Incorporated Reviewer Comments

cgi-bin/fathmm.py

@@ -96,6 +96,13 @@ def process_record(dbSNP, protein, substitution):
     
     """
 
+    # throw warning if prediction threshold is invalid
+    if not isinstance(options.threshold, float):
+        Predictions.write(
+            "\t".join([ str(idx), dbSNP, protein, substitution, "", "", "", "Invalid Prediction Threshold (" + str(options.threshold) + ")" ]) + "\n"
+        ); return False
+
+
     # fetch pre-computed sequence record
     dbCursor.execute("select a.* from Clusters a, Protein b where a.id=b.cluster and b.name='" + protein + "'")
     SeqRecord = dbCursor.fetchone()
@@ -184,24 +191,17 @@ def process_record(dbSNP, protein, substitution):
             "\t".join([ str(idx), dbSNP, protein, substitution, "", "", "", "No Prediction Available" ]) + "\n"
         ); return False
 
-    if not options.weights.upper() == "UNWEIGHTED":
-        if options.weights.upper() == "INHERITED":
-            # "Inherited Disease" predictions ...
-            Tag = "TOLERATED"
-
-            if float(Score) < -1.50:
-                Tag = "DAMAGING" 
-        else:
-            # "Cancer-Associated" predictions ...
-            Tag = "PASSENGER/OTHER"
-
-            if float(Score) < -1.00:
-                Tag = "CANCER" 
-    else:
-        Tag = "TOLERATED"
-
-        if float(Score) < -3.00:
+    if options.weights.upper() in [ "UNWEIGHTED", "INHERITED" ]:
+        # "Inherited Disease" predictions ...
+        Tag     = "TOLERATED"
+        if float(Score) < options.threshold:
             Tag = "DAMAGING"
+    else:
+        # "Cancer-Associated" predictions ...
+        Tag     = "PASSENGER/OTHER"
+        if float(Score) < options.threshold:
+            Tag = "CANCER"
+
 
     Predictions.write(
         "\t".join([ str(idx), dbSNP, protein, substitution, Tag, Score, "|".join([ x['description'] for x in Phenotypes ]), "" ]) + "\n"
@@ -211,14 +211,14 @@ def process_record(dbSNP, protein, substitution):
 if __name__ == '__main__':
 
     #
-    # PARSE PROGRAM ARGUMENTS
+    # OPTION PARSER
     #
 
     parser = OptionParser()
     parser.add_option(
                       "-i",
                       dest    = "input",
-                      help    = "process dbSNP rs IDs/protein missense mutations from <INPUT>", 
+                      help    = "process mutation data from <INPUT>", 
                       metavar = "<INPUT>",
                       default = None
                       )
@@ -234,30 +234,50 @@ def process_record(dbSNP, protein, substitution):
                       dest    = "weights",
                       help    = "return weighted predictions using pathogenicity weights <WEIGHTS>", 
                       metavar = "<WEIGHTS>",
-                      default = "Inherited"
+                      default = "INHERITED"
+                      )
+    parser.add_option(
+                      "-t",
+                      dest    = "threshold",
+                      help    = "return predictions using <THRESHOLD> as a prediction threshold", 
+                      metavar = "<THRESHOLD>",
+                      default = None
                       )
     parser.add_option(
                       "-p",
                       dest    = "phenotypes",
                       help    = "append domain-phenotype associations for mutations using phenotype ontology <PHENO>", 
                       metavar = "<PHENO>",
-                      default = "DO"
+                      default = ""
                       )
 
     (options, args) = parser.parse_args()
 
     #
-    # AUTHENTICATE PROGRAM PARAMETERS
+    # PARSE/AUTHENTICATE PROGRAM PARAMETERS
     #
 
     if not options.input:
-        parser.error("No Input File Given (-i parameter)")
-
+        parser.error("Warning: No Input File Specified ")
+        
     if not options.output:
-        parser.error("No Output File Given (-o parameter)")
+        parser.error("Warning: No Output File Specified ")
 
+    if not options.weights:
+        parser.error("Warning: No Pathogenicity Weights Specified ")
+
     if not options.weights.upper() in [ "UNWEIGHTED", "INHERITED", "CANCER" ]:
-        parser.error("Invalid Weighting Scheme")
+        parser.error("Warning: Invalid Pathogenicity Weights ")
+
+    if options.threshold:
+        try:
+            options.threshold = float(options.threshold)
+        except:
+            pass
+    else:
+        if options.weights.upper() == "UNWEIGHTED": options.threshold = -3.00
+        if options.weights.upper() == "INHERITED":  options.threshold = -1.50
+        if options.weights.upper() == "CANCER":     options.threshold = -0.75
 
     #
     # INITIALIZE DATABASE CONNECTION/CURSOR

cgi-bin/results.cgi

@@ -36,6 +36,7 @@ if __name__ == '__main__':
                        "# Time: " + time.strftime("%H:%M:%S", HTMLTime) + "\n",
                        "# Weights: " + str(HTMLForm['weighted'].value).upper() + "\n",
                        "# Phenotypes: " + str(HTMLForm['phenotypes'].value).upper() + "\n",
+                       "# Threshold: " + str(HTMLForm['threshold'].value) + "\n",
                        str(HTMLForm['batch'].value)
                      ]:
                 open("../tmp/" + HTMLSession + ".txt", "a").write(x)
@@ -45,7 +46,8 @@ if __name__ == '__main__':
                                      '-i', '../tmp/' + HTMLSession + '.txt',
                                      '-o', '../tmp/' + HTMLSession + '.tab',
                                      '-w', str(HTMLForm['weighted'].value),
-                                     '-p', str(HTMLForm['phenotypes'].value)
+                                     '-p', str(HTMLForm['phenotypes'].value),
+                                     '-t', str(HTMLForm['threshold'].value)
                                    ], stdout=subprocess.PIPE, stderr=subprocess.PIPE, stdin=subprocess.PIPE)
         #
         else:
@@ -58,10 +60,6 @@ if __name__ == '__main__':
             if os.path.exists("../tmp/" + HTMLSession + ".tab"):
                 print """
     <!DOCTYPE html>
-    <!--[if lt IE 7]> <html class="lt-ie9 lt-ie8 lt-ie7"> <![endif]-->
-    <!--[if IE 7]> <html class="lt-ie9 lt-ie8"> <![endif]-->
-    <!--[if IE 8]> <html class="lt-ie9"> <![endif]-->
-    <!--[if gt IE 8]><!--> <html class=""> <!--<![endif]-->
         <head>
             <title>fathmm - fathmm Predictions</title>
 
@@ -144,6 +142,7 @@ if __name__ == '__main__':
                 
                 <div class="hero-unit">
                     <h2>fathmm Predictions</h2>
+                    <br />
                     <p>
                         Your request has now been processed and our predictions have been written onto your screen - a "tab-delimited" report of our predictions
                         has been made available below.&nbsp;&nbsp;In addition, you can retrieve your results at any time using the below Job/Session Identifier.
@@ -308,6 +307,7 @@ if __name__ == '__main__':
             
             <div class="hero-unit">
                 <h2>fathmm Predictions</h2>
+                <br />
                 <p>
                     Your request is now being processed and our predictions will be written onto your screen once completed - if you submitted a large batch, 
                     please be patient as this may take a while.&nbsp;&nbsp;Alternatively, you can retrieve your results at any time using the below Job/Session 
@@ -416,6 +416,7 @@ if __name__ == '__main__':
             
             <div class="hero-unit">
                 <h2>Unknown Job/Session Identifier</h2>
+                <br />
                 <p>
                     You have entered an invalid or unknown Job/Session Identifier - please note, predictions are typically stored on our server for one week before being deleted.
                 </p>
@@ -514,6 +515,7 @@ if __name__ == '__main__':
             
             <div class="hero-unit">
                 <h2>Server Error</h2>
+                <br />
                 <p>
                     It appears there is a problem with our server - please try again and/or report the problem to the system administrator
                     using the following address: fathmm.biocompute.org.uk
@@ -551,8 +553,11 @@ if __name__ == '__main__':
             We welcome any comments and/or suggestions that you may have regarding our software and server - please send an email directly to fathmm@biocompute.org.uk
             </p>
             </footer>
-            
         </div>
+        
+        <script type="text/javascript" src="../js/bootstrap.min.js"></script>
+        <script type="text/javascript" src="../js/jquery.min.js"></script>
+        
     </body>
 </html>
         """

css/fathmm.css

@@ -34,3 +34,5 @@ a:hover {
 .modal, .btn-large { 
     outline: none;
 }
+
+.tab-content {overflow-x: hidden;}

index.html

@@ -77,7 +77,7 @@
             </div>
 
             <div class="hero-unit">
-                <h2>Functional Analysis through Hidden Markov Models (v2.1)</h2>
+                <h2>Functional Analysis through Hidden Markov Models</h2>
                 <br />
                 <p>
                     A high-throughput web-server capable of predicting the functional, molecular and phenotypic consequences of 
@@ -96,7 +96,7 @@ <h3 id="head">About our Software and Server:</h3>
                 <div class="modal-body">
                     <p>
                         <br />
-                        The Functional Analysis through Hidden Markov Models (FATHMM) software and server is a <b>sequence-based algorithm</b> capable of predicting the 
+                        The Functional Analysis through Hidden Markov Models (fathmm) software and server is a <b>sequence-based algorithm</b> capable of predicting the 
                         <b>functional and phenotypic consequences of protein missense variants</b> via the amalgamation of sequence conservation within hidden Markov 
                         models (HMMs), representing the alignment of homologous sequences and conserved protein domains, with <b>'pathogenicity weights'</b>, representing 
                         the tolerance of the corresponding model to mutations.
@@ -119,15 +119,15 @@ <h3 id="head">About our Software and Server:</h3>
                     <div class="well well-large" style="height: 150px;">
                         <h4>Analyze dbSNP/Protein Missense Variants</h4>
                         <br />
-                        <p>Obtain instant predictions for the <b>functional, molecular and phenotypic consequences</b> of protein missense variants.</p>
+                        <p>Obtain instant predictions describing the <b>functional, molecular and phenotypic consequences</b> of protein missense variants.</p>
                         <p><a href="./inherited.html" class="btn pull-right">go &raquo;</a></p>
                     </div>
                 </div>
                 <div class="span6">
                     <div class="well well-large" style="height: 150px; background-image:url('./img/new.png'); background-repeat:no-repeat; background-position:top right; ">
                         <h4>Analyze Cancer-Associated Variants</h4>
                         <br />
-                        <p>Obtain instant <b>disease-specific</b> predictions capable of distinguishing between <b>cancer-promoting/driver</b> and <b>neutral/passsenger mutations</b>.</p>
+                        <p>Obtain instant predictions capable of distinguishing between <b>cancer-promoting/driver mutations</b>, <b>passsenger mutations</b> and <b>other germline polymorphisms</b>.</p>
                         <p><a href="./cancer.html" class="btn pull-right">go &raquo;</a></p>
                     </div>
                 </div>