Vials

Visualizing Alternative Splicing of Genes

Hendrik Strobelt, Bilal Alsallakh,
Joseph Botros, Brant Peterson,
Mark Borowsky, Hanspeter Pfister, and Alexander Lex

Vials is an interactive, visual system to support investigation of measures for: Isoform Abundance, Base-Pair/Exon Reads, Junction Reads for a large set of Samples

“ Models are human-made simplifications for the complicated reality. ”
-- Hr. Richter

Visualizing Alternative Splicing of Genes

  • A gene is a functional region of DNA.

Visualizing Alternative Splicing of Genes

  • When DNA is converted to mRNA, non-coding regions are omitted. This process called splicing creates a building plan for proteins.
  • Alternative splicing describes alterations in this process.

Visualizing Alternative Splicing of Genes

  • RNA can be sequenced by a process called RNAseq.
  • After alignment, some reads span more than one exon - they are called Junction Reads.

Visualizing Alternative Splicing of Genes

Glossary

  • Isoforms ( )
  • Reads
  • Junction Reads ( )
  • A Sample is a measure for one tissue or one person or one pathological condition

Vials supports investigation of measures for:
Isoforms ,
Reads,
Junction Reads

for a large set of Samples

Visualizing Alternative Splicing of Genes

Why?

Domain Goals

  • G1 - Explore differences between samples and group of samples
  • G2 - Discover novel isoforms
  • G3 - Evaluate isoforms
  • G4 - Control Data Quality

How? Data Model

Multivariate Graph (ordered DAG)

  • Exons are nodes.
  • Junctions are edges.
  • Abundances of Junction Reads are edge attributes
    (many values from many samples)
  • Isoforms are paths through this directed graph.

Related Work - Sashimi Plots*

  • encode Junction Reads as line width

*Katz et. al., Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nature Methods (2010)

Related Work - Sashimi Plots II

Li, Sheng, et al. "Multi-platform assessment of transcriptome profiling using RNA-seq in the ABRF next-generation sequencing study." Nature biotechnology 32.9 (2014): 915-925.

How? - Visual Encoding for Vials

  • optimized for scalability towards number of samples
  • views are aligned along a genomic coordinate system
  • each data type has a unique highlighting color
    red for samples
    yellow for isoforms
    blue for junctions

Encoding of Sample Reads

  • Reads View is the central place to work with samples
  • depicts read abundance per gene location

Encoding of Sample Reads

Encoding of Isoforms

  • isoforms are encoded as combinations of exons (rectangles)
  • encode estimate value per isoform by position (dot plot and box plot)
  • allow sorting isforms by value mean or existance of a specific exon

Encoding of Isoforms

  • isoforms are encoded as combinations of exons (rectangles)
  • encode estimate value per isoform by position (dot plot and box plot)
  • allow sorting isforms by value mean or existance of a specific exon

Encoding for Junction Reads

  • encode abundance value per jxn and sample by position (dot plot)
  • asymmetric encoding of start (area) and end (line) of an edge

All Views Combined

Conclusion

  • For the first time, Vials allows efficient comparison between samples and groups of samples for alternative splicing events.
  • The paper contains more details about:
    • biological variants
    • design iterations
    • case studies
Feedback:
“I am very interested in trying Caleydo/Vials with some of my sequencing data...”

“... [X] told me that you might be able to help me out with looking at some splice variants of a few genes of interest”

“I took a look at the VIALS website and was very impressed. Easily among the best tools for visualizing AS that I have come across.”

Vials

Visualizing Alternative Splicing of Genes

Hendrik Strobelt, Bilal Alsallakh,
Joseph Botros, Brant Peterson,
Mark Borowsky, Hanspeter Pfister, and Alexander Lex

Open Source and Deployed at:
http://vials.io/