A unified statistical framework for single cell and bulk RNA sequencing data
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Publication:1647646
DOI10.1214/17-AOAS1110zbMATH Open1393.62120arXiv1609.08028OpenAlexW3099404564WikidataQ91266474 ScholiaQ91266474MaRDI QIDQ1647646FDOQ1647646
Authors: Lingxue Zhu, Jing Lei, Bernie Devlin, Kathryn Roeder 
Publication date: 26 June 2018
Published in: The Annals of Applied Statistics (Search for Journal in Brave)
Abstract: Recent advances in technology have enabled the measurement of RNA levels for individual cells. Compared to traditional tissue-level bulk RNA-seq data, single cell sequencing yields valuable insights about gene expression profiles for different cell types, which is potentially critical for understanding many complex human diseases. However, developing quantitative tools for such data remains challenging because of high levels of technical noise, especially the "dropout" events. A "dropout" happens when the RNA for a gene fails to be amplified prior to sequencing, producing a "false" zero in the observed data. In this paper, we propose a Unified RNA-Sequencing Model (URSM) for both single cell and bulk RNA-seq data, formulated as a hierarchical model. URSM borrows the strength from both data sources and carefully models the dropouts in single cell data, leading to a more accurate estimation of cell type specific gene expression profile. In addition, URSM naturally provides inference on the dropout entries in single cell data that need to be imputed for downstream analyses, as well as the mixing proportions of different cell types in bulk samples. We adopt an empirical Bayes approach, where parameters are estimated using the EM algorithm and approximate inference is obtained by Gibbs sampling. Simulation results illustrate that URSM outperforms existing approaches both in correcting for dropouts in single cell data, as well as in deconvolving bulk samples. We also demonstrate an application to gene expression data on fetal brains, where our model successfully imputes the dropout genes and reveals cell type specific expression patterns.
Full work available at URL: https://arxiv.org/abs/1609.08028
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Applications of statistics to biology and medical sciences; meta analysis (62P10) Generalized linear models (logistic models) (62J12) Protein sequences, DNA sequences (92D20)
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Cited In (16)
- Supervised Adversarial Alignment of Single-Cell RNA-seq Data
- Kinetic Foundation of the Zero-Inflated Negative Binomial Model for Single-Cell RNA Sequencing Data
- Detection of differentially expressed genes in discrete single‐cell RNA sequencing data using a hurdle model with correlated random effects
- A kernel non-negative matrix factorization framework for single cell clustering
- Exponential-Family Embedding With Application to Cell Developmental Trajectories for Single-Cell RNA-Seq Data
- LLE based K-nearest neighbor smoothing for scRNA-seq data imputation
- A unified statistical framework for single cell and bulk RNA sequencing data
- MSIQ: joint modeling of multiple RNA-seq samples for accurate isoform quantification
- Benchmarking penalized regression methods in machine learning for single cell RNA sequencing data
- Data denoising and post-denoising corrections in single cell RNA sequencing
- A hierarchical Bayesian model for single-cell clustering using RNA-sequencing data
- Unsupervised integration of single-cell multi-omics datasets with disproportionate cell-type representation
- A zero-inflated non-negative matrix factorization for the deconvolution of mixed signals of biological data
- Gene expression distribution deconvolution in single-cell RNA sequencing
- Nonparametric Bayesian multiarmed bandits for single-cell experiment design
- Model-based approach to the joint analysis of single-cell data on chromatin accessibility and gene expression
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