On the Analysis of the Illumina 450k Array Data: Probes Ambiguously Mapped to the Human Genome

Zhang, Xu; Mu, Wenbo; Zhang, Wei

doi:10.3389/fgene.2012.00073

Cited by 45 publications

(40 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite known limitations with CpG array technology [103], the changes in β values at various sites after a short exposure time to matrix suggests that the extracellular matrix environment may, in part, exert its effects on regulation of gene expression through alterations in DNA methylation [104]. The number of differentially methylated CpG sites is within the range of changes seen in other MethylArray comparisons, such as dilated cardiomyopathy and end-stage heart disease [105], [106].…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Switching Induced by Damaged Matrix Is Associated with DNA Methyltransferase 3A (DNMT3A) Activity and Nuclear Localization in Smooth Muscle Cells (SMC)

et al. 2013

View full text Add to dashboard Cite

Extracellular matrix changes are often crucial inciting events for fibroproliferative disease. Epigenetic changes, specifically DNA methylation, are critical factors underlying differentiated phenotypes. We examined the dependency of matrix-induced fibroproliferation and SMC phenotype on DNA methyltransferases. The cooperativity of matrix with growth factors, cell density and hypoxia was also examined. Primary rat visceral SMC of early passage (0–2) were plated on native collagen or damaged/heat-denatured collagen. Hypoxia was induced with 3% O2 (balanced 5% CO2 and 95% N2) over 48 hours. Inhibitors were applied 2–3 hours after cells were plated on matrix, or immediately before hypoxia. Cells were fixed and stained for DNMT3A and smooth muscle actin (SMA) or smooth muscle myosin heavy chain. Illumina 450 K array of CpG sites was performed on bisulfite-converted DNA from smooth muscle cells on damaged matrix vs native collagen. Matrix exquisitely regulates DNMT3A localization and expression, and influences differentiation in SMCs exposed to denatured matrix +/− hypoxia. Analysis of DNA methylation signatures showed that Matrix caused significant DNA methylation alterations in a discrete number of CpG sites proximal to genes related to SMC differentiation. Matrix has a profound effect on the regulation of SMC phenotype, which is associated with altered expression, localization of DNMTs and discrete changes DNA methylation.

show abstract

Section: Discussionmentioning

confidence: 99%

Phenotypic Switching Induced by Damaged Matrix Is Associated with DNA Methyltransferase 3A (DNMT3A) Activity and Nuclear Localization in Smooth Muscle Cells (SMC)

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Briefly, the M-values (log 2 ratio of the intensities of modified probe versus unmodified probe) (41) of CpG probes that passed quality control based on detection p-value (p<0.01) across at least 95% of samples were summarized and batch corrected using COMBAT (42). We also detected 15 CpG probes in MYLK that are mapped to multiple loci in the human genome (43) or contain known common genetic variants based on the dbSNP v135 (44). The final test set was comprised of 37 CpG sites located within the MYLK gene.…”

Section: Methodsmentioning

confidence: 99%

Epigenetic contribution of the myosin light chain kinase gene to the risk for acute respiratory distress syndrome

Szilágyi

Liu

Zhang

et al. 2017

Translational Research

Self Cite

View full text Add to dashboard Cite

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome with a considerable case fatality rate (~30-40%). Health disparities exist with African descent subjects (ADs) exhibiting greater mortality than European descent individuals (EDs). Myosin light chain kinase (MLCK) is encoded by MYLK whose genetic variants are implicated in ARDS pathogenesis and may influence ARDS mortality. As baseline population-specific epigenetic changes, i.e. cytosine modifications, have been observed between AD and ED individuals, epigenetic variations in MYLK may provide insights into ARDS disparities. We compared methylation levels of MYLK CpGs between ARDS patients and ICU controls overall and by ethnicity in a nested case control study of 39 ARDS cases and 75 non-ARDS intensive care unit controls. Two MYLK CpG sites (cg03892735, cg23344121) were differentially modified between ARDS subjects and controls (p<0.05; q<0.25) in a logistic regression model, where no effect modification from ethnicity or age was found. One CpG site was associated with ARDS in patients less than 58 years old, cg19611163 (intron 19,20). Two CpG sites were associated with ARDS in EDs only, gene body CpG (cg01894985, intron 2,3) and CpG (cg16212219, intron 31,32), with higher modification levels exhibited in ARDS subjects than controls. Cis-acting mQTL (modified cytosine quantitative trait loci) were identified using linear regression between local genetic variants and modification levels for two ARDS-associated CpGs (cg23344121, cg16212219). In summary, these ARDS-associated MYLK CpGs with effect modification by ethnicity and local mQTL, suggest that MYLK epigenetic variation and local genetic background may contribute to health disparities observed in ARDS.

show abstract

“…A total of 340,658 probes passed the analysis using Bowtie. [24] To avoid potential bias due to genetic polymorphisms, we also filtered 5,804 CpG probes with the presence of common single nucleotide polymorphisms (SNPs) (i.e., minor allele frequency (MAF) ≥ 0.01) within the range of 20 base pairs of the CpG sites based on the HapMap European origin populations (CEU: Caucasian residents from Utah, USA) in the dbSNP database (v135). To reduce the effects of differential methylation between males and females on the sex chromosomes, 7,953 CpG sites on chromosome X and Y were excluded.…”

Section: Methodsmentioning

confidence: 99%

Blood methylomics in response to arsenic exposure in a low-exposed US population

Liu

Zheng

Zhang

et al. 2013

J Expo Sci Environ Epidemiol

Self Cite

View full text Add to dashboard Cite

Exposure to arsenic (As) has been associated with cancers, CVD, and neurological disorder. To explore the possible underlying epigenetic mechanisms, a genome-wide study was conducted in low exposed healthy individuals. This study was nested within a prospective study of Coronary Artery Risk Development in Young Adults (CARDIA) by randomly selecting 46 non-smoker and non-diabetic White participants with low (N=23) and high (N=23) As exposure. based on toenail total As measures at examination year 2. We conducted methylomic profiling of white blood cell DNA collected at examination year 15 using the Illumina HumanMethylation450 BeadChip. Multivariate linear regression models were fitted to evaluate the associations between As exposure status and DNA methylation levels at each CpG site. We identified 29 CpG sites with methylation levels associated with As exposure status at a nominal p-value less than 0.0001. Some genes are known to be involved in cancers, CVD, and neurological disorder. Pathway analyses further revealed several canonical pathways relevant to the etiology of As-associated diseases. We demonstrated that As exposure is prospectively associated with DNA methylation levels in a number of genes implicated in As-associated diseases. Further studies are required for elucidating the role of epigenetic alterations in the pathogenesis of these diseases.

show abstract

On the Analysis of the Illumina 450k Array Data: Probes Ambiguously Mapped to the Human Genome

Cited by 45 publications

References 11 publications

Phenotypic Switching Induced by Damaged Matrix Is Associated with DNA Methyltransferase 3A (DNMT3A) Activity and Nuclear Localization in Smooth Muscle Cells (SMC)

Phenotypic Switching Induced by Damaged Matrix Is Associated with DNA Methyltransferase 3A (DNMT3A) Activity and Nuclear Localization in Smooth Muscle Cells (SMC)

Epigenetic contribution of the myosin light chain kinase gene to the risk for acute respiratory distress syndrome

Blood methylomics in response to arsenic exposure in a low-exposed US population

Contact Info

Product

Resources

About