Negative binomial distribution

Abstract: Office hours: MWF, immediately after class or early afternoon (time TBA). We will cover the mathematical foundations of probability theory. The basic terminology and concepts of probability theory include: random experiments, sample or outcome spaces (discrete and continuous case), events and their algebra, probability measures, conditional probability A First Course in Probability (8th ed.) by S. Ross. This is a lively text that covers the basic ideas of probability theory including those needed in statistics. Theoretical concepts are introduced via interesting concrete examples. In 394 I will begin my lectures with the basics of probability theory in Chapter 2. However, your first assignment is to review Chapter 1, which treats elementary counting methods. They are used in applications in Chapter 2. I expect to cover Chapters 2-5 plus portions of 6 and 7. You are encouraged to read ahead. In lectures I will not be able to cover every topic and example in Ross, and conversely, I may cover some topics/examples in lectures that are not treated in Ross. You will be responsible for all material in my lectures, assigned reading, and homework, including supplementary handouts if any.

Abstract: Zero-inflated Poisson (ZIP) regression is a model for count data with excess zeros. It assumes that with probability p the only possible observation is 0, and with probability 1 – p, a Poisson(λ) random variable is observed. For example, when manufacturing equipment is properly aligned, defects may be nearly impossible. But when it is misaligned, defects may occur according to a Poisson(λ) distribution. Both the probability p of the perfect, zero defect state and the mean number of defects λ in the imperfect state may depend on covariates. Sometimes p and λ are unrelated; other times p is a simple function of λ such as p = l/(1 + λ T ) for an unknown constant T . In either case, ZIP regression models are easy to fit. The maximum likelihood estimates (MLE's) are approximately normal in large samples, and confidence intervals can be constructed by inverting likelihood ratio tests or using the approximate normality of the MLE's. Simulations suggest that the confidence intervals based on likelihood ratio test...

Abstract: Single-cell RNA-seq (scRNA-seq) data exhibits significant cell-to-cell variation due to technical factors, including the number of molecules detected in each cell, which can confound biological heterogeneity with technical effects. To address this, we present a modeling framework for the normalization and variance stabilization of molecular count data from scRNA-seq experiments. We propose that the Pearson residuals from “regularized negative binomial regression,” where cellular sequencing depth is utilized as a covariate in a generalized linear model, successfully remove the influence of technical characteristics from downstream analyses while preserving biological heterogeneity. Importantly, we show that an unconstrained negative binomial model may overfit scRNA-seq data, and overcome this by pooling information across genes with similar abundances to obtain stable parameter estimates. Our procedure omits the need for heuristic steps including pseudocount addition or log-transformation and improves common downstream analytical tasks such as variable gene selection, dimensional reduction, and differential expression. Our approach can be applied to any UMI-based scRNA-seq dataset and is freely available as part of the R package sctransform, with a direct interface to our single-cell toolkit Seurat.

Abstract: Preface 1. Introduction 2. The concept of risk 3. Overview of count response models 4. Methods of estimation and assessment 5. Assessment of count models 6. Poisson regression 7. Overdispersion 8. Negative binomial regression 9. Negative binomial regression: modeling 10. Alternative variance parameterizations 11. Problems with zero counts 12. Censored and truncated count models 13. Handling endogeneity and latent class models 14. Count panel models 15. Bayesian negative binomial models Appendix A. Constructing and interpreting interactions Appendix B. Data sets and Stata files References Index.