The Illumina Infinium HumanMethylationEPIC BeadChip is the new platform for high-throughput DNA methylation analysis, effectively doubling the coverage compared to the older 450 K array. Here we ...present a significantly updated and improved version of the Bioconductor package ChAMP, which can be used to analyze EPIC and 450k data. Many enhanced functionalities have been added, including correction for cell-type heterogeneity, network analysis and a series of interactive graphical user interfaces.
ChAMP is a BioC package available from https://bioconductor.org/packages/release/bioc/html/ChAMP.html.
a.teschendorff@ucl.ac.uk or s.beck@ucl.ac.uk or a.feber@ucl.ac.uk.
Supplementary data are available at Bioinformatics online.
The Illumina Infinium HumanMethylation450 BeadChip is a new platform for high-throughput DNA methylation analysis. Several methods for normalization and processing of these data have been published ...recently. Here we present an integrated analysis pipeline offering a choice of the most popular normalization methods while also introducing new methods for calling differentially methylated regions and detecting copy number aberrations.
ChAMP is implemented as a Bioconductor package in R. The package and the vignette can be downloaded at bioconductor.org
Aquaculture of bivalve shellfish and seaweed represents a global opportunity to simultaneously advance coastal ecosystem recovery and provide substantive benefits to humanity. To identify marine ...ecoregions with the greatest potential for development of shellfish and seaweed aquaculture to meet this opportunity, we conducted a global spatial analysis using key environmental (e.g., nutrient pollution status), socioeconomic (e.g., governance quality), and human health factors (e.g., wastewater treatment prevalence). We identify a substantial opportunity for strategic sector development, with the highest opportunity marine ecoregions for shellfish aquaculture centered on Oceania, North America, and portions of Asia, and the highest opportunity for seaweed aquaculture distributed throughout Europe, Asia, Oceania, and North and South America. This study provides insights into specific areas where governments, international development organizations, and investors should prioritize new efforts to drive changes in public policy, capacity-building, and business planning to realize the ecosystem and societal benefits of shellfish and seaweed aquaculture.
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.
The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although ...microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing or remaining static. The cellular basis of this clinical observation is unknown. Here, we profile the genomic, transcriptomic, and epigenomic landscape of CIS in a unique patient cohort with longitudinally monitored pre-invasive disease. Predictive modeling identifies which lesions will progress with remarkable accuracy. We identify progression-specific methylation changes on a background of widespread heterogeneity, alongside a strong chromosomal instability signature. We observed mutations and copy number changes characteristic of cancer and chart their emergence, offering a window into early carcinogenesis. We anticipate that this new understanding of cancer precursor biology will improve early detection, reduce overtreatment, and foster preventative therapies targeting early clonal events in lung cancer.
The integration of genomic and epigenomic data is an increasingly popular approach for studying the complex mechanisms driving cancer development. We have developed a method for evaluating both ...methylation and copy number from high-density DNA methylation arrays. Comparing copy number data from Infinium HumanMethylation450 BeadChips and SNP arrays, we demonstrate that Infinium arrays detect copy number alterations with the sensitivity of SNP platforms. These results show that high-density methylation arrays provide a robust and economic platform for detecting copy number and methylation changes in a single experiment. Our method is available in the ChAMP Bioconductor package: http://www.bioconductor.org/packages/2.13/bioc/html/ChAMP.html.
•A method is presented for 5hmC detection and analysis using Infinium 450K BeadChips.•The oxBS-450K method can discriminate between 5mC and 5hmC in human gDNA•5hmC levels were quantified genome-wide ...in 3 distinct biological samples.•The reported 5hmC signal was validated using mass spectrometry and pyrosequencing.•The effects of differing amounts of input DNA on final 5hmC call rate are discussed.
DNA methylation analysis has become an integral part of biomedical research. For high-throughput applications such as epigenome-wide association studies, the Infinium HumanMethylation450 (450K) BeadChip is currently the platform of choice. However, BeadChip processing relies on traditional bisulfite (BS) based protocols which cannot discriminate between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Here, we report the adaptation of the recently developed oxidative bisulfite (oxBS) chemistry to specifically detect both 5mC and 5hmC in a single workflow using 450K BeadChips, termed oxBS-450K. Supported by validation using mass spectrometry and pyrosequencing, we demonstrate reproducible (R2>0.99) detection of 5hmC in human brain tissue using the optimised oxBS-450K protocol described here.
Imprinting is the preferential expression of one parental allele over the other. It is controlled primarily through differential methylation of cytosine at CpG dinucleotides. Here we combine 285 ...methylomes and 11,617 transcriptomes from peripheral blood samples with parent-of-origin phased haplotypes, to produce a new map of imprinted methylation and gene expression patterns across the human genome. We demonstrate how imprinted methylation is a continuous rather than a binary characteristic. We describe at high resolution the parent-of-origin methylation pattern at the 15q11.2 Prader-Willi/Angelman syndrome locus, with nearly confluent stochastic paternal methylation punctuated by 'spikes' of maternal methylation. We find examples of polymorphic imprinted methylation unrelated (at VTRNA2-1 and PARD6G) or related (at CHRNE) to nearby SNP genotypes. We observe RNA isoform-specific imprinted expression patterns suggestive of a methylation-sensitive transcriptional elongation block. Finally, we gain new insights into parent-of-origin-specific effects on phenotypes at the DLK1/MEG3 and GNAS loci.
Non-CG methylation is an unexplored epigenetic hallmark of pluripotent stem cells. Here we report that a reduction in non-CG methylation is associated with impaired differentiation capacity into ...endodermal lineages. Genome-wide analysis of 2,670 non-CG sites in a discovery cohort of 25 phenotyped human induced pluripotent stem cell (hiPSC) lines revealed unidirectional loss (Δβ=13%, P<7.4 × 10(-4)) of non-CG methylation that correctly identifies endodermal differentiation capacity in 23 out of 25 (92%) hiPSC lines. Translation into a simplified assay of only nine non-CG sites maintains predictive power in the discovery cohort (Δβ=23%, P<9.1 × 10(-6)) and correctly identifies endodermal differentiation capacity in nine out of ten pluripotent stem cell lines in an independent replication cohort consisting of hiPSCs reprogrammed from different cell types and different delivery systems, as well as human embryonic stem cell (hESC) lines. This finding infers non-CG methylation at these sites as a biomarker when assessing endodermal differentiation capacity as a readout.
Because surface treatments of high-performance fibers have previously resulted in increased friction and improved impact performance, it was of interest to evaluate the influence of multi-walled ...carbon nanotubes (MWNTs) on impact performance and contributing constituent properties of Kevlar. Kevlar K129 yarns and fabrics were modified via sonication in a solution of
N
-methylpyrrolidone (NMP) and MWNTs. This method has the potential to both improve the intrinsic properties of the fibers themselves as well as increase the friction, with very low mass addition. Tensile, static friction, and pull-out tests were performed to compare the properties of MWNT-treated materials to neat. As a result of MWNT augmentation, yarn modulus increased up to 15 %, and static and kinetic friction coefficients increased up to 30 %. Yarn pull-out tests revealed up to a 230 % increase in the forces required to pull-out yarns. To study the effects of MWNT augmentation on dynamic performance, low-velocity impact tests of steel spheres on a single ply of fabric were performed. These experiments demonstrated approximately 50 % increase in ballistic limit for MWNT-treated Kevlar with negligible (0.4–1.4 %) increase in mass. Entanglement among MWNTs along with increased surface roughness and surface area increased the resistance to motion, improving impact performance by increasing the energy required to pull-out yarns from the textile, while inhibiting textile windowing and driving a larger number of yarn failures. The observed changes in fabric response suggest that MWNT treatments have the potential to improve the ballistic limit of fabrics through increased interfilament and interyarn friction without compromising fiber strength or adding significant mass.
PDF
