Early-Onset Preeclampsia Placentas and Controls
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: John Blair
PROVIDER: E-GEOD-44712 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We investigated the DNA methylation and gene expression of 20 chorionic villi samples from early onset preeclampsia placentas to 20 gestational age matched controls. From this we were able to see a widespread disregulation in DNA methylation across a subset of genes in the genome. This may help to elucidate the underlying biological problems that lead to early onset preeclampsia. We noted that there were DNA methylation changes in many genes of importance as well as in different genomic elements such as enhancers. Bisulfite converted DNA from 20 third trimester early onset preeclampsia placentas and 20 gestational age matched controls
2013-06-21 | E-GEOD-44667 | biostudies-arrayexpress
Project description:Background: Measurement of genome-wide DNA methylation (DNAm) has become an important avenue for investigating potentially functional changes in various pathological conditions. Illumina Infinium is a relatively inexpensive and user-friendly DNAm microarray platform used by many researchers to measure DNAm on a large scale. However it has been suggested that a subset of probes may give rise to misleading results due to issues related to probe design. To facilitate biologically significant data interpretation, we set out to enhance probe annotation of the newest HumanMethylation450 BeadChip array (with >485,000 probes covering 99% of RefSeq genes). Results: Annotation that was added or expanded on includes 1) SNPs documented in the probe target, 2) probe binding specificity, 3) CpG classification of target sites and 4) gene feature classification of target sites. Probes with documented SNPs within 10bp of the target site and especially those with documented SNPs at the target CpG, were associated with increased within-tissue variation in DNAm. An example of a probe with a SNP at the target CpG was used to demonstrate how sample genotype can confound the measurement of DNAm. 8.6% of probes were identified as non-specific, in other words, these probes map to multiple locations in silico. DNAm measured from these non-specific probes likely represents a combination of DNAm from multiple genomic sites. The expanded biological annotation demonstrated that based on DNAm, grouping probes by alternative CpG classes rather than UCSC islands provides a more distinctive classification system of CpG sites. Finally variable enrichment for tissue-specific differentially methylated probes was noted across CpG classes and gene feature groups, depending on the tissues that were compared. Conclusion: Probes containing SNPs and non-specific probes may affect the assessment of DNAm using the 450k array. Additionally CpG enrichment classes and to a lesser extent gene feature groups were associated with distinct patterns of DNAm. Thus, we recommend that confounded probes be removed from analyses and that genomic trends be considered in analyses of the Illumina HumanMethylation450 BeadChip. DNAm arrays offer a powerful approach for which thoughtful use of probe content can be utilized to better understand the biological processes affected. Bisulfite converted DNA from 4 buccal, 4 blood and 4 chorionic villus samples was hybridized to the Illumina Infinium HumanMethylation450 BeadChip array.
2013-03-04 | E-GEOD-42409 | biostudies-arrayexpress
Project description:In short: Genome wide promoter DNA methylation profiling of 43 T-ALL samples and 5 T-cell controls (normal bone marrow and stimulated T-cells) . The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Manuscript abstract: Background: Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided. Design and Methods: Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n=43) using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n= 32). Results: Based on CpG island methylator phenotype (CIMP), T-ALL samples were subgrouped as CIMP+ (high methylation) and CIMP- (low methylation). CIMP- T-ALL patients had significantly worse overall and event free survival (p=0.02 and p=0.001, respectively) compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes. Conclusions: We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL. Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
2013-07-01 | E-GEOD-42079 | biostudies-arrayexpress
Project description:HIV-positive patients have a higher risk of non-Hodgkin's lymphoma with poor prognostic features. To characterize features of HIV-associated lymphoma, we compared the genome-wide DNA methylation profiles in between 11 HIV-associated and 20 non-HIV lymphoma samples by Illumina Infinium HumanMethylation450 BeadChip v1.0. Bisulfite-converted DNA from the 31 samples were analyzed to obtain the genome-wide methylation profile by using Illumina Infinium HumanMethylation450 BeadChip microarray.
2014-01-30 | E-GEOD-42372 | biostudies-arrayexpress
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2013-07-01 | E-GEOD-42080 | biostudies-arrayexpress
Project description:To broaden our understanding of the gene expression common to volar skin, we biopsied the dorsum of the hand, palm, dorsum of the foot and sole and collected DNA for methylation chip anlayses Total of 12 skin biopsy samples with 3 repeats from distinct individuals of each site: dorsum of hand, palm, dorstum of foot and sole. The samples below represent methylation data only.
2013-07-03 | E-GEOD-39131 | biostudies-arrayexpress
Project description:Gene expression is regulated by genetic variants and DNA methylation with evidence from molecular biology studies, as well as expression QTL (eQTL) mapping and methylation QTL (mQTL) mapping. In this study, we explored the interaction between genetic variants and DNA methylation for its influence on gene expression. We analyzed a postmortem brain data and identified 2,768 SNP-methylation interaction (SMI) that can survive Bonferroni correction for the number of tests in cis- region of each gene. Seven SNP-methylation pairs were significant after Bonferroni correction for all the tests, including number of gene expression traits, we performed in this study. Only a small proportion of the SMI had evidence from the exact same SNP-transcript pair in eQTL mapping or SNP-methylation pair in mQTL mapping. This suggested that the interaction analysis could uncover novel regulatory relationships, which would be missed by eQTL or mQTL analyses. Since methylation per se is regulated by both genetic and environmental factors, analysis indicates that the SMI detected in this study may involve both genetic and environmental regulation. A total of 155 postmortem cerebellum brains were used in this study, including 47 bipolar disorder, 46 schizophrenia, 15 depression patients and 47 normal controls. All were of European Ancestry. We also designed 13 random replicates in our experiment. Illumina Infinium HumanMethylation27 BeadChip was used for DNA methylation profiling. The assay was performed at the Genomics Core Facility at Northwestern University.
2013-06-30 | E-GEOD-38873 | biostudies-arrayexpress
Project description:Preeclampsia is one of the leading causes of maternal death worldwide. While the root cause is still unknown, the underlying biology of the disorder is becoming more clear. We recently published a study showing large, significant differences in DNA methylation in 3rd trimester placental samples associated with early-onset preeclampsia (EOPET) compared to controls. In this study, to identify DNA methylation differences associated with preeclampsia that occur early in pregnancy and to further delineate common EOPET-associated differences, we utilized a genetic defect, trisomy 16 (T16), that is predisposing to preeclampsia. We ran T16 placental samples from the 1st trimester (n=5) and 3rd trimester (n=10) against gestational age matched controls on the Illumina Infinium HumanMethylation450 BeadChip. Third trimester samples were from pregnancies with T16 confined to the placenta (confined placental mosaicism 16;CPM16), and consisted of samples that were and were not associated with EOPET (n=5 each). We identified a large number of DNA methylation differences in CPM16 samples compared to controls using stringent criteria (n=2254;False Discovery Rate <0.01, ->0.15). Several of these differences (11%) overlapped differences observed in chromosomally normal EOPET using similarly stringent criteria (FDR<0.01;->0.125). Isolating EOPET-associated probes produced a similar - distribution amongst CPM16 samples, although samples associated with EOPET showed a tendency towards larger DNA methylation differences. We also identified 262 DNA methylation differences between 1st trimester T16 and 1st trimester controls. Of these, 77 overlapped differences seen in 3rd trimester CPM16. Investigating these 77 T16/CPM16 specific DNA methylation differences, we identified three probes near two genes (ARGHEF37 and JUNB) that were also present as EOPET-associated methylation differences. In summary, we identified significant overlapping DNA methylation profiles of placentas with T16 and chromosomally normal placentas associated with EOPET. Specific DNA methylation marks within these profiles may be of future clinical utility in early identification of pregnancies susceptible to EOPET. Bisulfite converted DNA from 5 1st trimester trisomy 16 placentas, 5 chromosomally normal 1st trimester placentas, 10 third trimester placentas from confined placental mosaicism placentas and 10 chromosomally normal 3rd trimester placentas
2014-01-15 | E-GEOD-49343 | biostudies-arrayexpress
Project description:The Muscleblind-like (Mbnl) family of RNA-binding proteins plays important roles in muscle and eye development and in Myotonic Dystrophy (DM), where expanded CUG or CCUG repeats functionally deplete Mbnl proteins. We identified transcriptome-wide functional and biophysical targets of Mbnl proteins in brain, heart, muscle, and myoblasts using RNA sequencing and crosslinking/immunoprecipitation-sequencing approaches. This analysis identified several hundred splicing events whose regulation depended on Mbnl function, in a pattern indicative of functional interchangeability between Mbnl1 and Mbnl2. A nucleotide resolution RNA map associated repression or activation of exon splicing with Mbnl binding near either 3' splice site or near the downstream 5' splice site, respectively. Transcriptomic analysis of sub-cellular compartments uncovered a global role for Mbnls in regulating localization of mRNAs encoding membrane, synaptic and other proteins in both mouse and Drosophila cells, and Mbnls also contribute to protein secretion. These findings hold several new implications for DM pathogenesis. To assess global functions of Muscleblind proteins, RNA-Seq was performed using WT and Mbnl1 KO brain, heart, and muscle (5 mice each). Additionally, C2C12 mouse myoblasts were depleted of Mbnl1, Mbnl2, or both. Subcellular fractionation experiments were performed to analyze mRNA localization following depletion of Mbnl1 and Mbnl2 in C2C12 mouse myoblasts, and following depletion of Mbnl in Drosophila S-2R+ cells. CLIP-Seq was also performed against Mbnl1 in mouse brain, heart, muscle, and C2C12 myoblasts. Finally, ribosome footprinting was performed with C2C12 mouse myoblasts that were depleted of Mbnl1, Mbnl2, or both.
2012-08-17 | E-GEOD-39911 | biostudies-arrayexpress
Project description:We investigated the DNA methylation and gene expression of 20 chorionic villi samples from early onset preeclampsia placentas to 20 gestational age matched controls. From this we were able to see a widespread disregulation in DNA methylation across a subset of genes in the genome. This may help to elucidate the underlying biological problems that lead to early onset preeclampsia. We noted that there were DNA methylation changes in many genes of importance as well as in different genomic elements such as enhancers. RNA from 8 Early Onset Preeclampsia placentas and 8 gestational age matched controls
2013-06-21 | E-GEOD-44711 | biostudies-arrayexpress