scholarly journals DNA Methylation and Asthma Acquisition During and Post-Adolescence, an Epigenome-Wide Longitudinal Study.

2021 ◽  
Author(s):  
Aniruddha Rathod ◽  
Hongmei Zhang ◽  
Hasan Arshad ◽  
Susan Ewart ◽  
Caroline Relton ◽  
...  
Keyword(s):  
Birth Cohort ◽  
Repeated Measures ◽  
Statistical Power ◽  
Transition Period ◽  
Disease Onset ◽  
Enrichment Analysis ◽  
Interaction Effects ◽  
Biological Assessment ◽  
Pathway Enrichment Analysis ◽  
Interaction Terms

Abstract Background- While the majority of asthma starts in early childhood, asthma onset in some individuals occurs during adolescence or in adulthood. However, the pathogenesis of later onset asthma as well as the observed sex specificity are not well understood. Objective- We hypothesized that DNAm at specific CpG sites measured before disease onset, either in pre- or post-adolescence would be associated with asthma acquisition both during adolescence and in later adulthood. Methods- Subjects from the Isle of Wight Birth Cohort (IOWBC) were included. DNAm in blood at ages 10 (pre-adolescence) and 18 (post-adolescence), and asthma acquisition from age 10-18, and 18-26 years was studied. To improve statistical power, we first screened epigenome-wide CpGs based on the association of DNAm at 10 years with asthma acquisition from 10-18 years. Logistic regression with repeated measures were then applied to the CpGs that survived screening to examine the associations of pre-adolescence DNAm with asthma acquisition from pre-to post-adolescence, and post-adolescence DNAm with asthma acquisition from post-adolescence to adulthood. The effect of DNAm on asthma acquisition at different transition period was evaluated using interaction terms. The ALSPAC birth cohort was used for independent replication. For biological assessment of identified CpGs, pathway enrichment analysis and Differentially Methylated Regions were assessed. Results- Significant interaction effects of DNAm and transition period (10-18 or 18-26 years) on asthma acquisition were found for 17 CpGs in males and 98 CpGs in females (FDR=0.05) in IOWBC. Consistent interaction effects were observed for 9 CpGs in males and 53 CpGs in females in ALSPAC. For CpGs not showing interaction effects (i.e., effect of DNAm is stable over time), association with asthma acquisition was found for 38 CpGs in males and 52 CpGs in females in IOWBC. Of these 90 CpGs, at 13 CpG in males and 37 CpG in females, consistent direction of associations was observed in ALSPAC. Genes that the identified CpGs were mapped to, e.g., AKAP1 and ENO1, have shown to be associated with asthma. Conclusion- DNAm at specific CpGs is associated with asthma acquisition and such association is likely to be sex and transition period specific.

scholarly journals Plasma Metabolic Profiling of Pediatric Sepsis in a Chinese Cohort

2021 ◽  
Vol 9 ◽  
Author(s):  
Guo-Bang Li ◽  
Hong-Rong Hu ◽  
Wen-Feng Pan ◽  
Bo Li ◽  
Zhi-Ying Ou ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Disease Onset ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Control Subjects ◽  
Sepsis Survivors ◽  
Pediatric Sepsis

Sepsis represents one of the most pressing problems in pediatrics, characterized by pathogenic bacteria invading the blood, growing and multiplying in the blood circulation, and ultimately causing severe infections. Most children with sepsis have a rapid disease onset and frequently exhibit sudden high fever or first chills. Here we performed comprehensive metabolomic profiling of plasma samples collected from pediatric sepsis patients to identify specific metabolic alterations associated with these patients (n = 84, designated as case subjects) as compared to healthy cohorts (n = 59, designated as control subjects). Diagnostic models were constructed using MetaboAnalyst, R packages, and multiple statistical methods, such as orthogonal partial least squares-discriminant analysis, principal component analysis, volcano plotting, and one-way ANOVA. Our study revealed a panel of metabolites responsible for the discrimination between case and control subjects with a high predictive value of prognosis. Moreover, significantly altered metabolites in sepsis survivors versus deceased patients (non-survivors) were identified as those involved in amino acids, fatty acids, and carbohydrates metabolism. Nine metabolites including organic acids and fatty acids were also identified with significantly higher abundance in sepsis patients with related microbes, implicating greater potentials to distinguish bacterial species using metabolomic analysis than blood culture. Pathway enrichment analysis further revealed that fatty acid metabolism might play an important role in the pathogenesis of sepsis.

scholarly journals netgsa: Fast computation and interactive visualization for topology-based pathway enrichment analysis

2021 ◽  
Vol 17 (6) ◽  
pp. e1008979
Author(s):  
Michael Hellstern ◽  
Jing Ma ◽  
Kun Yue ◽  
Ali Shojaie
Keyword(s):  
Statistical Power ◽  
Expert Knowledge ◽  
Interactive Visualization ◽  
Enrichment Analysis ◽  
Gene Interaction ◽  
Network Visualization ◽  
Pathway Enrichment Analysis ◽  
Computationally Efficient ◽  
Pathway Enrichment ◽  
User Friendly

Existing software tools for topology-based pathway enrichment analysis are either computationally inefficient, have undesirable statistical power, or require expert knowledge to leverage the methods’ capabilities. To address these limitations, we have overhauled NetGSA, an existing topology-based method, to provide a computationally-efficient user-friendly tool that offers interactive visualization. Pathway enrichment analysis for thousands of genes can be performed in minutes on a personal computer without sacrificing statistical power. The new software also removes the need for expert knowledge by directly curating gene-gene interaction information from multiple external databases. Lastly, by utilizing the capabilities of Cytoscape, the new software also offers interactive and intuitive network visualization.

Power of Modified Brown-Forsythe and Mixed-Model Approaches in Split-Plot Designs

Methodology ◽  
2017 ◽  
Vol 13 (1) ◽  
pp. 9-22 ◽  
Author(s):  
Pablo Livacic-Rojas ◽  
Guillermo Vallejo ◽  
Paula Fernández ◽  
Ellián Tuero-Herrero
Keyword(s):  
Repeated Measures ◽  
Statistical Power ◽  
Mixed Model ◽  
Covariance Structure ◽  
Simulation Method ◽  
Future Research ◽  
Repeated Measures Design ◽  
Fixed And Random Effects ◽  
Split Plot ◽  
High Level

Abstract. Low precision of the inferences of data analyzed with univariate or multivariate models of the Analysis of Variance (ANOVA) in repeated-measures design is associated to the absence of normality distribution of data, nonspherical covariance structures and free variation of the variance and covariance, the lack of knowledge of the error structure underlying the data, and the wrong choice of covariance structure from different selectors. In this study, levels of statistical power presented the Modified Brown Forsythe (MBF) and two procedures with the Mixed-Model Approaches (the Akaike’s Criterion, the Correctly Identified Model [CIM]) are compared. The data were analyzed using Monte Carlo simulation method with the statistical package SAS 9.2, a split-plot design, and considering six manipulated variables. The results show that the procedures exhibit high statistical power levels for within and interactional effects, and moderate and low levels for the between-groups effects under the different conditions analyzed. For the latter, only the Modified Brown Forsythe shows high level of power mainly for groups with 30 cases and Unstructured (UN) and Autoregressive Heterogeneity (ARH) matrices. For this reason, we recommend using this procedure since it exhibits higher levels of power for all effects and does not require a matrix type that underlies the structure of the data. Future research needs to be done in order to compare the power with corrected selectors using single-level and multilevel designs for fixed and random effects.

A Method of Pathway Enrichment Analysis Based Gene Expression Variability

2013 ◽  
Vol 40 (12) ◽  
pp. 1256
Author(s):  
XiaoDong JIA ◽  
XiuJie CHEN ◽  
Xin WU ◽  
JianKai XU ◽  
FuJian TAN ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Expression Variability ◽  
Pathway Enrichment

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

Determination of Usnic Acid Responsive miRNAs in Breast Cancer Cell Lines

2019 ◽  
Vol 19 (12) ◽  
pp. 1463-1472 ◽  
Author(s):  
Nil Kiliç ◽  
Yasemin Ö. Islakoğlu ◽  
İlker Büyük ◽  
Bala Gür-Dedeoğlu ◽  
Demet Cansaran-Duman
Keyword(s):  
Breast Cancer ◽  
Hedgehog Signaling ◽  
Treatment Options ◽  
Usnic Acid ◽  
Enrichment Analysis ◽  
Breast Cancer Cell Lines ◽  
Pathway Enrichment Analysis ◽  
Molecular Heterogeneity ◽  
Proliferative Effect ◽  
Mcf 7

Objective: Breast Cancer (BC) is the most common type of cancer diagnosed in women. A common treatment strategy for BC is still not available because of its molecular heterogeneity and resistance is developed in most of the patients through the course of treatment. Therefore, alternative medicine resources as being novel treatment options are needed to be used for the treatment of BC. Usnic Acid (UA) that is one of the secondary metabolites of lichens used for different purposes in the field of medicine and its anti-proliferative effect has been shown in certain cancer types, suggesting its potential use for the treatment. Methods: Anti-proliferative effect of UA in BC cells (MDA-MB-231, MCF-7, BT-474) was identified through MTT analysis. Microarray analysis was performed in cells treated with the effective concentration of UA and UA-responsive miRNAs were detected. Their targets and the pathways that they involve were determined using a miRNA target prediction tool. Results: Microarray experiments showed that 67 miRNAs were specifically responsive to UA in MDA-MB-231 cells while 15 and 8 were specific to BT-474 and MCF-7 cells, respectively. The miRNA targets were mostly found to play role in Hedgehog signaling pathway. TGF-Beta, MAPK and apoptosis pathways were also the prominent ones according to the miRNA enrichment analysis. Conclusion: The current study is important as being the first study in the literature which aimed to explore the UA related miRNAs, their targets and molecular pathways that may have roles in the BC. The results of pathway enrichment analysis and anti-proliferative effects of UA support the idea that UA might be used as a potential alternative therapeutic agent for BC treatment.

scholarly journals Daycare attendance and respiratory tract infections: a prospective birth cohort study

BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e014635 ◽  
Author(s):  
Linnea Schuez-Havupalo ◽  
Laura Toivonen ◽  
Sinikka Karppinen ◽  
Anne Kaljonen ◽  
Ville Peltola
Keyword(s):  
Cohort Study ◽  
Respiratory Tract ◽  
Birth Cohort ◽  
Day Care ◽  
Repeated Measures ◽  
Respiratory Tract Infections ◽  
Birth Cohort Study ◽  
Tract Infections ◽  
Prospective Birth Cohort ◽  
Prospective Birth Cohort Study

ObjectiveWe explored the burden of respiratory tract infections (RTIs) in young children with regard to day-care initiation.DesignLongitudinal prospective birth cohort study.Setting and methodsWe recruited 1827 children for follow-up until the age of 24 months collecting diary data on RTIs and daycare. Children with continuous daycare type and complete data were divided into groups of centre-based daycare (n=299), family day care (FDC) (n=245) and home care (n=350). Using repeated measures variance analyses, we analysed days per month with symptoms of respiratory tract infection, antibiotic treatments and parental absence from work for a period of 6 months prior to and 9 months after the start of daycare.ResultsWe documented a significant effect of time and type of daycare, as well as a significant interaction between them for all outcome measures. There was a rise in mean days with symptoms from 3.79 (95% CI 3.04 to 4.53) during the month preceding centre-based daycare to 10.57 (95% CI 9.35 to 11.79) at 2 months after the start of centre-based daycare, with a subsequent decrease within the following 9 months. Similar patterns with a rise and decline were observed in the use of antibiotics and parental absences. The start of FDC had weaker effects. Our findings were not changed when taking into account confounding factors.ConclusionsOur study shows the rapid increase in respiratory infections after start of daycare and a relatively fast decline in the course of time with continued daycare. It is important to support families around the beginning of daycare.

scholarly journals Signature RNAS and related regulatory roles in type 1 diabetes mellitus based on competing endogenous RNA regulatory network analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qinghong Shi ◽  
Hanxin Yao
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Network Analysis ◽  
Type 1 Diabetes Mellitus ◽  
Regulatory Network ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Competing Endogenous Rna ◽  
Pathway Enrichment

Abstract Background Our study aimed to investigate signature RNAs and their potential roles in type 1 diabetes mellitus (T1DM) using a competing endogenous RNA regulatory network analysis. Methods Expression profiles of GSE55100, deposited from peripheral blood mononuclear cells of 12 T1DM patients and 10 normal controls, were downloaded from the Gene Expression Omnibus to uncover differentially expressed long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs). The ceRNA regulatory network was constructed, then functional and pathway enrichment analysis was conducted. AT1DM-related ceRNA regulatory network was established based on the Human microRNA Disease Database to carry out pathway enrichment analysis. Meanwhile, the T1DM-related pathways were retrieved from the Comparative Toxicogenomics Database (CTD). Results In total, 847 mRNAs, 41 lncRNAs, and 38 miRNAs were significantly differentially expressed. The ceRNA regulatory network consisted of 12 lncRNAs, 10 miRNAs, and 24 mRNAs. Two miRNAs (hsa-miR-181a and hsa-miR-1275) were screened as T1DM-related miRNAs to build the T1DM-related ceRNA regulatory network, in which genes were considerably enriched in seven pathways. Moreover, three overlapping pathways, including the phosphatidylinositol signaling system (involving PIP4K2A, INPP4A, PIP4K2C, and CALM1); dopaminergic synapse (involving CALM1 and PPP2R5C); and the insulin signaling pathway (involving CBLB and CALM1) were revealed by comparing with T1DM-related pathways in the CTD, which involved four lncRNAs (LINC01278, TRG-AS1, MIAT, and GAS5-AS1). Conclusion The identified signature RNAs may serve as important regulators in the pathogenesis of T1DM.

scholarly journals Income disparity in school readiness and the mediating role of perinatal maternal mental health: a longitudinal birth cohort study

2021 ◽  
Vol 30 ◽  
Author(s):  
E. C. Law ◽  
R. Aishworiya ◽  
S. Cai ◽  
A.-A. Bouvette-Turcot ◽  
B. F. P. Broekman ◽  
...  
Keyword(s):  
Mental Health ◽  
School Readiness ◽  
Birth Cohort ◽  
Growth Curve ◽  
Household Income ◽  
Repeated Measures ◽  
Maternal Mental Health ◽  
Child Outcomes ◽  
Readiness Skills ◽  
Pregnant Mothers

Abstract Aims There is compelling evidence for gradient effects of household income on school readiness. Potential mechanisms are described, yet the growth curve trajectory of maternal mental health in a child's early life has not been thoroughly investigated. We aimed to examine the relationships between household incomes, maternal mental health trajectories from antenatal to the postnatal period, and school readiness. Methods Prospective data from 505 mother–child dyads in a birth cohort in Singapore were used, including household income, repeated measures of maternal mental health from pregnancy to 2-years postpartum, and a range of child behavioural, socio-emotional and cognitive outcomes from 2 to 6 years of age. Antenatal mental health and its trajectory were tested as mediators in the latent growth curve models. Results Household income was a robust predictor of antenatal maternal mental health and all child outcomes. Between children from the bottom and top household income quartiles, four dimensions of school readiness skills differed by a range of 0.52 (95% Cl: 0.23, 0.67) to 1.21 s.d. (95% CI: 1.02, 1.40). Thirty-eight percent of pregnant mothers in this cohort were found to have perinatal depressive and anxiety symptoms in the subclinical and clinical ranges. Poorer school readiness skills were found in children of these mothers when compared to those of mothers with little or no symptoms. After adjustment of unmeasured confounding on the indirect effect, antenatal maternal mental health provided a robust mediating path between household income and multiple school readiness outcomes (χ2 126.05, df 63, p < 0.001; RMSEA = 0.031, CFI = 0.980, SRMR = 0.034). Conclusions Pregnant mothers with mental health symptoms, particularly those from economically-challenged households, are potential targets for intervention to level the playing field of their children.

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