NDLI: Computational methods for alternative splicing detection using RNA-seq

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Computational methods for alternative splicing detection using RNA-seq

Content Provider	ACM Digital Library
Author	Dickerson, Julie Liu, Ruolin
Abstract	RNA-seq technology promises a comprehensive picture of transcriptome. The traditional way of studying differential expression gene is questionable because it fails to consider alternative transcription and post-transcriptional modification. Although some studies have shown that transcript variants from a gene are predominantly generated from alternative transcription, including alternative promoters and transcriptional terminations, rather than splicing mechanisms, more computation methods focus on alternative splicing detection and quantification. Here we are only interested in methods which are able to detect condition-specific difference using RNA-seq and we categorize them into two major classes: Region Quantification (RQ) and Isoform Quantification (IQ). RQ breaks down the gene structure into"horizontally parallel pieces", exon units for example, and quantifies the expression in these "small pieces" and compares them across different conditions. While IR seeks to separate gene expression into "vertically parallel isoform", which itself is a challenging task but is more biologically meaningful, and compares a gene's isoform compositions across different conditions. In addition, based on their ability to localize significantly different regions we can further classify them into "gene-centric" or "exon-centric" method. The combination of two classification strategies yields 4 categories and we choose one representative for each category. These four representatives are Cufflinks-Cuffdiff package, DEXSeq, DiffSplice and SplicingCompass. We evaluate their performance on alternative splicing analysis using three experiments. The first experiment uses a published RNA-seq data of Arabidopsis under cold condition (NCBI SRA009031). The second experiment is a simulation study using a custom simulator by which we adopt negative binomial model to account for variability across biological replicates. The last experiment makes use of RT-PCR to evaluate the results from different methods.
Starting Page	663
Ending Page	663
Page Count	1
File Format	PDF
ISBN	9781450324342
DOI	10.1145/2506583.2506666
Language	English
Publisher	Association for Computing Machinery (ACM)
Publisher Date	2013-09-22
Publisher Place	New York
Access Restriction	Subscribed
Subject Keyword	Alternative splicing Rna sequencing Performance measures
Content Type	Text
Resource Type	Article

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