levy, Daniel, Beck, Stephan, Leslie, R. David, and Dupuis, Josée
- Subjects
- *
TYPE 2 diabetes , *EPIGENOMICS , *DEMETHYLATION , *HYPERGLYCEMIA , *DNA methylation - Abstract
Epigenetic changes may contribute substantially to risks of diseases of aging. Previous studies reported seven methylation variable positions (MVPs) robustly associated with incident type 2 diabetes mellitus (T2DM). However, their causal roles in T2DM are unclear. In an incident T2DM case-cohort study nested within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort, we used whole blood DNA collected at baseline, up to 11 years before T2DM onset, to investigate the role of methylation in the etiology of T2DM. We identified 15 novel MVPs with robust associations with incident T2DM and robustly confirmed three MVPs identified previously (near to TXNIP, ABCG1, and SREBF1). All 18 MVPs showed directionally consistent associations with incident and prevalent T2DM in independent studies. Further conditional analyses suggested that the identified epigenetic signals appear related to T2DM via glucose and obesity-related pathways acting before the collection of baseline samples. We integrated genome-wide genetic data to identify methylation-associated quantitative trait loci robustly associated with 16 of the 18 MVPs and found one MVP, cg00574958 at CPT1A, with a possible direct causal role in T2DM. None of the implicated genes were previously highlighted by genetic association studies, suggesting that DNA methylation studies may reveal novel biological mechanisms involved in tissue responses to glycemia. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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