HiCNorm: removing biases in Hi-C data via Poisson regression.
Ontology highlight
ABSTRACT: Summary
We propose a parametric model, HiCNorm, to remove systematic biases in the raw Hi-C contact maps, resulting in a simple, fast, yet accurate normalization procedure. Compared with the existing Hi-C normalization method developed by Yaffe and Tanay, HiCNorm has fewer parameters, runs >1000 times faster and achieves higher reproducibility.Availability
Freely available on the web at: http://www.people.fas.harvard.edu/?junliu/HiCNorm/.Contact
jliu@stat.harvard.eduSupplementary information
Supplementary data are available at Bioinformatics online.
SUBMITTER: Hu M
PROVIDER: S-EPMC3509491 | biostudies-literature | 2012 Dec
REPOSITORIES: biostudies-literature
Publications
HiCNorm: removing biases in Hi-C data via Poisson regression.
Hu Ming M Deng Ke K Selvaraj Siddarth S Qin Zhaohui Z Ren Bing B Liu Jun S JS
Bioinformatics (Oxford, England) 20120927 23
<h4>Summary</h4>We propose a parametric model, HiCNorm, to remove systematic biases in the raw Hi-C contact maps, resulting in a simple, fast, yet accurate normalization procedure. Compared with the existing Hi-C normalization method developed by Yaffe and Tanay, HiCNorm has fewer parameters, runs >1000 times faster and achieves higher reproducibility.<h4>Availability</h4>Freely available on the web at: http://www.people.fas.harvard.edu/∼junliu/HiCNorm/.<h4>Contact</h4>jliu@stat.harvard.edu<h4>S ...[more]
Similar Datasets
Project description:Background stratified Poisson regression is an approach that has been used in the analysis of data derived from a variety of epidemiologically important studies of radiation-exposed populations, including uranium miners, nuclear industry workers, and atomic bomb survivors. We describe a novel approach to fit Poisson regression models that adjust for a set of covariates through background stratification while directly estimating the radiation-disease association of primary interest. The approach makes use of an expression for the Poisson likelihood that treats the coefficients for stratum-specific indicator variables as 'nuisance' variables and avoids the need to explicitly estimate the coefficients for these stratum-specific parameters. Log-linear models, as well as other general relative rate models, are accommodated. This approach is illustrated using data from the Life Span Study of Japanese atomic bomb survivors and data from a study of underground uranium miners. The point estimate and confidence interval obtained from this 'conditional' regression approach are identical to the values obtained using unconditional Poisson regression with model terms for each background stratum. Moreover, it is shown that the proposed approach allows estimation of background stratified Poisson regression models of non-standard form, such as models that parameterize latency effects, as well as regression models in which the number of strata is large, thereby overcoming the limitations of previously available statistical software for fitting background stratified Poisson regression models.
| S-EPMC3288408 | biostudies-literature
Project description:The Atmospheric Infrared Sounder (AIRS) Observations for Model Intercomparison Projects (Obs4MIPs) Version 2.0 (V2.0) monthly mean tropospheric air temperature, specific humidity, and relative humidity profile data were designed for climate model evaluation in the context of the Coupled Model Intercomparison Project (CMIP). Due to the limitations of the Aqua satellite orbit and the AIRS retrieval algorithm, the sampling biases of the AIRS Obs4MIPs V2.0 data can be large for certain cases and must be considered when the AIRS Obs4MIPs V2.0 data are used for climate model evaluation. In this study, we estimate the sampling biases of the AIRS Obs4MIPs V2.0 data based on the fifth generation of the European Centre for Medium-Range Weather Forecasts (ECMWF) (ERA5) reanalysis and cross-check them using the Modern-Era Retrospective Analysis for Research and Application, Version 2 (MERRA-2) reanalysis. We then remove the estimated sampling biases from the AIRS Obs4MIPs V2.0 data and produce the sampling-bias-corrected AIRS Obs4MIPs V2.1 data that have been published at the Earth System Grid Federation (ESGF) data centers and should be used in the future for climate model evaluation.
| S-EPMC7757242 | biostudies-literature
Project description:This paper develops a semi-nonparametric Poisson regression model to analyze motor vehicle crash frequency data collected from rural multilane highway segments in California, US. Motor vehicle crash frequency on rural highway is a topic of interest in the area of transportation safety due to higher driving speeds and the resultant severity level. Unlike the traditional Negative Binomial (NB) model, the semi-nonparametric Poisson regression model can accommodate an unobserved heterogeneity following a highly flexible semi-nonparametric (SNP) distribution. Simulation experiments are conducted to demonstrate that the SNP distribution can well mimic a large family of distributions, including normal distributions, log-gamma distributions, bimodal and trimodal distributions. Empirical estimation results show that such flexibility offered by the SNP distribution can greatly improve model precision and the overall goodness-of-fit. The semi-nonparametric distribution can provide a better understanding of crash data structure through its ability to capture potential multimodality in the distribution of unobserved heterogeneity. When estimated coefficients in empirical models are compared, SNP and NB models are found to have a substantially different coefficient for the dummy variable indicating the lane width. The SNP model with better statistical performance suggests that the NB model overestimates the effect of lane width on crash frequency reduction by 83.1%.
| S-EPMC5965849 | biostudies-literature
Project description:Summary:We build a software package scHiCNorm that uses zero-inflated and hurdle models to remove biases from single-cell Hi-C data. Our evaluations prove that our models can effectively eliminate systematic biases for single-cell Hi-C data, which better reveal cell-to-cell variances in terms of chromosomal structures. Availability and implementation:scHiCNorm is available at http://dna.cs.miami.edu/scHiCNorm/. Perl scripts are provided that can generate bias features. Pre-built bias features for human (hg19 and hg38) and mouse (mm9 and mm10) are available to download. R scripts can be downloaded to remove biases. Contact:zheng.wang@miami.edu. Supplementary information:Supplementary data are available at Bioinformatics online.
| S-EPMC5860379 | biostudies-literature
Project description:MotivationSeveral computational and statistical methods have been developed to analyse data generated through the 3C-based methods, especially the Hi-C. Most of the existing methods do not account for dependency in Hi-C data.ResultsHere, we present ZipHiC, a novel statistical method to explore Hi-C data focusing on the detection of enriched contacts. ZipHiC implements a Bayesian method based on a hidden Markov random field (HMRF) model and the Approximate Bayesian Computation (ABC) to detect interactions in two-dimensional space based on a Hi-C contact frequency matrix. ZipHiC uses data on the sources of biases related to the contact frequency matrix, allows borrowing information from neighbours using the Potts model and improves computation speed by using the ABC model. In addition to outperforming existing tools on both simulated and real data, our model also provides insights into different sources of biases that affects Hi-C data. We show that some datasets display higher biases from DNA accessibility or Transposable Elements content. Furthermore, our analysis in D. melanogaster showed that approximately half of the detected significant interactions connect promoters with other parts of the genome indicating a functional biological role. Finally, we found that the micro-C datasets display higher biases from DNA accessibility compared to a similar Hi-C experiment, but this can be corrected by ZipHiC.
| S-EPMC9272800 | biostudies-literature
Project description:Understanding sensitive behaviors-those that are socially unacceptable or non-compliant with rules or regulations-is essential for creating effective interventions. Sensitive behaviors are challenging to study, because participants are unlikely to disclose sensitive behaviors for fear of retribution or due to social undesirability. Methods for studying sensitive behavior include randomized response techniques, which provide anonymity to interviewees who answer sensitive questions. A variation on this approach, the quantitative randomized response technique (QRRT), allows researchers to estimate the frequency or quantity of sensitive behaviors. However, to date no studies have used QRRT to identify potential drivers of non-compliant behavior because regression methodology has not been developed for the nonnegative count data produced by QRRT. We develop a Poisson regression methodology for QRRT data, based on maximum likelihood estimation computed via the expectation-maximization (EM) algorithm. The methodology can be implemented with relatively minor modification of existing software for generalized linear models. We derive the Fisher information matrix in this setting and use it to obtain the asymptotic variance-covariance matrix of the regression parameter estimates. Simulation results demonstrate the quality of the asymptotic approximations. The method is illustrated with a case study examining potential drivers of non-compliance with hunting regulations in Sierra Leone. The new methodology allows assessment of the importance of potential drivers of different quantities of non-compliant behavior, using a likelihood-based, information-theoretic approach. Free, open-source software is provided to support QRRT regression.
| S-EPMC6161884 | biostudies-literature
Project description:The parameters of logistic regression models are usually obtained by the method of maximum likelihood (ML). However, in analyses of small data sets or data sets with unbalanced outcomes or exposures, ML parameter estimates may not exist. This situation has been termed 'separation' as the two outcome groups are separated by the values of a covariate or a linear combination of covariates. To overcome the problem of non-existing ML parameter estimates, applying Firth's correction (FC) was proposed. In practice, however, a principal investigator might be advised to 'bring more data' in order to solve a separation issue. We illustrate the problem by means of examples from colorectal cancer screening and ornithology. It is unclear if such an increasing sample size (ISS) strategy that keeps sampling new observations until separation is removed improves estimation compared to applying FC to the original data set. We performed an extensive simulation study where the main focus was to estimate the cost-adjusted relative efficiency of ML combined with ISS compared to FC. FC yielded reasonably small root mean squared errors and proved to be the more efficient estimator. Given our findings, we propose not to adapt the sample size when separation is encountered but to use FC as the default method of analysis whenever the number of observations or outcome events is critically low.
| S-EPMC6926877 | biostudies-literature
Project description:Hi-C is one of the main methods for investigating spatial co-localisation of DNA in the nucleus. However, the raw sequencing data obtained from Hi-C experiments suffer from large biases and spurious contacts, making it difficult to identify true interactions. Existing methods use complex models to account for biases and do not provide a significance threshold for detecting interactions. Here we introduce a simple binomial probabilistic model that resolves complex biases and distinguishes between true and false interactions. The model corrects biases of known and unknown origin and yields a p-value for each interaction, providing a reliable threshold based on significance. We demonstrate this experimentally by testing the method against a random ligation dataset. Our method outperforms previous methods and provides a statistical framework for further data analysis, such as comparisons of Hi-C interactions between different conditions. GOTHiC is available as a BioConductor package (http://www.bioconductor.org/packages/release/bioc/html/GOTHiC.html).
| S-EPMC5381888 | biostudies-literature
Project description:BackgroundTsetse flies are the major vectors of human trypanosomiasis of the form Trypanosoma brucei rhodesiense and T.b.gambiense. They are widely spread across the sub-Saharan Africa and rendering a lot of challenges to both human and animal health. This stresses effective agricultural production and productivity in Africa. Delimiting the extent and magnitude of tsetse coverage has been a challenge over decades due to limited resources and unsatisfactory technology. In a bid to overcome these limitations, this study attempted to explore modelling skills that can be applied to spatially estimate tsetse abundance in the country using limited tsetse data and a set of remote-sensed environmental variables.MethodologyEntomological data for the period 2008-2018 as used in the model were obtained from various sources and systematically assembled using a structured protocol. Data harmonisation for the purposes of responsiveness and matching was carried out. The key tool for tsetse trapping was itemized as pyramidal trap in many instances and biconical trap in others. Based on the spatially explicit assembled data, we ran two regression models; standard Poisson and Zero-Inflated Poisson (ZIP), to explore the associations between tsetse abundance in Uganda and several environmental and climatic covariates. The covariate data were constituted largely by satellite sensor data in form of meteorological and vegetation surrogates in association with elevation and land cover data. We finally used the Zero-Inflated Poisson (ZIP) regression model to predict tsetse abundance due to its superiority over the standard Poisson after model fitting and testing using the Vuong Non-Nested statistic.ResultsA total of 1,187 tsetse sampling points were identified and considered as representative for the country. The model results indicated the significance and level of responsiveness of each covariate in influencing tsetse abundance across the study area. Woodland vegetation, elevation, temperature, rainfall, and dry season normalised difference vegetation index (NDVI) were important in determining tsetse abundance and spatial distribution at varied scales. The resultant prediction map shows scaled tsetse abundance with estimated fitted numbers ranging from 0 to 59 flies per trap per day (FTD). Tsetse abundance was found to be largest at low elevations, in areas of high vegetative activity, in game parks, forests and shrubs during the dry season. There was very limited responsiveness of selected predictors to tsetse abundance during the wet season, matching the known fact that tsetse disperse most significantly during wet season.ConclusionsA methodology was advanced to enable compilation of entomological data for 10 years, which supported the generation of tsetse abundance maps for Uganda through modelling. Our findings indicate the spatial distribution of the G. f. fuscipes as; low 0-5 FTD (48%), medium 5.1-35 FTD (18%) and high 35.1-60 FTD (34%) grounded on seasonality. This approach, amidst entomological data shortages due to limited resources and absence of expertise, can be adopted to enable mapping of the vector to provide better decision support towards designing and implementing targeted tsetse and tsetse-transmitted African trypanosomiasis control strategies.
| S-EPMC8648107 | biostudies-literature
Project description:Hi-C is a genome-wide assay based on Chromosome Conformation Capture and high-throughput sequencing to decipher 3D chromatin organization in the nucleus. However, computational methods to detect functional interactions utilizing Hi-C data face challenges including the correction for various sources of biases and the identification of functional interactions with low counts of interacting fragments. We present Chrom-Lasso, a lasso linear regression model that removes complex biases assumption-free and identifies functional interacting loci with increased power by combining information of local reads distribution surrounding the area of interest. We showed that interacting regions identified by Chrom-Lasso are more enriched for 5C validated interactions and functional GWAS hits than that of GOTHiC and Fit-Hi-C. To further demonstrate the ability of Chrom-Lasso to detect interactions of functional importance, we performed time-series Hi-C and RNA-seq during T cell activation and exhaustion. We showed that the dynamic changes in gene expression and chromatin interactions identified by Chrom-Lasso were largely concordant with each other. Finally, we experimentally confirmed Chrom-Lasso's finding that Erbb3 was co-regulated with distinct neighboring genes at different states during T cell activation. Our results highlight Chrom-Lasso's utility in detecting weak functional interaction between cis-regulatory elements, such as promoters and enhancers.
| S-EPMC8574949 | biostudies-literature