Dataset Information

DEIsoM: a hierarchical Bayesian model for identifying differentially expressed isoforms using biological replicates.

ABSTRACT:

Motivation

High-throughput mRNA sequencing (RNA-Seq) is a powerful tool for quantifying gene expression. Identification of transcript isoforms that are differentially expressed in different conditions, such as in patients and healthy subjects, can provide insights into the molecular basis of diseases. Current transcript quantification approaches, however, do not take advantage of the shared information in the biological replicates, potentially decreasing sensitivity and accuracy.

Results

We present a novel hierarchical Bayesian model called Differentially Expressed Isoform detection from Multiple biological replicates (DEIsoM) for identifying differentially expressed (DE) isoforms from multiple biological replicates representing two conditions, e.g. multiple samples from healthy and diseased subjects. DEIsoM first estimates isoform expression within each condition by (1) capturing common patterns from sample replicates while allowing individual differences, and (2) modeling the uncertainty introduced by ambiguous read mapping in each replicate. Specifically, we introduce a Dirichlet prior distribution to capture the common expression pattern of replicates from the same condition, and treat the isoform expression of individual replicates as samples from this distribution. Ambiguous read mapping is modeled as a multinomial distribution, and ambiguous reads are assigned to the most probable isoform in each replicate. Additionally, DEIsoM couples an efficient variational inference and a post-analysis method to improve the accuracy and speed of identification of DE isoforms over alternative methods. Application of DEIsoM to an hepatocellular carcinoma (HCC) dataset identifies biologically relevant DE isoforms. The relevance of these genes/isoforms to HCC are supported by principal component analysis (PCA), read coverage visualization, and the biological literature.

Availability and implementation

The software is available at https://github.com/hao-peng/DEIsoM.

Contact

pengh@alumni.purdue.edu.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Peng H

PROVIDER: S-EPMC5870796 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DEIsoM: a hierarchical Bayesian model for identifying differentially expressed isoforms using biological replicates.

Peng Hao H Yang Yifan Y Zhe Shandian S Wang Jian J Gribskov Michael M Qi Yuan Y

Bioinformatics (Oxford, England) 20171001 19

<h4>Motivation</h4>High-throughput mRNA sequencing (RNA-Seq) is a powerful tool for quantifying gene expression. Identification of transcript isoforms that are differentially expressed in different conditions, such as in patients and healthy subjects, can provide insights into the molecular basis of diseases. Current transcript quantification approaches, however, do not take advantage of the shared information in the biological replicates, potentially decreasing sensitivity and accuracy.<h4>Resu ...[more]

PMID: 28595376

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Dataset Information

DEIsoM: a hierarchical Bayesian model for identifying differentially expressed isoforms using biological replicates.

Motivation

Results

Availability and implementation

Contact

Supplementary information

Publications

DEIsoM: a hierarchical Bayesian model for identifying differentially expressed isoforms using biological replicates.

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