scholarly journals CloudASM: an ultra-efficient cloud-based pipeline for mapping allele-specific DNA methylation

2020 ◽  
Vol 36 (11) ◽  
pp. 3558-3560
Author(s):  
Emmanuel L P Dumont ◽  
Benjamin Tycko ◽  
Catherine Do
Keyword(s):  
Dna Methylation ◽  
Data Warehouse ◽  
Time Complexity ◽  
Cpg Methylation ◽  
Cloud Platform ◽  
Genome Wide ◽  
Allele Specific ◽  
Enterprise Data Warehouse

Abstract Summary Methods for quantifying the imbalance in CpG methylation between alleles genome-wide have been described but their algorithmic time complexity is quadratic and their practical use requires painstaking attention to infrastructure choice, implementation and execution. To solve this problem, we developed CloudASM, a scalable, ultra-efficient, turn-key, portable pipeline on Google Cloud Platform (GCP) that uses a novel pipeline manager and GCP’s serverless enterprise data warehouse. Availability and implementation CloudASM is freely available in the GitHub repository https://github.com/TyckoLab/CloudASM and a sample dataset and its results are also freely available at https://console.cloud.google.com/storage/browser/cloudasm. Contact [email protected]

scholarly journals CloudASM: an ultra-efficient cloud-based pipeline for mapping allele-specific DNA methylation

2020 ◽  
Author(s):  
Emmanuel LP Dumont ◽  
Benjamin Tycko ◽  
Catherine Do
Keyword(s):  
Dna Methylation ◽  
Cloud Computing ◽  
Data Warehouse ◽  
Time Complexity ◽  
Cpg Methylation ◽  
Supplementary Information ◽  
Link Type ◽  
Genome Wide ◽  
Allele Specific ◽  
Enterprise Data Warehouse

AbstractSummaryMethods for quantifying the imbalance in CpG methylation between alleles genome-wide have been described but their algorithmic time complexity is quadratic and their practical use requires painstaking attention to infrastructure choice, implementation, and execution. To solve this problem, we developed CloudASM, a scalable, ultra-efficient, turn-key, portable pipeline on Google Cloud Computing (GCP) that uses a novel pipeline manager and GCP’s serverless enterprise data warehouse.Availability and ImplementationCloudASM is freely available in the GitHub repository https://github.com/TyckoLab/CloudASM and a sample dataset and its results are also freely available at https://console.cloud.google.com/storage/browser/[email protected] informationNone.

scholarly journals Intergenerational epigenetic inheritance in reef-building corals

2018 ◽  
Author(s):  
Yi Jin Liew ◽  
Emily J. Howells ◽  
Xin Wang ◽  
Craig T. Michell ◽  
John A. Burt ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Intergenerational Transmission ◽  
Epigenetic Inheritance ◽  
Cpg Methylation ◽  
Epigenetic Mechanisms ◽  
Transgenerational Inheritance ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Hypermethylated Genes

MainThe notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants1,2and metazoans1,3. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations1–4. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals)4. Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

scholarly journals Genome-Wide DNA Methylation Analysis during Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yangyang Cao ◽  
Haoqing Yang ◽  
Luyuan Jin ◽  
Juan Du ◽  
Zhipeng Fan
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Biological Process ◽  
Cpg Methylation ◽  
Genome Wide ◽  
Marrow Mesenchymal Stem Cells ◽  
Go Terms

Bone marrow mesenchymal stem cells (BMSCs) nowadays are regarded as promising candidates in cell-based therapy for the regeneration of damaged bone tissues that are either incurable or intractable due to the insufficiency of current therapies. Recent studies suggest that BMSCs differentiate into osteoblasts, and that this differentiation is regulated by some specific patterns of epigenetic modifications, such as DNA methylation. However, the potential role of DNA methylation modification in BMSC osteogenic differentiation is unclear. In this study, we performed a genome-wide study of DNA methylation between the noninduced and induced osteogenic differentiation of BMSCs at day 7. We found that the majority of cytosines in a CpG context were methylated in induced BMSCs. Our results also revealed that, along with the induced osteogenic differentiation in BMSCs, the average genomic methylation levels and CpG methylation in transcriptional factor regions (TFs) were increased, the CpG methylation level of various genomic elements was mainly in the medium-high methylation section, and CpG methylation levels in the repeat element had highly methylated levels. The GO analysis of differentially methylated region- (DMR-) associated genes (DMGs) showed that GO terms, including cytoskeletal protein binding (included in Molecular Function GO terms), skeletal development (included in Biological Process GO terms), mesenchymal cell differentiation (included in Biological Process GO terms), and stem cell differentiation (included in Biological Process), were enriched in the hypermethylated DMGs. Then, the KEGG analysis results showed that the WNT pathway, inositol phosphate metabolism pathway, and cocaine addiction pathway were more correlative with the DMRs during the induced osteogenic differentiation in BMSCs. In conclusion, this study revealed the difference of methylated levels during the noninduced and induced osteogenic differentiation of BMSCs and provided useful information for future works to characterize the important function of epigenetic mechanisms on BMSCs’ differentiation.

scholarly journals Genome-Wide DNA Methylation Analysis in Melanoma Reveals the Importance of CpG Methylation in MITF Regulation

2015 ◽  
Vol 135 (7) ◽  
pp. 1820-1828 ◽  
Author(s):  
Martin Lauss ◽  
Rizwan Haq ◽  
Helena Cirenajwis ◽  
Bengt Phung ◽  
Katja Harbst ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cpg Methylation ◽  
Methylation Analysis ◽  
Genome Wide ◽  
Dna Methylation Analysis

scholarly journals Genome-wide regulation of CpG methylation by ecCEBPα in acute myeloid leukemia

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 204
Author(s):  
Adewale J. Ogunleye ◽  
Ekaterina Romanova ◽  
Yulia A. Medvedeva
Keyword(s):  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cpg Methylation ◽  
The Cancer Genome Atlas ◽  
Binding Potential ◽  
Hematopoietic Malignancy ◽  
Genome Wide ◽  
A Genome ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by genetic and epigenetic aberrations that alter the differentiation capacity of myeloid progenitor cells. The transcription factor CEBPα is frequently mutated in AML patients leading to an increase in DNA methylation in many genomic locations. Previously, it has been shown that ecCEBPα (extra coding CEBPα) - a lncRNA transcribed in the same direction as CEBPα gene - regulates DNA methylation of CEBPα promoter in cis. Here, we hypothesize that ecCEBPα could participate in the regulation of DNA methylation in trans. Method: First, we retrieved the methylation profile of AML patients with mutated CEBPα locus from The Cancer Genome Atlas (TCGA). We then predicted the ecCEBPα secondary structure in order to check the potential of ecCEBPα to form triplexes around CpG loci and checked if triplex formation influenced CpG methylation, genome-wide. Results: Using DNA methylation profiles of AML patients with a mutated CEBPα locus, we show that ecCEBPα could interact with DNA by forming DNA:RNA triple helices and protect regions near its binding sites from global DNA methylation. Further analysis revealed that triplex-forming oligonucleotides in ecCEBPα are structurally unpaired supporting the DNA-binding potential of these regions. ecCEBPα triplexes supported with the RNA-chromatin co-localization data are located in the promoters of leukemia-linked transcriptional factors such as MLF2. Discussion: Overall, these results suggest a novel regulatory mechanism for ecCEBPα as a genome-wide epigenetic modulator through triple-helix formation which may provide a foundation for sequence-specific engineering of RNA for regulating methylation of specific genes.

scholarly journals Genome-wide regulation of CpG methylation by ecCEBPα in acute myeloid leukemia

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 204
Author(s):  
Adewale J. Ogunleye ◽  
Ekaterina Romanova ◽  
Yulia A. Medvedeva
Keyword(s):  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cpg Methylation ◽  
The Cancer Genome Atlas ◽  
Binding Potential ◽  
Hematopoietic Malignancy ◽  
Genome Wide ◽  
A Genome ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by genetic and epigenetic aberrations that alter the differentiation capacity of myeloid progenitor cells. The transcription factor CEBPα is frequently mutated in AML patients leading to an increase in DNA methylation in many genomic locations. Previously, it has been shown that ecCEBPα (extra coding CEBPα) - a lncRNA transcribed in the same direction as CEBPα gene - regulates DNA methylation of CEBPα promoter in cis. Here, we hypothesize that ecCEBPα could participate in the regulation of DNA methylation in trans. Method: First, we retrieved the methylation profile of AML patients with mutated CEBPα locus from The Cancer Genome Atlas (TCGA). We then predicted the ecCEBPα secondary structure in order to check the potential of ecCEBPα to form triplexes around CpG loci and checked if triplex formation influenced CpG methylation, genome-wide. Results: Using DNA methylation profiles of AML patients with a mutated CEBPα locus, we show that ecCEBPα could interact with DNA by forming DNA:RNA triple helices and protect regions near its binding sites from global DNA methylation. Further analysis revealed that triplex-forming oligonucleotides in ecCEBPα are structurally unpaired supporting the DNA-binding potential of these regions. ecCEBPα triplexes supported with the RNA-chromatin co-localization data are located in the promoters of leukemia-linked transcriptional factors such as MLF2. Discussion: Overall, these results suggest a novel regulatory mechanism for ecCEBPα as a genome-wide epigenetic modulator through triple-helix formation which may provide a foundation for sequence-specific engineering of RNA for regulating methylation of specific genes.

scholarly journals Bumblebee worker castes show differences in allele-specific DNA methylation and allele-specific expression

2020 ◽  
Author(s):  
H. Marshall ◽  
A.R.C. Jones ◽  
Z.N. Lonsdale ◽  
E.B. Mallon
Keyword(s):  
Dna Methylation ◽  
Bombus Terrestris ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Genome Wide ◽  
Expression Bias ◽  
Allele Specific ◽  
Parent Of Origin ◽  
Worker Castes

AbstractAllele-specific expression is when one allele of a gene shows higher levels of expression compared to the other allele, in a diploid organism. Genomic imprinting is an extreme example of this, where some genes exhibit allele-specific expression in a parent-of-origin manner. Recent work has identified potentially imprinted genes in species of Hymenoptera. However, the molecular mechanism which drives this allelic expression bias remains unknown. In mammals DNA methylation is often associated with imprinted genes. DNA methylation systems have been described in species of Hymenoptera, providing a candidate imprinting mechanism. Using previously generated RNA-Seq and whole genome bisulfite sequencing from reproductive and sterile bumblebee (Bombus terrestris) workers we have identified genome-wide allele-specific expression and allele-specific DNA methylation. The majority of genes displaying allele-specific expression are common between reproductive castes and the proportion of allele-specific expression bias generally varies between colonies. We have also identified genome-wide allele-specific DNA methylation patterns in both castes. There is no significant overlap between genes showing allele-specific expression and allele-specific methylation. These results indicate that DNA methylation does not directly drive genome-wide allele-specific expression in this species. Only a small number of the genes identified may be ‘imprinted’ and it may be these genes which are associated with allele-specific DNA methylation. Future work utilising reciprocal crosses to identify parent-of-origin DNA methylation will further clarify the role of DNA methylation in parent-of-origin allele-specific expression.

scholarly journals Changes in DNA Methylation in Response to 6-Benzylaminopurine Affect Allele-Specific Gene Expression in Populus tomentosa

2020 ◽  
Author(s):  
Anran Xuan ◽  
Yuepeng Song ◽  
Chenhao Bu ◽  
Panfei Chen ◽  
Yousry A. El-Kassaby ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Patterns ◽  
Populus Tomentosa ◽  
Differentially Expressed ◽  
Specific Gene ◽  
Snp Analysis ◽  
Specific Gene Expression ◽  
Genome Wide ◽  
Allele Specific

The cytokinins play important roles in plant growth and development by regulating gene expression at genome wide level. DNA methylation is responsive to the external environment, but whether DNA methylation changes in response to cytokinin treatment to regulate gene expression is still unclear. Here, we used bisulfite sequencing and RNA sequencing to examine genome-wide DNA methylation and gene expression patterns in poplar (Populus tomentosa) after treatment with the synthetic cytokinin 6-benzylaminopurine (6-BA). We identified 566 significantly differentially methylated regions (DMRs) in response to 6-BA treatment. Transcriptome analysis showed that 501 protein-coding genes, 262 long non-coding RNAs, and 15,793 24-nt small interfering RNAs were differentially expressed under 6-BA treatment. Among these, 79% were differentially expressed between alleles in P. tomentosa. Combined DNA methylation and gene expression analysis demonstrated that DNA methylation plays an important role in regulating allele-specific gene expression. To further investigate the relationship between these 6-BA-responsive genes and phenotypic variation, we performed SNP analysis of 507 6-BA-responsive DMRs via re-sequencing using a natural population of P. tomentosa and identified 206 SNPs that were significantly associated with growth and wood properties. Association analysis indicated that 53% of loci with allele-specific expression had primarily dominant effects on poplar traits. Our comprehensive analyses of P. tomentosa DNA methylation and the regulation of allele-specific gene expression suggest that DNA methylation is an important regulator of imbalanced expression between allelic loci.

scholarly journals Bumblebee Workers Show Differences in Allele-Specific DNA Methylation and Allele-Specific Expression

2020 ◽  
Vol 12 (8) ◽  
pp. 1471-1481
Author(s):  
Hollie Marshall ◽  
Alun R C Jones ◽  
Zoë N Lonsdale ◽  
Eamonn B Mallon
Keyword(s):  
Dna Methylation ◽  
Bombus Terrestris ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Cis Acting ◽  
Genome Wide ◽  
Expression Bias ◽  
Hymenopteran Species ◽  
Allele Specific ◽  
Allele Specific Methylation

Abstract Allele-specific expression is when one allele of a gene shows higher levels of expression compared with the other allele, in a diploid organism. Recent work has identified allele-specific expression in a number of Hymenopteran species. However, the molecular mechanism which drives this allelic expression bias remains unknown. In mammals, DNA methylation is often associated with genes which show allele-specific expression. DNA methylation systems have been described in species of Hymenoptera, providing a candidate mechanism. Using previously generated RNA-Seq and whole-genome bisulfite sequencing from reproductive and sterile bumblebee (Bombus terrestris) workers, we have identified genome-wide allele-specific expression and allele-specific DNA methylation. The majority of genes displaying allele-specific expression are common between reproductive and sterile workers and the proportion of allele-specific expression bias generally varies between genetically distinct colonies. We have also identified genome-wide allele-specific DNA methylation patterns in both reproductive and sterile workers, with reproductive workers showing significantly more genes with allele-specific methylation. Finally, there is no significant overlap between genes showing allele-specific expression and allele-specific methylation. These results indicate that cis-acting DNA methylation does not directly drive genome-wide allele-specific expression in this species.

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