Characterization of DNA Methylation Associated Gene Regulatory Networks During Stomach Cancer Progression

DNA methylation plays a critical role in tumorigenesis through regulating oncogene activation and tumor suppressor gene silencing. Although extensively analyzed, the implication of DNA methylation in gene regulatory network is less characterized. To address this issue, in this study we performed an integrative analysis on the alteration of DNA methylation patterns and the dynamics of gene regulatory network topology across distinct stages of stomach cancer. We found the global DNA methylation patterns in different stages are generally conserved, whereas some significantly differentially methylated genes were exclusively observed in the early stage of stomach cancer. Integrative analysis of DNA methylation and network topology alteration yielded several genes which have been reported to be involved in the progression of stomach cancer, such as IGF2, ERBB2, GSTP1, MYH11, TMEM59, and SST. Finally, we demonstrated that inhibition of SST promotes cell proliferation, suggesting that DNA methylation-associated SST suppression possibly contributes to the gastric cancer progression. Taken together, our study suggests the DNA methylation-associated regulatory network analysis could be used for identifying cancer-related genes. This strategy can facilitate the understanding of gene regulatory network in cancer biology and provide a new insight into the study of DNA methylation at system level

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Peer reviewe

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.</p

Climatic Characteristics of Reference Evapotranspiration in the Hai River Basin and Their Attribution

Based on the meteorological data from 46 stations in the Hai River Basin (HRB) from 1961–2010, the annual and seasonal variation of reference evapotranspiration was analyzed. The sensitivity coefficients combined with the detrend method were used to discuss the dominant factor affecting the reference evapotranspiration (ETo). The obtained results indicate that the annual reference evapotranspiration is dominated by the decreasing trends at the confidence level of 95% in the southern and eastern parts of the HRB. The sensitivity order of climatic variables to ETo from strong to weak is: relativity humidity, temperature, shortwave radiation and wind speed, respectively. However, comprehensively considering the sensitivity and its variation strength, the detrend analysis indicates that the decreasing trends of ETo in eastern and southern HRB may be caused mainly by the decreasing wind speed and shortwave radiation. As for the relationship between human activity and the trend of ETo, we found that ETo decreased more significantly on the plains than in the mountains. By contrast, the population density increased more considerably from 2000 to 2010 on the plains than in the mountains. Therefore, in this paper, the correlation of the spatial variation pattern between ETo and population was further analyzed. The spatial correlation coefficient between population and the trend of ETo is −0.132, while the spatial correlation coefficient between the trend of ETo and elevation, temperature, shortwave radiation and wind speed is 0.667, 0.668, 0.749 and 0.416, respectively. This suggests that human activity has a certain influence on the spatial variation of ETo, while natural factors play a decisive role in the spatial variation of reference evapotranspiration in this area

A Forecasting Model Based on High-Order Fluctuation Trends and Information Entropy

Most existing high-order prediction models abstract logical rules that are based on historical discrete states without considering historical inconsistency and fluctuation trends. In fact, these two characteristics are important for describing historical fluctuations. This paper proposes a model based on logical rules abstracted from historical dynamic fluctuation trends and the corresponding inconsistencies. In the logical rule training stage, the dynamic trend states of up and down are mapped to the two dimensions of truth-membership and false-membership of neutrosophic sets, respectively. Meanwhile, information entropy is employed to quantify the inconsistency of a period of history, which is mapped to the indeterminercy-membership of the neutrosophic sets. In the forecasting stage, the similarities among the neutrosophic sets are employed to locate the most similar left side of the logical relationship. Therefore, the two characteristics of the fluctuation trends and inconsistency assist with the future forecasting. The proposed model extends existing high-order fuzzy logical relationships (FLRs) to neutrosophic logical relationships (NLRs). When compared with traditional discrete high-order FLRs, the proposed NLRs have higher generality and handle the problem caused by the lack of rules. The proposed method is then implemented to forecast Taiwan Stock Exchange Capitalization Weighted Stock Index and Heng Seng Index. The experimental conclusions indicate that the model has stable prediction ability for different data sets. Simultaneously, comparing the prediction error with other approaches also proves that the model has outstanding prediction accuracy and universality

Study on the Reservoir Heterogeneity of Different Volcanic Facies Based on Electrical Imaging Log in the Liaohe Eastern Sag

The volcanic rocks of the Es3 Formation (the third member of the Eocene Shahejie) in the Liaohe Eastern Sag can be divided into four facies and twelve subfacies. The porosity spectrum, porosity bin, variation coefficient (VC), and porosity width derived from electrical imaging log data were applied to study and characterize the heterogeneity of four facies and nine subfacies, both qualitatively and quantitatively. However, the VC and porosity width cannot be used to quantitatively classify heterogeneity when the VC is small and the porosity width is large. In the present study, the authors propose a new parameter, Pvcd = variation coefficient × porosity width. Based on this parameter, using a combination of porosity spectra, porosity bin features, VC, and porosity width, lithofacies heterogeneity is divided into three categories. The first is weak heterogeneity, which has a Pvcd vcd 1.1–1.6, a VC 0.15–0.25, and a porosity width 6–9. The third is strong heterogeneity, which has a Pvcd > 1.6, a porosity VC > 0.25, and a porosity width > 9. In these three cases, the porosity spectra mainly display unimodal features, the porosity bins are concentrated, the bimodal features with tails and porosity bins are less concentrated, or the multimodal features with tails and porosity bins are scattered, respectively. Favorable reservoirs of volcanic rocks are controlled by lithofacies. In the study area, the favorable reservoirs appear to be the diatreme subfacies with low or medium heterogeneity, the pyroclastic flow subfacies with low heterogeneity, the compound lava flow subfacies with low or medium heterogeneity, and the outer zone subfacies with strong heterogeneity