scholarly journals Thousands of CpGs Show DNA Methylation Differences in ACPA-Positive Individuals

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1349
Author(s):  
Yixiao Zeng ◽  
Kaiqiong Zhao ◽  
Kathleen Oros Oros Klein ◽  
Xiaojian Shao ◽  
Marvin J. Fritzler ◽  
...  
Keyword(s):  
Regression Models ◽  
Bisulfite Sequencing ◽  
Biological Process ◽  
Differential Methylation ◽  
Replication Study ◽  
Protein Coding ◽  
Cpg Sites ◽  
Binomial Regression ◽  
Citrullinated Protein ◽  
Gwas Catalog

High levels of anti-citrullinated protein antibodies (ACPA) are often observed prior to a diagnosis of rheumatoid arthritis (RA). We undertook a replication study to confirm CpG sites showing evidence of differential methylation in subjects positive vs. negative for ACPA, in a new subset of 112 individuals sampled from the population cohort and biobank CARTaGENE in Quebec, Canada. Targeted custom capture bisulfite sequencing was conducted at approximately 5.3 million CpGs located in regulatory or hypomethylated regions from whole blood; library and protocol improvements had been instituted between the original and this replication study, enabling better coverage and additional identification of differentially methylated regions (DMRs). Using binomial regression models, we identified 19,472 ACPA-associated differentially methylated cytosines (DMCs), of which 430 overlapped with the 1909 DMCs reported by the original study; 814 DMRs of relevance were clustered by grouping adjacent DMCs into regions. Furthermore, we performed an additional integrative analysis by looking at the DMRs that overlap with RA related loci published in the GWAS Catalog, and protein-coding genes associated with these DMRs were enriched in the biological process of cell adhesion and involved in immune-related pathways.

Detection of differentially methylated CpG sites between tumor samples with uneven tumor purities

2019 ◽  
Vol 36 (7) ◽  
pp. 2017-2024
Author(s):  
Weiwei Zhang ◽  
Ziyi Li ◽  
Nana Wei ◽  
Hua-Jun Wu ◽  
Xiaoqi Zheng
Keyword(s):  
Real Data ◽  
R Package ◽  
Differential Methylation ◽  
Least Square ◽  
Epigenetic Mechanism ◽  
Supplementary Information ◽  
Cpg Sites ◽  
Tumor Purity ◽  
Different Sources ◽  
Normal Controls

Abstract Motivation Inference of differentially methylated (DM) CpG sites between two groups of tumor samples with different geno- or pheno-types is a critical step to uncover the epigenetic mechanism of tumorigenesis, and identify biomarkers for cancer subtyping. However, as a major source of confounding factor, uneven distributions of tumor purity between two groups of tumor samples will lead to biased discovery of DM sites if not properly accounted for. Results We here propose InfiniumDM, a generalized least square model to adjust tumor purity effect for differential methylation analysis. Our method is applicable to a variety of experimental designs including with or without normal controls, different sources of normal tissue contaminations. We compared our method with conventional methods including minfi, limma and limma corrected by tumor purity using simulated datasets. Our method shows significantly better performance at different levels of differential methylation thresholds, sample sizes, mean purity deviations and so on. We also applied the proposed method to breast cancer samples from TCGA database to further evaluate its performance. Overall, both simulation and real data analyses demonstrate favorable performance over existing methods serving similar purpose. Availability and implementation InfiniumDM is a part of R package InfiniumPurify, which is freely available from GitHub (https://github.com/Xiaoqizheng/InfiniumPurify). Supplementary information Supplementary data are available at Bioinformatics online.

Managing Inflation

2016 ◽  
Vol 63 (1) ◽  
pp. 77-87 ◽  
Author(s):  
William H. Fisher ◽  
Stephanie W. Hartwell ◽  
Xiaogang Deng
Keyword(s):  
Count Data ◽  
Regression Models ◽  
Negative Binomial ◽  
Negative Binomial Regression ◽  
Excess Zeros ◽  
Binomial Regression ◽  
Negative Binomial Models ◽  
Using Data ◽  
Over Dispersion ◽  
Binomial Models

Poisson and negative binomial regression procedures have proliferated, and now are available in virtually all statistical packages. Along with the regression procedures themselves are procedures for addressing issues related to the over-dispersion and excessive zeros commonly observed in count data. These approaches, zero-inflated Poisson and zero-inflated negative binomial models, use logit or probit models for the “excess” zeros and count regression models for the counted data. Although these models are often appropriate on statistical grounds, their interpretation may prove substantively difficult. This article explores this dilemma, using data from a study of individuals released from facilities maintained by the Massachusetts Department of Correction.

Group regularization for zero-inflated negative binomial regression models with an application to health care demand in Germany

2018 ◽  
Vol 37 (20) ◽  
pp. 3012-3026 ◽  
Author(s):  
Saptarshi Chatterjee ◽  
Shrabanti Chowdhury ◽  
Himel Mallick ◽  
Prithish Banerjee ◽  
Broti Garai
Keyword(s):  
Health Care ◽  
Regression Models ◽  
Negative Binomial ◽  
Negative Binomial Regression ◽  
Health Care Demand ◽  
Binomial Regression

What Do We Know About Changing Economic Activity of Firms?

2019 ◽  
pp. 232102221886979
Author(s):  
Radhika Pandey ◽  
Amey Sapre ◽  
Pramod Sinha
Keyword(s):  
Economic Activity ◽  
Regression Models ◽  
Statistical Approach ◽  
Negative Binomial ◽  
Large Data ◽  
Poisson Model ◽  
Negative Binomial Regression ◽  
Data Set ◽  
Binomial Regression ◽  
History Of

Identification of primary economic activity of firms is a prerequisite for compiling several macro aggregates. In this paper, we take a statistical approach to understand the extent of changes in primary economic activity of firms over time and across different industries. We use the history of economic activity of over 46,000 firms spread over 25 years from CMIE Prowess to identify the number of times firms change the nature of their business. Using the count of changes, we estimate Poisson and Negative Binomial regression models to gain predictability over changing economic activity across industry groups. We show that a Poisson model accurately characterizes the distribution of count of changes across industries and that firms with a long history are more likely to have changed their primary economic activity over the years. Findings show that classification can be a crucial problem in a large data set like the MCA21 and can even lead to distortions in value addition estimates at the industry level. JEL Classifications: D22, E00, E01

scholarly journals A comparison of some link functions for binomial regression models with application to school drop-out rates in East Java

2019 ◽  
Author(s):  
Rindang Bangun Prasetyo ◽  
Heri Kuswanto ◽  
Nur Iriawan ◽  
Brodjol Sutijo Suprih Ulama
Keyword(s):  
Regression Models ◽  
Drop Out ◽  
Link Functions ◽  
Binomial Regression ◽  
School Drop Out ◽  
Drop Out Rates

Traffic accident modeling: some statistical issues

2006 ◽  
Vol 33 (9) ◽  
pp. 1115-1124 ◽  
Author(s):  
Z Sawalha ◽  
T Sayed
Keyword(s):  
Road Safety ◽  
Regression Models ◽  
Model Building ◽  
Negative Binomial ◽  
Prediction Models ◽  
Negative Binomial Regression ◽  
Outlier Analysis ◽  
Accident Prediction ◽  
Binomial Regression ◽  
Statistical Issues

Accident prediction models are invaluable tools that have many applications in road safety analysis. However, there are certain statistical issues related to accident modeling that either deserve further attention or have not been dealt with adequately in the road safety literature. This paper discusses and illustrates how to deal with two statistical issues related to modeling accidents using Poisson and negative binomial regression. The first issue is that of model building or deciding which explanatory variables to include in an accident prediction model. The study differentiates between applications for which it is advisable to avoid model over-fitting and other applications for which it is desirable to fit the model to the data as closely as possible. It then suggests procedures for developing parsimonious models, i.e., models that are not over-fitted, and best-fit models. The second issue discussed in the paper is that of outlier analysis. The study suggests a procedure for the identification and exclusion of extremely influential outliers from the development of Poisson and negative binomial regression models. The procedures suggested for model building and conducting outlier analysis are more straightforward to apply in the case of Poisson regression models because of an added complexity presented by the shape parameter of the negative binomial distribution. The paper, therefore, presents flowcharts detailing the application of the procedures when modeling is carried out using negative binomial regression. The described procedures are then applied in the development of negative binomial accident prediction models for the urban arterials of the cities of Vancouver and Richmond located in the province of British Columbia, Canada. Key words: accident prediction models, overfitting, parsimony, outlier analysis, Poisson regression, negative binomial regression.

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