共查询到20条相似文献,搜索用时 15 毫秒
1.
Ja-Rang Lee Chang Pyo Hong Jae-Woo Moon Yi-Deun Jung Dae-Soo Kim Tae-Hyung Kim Jeong-An Gim Jin-Han Bae Yuri Choi Jungwoo Eo Yun-Jeong Kwon Sanghoon Song Junsu Ko Young Mok Yang Hak-Kyo Lee Kyung-Do Park Kung Ahn Kyoung-Tag Do Hong-Seok Ha Kyudong Han Joo Mi Yi Hee-Jae Cha Byung-Wook Cho Jong Bhak Heui-Soo Kim 《BMC genomics》2014,15(1)
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Background
Human induced pluripotent stem cells (iPSCs) have a wide range of applications throughout the fields of basic research, disease modeling and drug screening. Epigenetic instable iPSCs with aberrant DNA methylation may divide and differentiate into cancer cells. Unfortunately, little effort has been taken to compare the epigenetic variation in iPSCs with that in differentiated cells. Here, we developed an analytical procedure to decipher the DNA methylation heterogeneity of mixed cells and further exploited it to quantitatively assess the DNA methylation variation in the methylomes of adipose-derived stem cells (ADS), mature adipocytes differentiated from ADS cells (ADS-adipose) and iPSCs reprogrammed from ADS cells (ADS-iPSCs).Results
We observed that the degree of DNA methylation variation varies across distinct genomic regions with promoter and 5’UTR regions exhibiting low methylation variation and Satellite showing high methylation variation. Compared with differentiated cells, ADS-iPSCs possess globally decreased methylation variation, in particular in repetitive elements. Interestingly, DNA methylation variation decreases in promoter regions during differentiation but increases during reprogramming. Methylation variation in promoter regions is negatively correlated with gene expression. In addition, genes showing a bipolar methylation pattern, with both completely methylated and completely unmethylated reads, are related to the carbohydrate metabolic process, cellular development, cellular growth, proliferation, etc.Conclusions
This study delivers a way to detect cell-subset specific methylation genes in a mixed cell population and provides a better understanding of methylation dynamics during stem cell differentiation and reprogramming.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-978) contains supplementary material, which is available to authorized users. 相似文献3.
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Bo Zhang XiaoYun Xing Jing Li Rebecca F Lowdon Yan Zhou Nan Lin Baoxue Zhang Vasavi Sundaram Katherine B Chiappinelli Ian S Hagemann David G Mutch Paul J Goodfellow Ting Wang 《BMC genomics》2014,15(1)
Background
Aberrant DNA methylation is a hallmark of many cancers. Classically there are two types of endometrial cancer, endometrioid adenocarcinoma (EAC), or Type I, and uterine papillary serous carcinoma (UPSC), or Type II. However, the whole genome DNA methylation changes in these two classical types of endometrial cancer is still unknown.Results
Here we described complete genome-wide DNA methylome maps of EAC, UPSC, and normal endometrium by applying a combined strategy of methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme digestion sequencing (MRE-seq). We discovered distinct genome-wide DNA methylation patterns in EAC and UPSC: 27,009 and 15,676 recurrent differentially methylated regions (DMRs) were identified respectively, compared with normal endometrium. Over 80% of DMRs were in intergenic and intronic regions. The majority of these DMRs were not interrogated on the commonly used Infinium 450K array platform. Large-scale demethylation of chromosome X was detected in UPSC, accompanied by decreased XIST expression. Importantly, we discovered that the majority of the DMRs harbored promoter or enhancer functions and are specifically associated with genes related to uterine development and disease. Among these, abnormal methylation of transposable elements (TEs) may provide a novel mechanism to deregulate normal endometrium-specific enhancers derived from specific TEs.Conclusions
DNA methylation changes are an important signature of endometrial cancer and regulate gene expression by affecting not only proximal promoters but also distal enhancers.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-868) contains supplementary material, which is available to authorized users. 相似文献7.
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Haroon Naeem Nicholas C Wong Zac Chatterton Matthew K H Hong John S Pedersen Niall M Corcoran Christopher M Hovens Geoff Macintyre 《BMC genomics》2014,15(1)
Background
The Illumina HumanMethylation450 BeadChip (HM450K) measures the DNA methylation of 485,512 CpGs in the human genome. The technology relies on hybridization of genomic fragments to probes on the chip. However, certain genomic factors may compromise the ability to measure methylation using the array such as single nucleotide polymorphisms (SNPs), small insertions and deletions (INDELs), repetitive DNA, and regions with reduced genomic complexity. Currently, there is no clear method or pipeline for determining which of the probes on the HM450K bead array should be retained for subsequent analysis in light of these issues.Results
We comprehensively assessed the effects of SNPs, INDELs, repeats and bisulfite induced reduced genomic complexity by comparing HM450K bead array results with whole genome bisulfite sequencing. We determined which CpG probes provided accurate or noisy signals. From this, we derived a set of high-quality probes that provide unadulterated measurements of DNA methylation.Conclusions
Our method significantly reduces the risk of false discoveries when using the HM450K bead array, while maximising the power of the array to detect methylation status genome-wide. Additionally, we demonstrate the utility of our method through extraction of biologically relevant epigenetic changes in prostate cancer.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-51) contains supplementary material, which is available to authorized users. 相似文献11.
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Naoki Kubo Hidehiro Toh Kenjiro Shirane Takayuki Shirakawa Hisato Kobayashi Tetsuya Sato Hidetoshi Sone Yasuyuki Sato Shin-ichi Tomizawa Yoshinori Tsurusaki Hiroki Shibata Hirotomo Saitsu Yutaka Suzuki Naomichi Matsumoto Mikita Suyama Tomohiro Kono Kazuyuki Ohbo Hiroyuki Sasaki 《BMC genomics》2015,16(1)
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Nina S McCarthy Phillip E Melton Gemma Cadby Seyhan Yazar Maria Franchina Eric K Moses David A Mackey Alex W Hewitt 《BMC genomics》2014,15(1)
Background
Several individual studies have suggested that autosomal CpG methylation differs by sex both in terms of individual CpG sites and global autosomal CpG methylation. However, these findings have been inconsistent and plagued by spurious associations due to the cross reactivity of CpG probes on commercial microarrays. We collectively analysed 76 published studies (n = 6,795) for sex-associated differences in both autosomal and sex chromosome CpG sites.Results
Overall autosomal methylation profiles varied substantially by study, and we encountered substantial batch effects. We accounted for these by conducting random effects meta-analysis for individual autosomal CpG methylation associations. After excluding non-specific probes, we found 184 autosomal CpG sites differentially methylated by sex after correction for multiple testing. In line with previous studies, average beta differences were small. Many of the most significantly associated CpG probes were new. Of note was differential CpG methylation in the promoters of genes thought to be involved in spermatogenesis and male fertility, such as SLC9A2, SPESP1, CRISP2, and NUPL1. Pathway analysis revealed overrepresentation of genes differentially methylated by sex in several broad Gene Ontology biological processes, including RNA splicing and DNA repair.Conclusions
This study represents a comprehensive analysis of sex-specific methylation patterns. We demonstrate the existence of sex-specific methylation profiles and report a large number of novel DNA methylation differences in autosomal CpG sites between sexes.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-981) contains supplementary material, which is available to authorized users. 相似文献14.
Chandra Sekhar Reddy Chilamakuri Susanne Lorenz Mohammed-Amin Madoui Daniel Vodák Jinchang Sun Eivind Hovig Ola Myklebost Leonardo A Meza-Zepeda 《BMC genomics》2014,15(1)
Background
Recent developments in deep (next-generation) sequencing technologies are significantly impacting medical research. The global analysis of protein coding regions in genomes of interest by whole exome sequencing is a widely used application. Many technologies for exome capture are commercially available; here we compare the performance of four of them: NimbleGen’s SeqCap EZ v3.0, Agilent’s SureSelect v4.0, Illumina’s TruSeq Exome, and Illumina’s Nextera Exome, all applied to the same human tumor DNA sample.Results
Each capture technology was evaluated for its coverage of different exome databases, target coverage efficiency, GC bias, sensitivity in single nucleotide variant detection, sensitivity in small indel detection, and technical reproducibility. In general, all technologies performed well; however, our data demonstrated small, but consistent differences between the four capture technologies. Illumina technologies cover more bases in coding and untranslated regions. Furthermore, whereas most of the technologies provide reduced coverage in regions with low or high GC content, the Nextera technology tends to bias towards target regions with high GC content.Conclusions
We show key differences in performance between the four technologies. Our data should help researchers who are planning exome sequencing to select appropriate exome capture technology for their particular application.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-449) contains supplementary material, which is available to authorized users. 相似文献15.
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Ruth Pidsley Joana Viana Eilis Hannon Helen Spiers Claire Troakes Safa Al-Saraj Naguib Mechawar Gustavo Turecki Leonard C Schalkwyk Nicholas J Bray Jonathan Mill 《Genome biology》2014,15(10)
Background
Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development. There is mounting evidence to support a role for developmentally regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development.Results
We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that schizophrenia-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development.Conclusions
Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0483-2) contains supplementary material, which is available to authorized users. 相似文献17.
Background
In invertebrates, genes belonging to dynamically regulated functional categories appear to be less methylated than “housekeeping” genes, suggesting that DNA methylation may modulate gene expression plasticity. To date, however, experimental evidence to support this hypothesis across different natural habitats has been lacking.Results
Gene expression profiles were generated from 30 pairs of genetically identical fragments of coral Acropora millepora reciprocally transplanted between distinct natural habitats for 3 months. Gene expression was analyzed in the context of normalized CpG content, a well-established signature of historical germline DNA methylation. Genes with weak methylation signatures were more likely to demonstrate differential expression based on both transplant environment and population of origin than genes with strong methylation signatures. Moreover, the magnitude of expression differences due to environment and population were greater for genes with weak methylation signatures.Conclusions
Our results support a connection between differential germline methylation and gene expression flexibility across environments and populations. Studies of phylogenetically basal invertebrates such as corals will further elucidate the fundamental functional aspects of gene body methylation in Metazoa.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-1109) contains supplementary material, which is available to authorized users. 相似文献18.
Jocelyn Charlton Richard D Williams Mark Weeks Neil J Sebire Sergey Popov Gordan Vujanic William Mifsud Marisa Alcaide-German Lee M Butcher Stephan Beck Kathy Pritchard-Jones 《Genome biology》2014,15(8)
Background
Wilms tumor is the most common pediatric renal malignancy and there is a clinical need for a molecular biomarker to assess treatment response and predict relapse. The known mutated genes in this tumor type show low mutation frequencies, whereas aberrant methylation at 11p15 is by far the most common aberration. We therefore analyzed the epigenome, rather than the genome, to identify ubiquitous tumor-specific biomarkers.Results
Methylome analysis of matched normal kidney and Wilms tumor identifies 309 preliminary methylation variable positions which we translate into three differentially methylated regions (DMRs) for use as tumor-specific biomarkers. Using two novel algorithms we show that these three DMRs are not confounded by cell type composition. We further show that these DMRs are not methylated in embryonic blastema but are intermediately methylated in Wilms tumor precursor lesions. We validate the biomarker DMRs using two independent sample sets of normal kidney and Wilms tumor and seven Wilms tumor histological subtypes, achieving 100% and 98% correct classification, respectively. As proof-of-principle for clinical utility, we successfully use biomarker DMR-2 in a pilot analysis of cell-free circulating DNA to monitor tumor response during treatment in ten patients.Conclusions
These findings define the most common methylated regions in Wilms tumor known to date which are not associated with their embryonic origin or precursor stage. We show that this tumor-specific methylated DNA is released into the blood circulation where it can be detected non-invasively showing potential for clinical utility.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0434-y) contains supplementary material, which is available to authorized users. 相似文献19.
Nicholas Redshaw Jim F Huggett Martin S Taylor Carole A Foy Alison S Devonshire 《BMC genomics》2014,15(1)
Background
DNA methylation is an important epigenetic mechanism in several human diseases, most notably cancer. The quantitative analysis of DNA methylation patterns has the potential to serve as diagnostic and prognostic biomarkers, however, there is currently a lack of consensus regarding the optimal methodologies to quantify methylation status. To address this issue we compared five analytical methods: (i) MethyLight qPCR, (ii) MethyLight digital PCR (dPCR), methylation-sensitive and -dependent restriction enzyme (MSRE/MDRE) digestion followed by (iii) qPCR or (iv) dPCR, and (v) bisulfite amplicon next generation sequencing (NGS). The techniques were evaluated for linearity, accuracy and precision.Results
MethyLight qPCR displayed the best linearity across the range of tested samples. Observed methylation measured by MethyLight- and MSRE/MDRE-qPCR and -dPCR were not significantly different to expected values whilst bisulfite amplicon NGS analysis over-estimated methylation content. Bisulfite amplicon NGS showed good precision, whilst the lower precision of qPCR and dPCR analysis precluded discrimination of differences of < 25% in methylation status. A novel dPCR MethyLight assay is also described as a potential method for absolute quantification that simultaneously measures both sense and antisense DNA strands following bisulfite treatment.Conclusions
Our findings comprise a comprehensive benchmark for the quantitative accuracy of key methods for methylation analysis and demonstrate their applicability to the quantification of circulating tumour DNA biomarkers by using sample concentrations that are representative of typical clinical isolates.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-1174) contains supplementary material, which is available to authorized users. 相似文献20.
Thomas Fleischer Arnoldo Frigessi Kevin C Johnson Hege Edvardsen Nizar Touleimat Jovana Klajic Margit LH Riis Vilde D Haakensen Fredrik W?rnberg Bj?rn Naume ?slaug Helland Anne-Lise B?rresen-Dale J?rg Tost Brock C Christensen Vessela N Kristensen 《Genome biology》2014,15(8)