PaVE: the papillomavirus episteme

DataTables has a built in search algorithm referred to as "smart" searching. A smart search in DataTables provides the following abilities:

• Match words out of order. For example if you search for Allan Fife it would match a row containing the words Allan and Fife, regardless of the order or position that they appear in the table.
• Partial word matching. As DataTables provides on-the-fly filtering with immediate feedback to the user, parts of words can be matched in the result set. For example All will match Allan.
• Preserved text. DataTables 1.10 adds the ability to search for an exact phrase by enclosing the search text in double quotes. For example "E1 " will match only text which contains the phrase E1 followed by a space or nothing. It will not match E1^E4 However, "E1" will still match E1^E4.

PaVE features a taxonomy search function. To search based on taxonomy click on the "Search Database" under the "Search" tab in the PaVE web site top navigation. In the "Select Filters" list click on "Taxonomy" to open the taxonomy filter modal window. To select a taxonomic group including all of the subgroups below it, simply click on the check box next to the group name. You may select multiple taxonomic groups in this way. Scroll up and down to see all of the groups. To make finer selections specific to taxonomic subgroups, select or deselect subgroups. When all of your selections have been made. Click the "Done" button at the top of the window. The search filter will instantly be applied to the search results. Each selection that you made will appear in the "Taxonomy" chip at the top of the search results table to indicate that your filter is applied.

The fastest way to clear a specific filter is to close the filter chip listed at the top of the table. Filters can also be deselected in the filter lists if you don't want to remove all selections for a given filter.

You can select rows from the table by clicking on them! If you want to select all of the displayed rows in the table, use the "Select All" link at the top of the table. The sequences can then be downloaded by selecting the desired format from the "Download" menu.

You can select subtrees in the phylogenetic tree by:

• Selecting a genus in the legend. Each genus selected will be highlighted in the tree. Multiple genera can be selected, but they will all be highlighted in the same color.
• Clicking on a node (the little circles at the branch junctions) and selecting what to highlight.

All selections made from the legend are highlighted in the same color. Selections made by clicking the nodes within the tree are made in a different color from the legend selections, but all node selections are highlighted in the same color.

Hiding all branches for a given genus based on selections from the legend is not possible, as the genera are often interleaved on parental branches, but branches in the tree can be hidden by clicking on the node circles and selecting "Collapse subtree."

There are several reasons that phylogenetic tree generation can fail. If the error says the "Jukes-Cantor-like Mk-model distances cannot be computed when only variable sites are present", the issue is that there is too much variability in the input sequences; they aren't related enough to form a phylogenetic tree. Additional FAQs related to PAUP*, the program used by PaVE to generate the phylogenetic tree, can be found in the official PAUP* documentation.

All BLAST searches in PaVE are run against our curated set of genomes. To run a BLAST search, either click on the "Search" tab in the PaVE web site top navigation, then select "PV Specific BLAST", or select a feature in the Locus Viewer by going to the "Search Database" page under the "Search" tab and clicking on the name of a genome and then select BLAST; the form will be filled in with the feature's sequence.

While the BLAST+ programs provide many options, PaVE only uses the '-evalue' and '-outfmt' flags to provide the user selected E-value to BLAST and request the output formats that we use for display and download. All other options are run with the default values for the selected program. This should work well for most searches, but is not ideal for all.

PaVE's BLAST form only accepts FASTA formatted input. A sequence in FASTA format begins with a single-line description, followed by lines of sequence data. The description line (defline) is distinguished from the sequence data by a greater-than (">") symbol at the beginning. Example:

>GENE X PROTEIN 
QIKDLLVSSSTDLDTTLVLVNAIYFKGMWKTAFNAEDTREMPFHVTKQESKPVQMMCMNNSFNVATLPAE
KMKILELPFASGDLSMLVLLPDEVSDLERIEKTINFEKLTEWTNPNTMEKRRVKVYLPQMKIEEKYNLTS
VLMALGMTDLFIPSANLTGISSAESLKISQAVHGAFMELSEDGIEMAGSTGVIEDIKHSPESEQFRADHP
FLFLIKHNPTNTIVYFGRYWSP

Blank lines are not allowed in the middle of FASTA input, but a blank line is allowed between sequences in the input.

Sequences are expected to be represented in the standard IUB/IUPAC amino acid and nucleic acid codes, with these exceptions: lower-case letters are accepted and are mapped into upper-case; a single hyphen or dash can be used to represent a gap of indeterminate length; and in amino acid sequences, U and * are acceptable letters. Before submitting a request, any numerical digits in the query sequence should either be removed or replaced by appropriate letter codes (e.g., N for unknown nucleic acid residue or X for unknown amino acid residue).

Use the E-value cutoff selection in PaVE's BLAST search window. Click on the "Search" tab in the PaVE web site top navigation, then select "PV Specific BLAST". Under the BLAST Search tab, you will see the E-value cutoff option. E-values are the probability of finding a similar hit by chance alone, thus the lower the E-value, the higher the quality of your BLAST hit. To set the filter to a higher stringency (and return fewer, higher quality results), lower the value. E-value cutoff value options are: 10, 0.1, 1e-05, and 1e-10. By default, the value is set to "1e-10".

BLAST results on PaVE are returned in a table format sorted by E-value. To view the sequence query aligned to the BLAST hit, click on the plus icon on the left hand side of the results table to open the alignment results.

The L1 typing tool is designed to assist users in gauging the probability that their sequence belongs to a novel PV type based on the similarity of its L1 gene sequence to current PV types in the PaVE database. The tool was developed by Piet Maes, at the Katholieke Universiteit Leuven. The tool generates alignments with MAFFT and uses PAUP* to construct the phylogenetic tree.

Users should refer to the Submission page for details regarding the official type assignment process.

PaVE's L1 typing tool only accepts FASTA formatted input of putative L1 genes. It is recommended that users not upload more than 10 sequences at a time. The more sequences the user submits, the longer the user will need to wait for a result.

A sequence in FASTA format begins with a single-line description, followed by lines of sequence data. The description line (defline) is distinguished from the sequence data by a greater-than (">") symbol at the beginning. Example:

>L1 gene new type
atgactttgtggctgccaacgacgggtaaagtatacttgcctccaacaccaccagtagcccgggtgcaaagcacggatgattatgtggaaagaacaagtgtgttctatcatgctatgagtgatcgtctactaactgtaggacacccattttatgatgtgagatccagtgatggctcaacaattgaggttcctaaagtctcaggaaatcaatatagagcttttagggtccgtttaccggatccgaataaatttgctttagcagacatgtcagtctataacccagaaaaagaaagattagtttgggcttgtgcaggcttggagataggccgaggacagccacttggagtaggtacatcaggccatcccttatttaataaattaagggatacagaaaacaatagtaattatcagggtgggtcacgggacgacagacagaacacatcttttgatccaaaacaggttcaaatgtttgttgtaggatgtgttccatatatgggagaacattgggataaagcacctgtttgtgcatccgaaaaaaataatcaaagagggctatgtccaccactagaactaaaaaatacagtaatagaagatggggatatgtttgacatagggtttgggaatattaataataaagagctttccattaacaagtcagatgttagtttagatatagtaaatgaaatatgcaaataccctgactttttaacaatgtctaatgatgtttatggggacgcatgtttcttttttgccagaagagagcaatgttatgccagacattattttgtaaggggaggtaatgtaggtgatgctattcccgatggcactgttaatcaggaccacaaatattacttgcctgccaaatcagaccaacaacagtatattttaggcaattctacttattttcccactgttagtggttctttggtaacctcagatgcacaactttttaataggcctttttggttacgtagagcacaaggacacaataatggtatactgtggggaaaccagatatttattacagttgctgacaatacaagaaacaccaacttttccattagtgtttccactgaagatggaccagttacagaatacaatgctcagcaaataagagaatatttaagacatgttgaagaatatcaactatcatttattttacagctttgtaaagtatctttaaaggctgaggtcttaacgcaaattaatgcaatgaattctgatatattggaggattggcaattaggatttgtacctactccagataattcagtacatgatttgtataggtacattagttccaaggctactaaatgtcctgatgctgctgtagaaaaagaaagagaagatccctttggaaaatacacgttttggaatgtagatttaagtgaaaagttatccttagatttagatcaatatcctttaggaaggaaattcttatttcagtctggattgcaaactagacctagaattgtacgatcctctgtaaaagtgtccaaaggcacaaagcgtaaacggtcgtga

Blank lines are not allowed in the middle of FASTA input, but a blank line is allowed between sequences in the input.

Sequences are expected to be represented in the standard IUB/IUPAC nucleic acid codes, with these exceptions: lower-case letters are accepted and are mapped into upper-case; a single hyphen or dash can be used to represent a gap of indeterminate length. Before submitting a request, any numerical digits in the query sequence should either be removed or replaced by appropriate letter codes (e.g., N for unknown nucleic acid residue).

Click on your feature of interest (coding sequence, origin of replication, source, etc.). The pane "Selected Feature Details" will display detailed information about the feature that you have selected. The pane "Selected Sequence Details" will display the entire locus sequence with your selected feature highlighted.

There are four (4) main components on the Structure Viewer page. The first component you see is the Mol* structure viewer. A detailed user guide for Mol* is available at https://molstar.org/viewer-docs/; be sure to check it out! The viewer will display the structure selected by the user (or the most similar structure to the protein the user selected), along with the sequence of the first chain listed in the PDB file. Use the drop down menus at the top of the viewer to change which chain is displayed.

The second component is the sequence alignment, which displays the alignment between the sequence of the displayed structure and a protein. The protein will either be the one the user requested to view the structure for, or the most similar protein to the structure sequence if no protein was selected. You can change which protein sequence is aligned to the structure sequence by selected a new protein from the Homologous Sequences table, which is the third major component on the page.

The Homologous Sequence table lists all of the proteins in PaVE that are the same type as the protein the currently viewed structure was made from (e.g. L1). The listed sequences can be filtered by minimum percent identity, either by changing the number displayed in the text above the table, or by using the slider. The table lists the protein ID, percent identity, and displays what portion of the protein is covered by the structure (grey).

The final component visible on the page is the Related Structures list. These are structures that either come from the same type of protein (e.g. L1), or that represent a different chain in the current structure. Selecting an ID from this list will refresh the page to display information related to that structure.

You can view the structure viewer in full screen mode by selecting the square corners icon (below the wrench) from the vertical tools list in the viewer window.

The tools menu on the right side of the viewer can be shown/hidden by selecting the wrench icon in the vertical tools list in the viewer.

Selections can be made by clicking directly on the structure, by clicking on an amino acid in the sequence at the top of the structure viewer, or by selecting a location in the alignment below the viewer. To select more than one location at a time you can click and drag along the seuqence at the top of the viewer, or hold the shift key to make multiple selections on the structure or alignment.