scholarly journals DiADeM: differential analysis via dependency modelling of chromatin interactions with robust generalized linear models

2019 ◽  
Author(s):  
Rafał Zaborowski ◽  
Bartek Wilczyński

AbstractHigh throughput Chromosome Conformation Capture experiments have become the standard technique to assess the structure and dynamics of chromosomes in living cells. As any other sufficiently advanced biochemical technique, Hi-C datasets are complex and contain multiple documented biases, with the main ones being the non-uniform read coverage and the decay of contact coverage with genomic distance. Both of these effects have been studied and there are published methods that are able to normalize different Hi-C data to mitigate these biases to some extent. It is crucial that this is done properly, or otherwise the results of any comparative analysis of two or more Hi-C experiments are bound to be biased. In this paper we study both mentioned biases present in the Hi-C data and show that normalization techniques aimed at alleviating the coverage bias are at the same time exacerbating the problems with contact decay bias. We also postulate that it is possible to use generalized linear models to directly compare non-normalized data an that it is giving better results in identification of differential contacts between Hi-C matrices than using the normalized data.

2019 ◽  
Author(s):  
Ilana Lambert ◽  
Christine Paysant-Le Roux ◽  
Stefano Colella ◽  
Marie-Laure Martin-Magniette

Abstract Background RNAseq is nowadays the method of choice for transcriptome analysis. In the last decades, a high number of statistical methods, and associated bioinformatics tools, for RNAseq analysis were developed. More recently, statistical studies realized neutral comparison studies using benchmark datasets, shedding light on the most appropriate approaches for RNAseq data analysis. Nevertheless, performing an RNAseq analysis remains a challenge for the biologists. Results DiCoExpress is a workspace implemented in R that includes methods chosen based on their performance in neutral comparisons studies. DiCoExpress uses the pre-existing R packages as well as FactoMineR, edgeR and coseq, to perform quality control, differential, and co-expression analysis of RNAseq data. Users can perform the full analysis, providing a mapped read expression data file and a file containing the information on the experimental design. Following the quality control step, the user can move on to the differential expression analysis performed using generalized linear models with no effort thanks to the automated contrast writing function. DiCoExpress proposes a list of comparisons based on the experimental design, and the user needs only to choose the one(s) of interest for his research question. A co-expression analysis is implemented using the coseq package. Identified co-expression clusters are automatically analyzed for enrichment of annotations provided by the user, and several result outputs proposed. We used DiCoExpress to analyze a publicly available Bra ssica napus L. RNAseq dataset on the transcriptional response to silicon treatment in plant roots and mature leaves. This dataset, including two biological factors and three replicates for each condition, allowed us to demonstrate in a tutorial all the features of DiCoExpress. Conclusions DiCoExpress is an R workspace to allow users without advanced statistical knowledge and programming skills to perform a full RNAseq analysis from quality controls to co-expression analysis through differential analysis based on contrasts inside generalized linear models . Hence, with DiCoExpress, the user can focus on the statistical modeling of gene expression according to the experimental design and on the interpretation of the results of such analysis in biological terms.


2020 ◽  
Author(s):  
Ilana Lambert ◽  
Christine Paysant-Le Roux ◽  
Stefano Colella ◽  
Marie-Laure Martin-Magniette

Abstract Background RNAseq is nowadays the method of choice for transcriptome analysis. In the last decades, a high number of statistical methods, and associated bioinformatics tools, for RNAseq analysis were developed. More recently, statistical studies realised neutral comparison studies using benchmark datasets, shedding light on the most appropriate approaches for RNAseq data analysis. Results DiCoExpress is a script-based tool implemented in R that includes methods chosen based on their performance in neutral comparisons studies. DiCoExpress uses pre-existing R packages including FactoMineR, edgeR and coseq , to perform quality control, differential, and co-expression analysis of RNAseq data. Users can perform the full analysis, providing a mapped read expression data file and a file containing the information on the experimental design. Following the quality control step, the user can move on to the differential expression analysis performed using generalized linear models thanks to the automated contrast writing function. A co-expression analysis is implemented using the coseq package. Lists of differentially expressed genes and identified co-expression clusters are automatically analyzed for enrichment of annotations provided by the user . We used DiCoExpress to analyze a publicly available RNAseq dataset on the transcriptional response of Bra ssica napus L. to silicon treatment in plant roots and mature leaves . This dataset, including two biological factors and three replicates for each condition, allowed us to demonstrate in a tutorial all the features of DiCoExpress. Conclusions DiCoExpress is an R script-based tool allowing users to perform a full RNAseq analysis from quality controls to co-expression analysis through differential analysis based on contrasts inside generalized linear models . DiCoExpress focuses on the statistical modelling of gene expression according to the experimental design and facilitates the data analysis leading the biological interpretation of the results.


2020 ◽  
Vol 02 ◽  
Author(s):  
RM Garcia ◽  
WF Vieira-Junior ◽  
JD Theobaldo ◽  
NIP Pini ◽  
GM Ambrosano ◽  
...  

Objective: To evaluate color and roughness of bovine enamel exposed to dentifrices, dental bleaching with 35% hydrogen peroxide (HP), and erosion/staining by red wine. Methods: Bovine enamel blocks were exposed to: artificial saliva (control), Oral-B Pro-Health (stannous fluoride with sodium fluoride, SF), Sensodyne Repair & Protect (bioactive glass, BG), Colgate Pro-Relief (arginine and calcium carbonate, AR), or Chitodent (chitosan, CHI). After toothpaste exposure, half (n=12) of the samples were bleached (35% HP), and the other half were not (n=12). The color (CIE L*a* b*, ΔE), surface roughness (Ra), and scanning electron microscopy were evaluated. Color and roughness were assessed at baseline, post-dentifrice and/or -dental bleaching, and after red wine. The data were subjected to analysis of variance (ANOVA) (ΔE) for repeated measures (Ra), followed by Tukey ́s test. The L*, a*, and b* values were analyzed by generalized linear models (a=0.05). Results: The HP promoted an increase in Ra values; however, the SF, BG, and AR did not enable this alteration. After red wine, all groups apart from SF (unbleached) showed increases in Ra values; SF and AR promoted decreases in L* values; AR demonstrated higher ΔE values, differing from the control; and CHI decreased the L* variation in the unbleached group. Conclusion: Dentifrices did not interfere with bleaching efficacy of 35% HP. However, dentifrices acted as a preventive agent against surface alteration from dental bleaching (BG, SF, and AR) or red wine (SF). Dentifrices can decrease (CHI) or increase (AR and SF) staining by red wine.


2020 ◽  
Vol 9 (16) ◽  
pp. 1105-1115
Author(s):  
Shuqing Wu ◽  
Xin Cui ◽  
Shaoyu Zhang ◽  
Wenqi Tian ◽  
Jiazhen Liu ◽  
...  

Aim: This real-world data study investigated the economic burden and associated factors of readmissions for cerebrospinal fluid leakage (CSFL) post-cranial, transsphenoidal, or spinal index surgeries. Methods: Costs of CSFL readmissions and index hospitalizations during 2014–2018 were collected. Readmission cost was measured as absolute cost and as percentage of index hospitalization cost. Factors associated with readmission cost were explored using generalized linear models. Results: Readmission cost averaged US$2407–6106, 35–94% of index hospitalization cost. Pharmacy costs were the leading contributor. Generalized linear models showed transsphenoidal index surgery and surgical treatment for CSFL were associated with higher readmission costs. Conclusion: CSFL readmissions are a significant economic burden in China. Factors associated with higher readmission cost should be monitored.


1989 ◽  
Vol 78 (5) ◽  
pp. 413-416
Author(s):  
Gerald Van Belle ◽  
Sue Leurgans ◽  
Pat Friel ◽  
Sunwei Guo ◽  
Mark Yerby

2021 ◽  
pp. 096228022110082
Author(s):  
Yang Li ◽  
Wei Ma ◽  
Yichen Qin ◽  
Feifang Hu

Concerns have been expressed over the validity of statistical inference under covariate-adaptive randomization despite the extensive use in clinical trials. In the literature, the inferential properties under covariate-adaptive randomization have been mainly studied for continuous responses; in particular, it is well known that the usual two-sample t-test for treatment effect is typically conservative. This phenomenon of invalid tests has also been found for generalized linear models without adjusting for the covariates and are sometimes more worrisome due to inflated Type I error. The purpose of this study is to examine the unadjusted test for treatment effect under generalized linear models and covariate-adaptive randomization. For a large class of covariate-adaptive randomization methods, we obtain the asymptotic distribution of the test statistic under the null hypothesis and derive the conditions under which the test is conservative, valid, or anti-conservative. Several commonly used generalized linear models, such as logistic regression and Poisson regression, are discussed in detail. An adjustment method is also proposed to achieve a valid size based on the asymptotic results. Numerical studies confirm the theoretical findings and demonstrate the effectiveness of the proposed adjustment method.


2021 ◽  
Vol 10 (6) ◽  
pp. 1211
Author(s):  
Li-Te Lin ◽  
Kuan-Hao Tsui

The relationship between serum dehydroepiandrosterone sulphate (DHEA-S) and anti-Mullerian hormone (AMH) levels has not been fully established. Therefore, we performed a large-scale cross-sectional study to investigate the association between serum DHEA-S and AMH levels. The study included a total of 2155 infertile women aged 20 to 46 years who were divided into four quartile groups (Q1 to Q4) based on serum DHEA-S levels. We found that there was a weak positive association between serum DHEA-S and AMH levels in infertile women (r = 0.190, p < 0.001). After adjusting for potential confounders, serum DHEA-S levels positively correlated with serum AMH levels in infertile women (β = 0.103, p < 0.001). Infertile women in the highest DHEA-S quartile category (Q4) showed significantly higher serum AMH levels (p < 0.001) compared with women in the lowest DHEA-S quartile category (Q1). The serum AMH levels significantly increased across increasing DHEA-S quartile categories in infertile women (p = 0.014) using generalized linear models after adjustment for potential confounders. Our data show that serum DHEA-S levels are positively associated with serum AMH levels.


2021 ◽  
Vol 1 (1) ◽  
pp. 99-112
Author(s):  
Richard Larouche ◽  
Nimesh Patel ◽  
Jennifer L. Copeland

The role of infrastructure in encouraging transportation cycling in smaller cities with a low prevalence of cycling remains unclear. To investigate the relationship between the presence of infrastructure and transportation cycling in a small city (Lethbridge, AB, Canada), we interviewed 246 adults along a recently-constructed bicycle boulevard and two comparison streets with no recent changes in cycling infrastructure. One comparison street had a separate multi-use path and the other had no cycling infrastructure. Questions addressed time spent cycling in the past week and 2 years prior and potential socio-demographic and psychosocial correlates of cycling, including safety concerns. Finally, we asked participants what could be done to make cycling safer and more attractive. We examined predictors of cycling using gender-stratified generalized linear models. Women interviewed along the street with a separate path reported cycling more than women on the other streets. A more favorable attitude towards cycling and greater habit strength were associated with more cycling in both men and women. Qualitative data revealed generally positive views about the bicycle boulevard, a need for education about sharing the road and for better cycling infrastructure in general. Our results suggest that, even in smaller cities, cycling infrastructure may encourage cycling, especially among women.


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