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<!-- XML Authors: Corinne Maufrais, Nicolas Joly and Bertrand Neron, -->
<!-- 'Biological Software and Databases' Group, Institut Pasteur, Paris. -->
<!-- Distributed under LGPLv2 License. Please refer to the COPYING.LIB document. -->
<program>
<head>
<name>signalp</name>
<version>4.0</version>
<xi:include xmlns:xi="http://www.w3.org/2001/XInclude" href="Entities/cbs_package.xml"/>
<doc>
<title>signalp</title>
<description>
<text lang="en"> predict signal peptides in proteins</text>
</description>
<sourcelink>http://www.cbs.dtu.dk/cgi-bin/nph-sw_request?signalp</sourcelink>
<reference doi="10.1038/nmeth.1701" >SignalP 4.0: discriminating signal peptides from transmembrane regions
Thomas Nordahl Petersen, Søren Brunak, Gunnar von Heijne & Henrik Nielsen
Nature Methods, 8:785-786, 2011
</reference>
<reference>Improved prediction of signal peptides: SignalP 3.0.
Jannick Dyrløv Bendtsen, Henrik Nielsen, Gunnar von Heijne and Søren Brunak.
J. Mol. Biol., 340:783-795, 2004.
</reference>
<reference>Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites.
Henrik Nielsen, Jacob Engelbrecht, Søren Brunak and Gunnar von Heijne.
Protein Engineering, 10:1-6, 1997.
</reference>
<reference>Prediction of signal peptides and signal anchors by a hidden Markov model.
Henrik Nielsen and Anders Krogh.
Proceedings of the Sixth International Conference on Intelligent Systems for Molecular Biology (ISMB 6),
AAAI Press, Menlo Park, California, pp. 122-130, 1998.
</reference>
<doclink>http://www.cbs.dtu.dk/services/SignalP/</doclink>
<comment>
<text lang="en">signalp predicts the presence and location of signal peptide cleavage sites in amino acid sequences from
different organisms: Gram-positive prokaryotes, Gram-negative prokaryotes, and eukaryotes.</text>
<text lang="en">The method incorporates a prediction of cleavage sites and a signal peptide/non-signal peptide prediction based on a
combination of several artificial neural networks.</text>
</comment>
</doc>
<category>sequence:protein:motifs</category>
<category>sequence:protein:pattern</category>
</head>
<parameters>
<parameter ishidden="1" iscommand="1">
<name>signalp</name>
<type>
<datatype>
<class>String</class>
</datatype>
</type>
<format>
<code proglang="perl">" signalp "</code>
<code proglang="python">" signalp "</code>
</format>
</parameter>
<parameter ismandatory="1" issimple="1" ismaininput="1">
<name>sequence</name>
<prompt lang="en">Input Sequence</prompt>
<type>
<datatype>
<class>Sequence</class>
</datatype>
<dataFormat>FASTA</dataFormat>
</type>
<format>
<code proglang="perl">" $value ""</code>
<code proglang="python">" " + str( value )</code>
</format>
<argpos>100</argpos>
<example>
>IPI:IPI00000001.2 SWISS-PROT:O95793-1 TREMBL:A8K622;Q59F99 Isoform L ong of Double-stranded RNA-binding protein Staufen homolog 1
MSQVQVQVQNPSAALSGSQILNKNQSLLSQPLMSIPSTTSSLPSENAGRPIQNSALPSAS
ITSTSAAAESITPTVELNALCMKLGKKPMYKPVDPYSRMQSTYNYNMRGGAYPPRYFYPF
PVPPLLYQVELSVGGQQFNGKGKTRQAAKHDAAAKALRILQNEPLPERLEVNGRESEEEN
LNKSEISQVFEIALKRNLPVNFEVARESGPPHMKNFVTKVSVGEFVGEGEGKSKKISKKN
AAIAVLEELKKLPPLPAVERVKPRIKKKTKPIVKPQTSPEYGQGINPISRLAQIQQAKKE
KEPEYTLLTERGLPRRREFVMQVKVGNHTAEGTGTNKKVAKRNAAENMLEILGFKVPQAQ
PTKPALKSEEKTPIKKPGDGRKVTFFEPGSGDENGTSNKEDEFRMPYLSHQQLPAGILPM
VPEVAQAVGVSQGHHTKDFTRAAPNPAKATVTAMIARELLYGGTSPTAETILKNNISSGH
VPHGPLTRPSEQLDYLSRVQGFQVEYKDFPKNNKNEFVSLINCSSQPPLISHGIGKDVES
CHDMAALNILKLLSELDQQSTEMPRTGNGPMSVCGRC
>IPI:IPI00000023.4 SWISS-PROT:P18507 TREMBL:B4DSA1 Gamma-aminobutyric acid receptor subunit gamma-2
MSSPNIWSTGSSVYSTPVFSQKMTVWILLLLSLYPGFTSQKSDDDYEDYASNKTWVLTPK
VPEGDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQT
WYDRRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLY
TLRLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQF
SFVGLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDA
VPARTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFV
SNRKPSKDKDKKKKNPAPTIDIRPRSATIQMNNATHLQERDEEYGYECLDGKDCASFFCC
FEDCRTGAWRHGRIHIRIAKMDSYARIFFPTAFCLFNLVYWVSYLYL
</example>
</parameter>
<parameter ismandatory="1" issimple="1">
<name>type</name>
<prompt lang="en">Use networks and models trained on sequences from the specified type of organisms</prompt>
<type>
<datatype>
<class>Choice</class>
</datatype>
</type>
<vdef>
<value>null</value>
</vdef>
<vlist>
<velem undef="1">
<value>null</value>
<label>Choose a type of organism</label>
</velem>
<velem>
<value>gram-</value>
<label>Gram-negative bacteria</label>
</velem>
<velem>
<value>gram+</value>
<label>Gram-positive bacteria</label>
</velem>
<velem>
<value>euk</value>
<label>eukaryotes</label>
</velem>
</vlist>
<format>
<code proglang="perl">(defined $value)? " -t " : ""</code>
<code proglang="python">" -t " + value</code>
</format>
<argpos>10</argpos>
</parameter>
<parameter ismandatory="1">
<name>format</name>
<prompt lang="en">Produce output in the specified format.</prompt>
<type>
<datatype>
<class>Choice</class>
</datatype>
</type>
<vdef>
<value>short</value>
</vdef>
<vlist>
<velem>
<value>short</value>
<label>short</label>
</velem>
<velem>
<value>long</value>
<label>long</label>
</velem>
<velem>
<value>all</value>
<label>all</label>
</velem>
<velem>
<value>summary</value>
<label>summary</label>
</velem>
</vlist>
<format>
<code proglang="perl">(defined $value and $value ne $vdef)? " -f $value" : ""</code>
<code proglang="python">( "" , " -f " + value)[ value is not None and value != vdef ]</code>
</format>
<comment>
<div xmlns="http://www.w3.org/1999/xhtml">
<p >The valid formats are:</p>
<ul>
<li><strong>short :</strong> Write only one line of concluding scores per sequence. Intended for
analysis of large datasets where machine-readable output is required.<em>This is the default</em>.</li>
<li><strong>long :</strong> Write the scores for each position in each sequnce.</li>
<li><strong>all :</strong> Write predictions for both Signalp-TM and SignalP-noTM networks. Five
columns with cleavage site (CS) and Signal Peptide (SP) predictions
for both SigP-noTM and SigP-TM methods and TM prediction for each
position.</li>
<li><strong>summary :</strong> Write only the concluding scores for each sequence. This is essen‐
tially the same information as the 'short' format.</li>
</ul>
</div>
</comment>
<argpos>10</argpos>
</parameter>
<parameter >
<name>graphics</name>
<prompt lang="en">generate graphics (-g).</prompt>
<type>
<datatype>
<class>Choice</class>
</datatype>
</type>
<vdef>
<value>null</value>
</vdef>
<vlist>
<velem undef="1">
<value>null</value>
<label>no graphics</label>
</velem>
<velem>
<value>gif</value>
<label>GIF</label>
</velem>
<velem>
<value>gif+eps</value>
<label>GIF and EPS</label>
</velem>
</vlist>
<format>
<code proglang="perl">( defined $value and $value ne $vdef) ? " -g $value" : ""</code>
<code proglang="python">( "" , " -g "+str( value ) )[ bool( value ) ]</code>
</format>
<comment>
<div xmlns="http://www.w3.org/1999/xhtml">
<ul>
<li><strong>gif :</strong> Save plots in Graphics Interchange Format (GIF) under the names 'plot.method.#.gif', where
method is nn or hmm, and # is the number of the input sequence.</li>
<li><strong>gif+eps :</strong> Save plots in both GIF and EPS formats as described above.</li>
</ul>
</div>
</comment>
<argpos>20</argpos>
</parameter>
<parameter>
<name>Method</name>
<prompt lang="en">Use the specified prediction method.</prompt>
<type>
<datatype>
<class>Choice</class>
</datatype>
</type>
<vdef>
<value>best</value>
</vdef>
<vlist>
<velem>
<value>best</value>
<label>best</label>
</velem>
<velem>
<value>notm</value>
<label>notm</label>
</velem>
</vlist>
<format>
<code proglang="perl">(defined $value and $value ne $vdef) ? " -s $value" : ""</code>
<code proglang="python">( "" , " -s " + value)[ value is not None and value != vdef ]</code>
</format>
<comment>
<div xmlns="http://www.w3.org/1999/xhtml">
<p>Input sequences may include or not TM regions.</p>
<ul>
<li><strong>best :</strong>
The method decides which neural networks predictions give the best
result choosing predictions from either SignalP-TM or SignalP-noTM
networks. For 'gram+' organisms it is always SignalP-TM networks.<em>(default)</em></li>
<li><strong>notm :</strong> The SignalP-noTM neural networks are specifically chosen.</li>
</ul>
</div>
</comment>
<argpos>30</argpos>
</parameter>
<parameter>
<name>noTM_cutoff</name>
<prompt>cutoff for noTM networks</prompt>
<type>
<datatype>
<class>Float</class>
</datatype>
</type>
<format>
<code proglang="perl">(defined $value and $value ne $vdef) ? " -u" : ""</code>
<code proglang="python">( "" , " -u " + str( value ) )[ value is not None]</code>
</format>
<ctrl>
<message>
<text lang="en">the cutoff must be >= 0 and <= 1</text>
</message>
<code proglang="python">value >= 0 and value <= 1</code>
</ctrl>
<comment>
<div xmlns="http://www.w3.org/1999/xhtml">
<p>user defined D-cutoff for noTM networks. A score above the specified
cutoff will result in a positive prediction of a signal peptide. The cutoff
determines the yes/no answer only, the prediction process is not affected.
The default cutoffs are:</p>
<ul>
<li><strong>euk</strong> : 0.45</li>
<li><strong>gram+</strong> : 0.57</li>
<li><strong>gram-</strong> : 0.57</li>
</ul>
</div>
</comment>
<argpos>50</argpos>
</parameter>
<parameter>
<name>TM_cutoff</name>
<prompt>cutoff for TM networks</prompt>
<type>
<datatype>
<class>Float</class>
</datatype>
</type>
<format>
<code proglang="perl">(defined $value and $value ne $vdef) ? " -c" : ""</code>
<code proglang="python">( "" , " -U " + str( value ) )[ value is not None]</code>
</format>
<ctrl>
<message>
<text lang="en">the cutoff must be >= 0 and <= 1</text>
</message>
<code proglang="python">value >= 0 and value <= 1</code>
</ctrl>
<comment>
<div xmlns="http://www.w3.org/1999/xhtml">user defined D-cutoff for TM networks. A score above the specified
cutoff will result in a positive prediction of a signal peptide. The cutoff
determines the yes/no answer only, the prediction process is not affected.
The default cutoffs are:
<ul>
<li><strong>euk</strong> : 0.50</li>
<li><strong>gram+</strong> : 0.45</li>
<li><strong>gram-</strong> : 0.51</li>
</ul>
</div>
</comment>
<argpos>50</argpos>
</parameter>
<parameter>
<name>truncate</name>
<prompt>Truncate each sequence to maximally n N-terminal residues</prompt>
<type>
<datatype>
<class>Integer</class>
</datatype>
</type>
<vdef>
<value>70</value>
</vdef>
<format>
<code proglang="perl">(defined $value and $value ne $vdef) ? " -c" : ""</code>
<code proglang="python">( "" , " -c " + str( value ) )[ value is not None and value != vdef ]</code>
</format>
<ctrl>
<message>
<text lang="en">enter a positive value</text>
</message>
<code proglang="python">value >= 0 </code>
</ctrl>
<comment>
<text lang="en"> truncate the input sequences to the specified length from the N-ter‐
minal. The default is 70 residues. The value of "0" disables truncation.
</text>
</comment>
<argpos>60</argpos>
</parameter>
<parameter>
<name>mature</name>
<prompt lang="en">generate a FASTA file with mature sequences based on the predictions.</prompt>
<type>
<datatype>
<class>Boolean</class>
</datatype>
</type>
<vdef>
<value>0</value>
</vdef>
<format>
<code proglang="python">( "" , " -m %s_mature.fasta"%sequence)[value]</code>
</format>
<argpos>70</argpos>
</parameter>
<parameter>
<name>n_s_e</name>
<prompt lang="en"> generate a GFF (name-start-end) file with the predicted signal peptides.</prompt>
<type>
<datatype>
<class>Boolean</class>
</datatype>
</type>
<vdef>
<value>0</value>
</vdef>
<format>
<code proglang="python">( "" , " -n %s.gff"%sequence)[value]</code>
</format>
<argpos>70</argpos>
</parameter>
<parameter isstdout="1">
<name>results</name>
<prompt lang="en">signalp report</prompt>
<type>
<datatype>
<superclass>Report</superclass>
<class>signalp</class>
</datatype>
</type>
<filenames>
<code proglang="perl">"signalp.out"</code>
<code proglang="python">"signalp.out"</code>
</filenames>
<comment>
<div xmlns="http://www.w3.org/1999/xhtml">
<p><strong>Neural network output</strong></p>
<p>For each input sequence the neural network (nn) module of signalp will first return three scores between 0
and 1 for each sequence position:</p>
<ul>
<li><strong>C-score (raw cleavage site score)</strong>
The output score from networks trained to recognize cleavage sites vs. other sequence positions.
Trained to be high at position +1 (immediately after the cleavage site), and low at all other posi‐
tions.</li>
<li><strong>S-score (signal peptide score)</strong>
The output score from networks trained to recognize signal peptide vs. non-signal-peptide positions.
Trained to be high at all positions before the cleavage site, and low at positions after the cleav‐
age site and in the N-terminals of non-secretory proteins.</li>
<li><strong>Y-score (combined cleavage site score)</strong>
The prediction of cleavage site location is optimized by observing where the C-score is high and the
S-score changes from a high to a low value. The Y-score formalizes this by combining the height of
the C-score with the slope of the S-score.<br />
Specifically, the Y-score is a geometric average between the C-score and a smoothed derivative of
the S-score (i.e. the difference between the mean S-score over d positions before and d positions
after the current position, where d varies with the chosen network ensemble).</li>
</ul>
<p>signalp will then report the maximal C-, S-, and Y-scores, the mean S-score in the interval between the
N-terminal and the site with the maximal Y-score and, finally, the D-score, the average of the S-mean and
Y-max score.</p>
<p>The high detail level of the output is intended to allow for interpretation of borderline cases by the
user.</p>
<p>If the sequence is predicted to have a signal peptide, the predicted cleavage site
is located immediately before the position with the maximal Y-score.</p>
</div>
</comment>
</parameter>
<parameter isout="1">
<name>gif</name>
<prompt lang="en">graphic in GIF</prompt>
<type>
<datatype>
<superclass>Binary</superclass>
<class>signalp_graphic</class>
</datatype>
<dataFormat>GIF</dataFormat>
</type>
<precond>
<code proglang="perl">$graphics eq "gif" or $graphics eq "gif+eps"</code>
<code proglang="python">graphics == "gif" or graphics == "gif+eps"</code>
</precond>
<filenames>
<code proglang="perl">"*.gif"</code>
<code proglang="python">"*.gif"</code>
</filenames>
</parameter>
<parameter isout="1">
<name>eps</name>
<prompt lang="en">graphic in eps</prompt>
<type>
<datatype>
<superclass>Binary</superclass>
<class>signalp_graphic</class>
</datatype>
<dataFormat>EPS</dataFormat>
</type>
<precond>
<code proglang="perl">$graphics eq "gif+eps"</code>
<code proglang="python">graphics == "gif+eps"</code>
</precond>
<filenames>
<code proglang="perl">"*.gif"</code>
<code proglang="python">"*.gif"</code>
</filenames>
</parameter>
<parameter isout="1">
<name>mature_result</name>
<prompt lang="en">a FASTA file with mature sequences based on the predictions</prompt>
<type>
<datatype>
<class>Sequence</class>
</datatype>
<dataFormat>FASTA</dataFormat>
</type>
<precond>
<code proglang="perl">$mature</code>
<code proglang="python">mature</code>
</precond>
<filenames>
<code proglang="perl">"${sequence}_mature.fasta"</code>
<code proglang="python">"%s_mature.fasta"%sequence</code>
</filenames>
</parameter>
<parameter isout="1">
<name>n_s_e_result</name>
<prompt lang="en">a GFF (name-start-end) file with the predicted signal peptides</prompt>
<type>
<datatype>
<class>Feature</class>
<superclass>AbstractText</superclass>
</datatype>
<dataFormat>GFF</dataFormat>
</type>
<precond>
<code proglang="perl">$n_s_e</code>
<code proglang="python">n_s_e</code>
</precond>
<filenames>
<code proglang="perl">"${sequence}.gff"</code>
<code proglang="python">"%s.gff"%sequence</code>
</filenames>
</parameter>
</parameters>
</program>
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