scholarly journals SMCKAT, a Sequential Multi-Dimensional CNV Kernel-Based Association Test

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1302
Author(s):  
Nastaran Maus Esfahani ◽  
Daniel Catchpoole ◽  
Paul J. Kennedy
Keyword(s):  
Random Effect ◽  
Random Effect Model ◽  
Copy Number Variants ◽  
Association Test ◽  
Biomedical Literature ◽  
Data Sets ◽  
Whole Genome ◽  
Sequential Order ◽  
Single Chromosome ◽  
Biologically Relevant

Copy number variants (CNVs) are the most common form of structural genetic variation, reflecting the gain or loss of DNA segments compared with a reference genome. Studies have identified CNV association with different diseases. However, the association between the sequential order of CNVs and disease-related traits has not been studied, to our knowledge, and it is still unclear that CNVs function individually or whether they work in coordination with other CNVs to manifest a disease or trait. Consequently, we propose the first such method to test the association between the sequential order of CNVs and diseases. Our sequential multi-dimensional CNV kernel-based association test (SMCKAT) consists of three parts: (1) a single CNV group kernel measuring the similarity between two groups of CNVs; (2) a whole genome group kernel that aggregates several single group kernels to summarize the similarity between CNV groups in a single chromosome or the whole genome; and (3) an association test between the CNV sequential order and disease-related traits using a random effect model. We evaluate SMCKAT on CNV data sets exhibiting rare or common CNVs, demonstrating that it can detect specific biologically relevant chromosomal regions supported by the biomedical literature. We compare the performance of SMCKAT with MCKAT, a multi-dimensional kernel association test. Based on the results, SMCKAT can detect more specific chromosomal regions compared with MCKAT that not only have CNV characteristics, but the CNV order on them are significantly associated with the disease-related trait.

scholarly journals MCKAT: a multi-dimensional copy number variant kernel association test

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nastaran Maus Esfahani ◽  
Daniel Catchpoole ◽  
Javed Khan ◽  
Paul J. Kennedy
Keyword(s):  
Copy Number ◽  
Kernel Method ◽  
Random Effect ◽  
Random Effect Model ◽  
Score Test ◽  
Copy Number Variants ◽  
Copy Number Variant ◽  
Association Test ◽  
Single Pair ◽  
Related Trait

Abstract Background Copy number variants (CNVs) are the gain or loss of DNA segments in the genome. Studies have shown that CNVs are linked to various disorders, including autism, intellectual disability, and schizophrenia. Consequently, the interest in studying a possible association of CNVs to specific disease traits is growing. However, due to the specific multi-dimensional characteristics of the CNVs, methods for testing the association between CNVs and the disease-related traits are still underdeveloped. We propose a novel multi-dimensional CNV kernel association test (MCKAT) in this paper. We aim to find significant associations between CNVs and disease-related traits using kernel-based methods. Results We address the multi-dimensionality in CNV characteristics. We first design a single pair CNV kernel, which contains three sub-kernels to summarize the similarity between two CNVs considering all CNV characteristics. Then, aggregate single pair CNV kernel to the whole chromosome CNV kernel, which summarizes the similarity between CNVs in two or more chromosomes. Finally, the association between the CNVs and disease-related traits is evaluated by comparing the similarity in the trait with kernel-based similarity using a score test in a random effect model. We apply MCKAT on genome-wide CNV datasets to examine the association between CNVs and disease-related traits, which demonstrates the potential usefulness the proposed method has for the CNV association tests. We compare the performance of MCKAT with CKAT, a uni-dimensional kernel method. Based on the results, MCKAT indicates stronger evidence, smaller p-value, in detecting significant associations between CNVs and disease-related traits in both rare and common CNV datasets. Conclusion A multi-dimensional copy number variant kernel association test can detect statistically significant associated CNV regions with any disease-related trait. MCKAT can provide biologists with CNV hot spots at the cytogenetic band level that CNVs on them may have a significant association with disease-related traits. Using MCKAT, biologists can narrow their investigation from the whole genome, including many genes and CNVs, to more specific cytogenetic bands that MCKAT identifies. Furthermore, MCKAT can help biologists detect significantly associated CNVs with disease-related traits across a patient group instead of examining each subject’s CNVs case by case.

scholarly journals MCKAT, a multi-dimensional copy number variant kernel association test

2021 ◽  
Author(s):  
Nastaran Maus Esfahani ◽  
Daniel Catchpoole ◽  
Javed Khan ◽  
Paul J. Kennedy
Keyword(s):  
Copy Number ◽  
Kernel Method ◽  
Random Effect ◽  
Random Effect Model ◽  
Score Test ◽  
Copy Number Variant ◽  
Association Test ◽  
P Value ◽  
Single Pair ◽  
Related Trait

AbstractBackgroundCopy number variants (CNVs) are the gain or loss of DNA segments in the genome. Studies have shown that CNVs are linked to various disorders, including autism, intellectual disability, and schizophrenia.Consequently, the interest in studying a possible association of CNVs to specific disease traits is growing. However, due to the specific multi-dimensional characteristics of the CNVs, methods for testing the association between CNVs and the disease-related traits are still underdeveloped. We propose a novel multi-dimensional CNV kernel association test (MCKAT) in this paper. We aim to find significant associations between CNVs and disease-related traits using kernel-based methods.ResultsWe address the multi-dimensionality in CNV characteristics. We first design a single pair CNV kernel, which contains three sub-kernels to summarize the similarity between two CNVs considering all CNV characteristics. Then, aggregate single pair CNV kernel to the whole chromosome CNV kernel, which summarizes the similarity between CNVs in two or more chromosomes. Finally, the association between the CNVs and disease-related traits is evaluated by comparing the similarity in the trait with kernel-based similarity using a score test in a random effect model. We apply MCKAT on genome-wide CNV datasets to examine the association between CNVs and disease-related traits, which demonstrates the potential usefulness the proposed method has for the CNV association tests. We compare the performance of MCKAT with CKAT, a uni-dimensional kernel method. Based on the results, MCKAT indicates stronger evidence, smaller p-value, in detecting significant associations between CNVs and disease-related traits in both rare and common CNV datasets.ConclusionA multi-dimensional copy number variant kernel association test can detect significantly associated CNVs with any disease-related trait. MCKAT can help biologists detect significantly associated CNVs with any disease-related trait across a patient group instead of examining the CNVs case by case in each subject.

scholarly journals Looking for a Signal in the Noise: Revisiting Obesity and the Microbiome

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Marc A. Sze ◽  
Patrick D. Schloss
Keyword(s):  
Random Effect ◽  
Random Effect Model ◽  
Human Microbiome ◽  
Alpha Diversity ◽  
Published Data ◽  
Human Populations ◽  
Data Sets ◽  
Data Set ◽  
Shannon Diversity ◽  
Obesity Status

ABSTRACT Two recent studies have reanalyzed previously published data and found that when data sets were analyzed independently, there was limited support for the widely accepted hypothesis that changes in the microbiome are associated with obesity. This hypothesis was reconsidered by increasing the number of data sets and pooling the results across the individual data sets. The preferred reporting items for systematic reviews and meta-analyses guidelines were used to identify 10 studies for an updated and more synthetic analysis. Alpha diversity metrics and the relative risk of obesity based on those metrics were used to identify a limited number of significant associations with obesity; however, when the results of the studies were pooled by using a random-effect model, significant associations were observed among Shannon diversity, the number of observed operational taxonomic units, Shannon evenness, and obesity status. They were not observed for the ratio of Bacteroidetes and Firmicutes or their individual relative abundances. Although these tests yielded small P  values, the difference between the Shannon diversity indices of nonobese and obese individuals was 2.07%. A power analysis demonstrated that only one of the studies had sufficient power to detect a 5% difference in diversity. When random forest machine learning models were trained on one data set and then tested by using the other nine data sets, the median accuracy varied between 33.01 and 64.77% (median, 56.68%). Although there was support for a relationship between the microbial communities found in human feces and obesity status, this association was relatively weak and its detection is confounded by large interpersonal variation and insufficient sample sizes. IMPORTANCE As interest in the human microbiome grows, there is an increasing number of studies that can be used to test numerous hypotheses across human populations. The hypothesis that variation in the gut microbiota can explain or be used to predict obesity status has received considerable attention and is frequently mentioned as an example of the role of the microbiome in human health. Here we assessed this hypothesis by using 10 independent studies and found that although there is an association, it is smaller than can be detected by most microbiome studies. Furthermore, we directly tested the ability to predict obesity status on the basis of the composition of an individual’s microbiome and found that the median classification accuracy is between 33.01 and 64.77%. This type of analysis can be used to design future studies and expanded to explore other hypotheses.

Association of FK506 binding protein 5 (FKBP5) gene rs4713916 polymorphism with mood disorders: a meta-analysis

2011 ◽  
Vol 23 (1) ◽  
pp. 12-19 ◽  
Author(s):  
Xiao-Liang Feng ◽  
Fang Wang ◽  
Yan-Feng Zou ◽  
Wen-Fei Li ◽  
Yang-Hua Tian ◽  
...  
Keyword(s):  
Mood Disorders ◽  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Biomedical Literature ◽  
Cochrane Library ◽  
China National Knowledge Infrastructure ◽  
Fk506 Binding Protein ◽  
Effect Model

Background: Several studies have investigated the association of FKBP5 gene polymorphisms with mood disorders, but findings are not always consistent. The aim of our study was to assess the association of FKBP5 gene polymorphisms with mood disorders using a meta-analysis.Methods: Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure and Wanfang, with the last report up to March 2010. Meta-analysis was performed in a fixed/random effect model.Results: We identified six studies using search, and one study was excluded because of unavailable data. One study contained data on two different ethnicities and we treated them independently. Thus, six separate studies (2655 cases and 3593 controls) were included in the meta-analysis. Meta-analysis was performed for three FKBP5 gene polymorphisms (rs1360780, rs3800373 and rs4713916) in overall and Caucasian populations. We did not detect any association of FKBP5 gene rs1360780 and rs3800373 polymorphisms with mood disorders (p > 0.05). However, a significant association of FKBP5 gene rs4713916 polymorphism with mood disorders was found, and the heterozygous individual (GA genotype) was more susceptible to mood disorders in comparison to homozygous analogues (GG or AA genotype) [overall: GA vs. GG: OR (odds ratio) = 1.20, 95% CI (confidence interval) = 1.03–1.40, p = 0.02; GA vs. AA: OR = 1.44, 95% CI = 1.09–1.90, p = 0.009; Caucasian: GA vs. GG: OR = 1.22, 95% CI = 1.04–1.44, p = 0.01; GA vs. AA: OR = 1.43, 95% CI = 1.09–1.89, p = 0.01].Conclusion: This meta-analysis shows that mood disorders are associated with FKBP5 gene rs4713916 polymorphism, but not with rs1360780 and rs3800373.

Acupuncture and Lifestyle Modification Treatment for Obesity: A Meta-Analysis

2017 ◽  
Vol 45 (02) ◽  
pp. 239-254 ◽  
Author(s):  
Sijia Fang ◽  
Miao Wang ◽  
Yiyuan Zheng ◽  
Shigao Zhou ◽  
Guang Ji
Keyword(s):  
Confidence Interval ◽  
Weight Control ◽  
Lifestyle Modification ◽  
Health Hazard ◽  
Random Effect ◽  
Random Effect Model ◽  
Biomedical Literature ◽  
Placebo Control ◽  
Lifestyle Interventions ◽  
Control Groups

Obesity is an epidemic health hazard associated with many medical conditions. Lifestyle interventions are foundational to the successful management of obesity. However, the body’s adaptive biological responses counteract patients’ desire to restrict food and energy intake, leading to weight regain. As a complementary and alternative medical approach, acupuncture therapy is widely used for weight control. The objective of this study was to assess the efficacy of acupuncture treatment alone and in combination with lifestyle modification. We searched the MEDLINE, EMBASE, CENTRAL and Chinese Biomedical Literature Databases for relevant publications available as of 24 October 2015 without language restriction. Eligible studies consisted of randomized controlled trials for acupuncture with comparative controls. A total of 23 studies were included with 1808 individuals. We performed meta-analyses of weighted mean differences based on a random effect model. Acupuncture exhibited a mean difference of body mass index reduction of 1.742[Formula: see text]kg/m2 (95% confidence interval [Formula: see text]) and 1.904[Formula: see text]kg/m2 (95% confidence interval [Formula: see text]) when compared with untreated or placebo control groups and when lifestyle interventions including basic therapy of both treatment and control groups. Adverse events reported were mild, and no patients withdrew because of adverse effects. Overall, our results indicate that acupuncture is an effective treatment for obesity both alone and together with lifestyle modification.

Qualitative Research on Critical Issues In Halal Logistics

2013 ◽  
Vol 1 (2) ◽  
pp. 131 ◽  
Author(s):  
Mohamed Syazwan Ab Talib ◽  
Lim Rubin ◽  
Vincent Khor Zhengyi
Keyword(s):  
Capital Structure ◽  
Agency Theory ◽  
Random Effect ◽  
Random Effect Model ◽  
Order Theory ◽  
Specific Factor ◽  
Pecking Order ◽  
Pecking Order Theory ◽  
Corporate Financing ◽  
Financing Decision

This is a preliminary study developed to explore the determinants of capital structure of Shariah-compliant firms listed in Bursa Malaysia. This study is primarily motivated by the issue of the determinants still being inconclusive in the area of capital structure. The study is performed using the static models namely Pool Ordinary Least Square, Fixed Effect and Random Effect Model. Empirical analysis on the determinants reveals that country specific factor which is GDP and sector specific factor which is industry concentration are also significant in influencing the corporate financing decisions in this country along with firm specific factors such as efficiency, bankruptcy risk, profitability, tangibility, liquidity and size of the firm. The findings revealed that results are sensitive to models employed in the study. Nevertheless, the applicability of capital structure theories such as the trade-off theory, agency theory and pecking order theory diverge across sectors in Malaysia. The pecking order theory and agency theory are found to be the dominant theories governing the corporate financing decision in the country as well. It indicates strong evidence of hierarchy practised in firms’ financing decision. The finding on agency theory being dominant justifies the function of short-term debt as a controlling mechanism to mitigate the agency problem arises within firms across sectors. 

0306 Exploring the feasibility of using copy number variants as genetic markers through large-scale whole genome sequencing experiments

2016 ◽  
Vol 94 (suppl_5) ◽  
pp. 146-146
Author(s):  
D. M. Bickhart ◽  
L. Xu ◽  
J. L. Hutchison ◽  
J. B. Cole ◽  
D. J. Null ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genetic Markers ◽  
Genome Sequencing ◽  
Copy Number ◽  
Large Scale ◽  
Copy Number Variants ◽  
Whole Genome

Analisis Pengaruh Kepemilikan Blockholder, Kepemilikan Manajerial, Kepemilikan Institusional, dan Komite Audit terhadap Nilai Perusahaan

2018 ◽  
Vol 2 (1) ◽  
pp. 96-121
Author(s):  
Iwan Wirawardhana ◽  
Meco Sitardja
Keyword(s):  
Firm Value ◽  
Audit Committee ◽  
Stock Exchange ◽  
Random Effect ◽  
Random Effect Model ◽  
Institutional Ownership ◽  
Managerial Ownership ◽  
Estimation Model ◽  
Effect Model ◽  
Positive Effect

The aim of this study is to analyse the effect of Blockholder Ownership, Managerial Ownership,Institutional Ownership, and Audit Committee towards Firm Value. The background of this research isthe agency theory and ownership theory. The population in this study are 46 property companies listedon the Indonesia Stock Exchange (IDX) for the period 2012-2016. By using purposive samplingtechnique, 35 companies are qualified as data samples. This research uses the random effect model asthe estimation model and multiple regression as the method of analysis. The results of this study showsthat Institutional Ownership has a positive effect on Firm Value. Meanwhile, Blockholder Ownership,Managerial Ownership, and Audit Committee have no effect on Firm Value. Moreover, the F-testimplies that the variables, blockholder ownership, managerial ownership, institutional ownership, andaudit committee, simultaneously influence firm value.

scholarly journals Prevalence and risk factors for antibiotic utilization in Chinese children

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shasha Guo ◽  
Qiang Sun ◽  
Xinyang Zhao ◽  
Liyan Shen ◽  
Xuemei Zhen
Keyword(s):  
Risk Factors ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Healthcare Research ◽  
Chinese Children ◽  
Rural Setting ◽  
Antibiotic Prescribing ◽  
Antibiotic Utilization ◽  
At Home

Abstract Background Antibiotic resistance poses a significant threat to public health globally. Irrational utilization of antibiotics being one of the main reasons of antibiotic resistant. Children as a special group, there's more chance of getting infected. Although most of the infection is viral in etiology, antibiotics still are the most frequently prescribed medications for children. Therefore, high use of antibiotics among children raises concern about the appropriateness of antibiotic prescribing. This systematic review aims to measuring prevalence and risk factors for antibiotic utilization in children in China. Methods English and Chinese databases were searched to identify relevant studies evaluating the prevalence and risk factors for antibiotic utilization in Chinese children (0-18 years), which were published between 2010 and July 2020. A Meta-analysis of prevalence was performed using random effect model. The Agency for Healthcare Research and Quality (AHRQ) and modified Jadad score was used to assess risk of bias of studies. In addition, we explored the risk factors of antibiotic utilization in Chinese children using qualitative analysis. Results Of 10,075 studies identified, 98 eligible studies were included after excluded duplicated studies. A total of 79 studies reported prevalence and 42 studies reported risk factors for antibiotic utilization in children. The overall prevalence of antibiotic utilization among outpatients and inpatients were 63.8% (35 studies, 95% confidence interval (CI): 55.1-72.4%), and 81.3% (41 studies, 95% CI: 77.3-85.2%), respectively. In addition, the overall prevalence of caregiver’s self-medicating of antibiotics for children at home was 37.8% (4 studies, 95% CI: 7.9-67.6%). The high prevalence of antibiotics was associated with multiple factors, while lacking of skills and knowledge in both physicians and caregivers was the most recognized risk factor, caregivers put pressure on physicians to get antibiotics and self-medicating with antibiotics at home for children also were the main factors attributed to this issue. Conclusion The prevalence of antibiotic utilization in Chinese children is heavy both in hospitals and home. It is important for government to develop more effective strategies to improve the irrational use of antibiotic, especially in rural setting.

Sign in / Sign up

Export Citation Format

Share Document