ArticleBMC bioinformatics2013
Estimation of CpG coverage in whole methylome next-generation sequencing studies.
Article in BMC bioinformatics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A methylation study implicates the rewiring of brain neural circuits during puberty in the emergence of sex differences in depression symptoms.Journal of child psychology and psychiatry, and allied disciplines · 2022Pooled it
- Design and experimental validation of OPERA_MET-A panel for deep methylation analysis by next generation sequencing.Frontiers in oncology · 2022Article
- A targeted solution for estimating the cell-type composition of bulk samples.BMC bioinformatics · 2021Article
- Methylome-wide association findings for major depressive disorder overlap in blood and brain and replicate in independent brain samples.Molecular psychiatry · 2020Article
- MBD-seq - realities of a misunderstood method for high-quality methylome-wide association studies.Epigenetics · 2020Article
- Review
- A Whole Methylome Study of Ethanol Exposure in Brain and Blood: An Exploration of the Utility of Peripheral Blood as Proxy Tissue for Brain in Alcohol Methylation Studies.Alcoholism, clinical and experimental research · 2018Article
- Review
- RaMWAS: fast methylome-wide association study pipeline for enrichment platforms.Bioinformatics (Oxford, England) · 2018Article
- A MBD-seq protocol for large-scale methylome-wide studies with (very) low amounts of DNA.Epigenetics · 2017Article
- Enrichment methods provide a feasible approach to comprehensive and adequately powered investigations of the brain methylome.Nucleic acids research · 2017Article
- A Whole Methylome CpG-SNP Association Study of Psychosis in Blood and Brain Tissue.Schizophrenia bulletin · 2016Article
- High density methylation QTL analysis in human blood via next-generation sequencing of the methylated genomic DNA fraction.Genome biology · 2015Article
- Combined Whole Methylome and Genomewide Association Study Implicates CNTN4 in Alcohol Use.Alcoholism, clinical and experimental research · 2015Article
- Article
- A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects.Human molecular genetics · 2014Article
- Methylome-wide association study of schizophrenia: identifying blood biomarker signatures of environmental insults.JAMA psychiatry · 2014Article
- Testing two models describing how methylome-wide studies in blood are informative for psychiatric conditions.Epigenomics · 2013Article
- High quality methylome-wide investigations through next-generation sequencing of DNA from a single archived dry blood spot.Epigenetics · 2013Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
backgroundMethylation studies are a promising complement to genetic studies of DNA sequence. However, detailed prior biological knowledge is typically lacking, so methylome-wide association studies (MWAS) will be critical to detect disease relevant sites. A cost-effective approach involves the next-generation sequencing (NGS) of single-end libraries created from samples that are enriched for methylated DNA fragments. A limitation of single-end libraries is that the fragment size distribution is not observed. This hampers several aspects of the data analysis such as the calculation of enrichment measures that are based on the number of fragments covering the CpGs.
resultsWe developed a non-parametric method that uses isolated CpGs to estimate sample-specific fragment size distributions from the empirical sequencing data. Through simulations we show that our method is highly accurate. While the traditional (extended) read count methods resulted in severely biased coverage estimates and introduces artificial inter-individual differences, through the use of the estimated fragment size distributions we could remove these biases almost entirely. Furthermore, we found correlations of 0.999 between coverage estimates obtained using fragment size distributions that were estimated with our method versus those that were "observed" in paired-end sequencing data.
conclusionsWe propose a non-parametric method for estimating fragment size distributions that is highly precise and can improve the analysis of cost-effective MWAS studies that sequence single-end libraries created from samples that are enriched for methylated DNA fragments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.