1. Home: Startpage of the tool: search and visualize variations.
2. About: Extra information about the project and the paper.
3. Cite: Information about the paper, contributers,...
4. Data: List of additional resources and download links.
5. Help: This help page.
6. IGV: Additional help specific to IGV
7. Search: Search specific variations by type, region, impact,...
8. Contact: Form to contact the authors.

1. Launch IGV

   Launch IGV at the specified location (3) See: Launch IGV from webtool.

2. Query

   The query-input-field accepts different types of input:

   • Genome Location (e.g.: chr17:38449837-38531026,...)
   • Gene Identifier (e.g.: BRCA1, ENSG00000012048,...)
   • Transcript Identifier (e.g.: NM_007294, ENST00000393691,...)

   When the input doesn't result in a unique genomic location (For example: gene has multiple transcripts), a popup is displayed which alows the user to select an unique location.

   1. Click a gene-identifier to show/hide the list of transcripts.
   2. Click a transcript to visualize the variations within this region.
   3. Click Cancel to abort the query.

3. Genome Location

   This field will always contain the current genome location visualized.
   It is also an editable field which enables direct modification of the current visualized location. (e.g.: chr17:38449837-38531026,...)

4. Genome- or exonview

   This select controls whether the complete region is visualized or only the exons within this region.
   This is of course only applicable when a transcript was selected via the Select transcript popup.

5. Go

   Submit the query.

6. Transcript

   The visualized transcript is displayed here. when the sequence is zoomed, this field will still display the visualized transcript.
   Logically, this field is empty when a none-transcript-region is visualized.

7. NCBI Blast

   When this button is clicked, a popup window will allow the user to paste a nucleotide sequence and blast it against the NCBI nucleotide blast database.
   The top results are listed and can be used as input to visualize the variations in the corresponding gene (transcript).

8. Select All cell-lines

   When this link is clicked, the boxes of ALL the cell-lines (9) will be checked.

9. History

   The webtool remembers all visualized locations during a session. The drop down menu provides an easy way to view this visualization history an to jump back (or forward) to a previously visited location.

   The history is grouped by query (2). Each transcript and its sub-locations are stored as en new entry. E.g.:

   • NM_000546 - chr17:7512444-7531593 : Initial visualization of transcript NM_000546.
   • NM_000546 - chr17:7518517-7521233 : Zoom of transcript NM_000546.
   • - chrX:1-250 : Direct genome location: no transcript info available.

10. Select cell-lines

    The tool allows the user to choose which cell-lines to include in the visualization. Checking the checkbox of a cell-line will include the line in the visualization. un-checking the box will exclude this line.

1. Variation Indicator

   Each variation is visualized as a bar on the graph overview. The color indicates the type of variation; see (6).

   Clicking a variation indicator will slide the corresponding 'Raw' Sequence into view and display the additional variation info of this specific variation.

2. Sequence frame indicator

   This triangle indicates the location the sequence frame is visualizing. (see Sequence frame)

3. Gene Annotation

   The graph is annotated with the genes overlapping with the visualized region.

   In the example RPSA - NM_001012321 is visualized. This region is indicated by the purple graph.
   The left arrow indicates the region associated to the gene RPSA extends to left of the visualized region.

   SNORA6 and SNORA62 are genes who are overlapping the visualized region of RPSA - NM_001012321

4. Exons

   The graph also highlights the exons, of the visualized transcript, by means of a transparent white square. In the example RPSA - NM_001012321 has six exons.

5. Copy number

   The copy-number of each cell-line is visualized via a black transparent square.
   The actual value can be found in the middle of the square (1) or by hovering over any position of the square (2).

6. Legend

   Each Variation-type gets a unique color assigned which is used throughout the graph and sequence.

   1. Deletion
   2. Substitution
   3. SNP
   4. Insertion

Zoom

The graph allows the user to zoom in to a certain region by clicking on the graph and dragging the mouse until the selection encompasses the desired region.

Once the user stopped dragging and releases the mouse-button, a dialog will pop up to confirm whether the jump to the new location should be made.

1. The new visualization location
2. Abort zoom
3. Zoom

The result of the zoom on the left is added below... (hover over the miniature to expand it...)

The previous zoom-example produced the following graph: This zoomed location will be used to describe the 'raw-sequence' -section.
The image below is a bit redacted so all variation-types could be displayed on one image. (A section was cut out, indicated by the dots...)

1. Position indicator

   Each twenty nucleotides the current chromosomal position is displayed.

2. Cell-line name

   On the left of the sequence the name of the visualized cell-line is displayed.

3. Variation

   

   Each variation is is color coded (see Graph - Legend).
   All variations are also clickable. The variation details of a specific variation will be shown when clicked.

   Each start of a new variation is indicated by a little triangle. This can come in handy when variations whiting a single cell-line overlap...

   Example: CDH1 - NM_004360 @ chr16:67334695-67334823

4. Scroll

   Scroll through the sequence via the scrollbar.
   Scrolling will updated Graph - Sequence frame indicator

1. Location

   The exact location of the variation.

2. IGV

   Open de variation location in IGV (see) Launch IGV from webtool.

3. Close

   Close the additional information.

4. Alternative 1

   The variation on the one the alleles

5. Alternative 2

   The variation on the one the other allele

6. Variation Annotation

   Extra information about the characteristics of the variation

It is possible that variations start at the same location. This is handled by displaying the information for both variations.
Example: chr10:67759342-67759343. (Hover over the image to expand.)