HPMV: Website Tutorial

HPMV can be used with a variety of different workflows with different inputs and outputs. This tutorial outlines a typical workflow starting with genome coordinates and exploring the interactive cartoon.

1. Mapping Genome Coordinates to Protein Mutations

Starting at the main page, follow the link to map genome coordinates for cartoons:

Main Page - with Genome Coordinates link highlighted

Then load the GRCh38 Example data, specify that the coordinates are relative to GRCh38, and Submit the form

Genome Coordinates Form - with GRCh38 Example ready to submit

…which forwards to the Protein Mutations form (below).

2. Showing Information for Protein Mutations

Protein accessions and their mutations can also be submitted using the main page and there is a separate form for FASTA sequences to calculate the cartoon features on-the-fly.

In this case, simply Submit the protein mutations that were mapped from the genome coordinates (above):

Protein Mutations Form - with Submit button highlighted

…which forwards to a page showing a cartoon for each protein (below).

3. Protein Cartoons

If more than one protein is submited (as above), then the cartoons for each protein are show together on a single page. As an aside, a standalone viewer embedded with the data for each protein can be downloaded using a link in the box at the top of the page.

But, for this tutorial, simply scroll down to the cartoon for the Amyloid beta A4 protein (at the bottom of the page)…

All cartoons on one page - top of page

…and click (anywhere) on the cartoon for the prion protein (PRIO_HUMAN) to go to its detailed interactive cartoon:

All cartoons on one page - bottom of page

4. Detailed Interactive Cartoon

The detailed interactive cartoon consists of a cartoon image at the top of the page showing the locations of features and mutations along the sequence, a multiple sequence alignment of similar sequences from other organisms in the middle of the page, and a Feature Tree show detailed information about each feature and mutation at the bottom of the page. When interpreted mutations are present a short paragraph of the interpretation is provided just above the feature tree. The underlying databases and algorithms are described separately.

interactive cartoon - initial view

Click on the "S230L" mutation and expand the relevant nodes of the Feature Tree to view the detailed information for this mutation and its interpretation:

interactive cartoon - mutant interpretation view

Finally, click on the "Prion" domain and the "4kml_A" structure and expand the relevant node to display the multiple sequence alignment for the Prion Pfam domain and to display the location of the "A117E" mutation on the 4kml_A structure (the numbering relative to the structure is shown in parentheses):

interactive cartoon - domain MSA and 3D structure

5. Direct URL Linking to Protein Information

Features are precalculated for each of the reviewed human UniProt (SwissProt) proteins. The detailed information page for each protein can be linked directly in a URL. For example, the link to the A4 protein information shown above is:

http://hpmv.bii.a-star.edu.sg/SeqLink?acc=P05067&mut=V123L

Note that multiple mutations can be listed as:

http://hpmv.bii.a-star.edu.sg/SeqLink?acc=P05067
&mut=V123L&mut=T456M&mut=D678N