SurvivalMeth: a web server to investigate the effect of DNA methylation-related functional elements on prognosis

2020 ◽  
Author(s):  
Chunlong Zhang ◽  
Ning Zhao ◽  
Xue Zhang ◽  
Jun Xiao ◽  
Junyi Li ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Survival Analysis ◽  
Cpg Island ◽  
Automated Analysis ◽  
Clinical Analysis ◽  
Ctcf Binding ◽  
Detailed Result ◽  
Differential Analysis ◽  
Functional Elements ◽  
The Impact

Abstract Aberrant DNA methylation is a fundamental characterization of epigenetics for carcinogenesis. Abnormality of DNA methylation-related functional elements (DMFEs) may lead to dysfunction of regulatory genes in the progression of cancers, contributing to prognosis of many cancers. There is an urgent need to construct a tool to comprehensively assess the impact of DMFEs on prognosis. Therefore, we developed SurvivalMeth (http://bio-bigdata.hrbmu.edu.cn/survivalmeth) to explore the prognosis-related DMFEs, which documented many kinds of DMFEs, including 309,465 CpG island-related elements, 104,748 transcript-related elements, 77,634 repeat elements, as well as cell-type specific 1,689,653 super enhancers (SE) and 1,304,902 CTCF binding regions for analysis. SurvivalMeth is a convenient tool which collected DNA methylation profiles of 36 cancers and allowed users to query their genes of interest in different datasets for prognosis. Furthermore, SurvivalMeth not only integrated different combinations, including single DMFE, multiple DMFEs, SEs and clinical data, to perform survival analysis on preupload data but also allowed for uploading customized DNA methylation profile of DMFEs from various diseases to analyze. SurvivalMeth provided a comprehensive resource and automated analysis for prognostic DMFEs, including DMFE methylation level, correlation analysis, clinical analysis, differential analysis, DMFE annotation, survival-related detailed result and visualization of survival analysis. In summary, we believe that SurvivalMeth will facilitate prognostic research of DMFEs in diverse cancers.

Stage-differentiated modelling of DNA methylation landscapes uncovers salient biomarkers and prognostic signatures in colorectal cancer progression

2021 ◽  
Author(s):  
Sangeetha Muthamilselvan ◽  
Abirami Raghavendran ◽  
Ashok Palaniappan
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cpg Island ◽  
Early Stage ◽  
P Value ◽  
Consensus Analysis ◽  
One Stage ◽  
Differentially Methylated Genes ◽  
Methylation Patterns ◽  
The Impact

Abstract Background: Aberrant DNA methylation acts epigenetically to skew the gene transcription rate up or down, with causative roles in the etiology of cancers. However research on the role of DNA methylation in driving the progression of cancers is limited. In this study, we have developed a comprehensive computational framework for the stage-differentiated modelling of DNA methylation landscapes in colorectal cancer (CRC), and unravelled significant stagewise signposts of CRC progression. Methods: The methylation β - matrix was derived from the public-domain TCGA data, converted into M-value matrix, annotated with AJCC stages, and analysed for stage-salient genes using multiple approaches involving stage-differentiated linear modelling of methylation patterns and/or expression patterns. Differentially methylated genes (DMGs) were identified using a contrast against controls (adjusted p-value <0.001 and |log fold-change of M-value| >2). These results were filtered using a series of all possible pairwise stage contrasts (p-value <0.05) to obtain stage-salient DMGs. These were then subjected to a consensus analysis, followed by Kaplan–Meier survival analysis to evaluate the impact of methylation patterns of consensus stage-salient biomarkers on disease prognosis.Results: We found significant genome-wide changes in methylation patterns in cancer cases relative to controls agnostic of stage. Our stage-differentiated analysis yielded the following stage-salient genes: one stage-I gene (FBN1), one stage-II gene (FOXG1), one stage-III gene (HCN1) and four stage-IV genes (NELL1, ZNF135, FAM123A, LAMA1). All the biomarkers were hypermethylated, indicating down-regulation and signifying a CpG island Methylator Phenotype (CIMP) manifestation. A significant prognostic signature consisting of FBN1 and FOXG1 survived all the steps of our analysis pipeline, and represents a novel early-stage biomarker. Conclusions: We have designed a workflow for stage-differentiated consensus analysis, and identified stage-salient diagnostic biomarkers and an early-stage prognostic biomarker panel. Our studies further yield a novel CIMP-like signature of potential clinical import underlying CRC progression.

scholarly journals SUN-715 IIM May Influence Matured Oocytes’ DNA Methylation of PCOS Patients

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Congru Li ◽  
Yang Yu
Keyword(s):  
Dna Methylation ◽  
In Vitro Fertilization ◽  
Embryonic Development ◽  
Embryo Transfer ◽  
Cpg Island ◽  
Reproductive Technologies ◽  
Childbearing Age ◽  
Vitro Fertilization ◽  
The Impact

Abstract Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age and is the main cause of anovulatory infertility. To increase the number of oocytes obtained, controlled ovarian stimulation (COS) has become a routine choice for in vitro fertilization-embryo transfer (IVF-ET), which is one of the common assisted reproductive technologies for PCOS patients. However, for these patients, there is a high risk of ovarian hyperstimulation syndrome (OHSS). Obtaining in vitro maturation (IVM) of immature oocytes, and then in vitro fertilization and embryo transfer of mature oocytes provides a possible way for people to solve the above problems. Since the IVM technology will expose oocytes to in vitro conditions for a longer period of time, theoretically increasing the risk of the oocytes being affected by the culture environment, further research and explorations are needed for study in gene programming, epigenetics, etc. Therefore, to explore the impact of IVM operation on embryonic development is of great significance for further clarifying assisted reproductive safety and improving IVM operation conditions. Here we focused on DNA methylation reprogramming process which was essential for embryonic development. We tested the DNA methylation of sperm, IVM oocytes and IVM generated early stage embryos including pronucleus, 4cell, 8cell, morula, inner cell mass, trophoectoderm (TE) as well as six-week embryos by Nimble Gen Human DNA Methylation 3x729K CpG Island Plus RefSeq Promoter Array and compared the data with our published genome-wide DNA methylomes of human gametes and early embryos generated from in vivo maturation oocytes. We showed that IVM embryos show abnormal DNA methylation reprogramming pattern. By analyzing the abnormally reprogrammed promoters, we further found that IVM may affect the functions of demethylation related genes. Oocytes from IVM manipulation were tested with higher DNA methylation levels, and their abnormal methylated promoters mainly enriched in immune and metabolism pathways. Furthermore, we investigated the DNA methylation of TE, which was directly related with implantation process and revealed the abnormal methylated promoters were related with metabolism pathway too. Our data support that IVM may influence the DNA methylome of oocytes, which in turn affects the methylome of their embryos. However, due to the limited number of samples and the inability of the chip to cover all CpG sites, the results of this study require further research and validation.

scholarly journals Epigenome-450K-wide methylation signatures of active cigarette smoking: The Young Finns Study

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Pashupati P. Mishra ◽  
Ismo Hänninen ◽  
Emma Raitoharju ◽  
Saara Marttila ◽  
Binisha H. Mishra ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Olfactory Receptor ◽  
Cpg Island ◽  
Receptor Activity ◽  
Gene Set Analysis ◽  
Gene Set ◽  
Cpg Sites ◽  
Gene Sets ◽  
The Impact ◽  
Young Finns Study

Abstract Smoking as a major risk factor for morbidity affects numerous regulatory systems of the human body including DNA methylation. Most of the previous studies with genome-wide methylation data are based on conventional association analysis and earliest threshold-based gene set analysis that lacks sensitivity to be able to reveal all the relevant effects of smoking. The aim of the present study was to investigate the impact of active smoking on DNA methylation at three biological levels: 5′-C-phosphate-G-3′ (CpG) sites, genes and functionally related genes (gene sets). Gene set analysis was done with mGSZ, a modern threshold-free method previously developed by us that utilizes all the genes in the experiment and their differential methylation scores. Application of such method in DNA methylation study is novel. Epigenome-wide methylation levels were profiled from Young Finns Study (YFS) participants’ whole blood from 2011 follow-up using Illumina Infinium HumanMethylation450 BeadChips. We identified three novel smoking related CpG sites and replicated 57 of the previously identified ones. We found that smoking is associated with hypomethylation in shore (genomic regions 0–2 kilobases from CpG island). We identified smoking related methylation changes in 13 gene sets with false discovery rate (FDR) ≤ 0.05, among which is olfactory receptor activity, the flagship novel finding of the present study. Overall, we extended the current knowledge by identifying: (i) three novel smoking related CpG sites, (ii) similar effects as aging on average methylation in shore, and (iii) a novel finding that olfactory receptor activity pathway responds to tobacco smoke and toxin exposure through epigenetic mechanisms.

scholarly journals A Long Polymorphic GT Microsatellite within a Gene Promoter Mediates Non-Imprinted Allele-Specific DNA Methylation of a CpG Island in a Goldfish Inter-Strain Hybrid

2019 ◽  
Vol 20 (16) ◽  
pp. 3923
Author(s):  
Zheng ◽  
Xu ◽  
Cao
Keyword(s):  
Dna Methylation ◽  
Cpg Island ◽  
Methylation Status ◽  
Repetitive Sequences ◽  
Gene Promoter ◽  
Dna Polymorphisms ◽  
Specific Expression ◽  
Cis Acting ◽  
Allele Specific ◽  
The Impact

It is now widely accepted that allele-specific DNA methylation (ASM) commonly occurs at non-imprinted loci. Most of the non-imprinted ASM regions observed both within and outside of the CpG island show a strong correlation with DNA polymorphisms. However, what polymorphic cis-acting elements mediate non-imprinted ASM of the CpG island remains unclear. In this study, we investigated the impact of polymorphic GT microsatellites within the gene promoter on non-imprinted ASM of the local CpG island in goldfish. We generated various goldfish heterozygotes, in which the length of GT microsatellites or some non-repetitive sequences in the promoter of no tail alleles was different. By examining the methylation status of the downstream CpG island in these heterozygotes, we found that polymorphisms of a long GT microsatellite can lead to the ASM of the downstream CpG island during oogenesis and embryogenesis, polymorphisms of short GT microsatellites and non-repetitive sequences in the promoter exhibited no significant effect on the methylation of the CpG island. We also observed that the ASM of the CpG island was associated with allele-specific expression in heterozygous embryos. These results suggest that a long polymorphic GT microsatellite within a gene promoter mediates non-imprinted ASM of the local CpG island in a goldfish inter-strain hybrid.

Epigenetic Studies in Psychotherapy: A Systematic Review

2020 ◽  
Vol 16 (2) ◽  
pp. 86-92
Author(s):  
Rafael Penadés ◽  
Bárbara Arias ◽  
Mar Fatjó-Vilas ◽  
Laura González-Vallespí ◽  
Clemente García-Rizo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Dna Methylation ◽  
Mental Disorders ◽  
Epigenetic Modifications ◽  
Symptom Improvement ◽  
Epigenetic Changes ◽  
Main Hypothesis ◽  
Psychological Treatments ◽  
Time Period ◽  
The Impact

Background: Epigenetic modifications appear to be dynamic and they might be affected by environmental factors. The possibility of influencing these processes through psychotherapy has been suggested. Objective: To analyse the impact of psychotherapy on epigenetics when applied to mental disorders. The main hypothesis is that psychological treatments will produce epigenetic modifications related to the improvement of treated symptoms. Methods: A computerised and systematic search was completed throughout the time period from 1990 to 2019 on the PubMed, ScienceDirect and Scopus databases. Results: In total, 11 studies were selected. The studies were evaluated for the theoretical framework, genes involved, type of psychotherapy and clinical challenges and perspectives. All studies showed detectable changes at the epigenetic level, like DNA methylation changes, associated with symptom improvement after psychotherapy. Conclusion: Methylation profiles could be moderating treatment effects of psychotherapy. Beyond the detected epigenetic changes after psychotherapy, the epigenetic status before the implementation could act as an effective predictor of response.

Maternal anxiety and depression in pregnancy and DNA methylation of the NR3C1 glucocorticoid receptor gene

Epigenomics ◽  
2020 ◽  
Author(s):  
Alexandra E Dereix ◽  
Rachel Ledyard ◽  
Allyson M Redhunt ◽  
Tessa R Bloomquist ◽  
Kasey JM Brennan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Depressive Symptoms ◽  
Trait Anxiety ◽  
Cpg Island ◽  
Depression Scale ◽  
Maternal Anxiety ◽  
Anxiety And Depression ◽  
Pregnancy Anxiety ◽  
Glucocorticoid Receptor Gene ◽  
Island Shore

Aim: To quantify associations of anxiety and depression during pregnancy with differential cord blood DNA methylation of the glucorticoid receptor ( NR3C1). Materials & methods: Pregnancy anxiety, trait anxiety and depressive symptoms were collected using the Pregnancy Related Anxiety Scale, State-Trait Anxiety Index and Edinburgh Postnatal Depression Scale, respectively. NR3C1 methylation was determined at four methylation sites. Results: DNA methylation of CpG 1 in the NR3C1 CpG island shore was higher in infants born to women with high pregnancy anxiety (β 2.54, 95% CI: 0.49–4.58) and trait anxiety (β 1.68, 95% CI: 0.14–3.22). No significant association was found between depressive symptoms and NR3C1 methylation. Conclusion: We found that maternal anxiety was associated with increased NR3C1 CpG island shore methylation.

scholarly journals Integrated analysis of DNA methylation profile in HLA-G gene and imaging in coronary heart disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Benincasa ◽  
C Schiano ◽  
T Infante ◽  
M Franzese ◽  
R Casale ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cpg Island ◽  
Methylation Profile ◽  
Integrated Analysis ◽  
Funding Source ◽  
Relevant Parameter ◽  
Cardiac Computed Tomography Angiography ◽  
Dna Methylation Profile

Abstract Aims Immune endothelial inflammation, underlie coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. Methods Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score=0, uninjured coronaries and with no obstructive CHD were considered as control subjects (Ctrls) (n=18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. Results For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p=0.05) of HLA-G gene in CHD patients compared to Ctrl group; 2) hypomethylation level of one specific fragment positively correlated with coronary Ca score, a relevant parameter of CCTA (p&lt;0.05) between two groups. Conclusions Our results showed that reduced levels of circulating HLA-G molecules could derive from epigenetic marks inducing hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive coronary stenosis vs non critical stenosis group. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Minister of Health

scholarly journals Clinicopathological features of Egyptian colorectal cancer patients regarding somatic genetic mutations especially in KRAS gene and microsatellite instability status: a pilot study

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Neemat M. Kassem ◽  
Gamal Emera ◽  
Hebatallah A. Kassem ◽  
Nashwa Medhat ◽  
Basant Nagdy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cpg Island ◽  
Human Cancer ◽  
Statistical Significance ◽  
Public Health Problem ◽  
World Health ◽  
Cpg Island Methylator Phenotype ◽  
Number Of Patients ◽  
The Impact

Abstract Background Colorectal cancer (CRC) is the third most common cause of cancer-related deaths which contributes to a significant public health problem worldwide with 1.8 million new cases and almost 861,000 deaths in 2018 according to the World Health Organization. It exhibits 7.4% of all diagnosed cancer cases in the region of the Middle East and North Africa. Molecular changes that happen in CRCs are chromosomal instability, microsatellite instability (MSI), and CpG island methylator phenotype. The human RAS family (KRAS, NRAS, and HRAS) is the most frequently mutated oncogenes in human cancer appearing in 45% of colon cancers. Determining MSI status across CRCs offers the opportunity to identify patients who are likely to respond to targeted therapies such as anti-PD-1. Therefore, a method to efficiently determine MSI status for every cancer patient is needed. Results KRAS mutations were detected in 31.6% of CRC patients, namely in older patients (p = 0.003). Codons 12 and 13 constituted 5/6 (83.3%) and 1/6 (16.7%) of all KRAS mutations, respectively. We found three mutations G12D, G12C, and G13D which occur as a result of substitution at c.35G>A, c.34G>T, and c.38G>A and have been detected in 4/6 (66.6%), 1/6 (16.7%), and 1/6 (16.7%) patients, respectively. Eleven (57.9%) patients had microsatellite instability-high (MSI-H) CRC. A higher percentage of MSI-H CRC was detected in female patients (p = 0.048). Eight patients had both MSI-H CRC and wild KRAS mutation with no statistical significance was found between MSI status and KRAS mutation in these studied patients. Conclusion In conclusion, considering that KRAS mutations confer resistance to EGFR inhibitors, patients who have CRC with KRAS mutation could receive more tailored management by defining MSI status. MSI-high patients have enhanced responsiveness to anti-PD-1 therapies. Thus, the question arises as to whether it is worth investigating this association in the routine clinical setting or not. Further studies with a larger number of patients are needed to assess the impact of MSI status on Egyptian CRC care.

scholarly journals The impact of socio-demographic factors on the survival of cancer patients in Zimbabwe

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Idika E. Okorie ◽  
Ricardo Moyo ◽  
Saralees Nadarajah
Keyword(s):  
Risk Factors ◽  
Survival Analysis ◽  
Marital Status ◽  
Cancer Patients ◽  
Hazard Rate ◽  
Significant Risk ◽  
Demographic Factors ◽  
Female Cancer Patients ◽  
Socio Demographic Factors ◽  
The Impact

AbstractWe provide a survival analysis of cancer patients in Zimbabwe. Our results show that young cancer patients have lower but not significant hazard rate compared to old cancer patients. Male cancer patients have lower but not significant hazard rate compared to female cancer patients. Race and marital status are significant risk factors for cancer patients in Zimbabwe.

scholarly journals Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3580
Author(s):  
Shatavisha Dasgupta ◽  
Patricia C. Ewing-Graham ◽  
Sigrid M. A. Swagemakers ◽  
Thierry P. P. van den Bosch ◽  
Peggy N. Atmodimedjo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Dna Sequences ◽  
Cpg Island ◽  
Epigenetic Modification ◽  
Vulvar Squamous Cell Carcinoma ◽  
Differentially Methylated Genes ◽  
Methylation Profiling

DNA methylation is the most widely studied mechanism of epigenetic modification, which can influence gene expression without alterations in DNA sequences. Aberrations in DNA methylation are known to play a role in carcinogenesis, and methylation profiling has enabled the identification of biomarkers of potential clinical interest for several cancers. For vulvar squamous cell carcinoma (VSCC), however, methylation profiling remains an under-studied area. We sought to identify differentially methylated genes (DMGs) in VSCC, by performing Infinium MethylationEPIC BeadChip (Illumina) array sequencing, on a set of primary VSCC (n = 18), and normal vulvar tissue from women with no history of vulvar (pre)malignancies (n = 6). Using a false-discovery rate of 0.05, beta-difference (Δβ) of ± 0.5, and CpG-island probes as cut-offs, 199 DMGs (195 hyper-methylated, 4 hypo-methylated) were identified for VSCC. Most of the hyper-methylated genes were found to be involved in transcription regulator activity, indicating that disruption of this process plays a vital role in VSCC development. The majority of VSCCs harbored amplifications of chromosomes 3, 8, and 9. We identified a set of DMGs in this exploratory, hypothesis-generating study, which we hope will facilitate epigenetic profiling of VSCCs. Prognostic relevance of these DMGs deserves further exploration in larger cohorts of VSCC and its precursor lesions.

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