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awesome-alternative-splicing

What is this?

This is a resource for software and information about alternative splicing. Contributions welcome...

Types of alternative splicing

  • Skipped exon or cassette exon (SE): An exon can be retained or spliced out of the primary transcript.
  • Mutually exclusion exons (MXE): One of two exons is retained in mRNA splicing, but not both.
  • Alternative 5' splice site (A5SS): An alternative 5' splice junction (donor site) is used that changes the 3' boundary of the upstream exon.
  • Alternative 3' splice site (A3SS): An alternative 3' splice junction (acceptor site) is used that changes the 5' boundary of the downstream exon.
  • Retained intron (RI): A sequence may be spliced out as an intron or retained, and there are no flanking introns.

Types of alternative splicing

Source: http://rnaseq-mats.sourceforge.net/rmats3.0.9/

Software

  • ALEXA-Seq - alternative expression analysis by massively parallel sequencing.
  • AltAnalyze - analyze alternative splicing from single-cell and RNA-Seq data.
  • Cufflinks - assemble and quantify transcripts.
  • DEXSeq - identify differential exon usage.
  • flotilla - reproduce machine learning analysis of gene expression and alternative splicing data.
  • GMAP and GSNAP - detect complex variants and splicing in short reads, SNP-tolerant.
  • G-Mo.R-Se - maps splice junctions to genome.
  • HMMSplicer - discovery canonical and non-canonical splice junctions in short read datasets.
  • JunctionSeq - identify differential splice junctions.
  • MapSplice - map RNA-seq data to reference genome for splice junction discovery.
  • MISO - determine alternative splicing expression.
  • MMES - statistically determine alternative splicing.
  • outrigger - calculate alternative splicing scores of RNA-Seq data based on junction reads and a de novo, custom annotation created with a graph database, especially made for single-cell analyses.
  • rMATS - RNA-Seq Multavariate Analysis of Transcript Splicing. Reading rMATS output
  • rmats2sashimiplot - visualize rMATS output using sashimi plots.
  • SAW - identify splicing events from RNA-Seq data.
  • Scripture - reconstruct transcript isoforms.
  • SingleSplice - detect biological variation in alternative splicing within a population of single cells.
  • SpliceMap - discover and align splice junctions for RNA-Seq reads.
  • SpliceR - detect alternative splicing and predict coding potential.
  • SplicingCompass - detect differential splicing using RNA-Seq data.
  • SplitSeek - predict splice events from RNA-Seq data.
  • STAR - identify alternative splicing.
  • SUPPA - identify alternative splicing.
  • TopHat - map splice junctions for RNA-Seq reads.

Databases

  • ASIP - Alternative Splicing in Plants.
  • ASG - Alternative Splicing Gallery for human genes.
  • ASPicDB - Alternative Splicing PredICtion DataBase.
  • ENSEMBL - Human and mouse genome annotations.
  • FAST DB/Easana - Friendly Alternative Splicing and Transcripts Database.
  • Hollywood exon annotation database - A website for querying a relational database of constitutive and alternative human exons, by using biological and descriptive features.
  • HS3D - Data set of Homo Sapiens Exon, Intron and Splice regions extracted from GenBank Rel.123.
  • H-DBAS - Human-transcriptome DataBase for Alternative Splicing.
  • MAASE - Convenient access, identification, and annotation of alternative splicing events (ASEs), designed specifically with experimentalists in mind.
  • Pro-Splicer - Alternative splicing database based on protein, mRNA, and EST Sequences.
  • SpliceNest - Visualizing splicing of genes from EST Data for human, mouse, Drodophila and Arabidopsis.

Review of RNA-Seq splicing tools

Tool Performs split-read alignment Transcript reconstruction (assembly) Expression Analysis (any) Gene expression analysis Transcript specific expression analysis Exon junction expression Quantitative alternative expression analysis Expression level sensitivity Output Minimum read length required or recommended Visualization tool Performs comparisons between conditions (ex. tumor vs normal) Relevant comparison to Alexa-seq Data type supported Citation
Alexa-Seq N N Y Y Y Y Y Junction "Expression and structure information for junctions and genes; UCSC track info extensive alternative expression visualization / statistics / graphs" No minimum (tested on 36bp-100bp reads) "Extensive includes custom graphs and links to UCSC browser" Y -
Cufflinks N Y Y Y Y N Y Transcript "Transcript information and expression statistics BED GTF" 75bp UCSC browser Y Y
Scripture N Y Y N N* N N Transcript* "Transcript structure information and non-parsimonious expression statistics BED" 75bp UCSC browser N N Illumina
SpliceMap N N Y Y N Y N Junction "Alignments. SAM BED Wig" 50bp UCSC browser N N
TopHat Y N N N N Y N Junction "Alignments. SAM BED Wig" 75bp N N N
MMES Y N N N N Y N Junction Identified splice junctions and p-values 25bp N N N Illumina "Wang et al.
G-Mo.R-Se Y Y N N N N N Transcript* Transcript structure information. GFF 25bp Grape Genome Browser N N Illumina "Denoeud et al.
SplitSeek Y N N N N Y N Junction Alignments. BED 50bp UCSC browser N N SOLiD only "Ameur et al.2010
GSNAP Y Y N N N N N N/A Alignments. SAM and FASTA Minimum 14bp (tested on 36bp reads) UCSC browser N N Illumina sodium bisulfite-treated DNA sequencing (for analysis of methylation status)
Tool Performs split-read alignment Transcript reconstruction (assembly) Expression Analysis (any) Gene expression analysis Transcript specific expression analysis Exon or Junction expression Quantitative alternative expression analysis Expression level sensitivity Output Minimum read length required or recommended Ability to identify rearrangements / indels Junction Identification Implementation Public tool Open Source
Alexa-seq N N Y Y Y Y Y Junction "Expression and structure information for junctions and genes; UCSC track info extensive alternative expression visualization / statistics / graphs" No minimum (tested on 36bp-100bp reads) N Database Perl/R/Unix Y
Cufflinks N Y Y Y Y N Y Transcript "Transcript information and expression statistics BED GTF" 75bp N Predicted from data C++
Scripture N Y Y N N* N N Transcript* "Transcript structure information and non-parsimonious expression statistics BED" 75bp N Predicted from data Java Y
SpliceMap N N Y Y N Y N Junction "Alignments. SAM BED Wig" 50bp N Predicted from data Python
TopHat Y N N N N Y N Junction "Alignments. SAM BED Wig" 75bp N Predicted from data C++/Python
MMES Y N N N N Y N Junction Identified splice junctions and p-values 25bp N Predicted from data Published algorithm only N N/A
G-Mo.R-Se Y Y N N N N N Transcript* Transcript structure information. GFF 25bp N Predicted from data Perl Y** Y
SplitSeek Y N N N N Y N Junction Alignments. BED 50bp Y Predicted from data Perl Y Y (GPL)
GSNAP Y Y N N N N N N/A Alignments. SAM and FASTA Minimum 14bp (tested on 36bp reads) Y Database or predicted form data "Source code in C utility programs in Perl" Y
Tool Performs split-read alignment Transcript reconstruction (assembly) Expression Analysis (any) Gene expression analysis Transcript specific expression analysis Exon or Junction expression Quantitative alternative expression analysis Expression level sensitivity Output Minimum read length required or recommended Ability to identify rearrangements / indels Junction Identification Implementation Public tool Open Source
Alexa-seq N N Y Y Y Y Y Junction "Expression and structure information for junctions and genes; UCSC track info extensive alternative expression visualization / statistics / graphs" No minimum (tested on 36bp-100bp reads) N Database Perl/R/Unix Y
Cufflinks N Y Y Y Y N Y Transcript "Transcript information and expression statistics BED GTF" 75bp N Predicted from data C++
Scripture N Y Y N N* N N Transcript* "Transcript structure information and non-parsimonious expression statistics BED" 75bp N Predicted from data Java Y
SpliceMap N N Y Y N Y N Junction "Alignments. SAM BED Wig" 50bp N Predicted from data Python
TopHat Y N N N N Y N Junction "Alignments. SAM BED Wig" 75bp N Predicted from data C++/Python
MMES Y N N N N Y N Junction Identified splice junctions and p-values 25bp N Predicted from data Published algorithm only N N/A
G-Mo.R-Se Y Y N N N N N Transcript* Transcript structure information. GFF 25bp N Predicted from data Perl Y** Y
SplitSeek Y N N N N Y N Junction Alignments. BED 50bp Y Predicted from data Perl Y Y (GPL)
GSNAP Y Y N N N N N N/A Alignments. SAM and FASTA Minimum 14bp (tested on 36bp reads) Y Database or predicted form data "Source code in C utility programs in Perl" Y

* Transcript expression values are non-parsimonious

** Not supported (current version not stable)

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