diff --git a/mutalyzer/templates/disclaimer.html b/mutalyzer/templates/disclaimer.html
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-<html>
- <head>
- <title></title>
- </head>
- <body>
- <div metal:define-macro="content">
- <center>
- <h3>Disclaimer</h3>
- </center>
- We have used all reasonable efforts to ensure that the information
- displayed on these pages is of high quality. We make no warranty, express
- or implied, as to its accuracy or that the information is fit for a
- particular purpose, and will not be held responsible for any consequences
- arising out of any inaccuracies or omissions. Individuals, organizations
- and companies which use this program do so on the understanding that no
- liability whatsoever either direct or indirect shall rest upon the Leiden
- University Medical Center (LUMC) or any of their employees or agents for
- the effects of any product, process or method that may be produced or
- adopted by any part, notwithstanding that the formulation of such
- product, process or method may be based upon information here provided.
- <br>
- <br>
- <br>
- Please note that all input is logged. We do this to monitor the
- correctness of Mutalyzer by identifying input that causes an error. In
- this way, bugs in the software are automatically detected without the
- user having to file a bug report. We will under no circumstance publish
- the variants in this log, share it with anyone or use it for purposes
- other than the one stated above.
- </div>
- </body>
-</html>
diff --git a/mutalyzer/templates/exercise.html b/mutalyzer/templates/exercise.html
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-<html>
- <head>
- <link rel="stylesheet"
- type="text/css"
- href="base/css/style.css">
- <title></title>
- </head>
- <body>
- <div metal:define-macro="content">
- <center>
- <h3>Sequence variation nomenclature checker demonstration</h3>
- </center>
-
- <h3>Checking sequence variation nomenclature</h3>
- <p>
- A few tools are available to check sequence variation nomenclature:
- </p>
- <ul>
- <li>
- <a href="http://mutation.sanbi.ac.za/checker">DNA Mutation Checker
- 3</a> - Basic sequence variation check.<br> This basic mutation check
- should be followed/supplemented by a sequence variation check
- including splice site changes
- </li>
- <li>
- <a href="index">Mutalyzer</a> - Sequence variation nomenclature
- checker generating descriptions according to <a
- href="http://www.hgvs.org/mutnomen/">HGVS nomenclature guidelines</a>
- </li>
- </ul>
-
- <h3>Mutalyzer sequence variation nomenclature checker</h3>
- <p>
- <a href="index">The Mutalyzer sequence variation nomenclature
- checker</a> has been developed as the first part of an integrated
- modular package of tools, which should allow users to obtain
- information about the effect of sequence variations in genes associated
- with human disease. The <a href="index">Mutalyzer</a> package (under
- development) should assist decision-making in molecular diagnosis based
- on a sequence change detected in a patient's DNA and prevent
- misdiagnosis caused by either missing the pathogenic effect of a
- sequence variation reported as "polymorphic" or, more
- seriously, reporting a polymorphic change as non-pathogenic.
- </p>
-
- <h3>Exercise</h3>
- <p>
- For this exercise, it is most convenient to right-click this
- <a href="check">link</a> and open a separate window for Mutalyzer. The
- exercise will demonstrate the use of the different functionalities of
- the Mutalyzer sequence variation nomenclature checker. Its main
- functions can be selected from the
- <a href="index">index page</a> or the list on the left side of any
- Mutalyzer window. For more information, please check this
- <a href="help">help</a> file. Although the performance of Mutalyzer has
- been checked using complete sequence variation database contents, some
- changes might not be processed correctly. Please report any strange
- results to <a href="mailto:mutalyzer@humgen.nl">mutalyzer@humgen.nl</a>
- </p>
-
- <h3>Selecting a reference file</h3>
- <p>
- Mutalyzer needs the annotation of a Genbank reference sequence file to
- retrieve basic information for the check. Its functionality can be
- appreciated best using well-annotated genomic reference sequences,
- which contain information about all the transcripts and proteins
- encoded by the reference sequence.
- </p>
- <p>
- For many disease genes, LSDB curators should have specified a reference
- sequence, preferably by listing its GenBank accession number. In many
- cases, this will be a RefSeq record with an accession number starting
- with NM_ (or XM_). These records describe transcript sequences and
- cannot be used by Mutalyzer to describe intron variants. If you need to
- check intron variants, please ask the LSDB curator to specify a
- well-annotated genomic reference sequence. (See
- <a href="http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=Nucleotide&dopt=GenBank&val=16944057">AL449423.14</a> or NCBI's new
- <a href="http://www.ncbi.nlm.nih.gov/RefSeq/RSG/">RefSeqGene</a>
- records for example). Alternatively, you can use the Reference File Loader
- options described below to obtain a suitable genomic reference
- sequence. If the annotation of this record contains information about
- the transcript specified by the NM_ number, Mutalyzer can use the
- genomic sequence record to describe any variant relative to this
- transcript. Always use an Accession number (AL449423) in combination
- with a specific version number (14). Otherwise, Mutalyzer automatically
- uses the last version and may present unexpected results.
- </p>
- <p> </p>
-
- <h3>
- Before you start: Save
- <a href="downloads/batchtestnew.txt">this tab-delimited text file</a>
- to your Desktop and open it in WordPad.
- </h3>
-
- <p>
- 1) The Mutalyzer Name Generator
- </p>
- <p>
- The Mutalyzer Name Generator provides an easy check of a sequence
- variation by returning the correct name of the variation according to
- HGVS nomenclature guidelines with information about the sequence
- surrounding the variation and the transcripts and proteins affected by
- the variation. Mutalyzer accepts in principle any Genbank sequence as a
- reference, but its functionality can be appreciated best using
- well-annotated genomic reference sequences.
- </p>
- <p>
- <i>Enter the accession number AL449423.14 as a reference sequence,
- select "genomic DNA", enter start position "1", stop
- position "1", select "deletion" and press
- submit.</i>
- </p>
-
- <p>
- The legend of the results describes the transcripts and proteins
- annotated in the reference sequence.
- </p>
-
- <h3>
- Add the description generated by Mutalyzer as a new line to the
- tab-delimited text file. Make sure that the AccNo, Gene symbol and
- description are separated by a single tab. Repeat this for all variants
- in this part of the exercise.
- </h3>
- <p>
- <i>On the Mutalyzer page, now select "coding DNA", enter one
- of the gene symbols from the legend, and press submit to see the effect
- of a change on the major transcript </i>(optional: enter, in addition
- to the gene symbol, the number of a transcript variant, e.g., 2 or v002
- for the second transcript annotated in the record)<i>.</i>
- </p>
- <p>
- <i>Repeat this for the other gene symbols, additional sequence
- variation types, changes in introns, across intron exon boundaries,
- etc. </i>You may check the <a href="http://www.hgvs.org/mutnomen/">
- HGVS nomenclature guidelines</a> or <a
- href="http://www.hgvs.org/dblist/dblist.html">sequence variation
- databases</a> for inspiration.
- </p>
- <p> </p>
-
- <h3>
- Save theWordPad file containing the sequence variation descriptions to
- generate the text file for use with the batch checker in the third part
- of the exercise.
- </h3>
- <p> </p>
- <p>
- 2) The Mutalyzer Name Checker
- </p>
- <p>
- The Name Checker is most convenient when checking a few sequence
- variations, which have been described in a putative correct format. The
- description made by the generator can be submitted to the name checker
- to regenerate the additional information. It also allows you to change
- and check descriptions fast, once you get a feeling for it.
- </p>
- <p>
- <i>Submit one of the descriptions generated by the Mutalyzer Name
- Generator by pasting it into the submission box and pressing the submit
- button.</i>
- </p>
- <p>
- <i>Repeat this after changing the positions or nucleotide(s).</i>
- </p>
- <p>
- Submit these descriptions to see the importance of a version number:
- NM_000787.3:c.61A>G and NM_000787.2:c.61A>G.
- </p>
- <p>
- Compare the CDS annotation of the corresponding files
- <a href="http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nuccore&id=116534899">NM_000787.3</a> and
- <a href="http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=18426905">
- NM_000787.2</a> to see why Mutalyzer gives a different result.
- </p>
- <p>
- How does NM_000787.3:c.61A>G compare to NM_000787.2:c.19A>G ?
- </p>
- <p> </p>
- <p>
- 3) The Mutalyzer SNP converter
- </p>
- <p>
- The SNP converter has been developed to convert dbSNP identifiers to
- HGVS compliant variant descriptions, based on the GenBank nucleotide
- reference sequence specified by the user.
- </p>
- <p>
- <i>Submit</i> rs9919552 <i>as SNP Accession number and</i> NM_003002
- <i> as Nucleotide Accession number.</i>
- </p>
- <p>
- <i>Open the UCSC Human Genome Browser in a new window to see additional
- SNPs for this gene.</i>
- </p>
- <p> </p>
- <p>
- 4) The Mutalyzer sequence variation description batch checker
- </p>
- <p>
- The batch checker has been developed for database curators, but can be
- used with any list of sequence variations provided that they are
- submitted in the correct format: a tab-delimited text file.
- </p>
- <p>
- <i>Open the WordPad file containing the sequence variation descriptions
- that you have checked before. </i>
- </p>
- <p>
- <i>Duplicate some of the entries and create a few mistakes in
- numbering, sequence type (e.g., replace duplication by insertion),
- nucleotides, description format. </i>
- </p>
- <p>
- <i>Submit the file together with your e-mail address (lower case only!)
- to see the alerts and automatic corrections created by
- Mutalyzer.</i>
- </p>
- <p> </p>
- <p>
- 4) The Mutalyzer reference file loader
- </p>
- <p>
- <span style="font-size: 12.0pt; font-family: Times New Roman">Users can
- upload their own reference sequence file in GenBank format, retrieve
- the genomic sequence of a gene with its flanking regions, or specify
- a chromosomal range for use as a reference sequence. Mutalyzer checks
- whether the file is in valid GenBank format. If so, Mutalyzer stores
- the file locally for a limited time and returns a unique
- <i> UD identifier</i> that can be used with all different forms of
- the Mutalyzer Sequence Variation Nomenclature Checker, except the SNP
- converter. This option allows users to use reference files, which are
- not present in GenBank, or add information about alternative
- transcripts or proteins or additional genes contained within or
- derived from the reference sequence to an existing GenBank file. We
- strongly recommend to limit your use of this option
- </span>
- and to send a request for a new RefSeqGene record to
- <a href="mailto:rsgene@ncbi.nlm.nih.gov">rsgene@ncbi.nlm.nih.gov</a>.
- <span style="font-size: 12.0pt; font-family: Times New Roman">
- Alternatively, you can submit annotation updates and corrections of
- existing GenBank files following <a style="color: blue;
- text-decoration: underline; text-underline: single"
- href="http://www.ncbi.nlm.nih.gov/Genbank/update.html">these
- instructions</a>.
- </span>
- </p>
- <p>
- <i>
- <span style="font-family: Times New Roman">Click the Reference File Loader
- link in
- </span> the list on the left side of any Mutalyzer window to see its
- options.
- </i>
- </p>
- <p>
- <span style="font-family: Times New Roman">
- If you already have a well-annotated GenBank file on your computer or
- stored on a web server, the first two Reference File Loader options
- facilitate easy uploading and will return the
- </span>
- <span style="font-size: 12.0pt; font-family: Times New Roman">
- unique <i>UD identifier</i>. This identifier can be used in the Name
- generator or Name Checker, which will then provide a link to download
- the record. This record can also be used as input for the LOVD
- reference sequence parser.
- </span>
- </p>
- <p>
- <span style="font-size: 12.0pt; font-family: Times New Roman">
- If you do not have
- </span>
- <span style="font-family: Times New Roman">
- a well-annotated GenBank file, the last two options can provide one.
- </span>
- Curators of LOVD databases can use these options to generate
- <span style="font-family: Times New Roman">
- well-annotated
- </span> genomic reference sequence files for import into LOVD2.0 using
- the Reference Sequence Parser 2.0.
- </p>
- <p>
- <span style="font-family: Times New Roman">
- Option 3: Retrieving a well-annotated
- </span>
- genomic reference sequence file
- <span style="font-family: Times New Roman">
- using a (<a
- href="http://www.genenames.org/guidelines.html">HGNC</a>-approved)
- gene symbol in combination with the name of the organism (e.g. human,
- mouse, etc.).
- </span>
- </p>
- <p>
- <span style="font-family: Times New Roman; font-style:italic">
- Click the corresponding radio button and try this for your favourite
- gene.
- </span>
- </p>
-
- <p>
- <span style="font-family: Times New Roman">
- In some cases, this may not work for your gene due to ambiguous gene
- symbols. If Mutalyzer mentions other problems, please report them! In
- those cases, or when you would like to include additional flanking
- sequences (e.g., promoters) you can also specify the range of a
- chromosomal sequence using the fourth option. The easiest way to find
- a chromosomal range is to search
- <a
- href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene">Entrez
- Gene</a> using the gene symbol in combination with the name of the
- organism.
- </span>
- </p>
- <p>
- <span style="font-family: Times New Roman">
- <i>
- Open <a
- href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene">Entrez
- Gene</a> in a new window and search with the gene symbol of your
- favorite gene in combination with the name of the organism. Open
- the correct link in the list of results and click on the link to
- reference sequence details under the heading "Genomic regions,
- transcripts and products".
- </i>
- </span>
- </p>
- <p>
- <span style="font-family: Times New Roman">
- Under the header "RefSeqs of Annotated Genomes", you will
- find an Acc. No starting with NC_, which refers to a
- chromosomal reference sequence. The positions behind Range refer to
- the start of the most upstream exon and the end of the most
- downstream exon, respectively.
- </span>
- </p>
- <p>
- <i>
- Click on the Genbank link to view the sequence and its annotation.
- You can save the file by changing "Send to" in the Entrez
- menu bar to "Save".
- </i>
- </p>
- <p>
- <span style="font-family: Times New Roman">
- Option 4: Retrieving a well-annotated
- </span>
- genomic reference sequence file
- <span style="font-family: Times New Roman">
- using chromosomal positions
- </span>
- </p>
- <p>
- <span style="font-family: Times New Roman; font-style:italic">
- Click the corresponding radio button and
- </span>
- <i>
- enter the NC_ Accession number and the range positions corresponding
- to the gene of interest.
- </i>
- </p>
- <p>
- You can modify the (annotation of the) genomic reference sequence file
- obtained via
- <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene">Entrez
- Gene</a>.using
- <a href="http://www.ncbi.nlm.nih.gov/Sequin/netaware.html">Network
- aware Sequin.</a>
- </p>
- <hr>
- <p>
- If you have any comments or suggestions, please let us know!<a href="mailto:mutalyzer@humgen.nl"><address>mutalyzer@humgen.nl</address></a>
- </p>
- </div>
- </body>
-</html>
diff --git a/mutalyzer/templates/faq.html b/mutalyzer/templates/faq.html
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-<html>
- <head>
- <link rel="stylesheet"
- type="text/css"
- href="base/css/style.css">
- <title></title>
- </head>
- <body>
- <div metal:define-macro="content">
- <center>
- <h3>Frequently Asked Questions</h3>
- </center>
-
- <h3>How should I refer to Mutalyzer? </h3>
- <p>
- Mutalyzer is described in:
- </p>
- <p>
- Wildeman M, van Ophuizen E, den Dunnen JT, Taschner PE. Improving
- sequence variant descriptions in mutation databases and literature using
- the MUTALYZER sequence variation nomenclature checker.
- <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3058&itool=AbstractPlus-def&uid=18000842&db=pubmed&url=http://dx.doi.org/10.1002/humu.20654">Hum Mutat 29:6-13 (2008)</a> [
- <a href="http://www.ncbi.nlm.nih.gov/pubmed/18000842?">PMID:
- 18000842</a>].
- </p>
-
- <h3>What does Mutalyzer do?</h3>
- <p>
- Mutalyzer checks sequence variant descriptions given a certain reference
- sequence and, if necessary, tries to correct them according to the
- <a href="http://www.hgvs.org/mutnomen/">HGVS nomenclature guidelines</a>.
- Descriptions of its functionality can be found in the
- <a href="help">Help file</a>.
- </p>
-
- <h3>Were can I find examples of Mutalyzer input data?</h3>
- <p>
- Most Mutalyzer web pages show an example of the input data accepted.
- Additional descriptions of input data formats can be found in the
- <a href="help">Help file</a>.
- </p>
-
- <h3>Can Mutalyzer analyze sequence traces?</h3>
- <p>
- No, Mutalyzer only checks sequence variant descriptions. Sequence
- variant descriptions can be generated from sequence traces using third
- party software, e.g., MutationSurveyor.
- </p>
-
- <h3>
- Why does Mutalyzer only accept GenBank Accession Numbers or files in
- GenBank format?
- </h3>
- <p>
- Mutalyzer has been developed to extract sequence and annotation
- information from files in GenBank format. This extraction of
- information will not work properly with other formats.
- </p>
-
- <h3>
- Why does Mutalyzer not work directly with GenBank Accession Numbers
- starting with NC_ or NT_?
- </h3>
- <p>
- GenBank Accession Numbers starting with NC_ or NT_ refer to contigs of
- smaller sequences, potentially interspaced with gaps. Mutalyzer will
- try to retrieve the underlying sequences to check the sequence variant,
- but it may lose track of the corresponding positions due to the
- different levels of assembly and return errors. Users are advised
- circumvent this problem by using the Reference File Loader when (part of)
- these NC_ or NT references are used. The
- <a href="http://www.humgen.nl/mutalyzer_exercise.html">
- Mutalyzer exercise</a> provides more detailed information.
- </p>
-
- <h3>
- Why does Mutalyzer not accept positions outside exons when using a
- coding DNA reference sequence?
- </h3>
- <p>
- Mutalyzer uses the reference sequence to check for the presence of the
- nucleotides at the positions specified. Since promoter sequences,
- intron sequences and intergenic sequences are not included in a coding
- DNA reference sequence, Mutalyzer is unable to check these and will
- issue an "Out of bounds" error. We strongly suggest to use genomic
- reference sequences to describe changes in promoter sequences, intron
- sequences and intergenic sequences.
- </p>
-
- <h3>
- I am using a genomic reference sequence, but I am still unable to check
- intron variants
- </h3>
- <p>
- Mutalyzer checks the annotation of the genomic reference sequence for
- information about the genes, their exons and protein coding sequence.
- When these features are not annotated, Mutalyzer is unable to use the
- coding DNA numbering scheme and will return an error. Please note that
- Mutalyzer ignores non-coding transcripts, because the coding DNA
- numbering scheme can not be applied in the absence of a start codon.
- The HGVS sequence variation nomenclature guidelines do not yet provide
- guidance on this issue.
- </p>
-
- <h3>How do I find the correct reference sequence?</h3>
- <p>
- Although any file in GenBank format can be used, curated RefSeq
- sequences are preferred (See
- <a href="http://www.hgvs.org/mutnomen/refseq.html">HGVS Reference
- Sequence discussion</a>). Most locus-specific mutation databases
- (LSDBs) specify reference sequences for the genes of interest. In many
- cases, these will be coding DNA reference sequences. If you want to
- check changes in promoter sequences, intron sequences and intergenic
- sequences, you should contact the curator of the LSDB to get a genomic
- DNA reference sequence.
- </p>
- <p>
- If you are the curator of an LSDB in need of an appropriate genomic
- reference sequence, you can use the options on the Reference File Loader
- page to select a genomic reference sequence. More information about the
- selection and modification of reference sequences can be found in the
- <a href="http://www.humgen.nl/mutalyzer_exercise.html">
- Mutalyzer exercise</a>.
- </p>
-
- <h3>
- I am using the correct RefSeq Accession number. Why is the position of
- most or all sequence variants on transcript or protein level different
- from what I expected?
- </h3>
- <p>
- Every GenBank file has an Accession number and a version number (e.g.
- AB026906.1). If the version number has not been specified, Mutalyzer
- will use the last version of this file. The sequence annotation of the
- last version may differ from that of an earlier version, leading to
- new/changed transcripts and protein sequence information, which is
- automatically used by Mutalyzer to describe the variants. Most
- locus-specific mutation databases (LSDBs) specify the accession numbers
- of reference sequences for the genes of interest, but they should also
- include the version number to prevent unexpected Mutalyzer results. You
- can check the influence of the version number on Mutalyzer's analysis
- by specifying a previous version number. If this solves the problem,
- please ask the curator of the LSDB to specify the correct version of
- the reference sequence.
- </p>
-
- <h3>Why does Mutalyzer fail to recognize my SNP descriptions?</h3>
- <p>
- Mutalyzer checks if
- <span style="font-size: 12pt; font-family: Times New Roman;">
- the nucleotide changed is present in the reference sequence. SNPs are
- commonly indicated in dbSNP as two or more possible alleles at the
- same position of the sequence.
- </span>
- According to the HGVS nomenclature guidelines, only alleles which
- differ from the reference can be described. As a result,
- NM_003002.1:c.204C>T is approved, but NM_003002.1:c.204T>C will
- result in an error. When the dbSNP identifier is known, the SNP
- converter can be used to generate the correct description (see the
- <a href="help">Help file</a> for more information.
- </p>
-
- <h3>
- Why does the Reference File Loader not work with my local file or the URL
- provided?
- </h3>
- <p>
- Mutalyzer checks if it gets a
- <span style="font-size: 12pt; font-family: Times New Roman;">
- <a
- href="http://www.ncbi.nlm.nih.gov/Sitemap/samplerecord.html">GenBank
- Flat file</a> in both cases. Other formats can not be processed
- correctly and will generate an error.
- </span>
- </p>
-
- <h3>
- Why do large deletions seem shorter using coding DNA position numbering
- than genomic position numbering?
- </h3>
- <p>
- The difference in deletion size is caused by our intention to reflect
- the effect of variations on transcript level, when coding DNA position
- numbering is used. Therefore, ranges of deleted nucleotides are limited
- to positions present in the coding DNA reference sequence.
- </p>
-
- <h3>
- Can Mutalyzer analyze sequence variant descriptions from other
- organisms?
- </h3>
- <p>
- Yes, Mutalyzer can check sequence variant descriptions from other
- organisms as long as a proper reference sequence is provided and the
- HGVS sequence variation nomenclature guidelines are applied. Mutalyzer
- will check the reference sequence annotation to determine which codon
- table should be used for proper translation of coding sequences.
- </p>
-
- <h3>How do I create a batch checker file?</h3>
- <p>
- The easiest way to create a batch checker file is to download the
- <a href="downloads/batchtestnew.txt">Example</a>
- file. Please right-click the link and select "Save as" to download the
- example file for modification. Open the batchtest.txt file in Excel.
- The Text Import Wizard window will open to guide you through the import
- procedure. Click "Finish" to finalize the import. The Excel spreadsheet
- created should have three columns and a header row containing the
- column names. You can add your data to the batchtest.txt file by typing
- or pasting the required information into the appropriate fields. When
- you are finished select "Save as" from the File menu and save your file
- using a different name (without spaces!) as type: Text (tab
- delimited)(*.txt).
- </p>
- <p>
- In case of problems follow the separate import steps by verifying the
- correct selections before clicking the "Next" button to go to step 2.
- Click the "Next" button to go to step 3, click "Finish" to finalize the
- import.
- </p>
-
- <h3>I am having trouble with the batch checker. What should I do?</h3>
- <p>
- The batch checker is relatively sensitive to unexpected file and file
- name formats. Users are advised to check the following:
- </p>
- <p>
- File name: The file name should not contain any spaces. Windows users
- can check the file extension: if it is not .txt, but .doc or .xls, the
- file is unlikely to be a tab-delimited textfile.
- </p>
- <p>
- File format: The tab-delimited textfile should contain a header row
- (the first line) containing the words
- <b><i>AccNo Genesymbol Mutation</i></b> separated by a single tab.
- </p>
- <p>
- File format: The file should be a tab-delimited text file. Excel users
- can import the file to check its format. The file should have three
- columns with the appropriate column names,
- <b><i>AccNo Genesymbol Mutation</i></b>, respectively. The variant
- information should be present in the corresponding columns.
- </p>
- <p>
- The Genesymbol column/field may be left blank, when the reference
- sequence contains only one gene, but a tab should be present. Please
- note that Mutalyzer does not check the correctness of the gene symbol
- in this case.
- </p>
-
- <h3>Why can't I use the bugtracker?</h3>
- <p>
- The bugtracker can only be accessed via a secure connection. Normally,
- when you try to connect securely, sites will present trusted
- identification to prove that you are going to the right place. However,
- this site's identity can't be verified by the browser because the
- security certificate is self signed (and not signed by the proper
- authorities).<br>
- A certificate that is signed by the proper authorities costs a lot of
- money, so for the time being we have solved it in this way.<br>
- To get access to the bugtracker, you need to add a security exception.
- Usually the browser presents this option.
- </p>
- <p>
-
- </p>
- <hr>
- <p>
- If you have any comments or suggestions be sure to let us know!
- </p>
- <p>
- Last modified: January 14, 2011
- </p>
- <a href="mailto:mutalyzer@humgen.nl"><address>mutalyzer@humgen.nl</address></a>
- </div>
- </body>
-</html>
diff --git a/mutalyzer/templates/help.html b/mutalyzer/templates/help.html
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-<html>
- <head>
- <title>Mutalyzer - Sequence variant nomenclature check - Help</title>
- </head>
- <body>
- <div metal:define-macro="content">
- <center><h3>Mutalyzer 2 Help</h3></center>
-
- <h3>About Mutalyzer</h3>
- <p>
- Mutalyzer is a tool primarily designed to check descriptions of
- sequence variants according to the standard human sequence variant
- nomenclature of the Human Genome Sequence Variation Society
- (<a href="http://www.hgvs.org/">HGVS</a>) (For an overview, visit
- <a href="http://www.hgvs.org/mutnomen/"
- >http://www.hgvs.org/mutnomen/</a>).
- Mutalyzer aims to encourage the proper use of nomenclature in
- publications and reduce redundancy in sequence variation databases. In
- principle, Mutalyzer can check descriptions of sequence variants
- detected in other organisms, provided that the standard HGVS
- nomenclature is applied.
- </p>
-
- <h3>Mutalyzer 2 flow</h3>
- <p>
- The user specifies a reference sequence (file) and a variant using the
- <a href="#NameGenerator">Name Generator</a> or the
- <a href="#NameChecker">Name checker</a> interface. The Name Generator
- builds the complete variant description for the Name Checker (e.g.,
- Mutalyzer uses this input to perform the nomenclature check in the
- following steps:
- </p>
- <p>
- 1) Retriever: retrieves
- <a href="#Ref">reference sequence records</a> from the
- <a href="http://www.ncbi.nlm.nih.gov/">NCBI</a> or
- <a href="http://www.lrg-sequence.org/">LRG</a> websites.
- </p>
- <p>
- 2) Reference sequence parser: extracts sequence and annotation from
- reference sequence records
- </p>
- <p>
- 3) <a href="#SyntaxChecker">Syntax checker</a>: context-free parser
- using the complete sequence variant description to check whether the
- syntax is correct according to standard HGVS sequence variant
- nomenclature
- </p>
- <p>
- 4) <a href="#NameChecker">Name checker</a>: the core nomenclature
- checker using the complete sequence variant description to check
- whether it is correct according to standard HGVS sequence variant
- nomenclature
- </p>
- <p> </p>
- <p>
- <b>Additional Mutalyzer 2 functionality:</b>
- </p>
- <p>
- - <a href="#PositionConverter">Position Converter</a>: converts hg18
- and hg19 chromosomal positions to transcript positions in HGVS n. or
- c. notation and vice versa. The n. or c. notation should be checked
- with the Name checker
- </p>
- <p>
- - <a href="#GenBankUploader">Reference File Loader</a>: allows you to
- upload and use your own reference sequence.
- </p>
- <p>
- - <a href="#SNPConverter">SNP converter</a>: allows you to convert a
- <a href="http://www.ncbi.nlm.nih.gov/projects/SNP/">dbSNP</a> rsId to
- HGVS notation.
- </p>
- <p>
- - <a href="#BatchChecker">Batch Checkers</a>: interfaces for the
- different checkers that accept a large list of descriptions as input.
- </p>
- <p>
- - <a href="#Webservices">Web services</a>: programmatic access to
- Mutalyzer's functionality.
- </p>
- <p> </p>
-
- <h2>Introduction</h2>
-
- <h3>Reference sequences<a name="Ref"></a></h3>
- <p>
- <b>
- We strongly recommend the use of genomic reference sequences
- containing proper annotation for optimal use of Mutalyzer's
- capabilities to generate descriptions for all transcripts and protein
- isoforms of the gene(s) affected by the sequence variation.
- </b>
- </p>
- <p>
- Mutalyzer accepts the following reference sequences:
- </p>
- <p>
- 1) GenBank files
- </p>
- <p>
- GenBank records (e.g., NG_007400.1) are specified by a
- <i>GenBank accession number</i> (NG_007400) and a version number (.1).
- Omission of the version number automatically results in selection of
- the most recent version of that record. In case of outdated versions,
- Mutalyzer will issue a warning. Alternatively, the unique
- <i>GenInfo identifier</i> (gi) of the reference sequence (e.g.,
- 4506864) can be used with or without the letters ''gi'';.
- Mutalyzer does not accept GenBank records containing no sequence (e.g.
- chromosomal reference sequence identifiers referring to contig
- accession numbers) or files larger than 10 MB. Mutalyzer also accepts
- user-defined files in GenBank format, including slices of chromosomal
- reference sequences. These files are specified by unique
- <i><a href="#UD">UD identifiers</a></i>, which are returned by Mutalyzer
- after upload (See the <a href="#GenBankUploader">Reference File Loader</a>
- section for more information).<br>
- </p>
- <p>
- 2) LRG files
- </p>
- <p>
- Locus Reference Genomic (LRG) files containing uniquely and stable
- reference DNA sequences along with all relevant transcript and protein
- sequences essential to the description of gene variants (see the
- <a href="http://www.lrg-sequence.org/"> LRG website</a> for more
- information). LRG files are based on
- <a href="http://www.ncbi.nlm.nih.gov/">NCBI</a>'s
- <a href="http://www.ncbi.nlm.nih.gov/RefSeq/RSG/">RefSeqGene project</a>
- and created in collaboration with the community of research and
- diagnostic labs, LSDB curators and mutation consortia. LRG files are
- specified by the prefix "LRG_" followed by a number (e.g.,
- LRG_1). The <a href="http://www.lrg-sequence.org/"> LRG website</a>
- lists existing LRG sequences and has an
- <a href="ftp://ftp.ebi.ac.uk/pub/databases/lrgex/">FTP site</a> for
- downloading LRGs. To maintain LRG stability, Mutalyzer's Reference File Loader does
- not accept user-defined LRG files.
- </p>
-
- <h3>Variant descriptions</h3>
- <p>
- The Mutalyzer nomenclature checker accepts variant descriptions in
- standard human sequence variant nomenclature format. For users, who are
- not familiar with the nomenclature syntax, Mutalyzer's
- <a href="#NameGenerator">Name Generator</a> provides a form to acquire
- the separate components necessary to construct variant descriptions.
- </p>
- <p>
- These components, which are discussed in more detail below are:
- </p>
- <p>
- 1) <a href="#Position">Position numbering scheme (Sequence Type)</a>
- </p>
- <p>
- 2) <a href="#GeneSymbol"
- >Gene symbol, transcript variant and protein isoform</a>
- </p>
- <p>
- 3) <a href="#Start">Variant start and end positions</a>
- </p>
- <p>
- 4) <a href="#Mutation">Mutation type</a>
- </p>
- <p>
- 5) <a href="#Deleted">Deleted and Inserted sequence</a>
- </p>
- <p>
- <b><a name="Position"></a>Position numbering scheme (Sequence Type)</b>
- </p>
- <p>
- The standard human sequence variant nomenclature uses different
- position numbering schemes to describe variants relative to the
- reference sequence. Mutalyzer checks if the specified reference
- sequence is compatible with the selected position numbering scheme for
- the sequence variation. Variant descriptions involving upstream or
- downstream regulatory sequences and intron sequences can only be
- checked using genomic sequence records. Therefore, genomic records with
- correct annotation of all genes, transcripts and protein isoforms
- support most position numbering schemes. Mutalyzer automatically
- converts the given variant description to other position numbering
- schemes supported by the reference sequence and its annotation.
- Mutalyzer will not return results when the selected reference sequence
- does not contain sufficient sequence or annotation to support the
- nomenclature check of the variant.
- </p>
- <p>
- There are six position numbering schemes (Sequence Types):
- </p>
- <p>
- <i>Genomic</i>
- </p>
- <p>
- The <i>Genomic</i> position numbering scheme is applied to raw genomic
- records. The value 1 is assigned to the first base in the record and
- all bases are counted from there. In the output, genomic numbering is
- indicated by the g. prefix preceding the position number(s). LRG
- records and all <i>GenBank</i> records with 'DNA' in the first line
- will be accepted.
- </p>
- <p>
- Please note that well-annotated genomic sequence records containing
- annotated transcripts and corresponding coding sequences can be used in
- combination with non-coding DNA, coding DNA and protein position
- numbering schemes.
- </p>
- <p>
- <i>Non-coding DNA (ncDNA)</i>
- </p>
- <p>
- The <i>Non-coding DNA</i> or <i>ncDNA</i> position numbering scheme can
- be used with:<br>
- a) <i> GenBank</i> records containing genomic sequences with annotated
- transcripts without a corresponding coding sequence.<br>
- b) LRG records<br>
- c) <i> Genbank </i>records containing transcript sequences without
- annotated coding sequences, provided that no intronic bases are
- involved in the variation. Mutalyzer needs a correctly annotated
- genomic reference sequence to check HGVS Non-coding DNA numbering of
- intron positions.
- </p>
- <p>
- The value 1 is assigned to to the first base of the transcript in the
- record and all the exonic bases are counted from there. Intronic bases
- are numbered x+1, x+2, x+3, ... y-3, y-2, y-1 where x is the value
- of the last exonic base upstream of the intron, y is the value of the
- first exonic base downstream of the intron and x and y are consecutive
- numbers. Intronic position numbers are always counted from the closest
- exonic base. In case of a tie, the upstream base is used. In the
- output, ncDNA numbering is indicated by the n. prefix preceding the
- position number(s).
- </p>
- <p>
- <i>Coding DNA (cDNA)</i>
- </p>
- <p>
- The <i>Coding DNA</i> or <i>cDNA</i> position numbering scheme can be
- used with:<br>
- a) <i> Genbank</i> records containing genomic sequences with annotated
- transcripts and corresponding coding sequences. <br>
- b) LRG records<br>
- c) <i>Genbank </i>records containing transcript sequences with
- annotated coding sequences, provided that no intronic bases are
- involved in the variation. Mutalyzer needs a correctly annotated
- genomic reference sequence to check HGVS Coding DNA numbering of intron
- positions.
- </p>
- <p>
- The value 1 is assigned to the A of the ATG start codon and all the
- exonic bases between start and stop are counted normally.<br>
- 5' untranslated region: Exonic bases upstream of (i.e. before) the ATG
- are numbered -1, -2, -3 and so on.<br>
- 3' untranslated region: Exonic bases downstream of (i.e. behind) the
- stop codon are numbered *1, *2, *3 and so on.<br>
- Intronic bases in the Coding sequence are numbered x+1, x+2, x+3, ...
- y-3, y-2, y-1 where x is the value of the last exonic base
- upstream of the intron, y is the value of the first exonic base
- downstream of the intron and x and y are consecutive numbers. Intronic
- position numbers are always counted from the closest exonic base. In
- case of a tie, the upstream base is used.<br>
- In case of: a 5' untranslated region split over two or more exons:
- Intronic bases are numbered -x+1, -x+2, -x+3, ... -y-3, -y-2, -y-1
- where -x is the value of the last exonic base upstream of the intron,
- -y is the value of the first exonic base downstream of the intron and x
- and y are consecutive numbers.<br>
- In case of: a 3' untranslated region split over two or more exons:
- Intronic bases are numbered *x+1, *x+2, *x+3, ... *y-3, *y-2, *y-1
- where *x is the value of the last exonic base upstream of the intron,
- *y is the value of the first exonic base downstream of the intron and y
- are consecutive numbers.
- <br>
- In the output, cDNA numbering is indicated by the c. prefix preceding
- the position number(s).
- </p>
- <p>
- <i>RNA</i>
- </p>
- <p>
- The <i>RNA</i> position numbering scheme has not yet been implemented
- in Mutalyzer 2. The value 1 is assigned to the first base in the record
- and from there all bases are counted normally. In the output, RNA
- numbering is indicated by the r. notation preceding the position
- number(s).
- </p>
- <p>
- <i>Mitochondrial DNA (mtDNA)</i>
- </p>
- <p>
- The <i>Mitochondrial DNA (mtDNA)</i> position numbering scheme uses raw
- genomic records. The value 1 is assigned to the first base in the
- record and from there all bases are counted normally.
- </p>
- <p>
- <i>Protein</i>
- </p>
- <p>
- The <i>Protein</i> position numbering scheme is used to generate
- variant descriptions at protein level from genomic or Coding DNA
- descriptions by translation of the Coding sequence. The current version
- of Mutalyzer 2 does not yet support checks of protein variants using a
- <i>GenBank</i> protein record. The value 1 is assigned to the first
- amino acid of the translated Coding sequence and from there all amino
- acids are counted normally. In the output, protein variants have the
- prefix p. folllowed by the amino acid changes between parentheses to
- indicate that they are predicted by translation of the modified Coding
- sequence.
- </p>
- <p>
- <i>EST</i>
- </p>
- <p>
- The <i>EST</i> position numbering scheme can be used with
- <i>GenBank</i> <i>EST</i> records. The value 1 is assigned to the first
- base in the record and from there all bases are counted normally.
- Sequence variation descriptions based on EST sequences lack the c.
- prefix to indicate that only part of the coding sequence may be
- present. All records with 'EST' in the first line will be accepted.
- These records do not allow checks of intronic sequence variations.
- </p>
- <p>
- <b><a name="GeneSymbol"></a>Gene Symbol and Variant</b>
- </p>
- <p>
- In genomic records containing annotation of multiple genes, alternative
- transcript variants and protein isoforms, only genomic positions are
- unambiguous. Descriptions at <i>Non-coding DNA, coding DNA, </i>or
- protein level may be ambiguous. Mutalyzer parses the annotation of the
- reference sequence record and displays the detected genes, transcript
- variants or protein isoforms in the legend at the bottom of the output
- page. Mutalyzer uses the annotation to detect potential ambiguity in a
- variant description. Further specification of genes, transcript
- variants or protein isoforms may be required to solve it. Only Gene
- Symbols matching the reference sequence annotation are allowed.
- Usually, gene symbols have to be combined with the desired transcript
- variant or protein isoform
- </p>
- <p>
- Variant descriptions are accepted in two formats:
- </p>
- <p>
- - A positive integer referring to the order of the transcripts in the
- annotation, e.g. <b>1</b>, <b>2</b>, <b>3</b>, ...<br>
- - The exact identifier following the underscore behind the Gene symbol
- in the legend, e.g. v002 for a transcript variant or i002 for a
- protein isoform
- </p>
- <p>
- <b><a name="Start"></a>Start and End Position</b>
- </p>
- <p>
- The Start position is the positional value of the most upstream base or
- amino acid in the reference sequence affected by the mutation. The End
- position is the positional value of the most downstream base or amino
- acid in the reference sequence affected by the mutation. Mutalyzer only
- accepts positions contained within the reference sequence. The values
- should be a positive integer (whole number) for all position numbering
- schemes, except <i>Non-coding DNA </i> and<i> Coding DNA </i> . For
- <i>Non-coding </i> and<i> Coding DNA,</i> these positions may also
- contain + and - signs to indicate intron positions. For
- <i> Coding DNA,</i> positions can also have prefixes - and * to
- indicate exonic positions in 5' or 3' untranslated regions.
- Furthermore, in descriptions of deletions, exonic positions can be
- followed by +? or -? to indicate unknown intronic positions.<br>
- The Mutalyzer nomenclature checker has a strict implementation of Start
- and End positions in <i>Non-coding DNA </i> and<i> Coding DNA</i>
- position numbering schemes. To prevent discrepancies between
- <i>Non-coding DNA </i> and<i> Coding DNA</i> descriptions based on
- genomic RefSeqGene (NG_) records and the corresponding RefSeq
- transcript (NR_ or NM_) records, exon positions may not exceed those of
- the transcript annotated in the genomic reference sequence record.
- Therefore, Mutalyzer cannot use - or * prefixes to indicate positions
- in upstream or downstream intergenic regions.
- </p>
- <p>
- For upstream intergenic positions, Mutalyzer combines the position of
- the first nucleotide of the transcript with the suffix -u followed by
- the position of the upstream nucleotide. Intergenic bases upstream of
- <i>Non-coding DNA </i>are numbered n.1-uy, ..., n.1-u3, n.1-u2, n.1-u1
- where y is the value of the most upstream base and n.1-u1 is the value
- of the first intergenic base upstream of the first exon. Intergenic
- bases upstream of <i>Coding DNA </i>are numbered c.x-uy, ..., c.x-u3,
- c.x-u2, c.x-u1 where x is the value of the first nucleotide of the
- first exon and y is the value of the most upstream base. The advantage
- of this notation is that the -u position corresponds to the - position
- used by to describe transcription factor binding sites.
- </p>
- <p>
- For downstream intergenic positions, Mutalyzer combines the position of
- the last nucleotide of the transcript with the suffix +d followed by
- the position of the downstream nucleotide. Intergenic bases downstream
- of <i>Non-coding DNA </i>are numbered n.x+d1, n.x+d2, n.x+d3 ... where
- x is the value of the last nucleotide of the last exon. Intergenic
- bases downstream of <i>Coding DNA </i>are numbered c.x+d1, c.x+d2,
- c.x+d3, ... where x is the value of the last nucleotide of the last
- exon.
- </p>
- <p>
- <b><a name="Mutation"></a>Mutation Type</b>
- </p>
- <p>
- The syntax of the standard human sequence variant nomenclature depends
- on the type of mutation. Six mutation types are supported:
- </p>
- <p>
- <i>Substitution</i>
- </p>
- <p>
- A substitution is the replacement of a single nucleotide or amino acid
- by another. A substitution involving multiple residues is classified as
- an indel. The start and end position should be identical. The original
- residue and the new residue have to be specified and must be
- non-identical. In the Name Generator, the Deleted Sequence and Inserted
- Sequence fields must be filled in.
- </p>
- <p>
- <i>Deletion</i>
- </p>
- <p>
- A deletion is the removal of one or more nucleotides or amino acids
- without replacement. In the Name Generator, the Inserted Sequence field
- must remain empty. The Deleted Sequence field can be filled in to check
- the start and end positions and to match the deleted residues with the
- reference sequence (Optional). Please note that the start and end
- positions should be equal when only one nucleotide or amino acid is
- deleted.
- </p>
- <p>
- <i>Insertion</i>
- </p>
- <p>
- An insertion is the addition of one or more nucleotides or amino acids
- without removing any previously existing ones. The starting and end
- positions should differ by exactly one. In the Name Generator, Inserted
- Sequence must be filled in with the actual new sequence. If the
- inserted sequence is already present in the reference sequence at the
- location of the insertion, it should be represented as a
- duplication.
- </p>
- <p>
- <i>Duplication</i>
- </p>
- <p>
- Duplication is the addition of one or more nucleotides or amino acids
- identical to the sequence from the specified start position to the
- specified end position, at the end position. In the Name
- Generator, Deleted Sequence must remain empty. Inserted Sequence
- can be filled in to check the start and end positions and to match the
- duplicated residues with the reference sequence (Optional).
- </p>
- <p>
- <i>Insertion/Deletion (indel)</i>
- </p>
- <p>
- An indel is the removal of one or more bases or amino acids, combined
- with the addition of one or more bases or amino acids. In case a single
- residue is deleted and another residue is inserted, the mutation should
- be described as a substitution, not an indel. If the inserted sequence
- is the reverse complement of the original sequence, it should be
- described as an inversion. Start and end position define the boundaries
- of the deletion in the original sequence. In the Name Generator, the
- deleted sequence should be entered in the Deleted Sequence field and
- the Inserted sequence in the New Sequence field.
- </p>
- <p>
- <i>Inversion (nucleotide sequences only)</i>
- </p>
- <p>
- An inversion is a sequence of two or more bases inserted as its reverse
- complement. Start and end position must be non-identical. In the Name
- Generator, the Deleted Sequence and Inserted Sequence fields must
- remain empty.
- </p>
- <p>
- <b><a name="Deleted"></a>Deleted and Inserted Sequence</b>
- </p>
- <p>
- The syntax of the standard human sequence variant nomenclature requires
- specification of the inserted residue(s) for several mutation types.
- Specification of the original residue(s) is optional for most types,
- except for subsitutions. In the Name Generator, the presence or absence
- of these fields depends on the selected Mutation Type. These fields
- should be used:<br>
- -to enter the original amino acid or nucleotide residue(s) present in
- the reference sequence (Deleted Sequence).<br>
- -to enter the amino acid(s) or nucleotide residue(s) introduced by the
- change (Inserted Sequence).
- </p>
-
- <hr>
-
- <h3>Mutalyzer Name Checker Help<a name="NameChecker"></a></h3>
- <p>
- Users can check the correctness of a variant description. The Name
- Checker will try to regenerate the variant sequence and name it
- according to the HGVS standard human sequence variant nomenclature.
- </p>
- <p>
- Examples: <br>
- AB026906.1:c.3_4insG<br>
- AB026906.1:c.[1del;4G>T]<br>
- AL449423.14(CDKN2A_v1):c.1_10del<br>
- UD_127955523176(DMD_v002):c.136G>T<br>
- LRG_1t1:c.266G>T
- </p>
-
- <hr>
-
- <h3>Mutalyzer Syntax Checker Help<a name="SyntaxChecker"></a></h3>
- <p>
- Users can check the correctness of the standard nomenclature syntax.
- The Syntax Checker uses a context-free parser to detect deviations from
- the standard nomenclature syntax in the input. The position of
- the deviation is indicated in the error message and by a caret (^)
- below the description.
- </p>
- <p>
- Examples: <br>
- AB026906:c.3_4inG<br>
- AB026906.1:c.35_36ins<br>
- LRG_1t1:c.266G>T
- </p>
-
- <hr>
-
- <h3>
- Mutalyzer Position Converter Help<a name="PositionConverter"></a>
- </h3>
- <p>
- The Position Converter will convert the positions of the variation
- description from the chromosomal position for a specific human genome
- build to a position relative to RefSeq transcript reference sequences.
- The Position Converter uses a local database containing the mapping
- information from the
- <a href="http://genome.ucsc.edu/index.html?org=Human"
- >UCSC genome browser</a> for human genome builds hg18 (NCBI 36) and
- hg19 (GRCh37). The specified version of the RefSeq transcript Accession
- number has to be present in the database. The sequence variation
- description has <u>not</u> been checked by Mutalyzer's
- <a href="#NameChecker">Name Checker</a>.
- </p>
- <p>
- Examples:<br>
- NM_003002.2:c.274G>T<br>
- chr11:g.111959693G>T<br>
- NC_000011.9:g.111959693G>T
- </p>
-
- <hr>
-
- <h3>Mutalyzer SNP Converter Help<a name="SNPConverter"></a></h3>
- <p>
- The SNP Converter will submit a <a
- href="http://www.ncbi.nlm.nih.gov/projects/SNP/">dbSNP</a> rsID to
- dbSNP to retrieve the sequence variation description according to the
- HGVS sequence variation description listed in dbSNP.<br>
- The sequence variation description has <u>not</u> been checked by
- Mutalyzer's <a href="#NameChecker">Name Checker</a>.
- </p>
- <p>
- Example:<br>
- SNP Accession number: rs9919552
- </p>
-
- <hr>
-
- <h3>Mutalyzer Name Generator Help<a name="NameGenerator"></a></h3>
- <p>
- The Name Generator aims to assist users, who are not familiar with all
- the details of the HGVS standard human sequence variant nomenclature,
- to construct variant descriptions. The Name Generator presents a form
- to collect the separate components of a variant description described
- above. The variant description generated is subsequently used by the
- Name Checker to construct the variant sequence and name it according to
- the HGVS standard human sequence variant nomenclature.
- </p>
- <p>
- Example: <br>
- Reference: AL449423.14<br>
- Sequence Type: Coding DNA<br>
- Gene symbol: CDKN2A<br>
- Transcript: v_1
- </p>
- <p>
- Variant 1<br>
- Mutation Type: Substitution<br>
- Start Position: 112<br> End Position: 112<br>
- Deleted Sequence: C<br>
- Inserted Sequence: T
- </p>
-
- <hr>
-
- <h3>Mutalyzer Batch Checker Help<a name="BatchChecker"></a></h3>
- <p>
- <br>
- The Batch checkers support submission of files containing large
- datasets to the <a href="#NameChecker">Name Checker</a>,
- <a href="#SyntaxChecker">Syntax Checker</a>, and
- <a href="#PositionConverter">Position Converter</a> tools.
- </p>
- <p>The Mutalyzer batch checker accepts the following file formats
- <ul>
- <li>Tab Delimited Text File</li>
- <li>Microsoft Excel XML File</li>
- <li>OpenOffice .odt File</li>
- </ul>
- </p>
-
- <h5>
- We accept two types of input files, you can download examples below
- </h5>
-
- <h5>
- New Style <a href="downloads/batchtestnew.txt">Download Example File</a>
- </h5>
- <div style="padding-left:20px; width:400px">
- <p>
- This file format has no header-row and no columns. Instead each row
- contains a single variant for the Batch check.
- </p>
- <table>
- <tr>
- <td>AB026906.1:c.274G>T</td>
- </tr>
- <tr>
- <td>AL449423.14(CDKN2A_v002):c.5_400del<td>
- </tr>
- </table>
- </div>
-
- <h5>
- Old Style:
- <a href="downloads/batchtestold.txt">Download Example File</a>
- </h5>
- <div style="padding-left:20px; width:400px">
- <p>
- This file format has a header-row, which consists of three tab
- delimited fields. In each following row, the corresponding data is
- also tab delimited.The gene symbol field may be left empty, when it
- is not nessary to select a particular gene or transcript.
- </p>
- <table>
- <tr>
- <td>AccNo</td><td>Genesymbol</td><td>Mutation</td>
- </tr>
- <tr>
- <td>AB026906.1</td><td>SDHD</td><td>g.7872G>T</td>
- </tr>
- </table>
- </div>
-
- <h5>Output Format</h5>
- <div style="padding-left:20px; width:400px">
- <p>
- The output of a Mutalyzer Batch run is a Tab Delimited Text file,
- which has a header-row to clarify the results.
- </p>
- </div>
- <p>
- Users can upload a tab-delimited text file with the sequence
- variations to be checked. Files for the Name Checker and the Syntax
- Checker may contain any combination of reference sequences and sequence
- types for different genes. Mutalyzer's
- <i><a href="#UD">UD identifiers</a></i> can also be used, but we
- strongly suggest to update any GenBank record following
- <a href="http://www.ncbi.nlm.nih.gov/Genbank/update.html"
- >these instructions</a>.<br>
- </p>
- <p>
- A message containing a link to the results will be send to the e-mail
- address specified, when the analysis is finished, but Mutalyzer's
- progress can be followed in the browser window also. Performance
- depends on the server load and the number of reference sequence records
- to be downloaded. The program will process approximately 100 variations
- per minute, when using a single reference sequence record.
- </p>
- <p>
- The Batch checkers use JavaScript to update the progress report. In
- Internet Explorer, progress may not be reported correctly. Adding
- Mutalyzer to your trusted sites is one option to solve this.
- </p>
-
- <hr>
-
- <h2>Mutalyzer Output</h2>
- <p>
- Mutalyzer has been designed to issue warnings, when correcting entries,
- encountering inconsistencies, incomplete sequences or annotation, or
- identifying variations with potential effects on splicing before
- presenting the results of the analysis. Errors will be generated when
- the entries can not be processed properly (see below for more
- information). <br>
- The sequence variation description will always be in the format:
- </p>
- <p>
- <<i>Accession Number</i>>.<<i>version number></i>:<i><sequence type</i>>.<<i >mutation</i>><br>
-
- (Examples: NM_003002.1:c.5delC or AL449423.14:g.61866_85191del)<br>
- or<br>
- <<i>Accession Number</i>>.<<i>version number><(Gene Symbol)></i>:<i ><sequence type</i>>.<<i >mutation</i>><br>
- In the latter case, the gene symbol may be followed by transcript
- variant or protein isoform numbers (e.g., _v001 or _i001,
- respectively).<br>
- Example: the fictitious sequence variation AL449423.14:g.61866_85191del
- corresponds with the following changes in transcript variants and
- protein isoforms:<br>
- AL449423.14(CDKN2A_v001):c.-271_234del<br>
- AL449423.14(CDKN2A_v002):c.5_400del<br>
- AL449423.14(CDKN2A_v003):c.1_*3352del<br>
- and<br>
- CAH70600.1(CDKN2A_i001):p.Met1?<br>
- CAH70601.1(CDKN2A_i002):p.Gly2AspfsX41<br>
- CAH70599.1(CDKN2A_i003):p.Met1?
- </p>
- <p>
- From the example “CAD55702.1:p.Pro2Arg (missense
- mutation)”, you can conclude that the protein in version 1 of the
- record CAD55702 has a mutation denoted as Pro2Arg (which signifies an
- arginine substituted for a proline at position 2).
- </p>
- <p>
- Please note the following:
- </p>
- <p>
- - Sequence variation descriptions using genomic references in
- combination with Sequence Type "Coding DNA" will result in
- the use of nucleotides in reverse complement for genes transcribed in
- the opposite orientation.
- </p>
- <p>
- - Genbank Identifiers are always converted to Genbank Accession
- Numbers, which are automatically retrieved from the annotation based
- on the selected Sequence Type. Example: 4506864:c.5del will be
- converted into NM_003002.1:c.5delC
- </p>
-
- <hr>
-
- <h3>Reference File Loader Help<a name="GenBankUploader"></a></h3>
- <p>
- Users can upload their own reference sequence file in
- <a href="http://www.ncbi.nlm.nih.gov/Sitemap/samplerecord.html"
- >GenBank Flat file format</a>, retrieve the genomic sequence of a
- gene with its flanking regions, or specify a chromosomal range for use
- as a reference sequence. Mutalyzer checks whether the file is in valid
- GenBank Flat file format. If so, Mutalyzer stores the file locally and
- returns a unique number the <i><a href="#UD">UD identifier</a></i> that
- can be used with all different forms of the Mutalyzer Sequence
- Variation Nomenclature Checker. This option allows users to use
- reference files, which are not present in GenBank, or add information
- about alternative transcripts or proteins or additional genes contained
- within or derived from the reference sequence to an existing GenBank
- file. Users are encouraged to limit their use of this option by
- submitting annotation updates and corrections of existing GenBank files
- following <a href="http://www.ncbi.nlm.nih.gov/Genbank/update.html"
- >these instructions</a>.
- </p>
- <p>
- Loader options:
- </p>
- <p>
- <b>The reference sequence file is a local file</b>
- </p>
- <p>
- Browse to locate your Genbank Flat file with a .gb extension and press
- the submit button.
- </p>
- <p> </p>
- <p>
- <b>The reference sequence file can be found at the following URL</b>
- </p>
- <p>
- Enter the URL of the website, where the Genbank Flat file with a .gb
- extension can be found and press the submit button.
- </p>
- <p> </p>
- <p>
- <b>
- Retrieve part of the reference genome for a
- (<a href="http://www.genenames.org">HGNC</a>) gene symbol
- </b>
- </p>
- <p>
- This option retrieves part of the chromosomal reference sequence, which
- is annotated for this gene in the last genome build of the
- organism.
- </p>
- <p>
- The organism name should not contain any spaces (e.g., use
- homo_sapiens, human or man)
- </p>
- <p>
- Input:
- </p>
- <div style="padding-left:20px; width:400px">
- <i>Please enter the Gene symbol and organism name without spaces and
- specify the length of the flanking sequences</i>
- <table>
- <tr>
- <td>Gene symbol</td>
- <td><input type="text" name="genesymbol"></td>
- </tr>
- <tr>
- <td>Organism name</td>
- <td><input type="text" name="organism"></td>
- </tr>
- <tr>
- <td>Number of 5' flanking nucleotides</td>
- <td><input type="text" name="5utr" value="5000"></td>
- </tr>
- <tr>
- <td>Number of 3' flanking nucleotides</td>
- <td><input type="text" name="3utr" value="2000"></td>
- </tr>
- </table>
- </div>
- <p>
- <b>Retrieve a range of a chromosome</b>
- </p>
- <p>
- Use of NC_accession numbers without version number will result in
- retrieval of the latest version.
- </p>
- <p>
- Input:
- </p>
- <div style="padding-left:20px; width:400px">
- <i>Please enter the accession number of the chromosome or contig and
- specify the range</i><br>
- <table>
- <tr>
- <td>Chromosome Accession Number</td>
- <td><input type="text" name="chracc"></td>
- </tr>
- <tr>
- <td>Start Position</td>
- <td><input type="text" name="start"></td>
- </tr>
- <tr>
- <td>Stop Position</td>
- <td><input type="text" name="stop"></td>
- </tr>
- <tr>
- <td>Orientation</td>
- <td>
- <select name="orientation">
- <option value="1">Forward</option>
- <option value="-1">Reverse</option>
- </select>
- </td>
- </tr>
- </table>
- </div>
- <p>
- <b>Mutalyzer output for all options:</b>
- </p>
- <p>
- Output:<a name="UD"></a>
- </p>
- <div style="padding-left:20px; width:400px">
- <p>
- Your reference sequence was loaded successfully. You now can use
- mutalyzer with the following accession number as reference:
- UD_127955523176 <br>
- Download this reference sequence.
- </p>
- </div>
- <p>
- The Reference File Loader uses JavaScript to change the form depending on
- the selected option. In Internet Explorer, forms may not be displayed
- correctly. Adding Mutalyzer to your trusted sites is one option to
- solve this.
- </p>
-
- <hr>
-
- <h3>Mutalyzer Web services <a name="Webservices"></a></h3>
- <p>
- Mutalyzer's web services provide programmatic access to different parts
- of Mutalyzer's functionality. In the future, these will be used by
- <a href="http://www.LOVD.nl">LOVD</a> to convert coding DNA positions
- to chromosomal positions for mapping and display purposes. A full
- description of available web services can be found at the
- <a href="documentation">Web service documentation page</a>.
- Example scripts and requirements can be found at the
- <a href="webservices">Web service page</a>.
- </p>
-
- <hr>
-
- <h3>Using Mutalyzer with sequences from other organisms</h3>
- <p>
- Mutalyzer can process Genbank reference files from other organisms than
- man and will apply the appropriate coding table to translate an open
- reading frame into a protein sequence. Please note that all variants
- will be described according to the HGVS
- <a href="http://www.hgvs.org/mutnomen/"
- >standard human sequence variation nomenclature</a>. When trying to
- retrieve genomic reference sequences using gene symbols with the
- Reference File Loader or when specifying a particular gene in a genomic
- reference sequence, the gene symbol should be similar to that used in
- the (genome) sequence annotation.
- </p>
-
- <h3>Errors and feature requests</h3>
- <p>
- Any error message gives an indication of the problem encountered and
- replicates the input of the user. Most errors occurring after mistyping
- should be easy to understand and can be corrected immediately by
- altering the data in the field specified. In other cases, Mutalyzer
- should advise you to contact
- <a href="mailto:Mutalyzer@humgen.nl">us</a> when the error persists.
- Please specify your input and which tool you used.
- </p>
- <p>
- Occasionally, Mutalyzer will display an Internal Server Error message
- due to unexpected behavior. You can use Mutalyzer's
- <a href="https://humgenprojects.lumc.nl/trac/mutalyzer"
- >bugtracking system</a> to report errors and send in feature requests.
- </p>
-
- <h3>Citing Mutalyzer </h3>
- <p>
- When you use Mutalyzer, please cite this paper: Wildeman M, van
- Ophuizen E, den Dunnen JT, Taschner PE. Improving sequence variant
- descriptions in mutation databases and literature using the MUTALYZER
- sequence variation nomenclature checker.
- <a href="http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3058&itool=AbstractPlus-def&uid=18000842&db=pubmed&url=http://dx.doi.org/10.1002/humu.20654">Hum Mutat 29:6-13 (2008)</a>
- [<a href="http://www.ncbi.nlm.nih.gov/pubmed/18000842?"
- >PMID: 18000842</a>].
- </p>
- <p>
- Mutalyzer 2 has been completely redesigned by Jeroen F.J. Laros, with
- help from Gerben R. Stouten and Gerard C. P. Schaafsma, according to
- specifications provided by Peter E. M. Taschner and Johan T. den
- Dunnen. The different parts of the nomenclature checker functionality
- have been separated into modules, which can be used as independent
- web services and undergo further development and extension in the
- future.
- </p>
-
- <hr>
-
- <p>
- If you have any comments or suggestions be sure to let us know!
- </p>
-
- <p>
- Last modified: November 5, 2010
- </p>
- <a href="mailto:mutalyzer@humgen.nl">
- <address>mutalyzer@humgen.nl</address></a>
- </div>
- </body>
-</html>
diff --git a/mutalyzer/templates/menu.html b/mutalyzer/templates/menu.html
index 574e304cdc7989537356f187aa73cb7e8b885c3f..c9ed9d363fd81a81d00e5ef190123d6cd8d51799 100644
--- a/mutalyzer/templates/menu.html
+++ b/mutalyzer/templates/menu.html
@@ -218,28 +218,28 @@
<tr tal:attributes="class active/help">
<td valign="top" width="20" class="bullet"></td>
<td colspan="3">
- <a href="help">Help</a>
+ <a href="https://humgenprojects.lumc.nl/trac/mutalyzer/wiki/MutalyzerDocumentation">Documentation</a>
</td>
</tr>
<tr tal:attributes="class active/faq">
<td valign="top" width="20" class="bullet"></td>
<td colspan="3">
- <a href="faq">FAQ</a>
+ <a href="https://humgenprojects.lumc.nl/trac/mutalyzer/wiki/MutalyzerFaq">FAQ</a>
</td>
</tr>
<tr tal:attributes="class active/exercise">
<td valign="top" width="20" class="bullet"></td>
<td colspan="3">
- <a href="exercise">Exercise</a>
+ <a href="https://humgenprojects.lumc.nl/trac/mutalyzer/wiki/MutalyzerExercise">Exercise</a>
</td>
</tr>
<tr tal:attributes="class active/disclaimer">
<td valign="top" width="20" class="bullet"></td>
<td colspan="3">
- <a href="disclaimer">Disclaimer</a>
+ <a href="https://humgenprojects.lumc.nl/trac/mutalyzer/wiki/MutalyzerDisclaimer">Disclaimer</a>
</td>
</tr>
diff --git a/mutalyzer/website.py b/mutalyzer/website.py
index 2381b5aba06a50b5e0db688be808380d4757574a..37d82fb9cffb4250d4ffad397fabfff780ea05da 100644
--- a/mutalyzer/website.py
+++ b/mutalyzer/website.py
@@ -56,10 +56,6 @@ urls = (
'', 'RedirectHome',
'/(index)?', 'Static',
'/(about)', 'Static',
- '/(help)', 'Static',
- '/(faq)', 'Static',
- '/(exercise)', 'Static',
- '/(disclaimer)', 'Static',
'/(nameGenerator)', 'Static',
'/(webservices)', 'Static',
'/checkForward', 'CheckForward',