Visualizing the genome: techniques for presenting human genome data and annotations

Abstract

Background: In order to take full advantage of the newly available public human genome sequence data and associated annotations, biologists require visualization tools ("genome browsers") that can accommodate the high frequency of alternative splicing in human genes and other complexities.

Results: In this article, we describe visualization techniques for presenting human genomic sequence data and annotations in an interactive, graphical format. These techniques include: one-dimensional, semantic zooming to show sequence data alongside gene structures; color-coding exons to indicate frame of translation; adjustable, moveable tiers to permit easier inspection of a genomic scene; and display of protein annotations alongside gene structures to show how alternative splicing impacts protein structure and function. These techniques are illustrated using examples from two genome browser applications: the Neomorphic GeneViewer annotation tool and ProtAnnot, a prototype viewer which shows protein annotations in the context of genomic sequence.

Conclusion: By presenting techniques for visualizing genomic data, we hope to provide interested software developers with a guide to what features are most likely to meet the needs of biologists as they seek to make sense of the rapidly expanding body of public genomic data and annotations.

Figure 1

Annotated GeneViewer screen capture showing FLJ22324, a six-exon gene inferred from a cDNA-to-genomic sequence alignment.(a) The high-level structure at low zoom. (b) A close-up view of a questionable small intron separating exons 5 and 6. Dinucleotide bases at this intron's 5' and 3' boundaries are underlined.

Figure 2

Hypothetical example showing how semantic zooming could be used to represent gene structure annotations based on cDNA-to-genomic sequence alignments.(a) Low zoom. (b) High zoom.

Figure 3

SNURF locus.(a) The full scene is shown with multiple annotation types sorted into labeled tiers. (b) A simplified scene is shown in which several tiers shown in (a) have been hidden, collapsed, or moved to new positions. The horizontal slider has been used to expand the display in the vertical direction.

Figure 4

Using color to represent frame of translation at the ARG1 locus. Coding regions in each exon are colored according to which frame of the genomic sequence is translated. A different color for overlapping exons from different transcripts indicates these exons are translated in different frames.

Figure 5

Protein motifs detected by Pfam are displayed beneath alternative transcript structures (a,b) at the PLAT locus. Alignments between genomic sequence and cDNA sequences (a) BC002795.1 and (b) NM_0009301 are shown. Regions encoding matches to Pfam motifs PF00008 (EGF-like domain), PF00051 (Kringle), PF00089 (Serine proteases, trypsin family), and PF00039 (Type I fibronectin) are shown as linked green rectangles below each alignment.