Dataset Information

Normalizing Metagenomic Hi-C Data and Detecting Spurious Contacts Using Zero-Inflated Negative Binomial Regression.

ABSTRACT: High-throughput chromosome conformation capture (Hi-C) has recently been applied to natural microbial communities and revealed great potential to study multiple genomes simultaneously. Several extraneous factors may influence chromosomal contacts rendering the normalization of Hi-C contact maps essential for downstream analyses. However, the current paucity of metagenomic Hi-C normalization methods and the ignorance for spurious interspecies contacts weaken the interpretability of the data. Here, we report on two types of biases in metagenomic Hi-C experiments: explicit biases and implicit biases, and introduce HiCzin, a parametric model to correct both types of biases and remove spurious interspecies contacts. We demonstrate that the normalized metagenomic Hi-C contact maps by HiCzin result in lower biases, higher capability to detect spurious contacts, and better performance in metagenomic contig clustering.

SUBMITTER: Du Y

PROVIDER: S-EPMC8892984 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Normalizing Metagenomic Hi-C Data and Detecting Spurious Contacts Using Zero-Inflated Negative Binomial Regression.

Du Yuxuan Y Laperriere Sarah M SM Fuhrman Jed J Sun Fengzhu F

Journal of computational biology : a journal of computational molecular cell biology 20220112 2

High-throughput chromosome conformation capture (Hi-C) has recently been applied to natural microbial communities and revealed great potential to study multiple genomes simultaneously. Several extraneous factors may influence chromosomal contacts rendering the normalization of Hi-C contact maps essential for downstream analyses. However, the current paucity of metagenomic Hi-C normalization methods and the ignorance for spurious interspecies contacts weaken the interpretability of the data. Here ...[more]

PMID: 35020412

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Project description:BackgroundTwo characteristics of commonly used outcomes in medical research are zero inflation and non-negative integers; examples include the number of hospital admissions or emergency department visits, where the majority of patients will have zero counts. Zero-inflated regression models were devised to analyze this type of data. However, the performance of zero-inflated regression models or the properties of data best suited for these analyses have not been thoroughly investigated.MethodsWe conducted a simulation study to evaluate the performance of two generalized linear models, negative binomial and zero-inflated negative binomial, for analyzing zero-inflated count data. Simulation scenarios assumed a randomized controlled trial design and varied the true underlying distribution, sample size, and rate of zero inflation. We compared the models in terms of bias, mean squared error, and coverage. Additionally, we used logistic regression to determine which data properties are most important for predicting the best-fitting model.ResultsWe first found that, regardless of the rate of zero inflation, there was little difference between the conventional negative binomial and its zero-inflated counterpart in terms of bias of the marginal treatment group coefficient. Second, even when the outcome was simulated from a zero-inflated distribution, a negative binomial model was favored above its ZI counterpart in terms of the Akaike Information Criterion. Third, the mean and skewness of the non-zero part of the data were stronger predictors of model preference than the percentage of zero counts. These results were not affected by the sample size, which ranged from 60 to 800.ConclusionsWe recommend that the rate of zero inflation and overdispersion in the outcome should not be the sole and main justification for choosing zero-inflated regression models. Investigators should also consider other data characteristics when choosing a model for count data. In addition, if the performance of the NB and ZINB regression models is reasonably comparable even with ZI outcomes, we advocate the use of the NB regression model due to its clear and straightforward interpretation of the results.

Dataset Information

Normalizing Metagenomic Hi-C Data and Detecting Spurious Contacts Using Zero-Inflated Negative Binomial Regression.

Publications

Normalizing Metagenomic Hi-C Data and Detecting Spurious Contacts Using Zero-Inflated Negative Binomial Regression.

Similar Datasets

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