scholarly journals Genome-wide and single-base resolution DNA methylomes of the Sea Lamprey (Petromyzon marinus) Reveal Gradual Transition of the Genomic Methylation Pattern in Early Vertebrates

2015 ◽  
Author(s):  
Zhao Zhang ◽  
Gangbiao Liu ◽  
Yangyun Zhou ◽  
James P. B. Lloyd ◽  
David W. McCauley ◽  
...  
Keyword(s):  
Methylation Level ◽  
Sea Lamprey ◽  
Methylation Pattern ◽  
Gradual Transition ◽  
Whole Genome ◽  
Pwwp Domain ◽  
Genome Wide ◽  
Genome Methylation ◽  
Early Vertebrates ◽  
Genomic Methylation

In eukaryotes, cytosine methylation is a primary heritable epigenetic modification of the genome that regulates many cellular processes. While the whole-genome methylation pattern has been generally conserved in different eukaryotic groups, invertebrates and vertebrates exhibit two distinct patterns. Whereas almost all CpG sites are methylated in most vertebrates, with the exception of short unmethylated regions call CpG islands, the most frequent pattern in invertebrate animals is ‘mosaic methylation’, comprising domains of heavily methylated DNA interspersed with domains that are methylation free. The mechanism by which the genome methylation pattern transited from a mosaic to a global pattern and the role of the one or two-round whole-genome duplication in this transition remain largely elusive, partly owing to the lack of methylome data from early vertebrates. In this study, we used the whole-genome bisulfite-sequencing technology to investigate the genome-wide methylation in three tissues (heart, muscle, and sperm) from the sea lamprey, an extant Agarthan vertebrate. Analyses of methylation level and the extent of CpG dinucleotide depletion of gene-encoding, intergenic and promoter regions revealed a gradual increase in the methylation level from invertebrates to vertebrates, with the sea lamprey exhibiting an intermediate position. In addition, the methylation level of the majority of CpGs was intermediate in each sea lamprey tissue, indicating a high level of heterogeneity of methylation status between individual cells. In this regard, we defined the genomic methylation pattern of sea lamprey as ???global genomic DNA intermediate methylation???. The methylation features in different genomic regions, such as the transcription start site (TSS) region of the gene body, exon-intron boundaries, transposons, as well as genes grouping with different expression levels, supported the gradual methylation transition hypothesis. We further discussed that the copy number difference in DNA methylation transferases and the loss of the PWWP domain and/or DNTase domain in DNMT3 sub-family enzymes may have contributed to the methylation pattern transition in early vertebrates. These findings demonstrate an intermediate genomic methylation pattern between invertebrates and jawed vertebrates, providing evidence that supports the hypothesis that methylation patterns underwent a gradual transition from invertebrates (mosaic) to vertebrates (global).

scholarly journals MeDEStrand: an improved method to infer genome-wide absolute methylation level from DNA enrichment experiment

2017 ◽  
Author(s):  
Jingting Xu ◽  
Shimeng Liu ◽  
Ping Yin ◽  
Serdar Bulun ◽  
Yang Dai
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Computational Models ◽  
Epigenetic Modification ◽  
Methylation Status ◽  
Whole Genome ◽  
Sigmoid Function ◽  
Bisulfite Conversion ◽  
Genome Wide ◽  
Dna Strands

AbstractBackgroundDNA methylation of dinucleotide CpG is an essential epigenetic modification that plays a key role in transcription. Bisulfite conversion method is a “gold standard” for DNA methylation profiling that provides single nucleotide resolution. However, whole-genome bisulfite conversion is very expensive. Alternatively, DNA enrichment-based methods offer high coverage of methylated CpG dinucleotides with the lowest cost per CpG covered genome-wide and have been used widely. They measure the DNA enrichment of methyl-CpG binding, therefore do not directly provide absolute methylation levels. Further, the enrichment is influenced by confounding factors besides the methylation status, e.g., CpG density. Computational models that can accurately derive the absolute methylation levels from the enrichment data are necessary.ResultsWe present ‘MeDEStrand’, a method uses sigmoid function to estimate and correct the CpG bias from the numbers of reads that fell within bins that divide the genome. In addition, unlike the previous methods, which estimate CpG bias based on reads mapped at the same genomic loci, ‘MeDEStrand’ processes the reads for the positive and negative DNA strands separately. We compare the performance of ‘MeDEStrand’ with three other state-of-the-art methods ‘MEDIPS’, ‘BayMeth’ and ‘QSEA’ on four independent datasets generated using immortalized cell lines (GM12878 and K562) and human patient primary cells (foreskin fibroblast and mammary epithelial). Based on the comparison between the inferred absolute methylation levels from MeDIP-seq and the corresponding RRBS data, ‘MeDEStrand’ shows the best performance at high resolution of 25, 50 and 100 base pairs.Conclusions‘MeDEStrand’ benefits from the estimation of CpG bias with a sigmoid function and the procedure to process reads mapped to the positive and negative DNA strands separately. ‘MeDEStrand’ is a tool to infer whole-genome absolute DNA methylation level at the cost of enrichment-based methods with adequate accuracy and resolution. R package ‘MeDEStrand’ and its tutorial is freely available for download at https://github.com/jxu1234/MeDEStrand.git

scholarly journals Genome-wide DNA methylation patterns reveal clinically relevant predictive and prognostic subtypes in osteosarcoma

2020 ◽  
Author(s):  
Christopher E. Lietz ◽  
Erik T. Newman ◽  
Andrew D. Kelly ◽  
Santiago A. Lozano-Calderon ◽  
David H. Ebb ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Pattern ◽  
Transcriptional Analysis ◽  
Chemotherapy Response ◽  
Methylation Array ◽  
Genome Wide ◽  
Recurrent Mutations ◽  
Methylation Patterns ◽  
Genomic Methylation

ABSTRACTBackgroundOsteosarcoma (OSA) is an aggressive malignancy predominantly affecting children and young-adults. Genetic analysis has characterized very few recurrent mutations in OSA, and an improved understanding of interpatient tumor heterogeneity is needed for clinical management.MethodsWe analyzed genome-wide DNA methylation in primary OSA tumors from the NCI Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program (n = 83) profiled using the Illumina 450K methylation array. We tested if broad genomic methylation predicted outcomes and defined supervised methylomic signatures predictive of Recurrence Free Survival (RFS), Chemotherapy Response (CR), and Metastatic disease at Diagnosis (MetDx). We assessed methylation pattern reproducibility in two independent clinical datasets (n = 28 and 34) and in an in vitro dataset (n = 11). Correlations between genomic methylation and transcription were tested using TARGET RNA-seq data. An in silico pharmacogenomic screen was performed to identify agents for future stratified application.ResultsGenome-wide methylation defined two subgroups. Relatively hypomethylated tumors experienced better chemotherapy response (Odds Ratio = 6.429, Fisher’s p = 0.007), longer RFS (metastatic, median 2.3 vs 26.7 months, localized, median 63.5 vs 104.7 months, stratified log-rank p = 0.006), and Overall Survival (p = 5×10-4) than hypermethylated tumors. Robust genomic methylation signatures predictive of RFS and CR were defined, and the signatures’ methylation patterns were reproducible in the independent clinical and in vitro datasets. The RFS signature was enriched for intragenic sites, whereas the CR signature and clinically relevant genome-wide methylation patterns were enriched for intergenic sites. Normal-tissue-like methylation patterns were associated with poor prognosis and in vitro analysis suggested that the methylation signatures are associated with tumor aggressiveness. Downstream transcriptional analysis revealed that genes annotated to the RFS methylation signature were also predictive survival. The transcriptional program represented in the RFS signature included several critical cellular pathways, whereas the CR signature was associated with much fewer known pathways, possibly reflecting a much broader cellular “methylation state” related to chemoresponse. A pharmacogenomic screen identified potential therapies, including epigenomic modifiers, for future stratified clinical application.ConclusionGenomic methylation offers insight into patient prognosis and could be a useful tool for developing alternate adjuvant therapeutic strategies.

scholarly journals Gene set enrichment analysis for genome-wide DNA methylation data

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jovana Maksimovic ◽  
Alicia Oshlack ◽  
Belinda Phipson
Keyword(s):  
Dna Methylation ◽  
Enrichment Analysis ◽  
R Package ◽  
Gene Set Enrichment Analysis ◽  
Methylation Array ◽  
Gene Set ◽  
Genome Wide ◽  
Genome Methylation ◽  
Unbiased Gene ◽  
Gene Set Testing

AbstractDNA methylation is one of the most commonly studied epigenetic marks, due to its role in disease and development. Illumina methylation arrays have been extensively used to measure methylation across the human genome. Methylation array analysis has primarily focused on preprocessing, normalization, and identification of differentially methylated CpGs and regions. GOmeth and GOregion are new methods for performing unbiased gene set testing following differential methylation analysis. Benchmarking analyses demonstrate GOmeth outperforms other approaches, and GOregion is the first method for gene set testing of differentially methylated regions. Both methods are publicly available in the missMethyl Bioconductor R package.

scholarly journals On the Expansion of “Dangerous” Gene Repertoires by Whole-Genome Duplications in Early Vertebrates

Cell Reports ◽  
2012 ◽  
Vol 2 (5) ◽  
pp. 1387-1398 ◽  
Author(s):  
Param Priya Singh ◽  
Séverine Affeldt ◽  
Ilaria Cascone ◽  
Rasim Selimoglu ◽  
Jacques Camonis ◽  
...  
Keyword(s):  
Whole Genome ◽  
Whole Genome Duplications ◽  
Genome Duplications ◽  
Early Vertebrates

scholarly journals A curated dataset of modern and ancient high-coverage shotgun human genomes

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Pierpaolo Maisano Delser ◽  
Eppie R. Jones ◽  
Anahit Hovhannisyan ◽  
Lara Cassidy ◽  
Ron Pinhasi ◽  
...  
Keyword(s):  
Sequence Data ◽  
Whole Genome ◽  
Reference Dataset ◽  
High Coverage ◽  
Sample Distribution ◽  
Human Samples ◽  
Human Genomes ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Computationally Intensive

AbstractOver the last few years, genome-wide data for a large number of ancient human samples have been collected. Whilst datasets of captured SNPs have been collated, high coverage shotgun genomes (which are relatively few but allow certain types of analyses not possible with ascertained captured SNPs) have to be reprocessed by individual groups from raw reads. This task is computationally intensive. Here, we release a dataset including 35 whole-genome sequenced samples, previously published and distributed worldwide, together with the genetic pipeline used to process them. The dataset contains 72,041,355 sites called across 19 ancient and 16 modern individuals and includes sequence data from four previously published ancient samples which we sequenced to higher coverage (10–18x). Such a resource will allow researchers to analyse their new samples with the same genetic pipeline and directly compare them to the reference dataset without re-processing published samples. Moreover, this dataset can be easily expanded to increase the sample distribution both across time and space.

scholarly journals Integration of genome wide association studies and whole genome sequencing provides novel insights into fat deposition in chicken

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Gabriel Costa Monteiro Moreira ◽  
Clarissa Boschiero ◽  
Aline Silva Mello Cesar ◽  
James M. Reecy ◽  
Thaís Fernanda Godoy ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Association Studies ◽  
Fat Deposition ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Genome Wide

scholarly journals Low-pass whole genome bisulfite sequencing of neonatal dried blood spots identifies a role for RUNX1 in Down syndrome DNA methylation profiles

2020 ◽  
Author(s):  
Benjamin I Laufer ◽  
Hyeyeon Hwang ◽  
Julia M Jianu ◽  
Charles E Mordaunt ◽  
Ian F Korf ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Down Syndrome ◽  
Early Life ◽  
Trisomy 21 ◽  
Bisulfite Sequencing ◽  
Dried Blood Spots ◽  
Whole Genome ◽  
Genome Wide ◽  
Low Pass ◽  
Genome Bisulfite Sequencing

Abstract Neonatal dried blood spots (NDBS) are a widely banked sample source that enables retrospective investigation into early life molecular events. Here, we performed low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA to examine early life Down syndrome (DS) DNA methylation profiles. DS represents an example of genetics shaping epigenetics, as multiple array-based studies have demonstrated that trisomy 21 is characterized by genome-wide alterations to DNA methylation. By assaying over 24 million CpG sites, thousands of genome-wide significant (q < 0.05) differentially methylated regions (DMRs) that distinguished DS from typical development and idiopathic developmental delay were identified. Machine learning feature selection refined these DMRs to 22 loci. The DS DMRs mapped to genes involved in neurodevelopment, metabolism, and transcriptional regulation. Based on comparisons with previous DS methylation studies and reference epigenomes, the hypermethylated DS DMRs were significantly (q < 0.05) enriched across tissues while the hypomethylated DS DMRs were significantly (q < 0.05) enriched for blood-specific chromatin states. A ~28 kb block of hypermethylation was observed on chromosome 21 in the RUNX1 locus, which encodes a hematopoietic transcription factor whose binding motif was the most significantly enriched (q < 0.05) overall and specifically within the hypomethylated DMRs. Finally, we also identified DMRs that distinguished DS NDBS based on the presence or absence of congenital heart disease (CHD). Together, these results not only demonstrate the utility of low-pass WGBS on NDBS samples for epigenome-wide association studies, but also provide new insights into the early life mechanisms of epigenomic dysregulation resulting from trisomy 21.

scholarly journals Clonal Lineages of Erysipelothrix rhusiopathiae Responsible for Acute Swine Erysipelas in Japan Identified by Using Genome-Wide Single-Nucleotide Polymorphism Analysis

2017 ◽  
Vol 83 (11) ◽  
Author(s):  
Yohsuke Ogawa ◽  
Kazumasa Shiraiwa ◽  
Yoshitoshi Ogura ◽  
Tadasuke Ooka ◽  
Sayaka Nishikawa ◽  
...  
Keyword(s):  
Polymorphism Analysis ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Erysipelothrix Rhusiopathiae ◽  
Single Nucleotide ◽  
Content Type ◽  
Genome Wide ◽  
Wide Range ◽  
Swine Erysipelas ◽  
Lineage Iv

ABSTRACTErysipelothrix rhusiopathiaecauses swine erysipelas, an important infectious disease in the swine industry. In Japan, the incidence of acute swine erysipelas due toE. rhusiopathiaeserovar 1a has recently increased markedly. To study the genetic relatedness of the strains from the recent cases, we analyzed 34E. rhusiopathiaeserovar 1a swine isolates collected between 1990 and 2011 and further investigated the possible association of the live Koganei 65-0.15 vaccine strain (serovar 1a) with the increase in cases. Pulsed-field gel electrophoresis analysis revealed no marked variation among the isolates; however, sequencing analysis of a hypervariable region in the surface-protective antigen A gene (spaA) revealed that the strains isolated after 2007 exhibited the samespaAgenotype and could be differentiated from older strains. Phylogenetic analysis based on genome-wide single-nucleotide polymorphisms (SNPs) revealed that the Japanese strains examined were closely related, showing a relatively small number of SNPs among them. The strains were classified into four major lineages, with Koganei 65-0.15 (lineage III) being phylogenetically separated from the other three lineages. The strains isolated after 2007 and the two older strains constituted one major lineage (lineage IV) with a specificspaAgenotype (M203/I257-SpaA), while the recent isolates were further divided into two geographic groups. The remaining older isolates belonged to either lineage I, with the I203/L257-SpaA type, or lineage II, with the I203/I257-SpaA type. These results indicate that the recent increased incidence of acute swine erysipelas in Japan is associated with two sublineages of lineage IV, which have independently evolved in two different geographic regions.IMPORTANCEUsing large-scale whole-genome sequence data fromErysipelothrix rhusiopathiaeisolates from a wide range of hosts and geographic origins, a recent study clarified the existence of three distinct clades (clades 1, 2, and 3) that are found across multiple continents and host species, representing both livestock and wildlife, and an “intermediate” clade between clade 2 and the dominant clade 3 within the species. In this study, we found that theE. rhusiopathiaeJapanese strains examined exhibited remarkably low levels of genetic diversity and confirmed that all of the Japanese and Chinese swine isolates examined in this study belong to clonal lineages within the intermediate clade. We report thatspaAgenotyping ofE. rhusiopathiaestrains is a practical alternative to whole-genome sequencing analysis of theE. rhusiopathiaeisolates from eastern Asian countries.

scholarly journals Detection and characterization of copy number variants based on whole-genome sequencing by DNBSEQ platforms

2019 ◽  
Author(s):  
Junhua Rao ◽  
Lihua Peng ◽  
Fang Chen ◽  
Hui Jiang ◽  
Chunyu Geng ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Copy Number Variant ◽  
Whole Genome ◽  
Genome Wide ◽  
Wide Range ◽  
Distribution Sensitivity ◽  
Cnv Detection

AbstractBackgroundNext-generation sequence (NGS) has rapidly developed in past years which makes whole-genome sequencing (WGS) becoming a more cost- and time-efficient choice in wide range of biological researches. We usually focus on some variant detection via WGS data, such as detection of single nucleotide polymorphism (SNP), insertion and deletion (Indel) and copy number variant (CNV), which playing an important role in many human diseases. However, the feasibility of CNV detection based on WGS by DNBSEQ™ platforms was unclear. We systematically analysed the genome-wide CNV detection power of DNBSEQ™ platforms and Illumina platforms on NA12878 with five commonly used tools, respectively.ResultsDNBSEQ™ platforms showed stable ability to detect slighter more CNVs on genome-wide (average 1.24-fold than Illumina platforms). Then, CNVs based on DNBSEQ™ platforms and Illumina platforms were evaluated with two public benchmarks of NA12878, respectively. DNBSEQ™ and Illumina platforms showed similar sensitivities and precisions on both two benchmarks. Further, the difference between tools for CNV detection was analyzed, and indicated the selection of tool for CNV detection could affected the CNV performance, such as count, distribution, sensitivity and precision.ConclusionThe major contribution of this paper is providing a comprehensive guide for CNV detection based on WGS by DNBSEQ™ platforms for the first time.

scholarly journals Longitudinal whole-genome based comparison of carriage and infection associated Staphylococcus aureus in northern Australian dialysis clinics

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245790
Author(s):  
Deborah C. Holt ◽  
Tegan M. Harris ◽  
Jaquelyne T. Hughes ◽  
Rachael Lilliebridge ◽  
David Croker ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Skin Lesions ◽  
Clinical Strain ◽  
Whole Genome ◽  
Study Objective ◽  
Client Group ◽  
Genome Wide ◽  
Client Population ◽  
Definition Of ◽  
Study Participants

Background The study objective was to reveal reservoirs potentially leading to Staphylococcus aureus infections in haemodialysis clinic clients in the tropical north of the Australian Northern Territory (NT). This client population are primarily Aboriginal Australians who have a greater burden of ill health than other Australians. Reservoir identification will enhance infection control in this client group, including informing potential S. aureus decolonisation strategies. Methods and findings The study participants were 83 clients of four haemodialysis clinics in the Darwin region of the NT, and 46 clinical staff and researchers who had contact with the clinic clients. The study design was longitudinal, encompassing swabbing of anatomical sites at two month intervals to yield carriage isolates, and also progressive collection of infection isolates. Swab sampling was performed for all participants, and infection isolates collected for dialysis clients only. Analysis was based on the comparison of 139 carriage isolates and 27 infection isolates using whole genome sequencing. Genome comparisons were based on of 20,651 genome-wide orthologous SNPs, presence/absence of the mecA and pvl genes, and inferred multilocus sequence type and clonal complex. Pairs of genomes meeting the definition of “not discriminated” were classed as defining potential transmission events. The primary outcome was instances of potential transmission between a carriage site other than a skin lesion and an infection site, in the same individual. Three such instances were identified. Two involved ST762 (CC1) PVL- MRSA, and one instance ST121 PVL+ MSSA. Three additional instances were identified where the carriage strains were derived from skin lesions. Also identified were six instances of potential transmission of a carriage strains between participants, including transmission of strains between dialysis clients and staff/researchers, and one potential transmission of a clinical strain between participants. There were frequent occurrences of longitudinal persistence of carriage strains in individual participants, and two examples of the same strain causing infection in the same participants at different times. Strains associated with infections and skin lesions were enriched for PVL and mecA in comparison to strains associated with long term carriage. Conclusions This study indicated that strains differ with respect to propensity to stably colonise sites such as the nose, and cause skin infections. PVL+ strains were associated with infection and skin lesions and were almost absent from the carriage sites. PVL- MRSA (mainly CC1) strains were associated with infection and also with potential transmission events involving carriage sites, while PVL- MSSA were frequently observed to stably colonise individuals without causing infection, and to be rarely transmitted. Current clinical guidelines for dialysis patients suggest MRSA decolonisation. Implementation in this client group may impact infections by PVL- MRSA, but may have little effect on infection by PVL+ strains. In this study, the PVL+ strains were predominant causes of infection but rarely colonised typical carriage sites such as the nose, and in the case of ST121, were MSSA. The important reservoirs for infection by PVL+ strains appeared to be prior infections.

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