Quantifying alternative splicing from paired-end RNA-sequencing data

DOI10.1214/13-AOAS687zbMATH Open1454.62388arXiv1405.0788WikidataQ30577352 ScholiaQ30577352MaRDI QIDQ2453673FDOQ2453673

Authors: David Rossell, Camille Stephan-Otto Attolini, Manuel Kroiss, Almond Stöcker 

Publication date: 10 June 2014

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: RNA-sequencing has revolutionized biomedical research and, in particular, our ability to study gene alternative splicing. The problem has important implications for human health, as alternative splicing may be involved in malfunctions at the cellular level and multiple diseases. However, the high-dimensional nature of the data and the existence of experimental biases pose serious data analysis challenges. We find that the standard data summaries used to study alternative splicing are severely limited, as they ignore a substantial amount of valuable information. Current data analysis methods are based on such summaries and are hence suboptimal. Further, they have limited flexibility in accounting for technical biases. We propose novel data summaries and a Bayesian modeling framework that overcome these limitations and determine biases in a nonparametric, highly flexible manner. These summaries adapt naturally to the rapid improvements in sequencing technology. We provide efficient point estimates and uncertainty assessments. The approach allows to study alternative splicing patterns for individual samples and can also be the basis for downstream analyses. We found a severalfold improvement in estimation mean square error compared popular approaches in simulations, and substantially higher consistency between replicates in experimental data. Our findings indicate the need for adjusting the routine summarization and analysis of alternative splicing RNA-seq studies. We provide a software implementation in the R package casper.

Full work available at URL: https://arxiv.org/abs/1405.0788

Recommendations

• Statistical modeling of RNA-Seq data
• Searching for alternative splicing with a joint model on probe measurability and expression intensities
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• Exact transcript quantification over splice graphs
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zbMATH Keywords

estimationBayesian modelingalternative splicingRNA-Seq

Mathematics Subject Classification ID

Computational methods for problems pertaining to statistics (62-08) Bayesian inference (62F15) Applications of statistics to biology and medical sciences; meta analysis (62P10)

Cites Work

• Title not available (Why is that?)
• Nonparametric Estimation from Incomplete Observations
• Title not available (Why is that?)
• Quantifying alternative splicing from paired-end RNA-sequencing data
• Statistical modeling of RNA-Seq data

Cited In (13)

• New Tools for Expression Alternative Splicing Validation
• Identification and Exploitation of Linkage by Means of Alternative Splicing
• Title not available (Why is that?)
• Transcriptomics: quantifying non-uniform read distribution using MapReduce
• A Markov random field-based approach for joint estimation of differentially expressed genes in mouse transcriptome data
• Exact transcript quantification over splice graphs
• MSIQ: joint modeling of multiple RNA-seq samples for accurate isoform quantification
• ExactDAS: an exact test procedure for the detection of differential alternative splicing in microarray experiments
• Corrigendum: Quantifying alternative splicing from paired-end RNA-sequencing data
• Bayesian estimation of differential transcript usage from RNA-seq data
• Searching for alternative splicing with a joint model on probe measurability and expression intensities
• Quantifying alternative splicing from paired-end RNA-sequencing data
• Yanagi: transcript segment library construction for RNA-seq quantification

Uses Software

• R
• survival
• Soap
• casper
• TopHat
• SpliceTrap
• BWA

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