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PLNseq: a multivariate Poisson lognormal distribution for high-throughput matched RNA-sequencing read count data.

Authors: Luo, Z; Hu, X; Jiang, N; Xu, J; Zhang, H;

PLNseq: a multivariate Poisson lognormal distribution for high-throughput matched RNA-sequencing read count data.

Abstract

High-throughput RNA-sequencing (RNA-seq) technology provides an attractive platform for gene expression analysis. In many experimental settings, RNA-seq read counts are measured from matched samples or taken from the same subject under multiple treatment conditions. The induced correlation therefore should be evaluated and taken into account in deriving tests of differential expression. We proposed a novel method 'PLNseq', which uses a multivariate Poisson lognormal distribution to model matched read count data. The correlation is directly modeled through Gaussian random effects, and inferences are made by likelihood methods. A three-stage numerical algorithm is developed to estimate unknown parameters and conduct differential expression analysis. Results using simulated data demonstrate that our method performs reasonably well in terms of parameter estimation, DE analysis power, and robustness. PLNseq also has better control of FDRs than the benchmarks edgeR and DESeq2 in the situations where the correlation is different across the genes but can still be accurately estimated. Furthermore, direct evaluation of correlation through PLNseq enables us to develop a new and more powerful test for DE analysis. Application to a lung cancer study is provided to illustrate the practical utilities of our method. An R package implementing the method is also publicly available.

Country
China (People's Republic of)
Related Organizations
Keywords

Analysis of Variance, Likelihood Functions, Lung Neoplasms, Base Sequence, Poisson Lognormal Model, Sequence Analysis, RNA, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Matched Samples, Differential Expression Analysis, ROC Curve, Multivariate Analysis, Humans, Computer Simulation, Rna‐Seq, Poisson Distribution, Algorithms

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
12
Top 10%
Average
Top 10%
Related to Research communities
Cancer Research
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