Team:EPF-Lausanne/PrimerDesignHelper.js

   i = 0;
   this.choices.forEach(function(_arg) {
     var elem, help, label, name;
     name = _arg.name, label = _arg.label, help = _arg.help;
     elem = $("<label>").attr("class", "radio").text(label).prepend($("<input>").attr("checked", _this.data.value === name).attr("type", "radio").attr("id", _this.id + "-" + name).attr("name", _this.id).on("change", _this.callback).on("click", _this.callback)).append(_this.generateHelpDOM(help));
     return container.append(elem);
   });
   return container;
 };

 RadioInput.prototype.value = function(value) {
   var output,
     _this = this;
   if (value === void 0) {
     output = {};
     this.choices.forEach(function(_arg) {
       var name;
       name = _arg.name;
       return output[name] = $("#" + _this.id + "-" + name).attr("checked") === "checked";
     });
     return output;
   } else {
     if (value instanceof String) {
       this.choices.forEach(function(_arg) {
         var name;
         name = _arg.name;
         return $("#" + _this.id + "-" + name).attr("checked", name === value);
       });
     } else {
       this.choices.forEach(function(_arg) {
         var name;
         name = _arg.name;
         return $("#" + _this.id + "-" + name).attr("checked", value[name]);
       });
     }
     return value;
   }
 };

 return RadioInput;

{{primer1}}

{{primer2}}

 window.output.attach("#outputAttach");
 window.primerFinder = new PrimerFinder({
   output: function(data, messages) {
     window.output.setMessages(messages);
     return window.output.set(data);
   }
 });
 window.form = InputForm.create({
   name: "Primer design helper",
   submit: function(data, messages, error) {
     return window.primerFinder.calc(data, messages, error);
   },
   update: function(data, messages, error) {
     return window.primerFinder.calc(data, messages, error);
   }
 }, [
   {
     name: "dna",
     label: "DNA Sequence of interest",
     type: "DNAInput",
     value: "",
     help: "Most of the time you should just paste the DNA sequence (in the 5' → 3' direction) you want to extract/edit in this field"
   }, {
     type: "Separator"
   }, {
     name: "type",
     label: "Primer type",
     type: "RadioInput",
     choices: [
       {
         name: "normal",
         label: "Primers that extract the whole sequence",
         help: "Running a PCR using these primers will extract the entire sequence"
       }, {
         name: "rs",
         label: "Add restriction sites",
         help: "Running a PCR using these primers will result in the sequence with added standardized restriction sites on both sides."
       }, {
         name: "known",
         label: "Add a standard prefix/suffix to the sequence",
         help: "Running a PCR using these primers will result in the sequence with added standardized tails on both sides (for example for biobricking)."
       }, {
         name: "custom",
         label: "Add custom tails to the sequence",
         help: "Running a PCR using these primers will result in the sequence with added tails on both sides."
       }
     ],
     value: "normal"
   }, {
     type: "Separator"
   }, {
     name: "standardTail",
     label: "Standardized tails",
     type: "SelectInput",
     value: "biobrickGene",
     choices: [
       {
         name: "biobrickGene",
         value: "Biobrick (gene)"
       }, {
         name: "biobrickOther",
         value: "Biobrick (other)"
       }
     ],
     visible: function(_arg) {
       var type;
       type = _arg.type;
       return type.known;
     }
   }, {
     name: "randomBases",
     label: "Random Bases",
     type: "NumberInput",
     value: "4",
     help: "This is the number of random bases will be added on both ends.",
     visible: function(_arg) {
       var type;
       type = _arg.type;
       return type.rs;
     }
   }, {
     name: "leftRS",
     label: "Left restriction site",
     type: "DNARSInput",
     value: "",
     help: "You can also enter the name of the restriction enzyme (i.e. EcoRI).",
     visible: function(_arg) {
       var type;
       type = _arg.type;
       return type.rs;
     }
   }, {
     name: "rightRS",
     label: "Right restriction site",
     type: "DNARSInput",
     value: "",
     help: "You can also enter the name of the restriction enzyme (i.e. EcoRI).",
     visible: function(_arg) {
       var type;
       type = _arg.type;
       return type.rs;
     }
   }, {
     name: "leftTail",
     label: "Left tail",
     type: "DNASmallInput",
     value: "",
     visible: function(_arg) {
       var type;
       type = _arg.type;
       return type.custom;
     }
   }, {
     name: "rightTail",
     label: "Right tail",
     type: "DNASmallInput",
     value: "",
     visible: function(_arg) {
       var type;
       type = _arg.type;
       return type.custom;
     }
   }, {
     type: "Separator",
     visible: function(_arg) {
       var type;
       type = _arg.type;
       return !type.normal;
     }
   }, {
     name: "tm",
     label: "Target Tm",
     type: "TemperatureInput",
     value: "50",
     help: "The program will try to create primers that have an annealing temperature close to this one."
   }, {
     value: "Generate",
     type: "Submit"
   }
 ]);
 return window.form.attach($("#formAttach"));

 {
   name: "Biobrick (gene)",
   value: "biobrickGene",
   primer1Tail: "GTT TCT TCG AAT TCG CGG CCG CTT CTA G",
   primer2Tail: "GTT TCT TCC TGC AGC GGC CGC TAC TAG TA TTA TTA",
   messages: ["Don't forget to include the first ATG and to exclude the stop codon!", "The recommended minimum length of a BioBrick primer is 20bp", "The recommended Tm of a BioBrick primer is between 55 and 65\u00B0C", "Check that the following restriction sites are absent: EcoRI, SpeI, XbaI, PstI, NotI", "Check out <a href='http://openwetware.org/wiki/Synthetic_Biology:BioBricks/Part_fabrication'>OpenWetWare's reference page</a>"],
   validate: function(primer1, primer2, dna) {
     var end, start;
     start = primer1.substr(0, 3).toUpperCase();
     if (start !== "ATG") return "The starting ATG seems to be absent.";
     end = primer2.substr(0, 3).toUpperCase();
     if (end === "TTA" || end === "TCA" || end === "CTA") {
       return "Remove the stop codons from the sequence!";
     }
     if (dna.containsRS(["EcoRI", "SpeI", "XbaI", "PstI", "NotI"])) {
       return "One of the following restriction sites is present (and shouldn't be): EcoRI, SpeI, XbaI, PstI, NotI";
     }
     return;
   }
 }, {
   name: "Biobrick (other)",
   value: "biobrickOther",
   primer1Tail: "GTT TCT TCG AAT TCG CGG CCG CTT CTA GAG",
   primer2Tail: "GTT TCT TCC TGC AGC GGC CGC TAC TAG TA",
   messages: ["The recommended minimum length of a BioBrick primer is 20bp", "The recommended Tm of a BioBrick primer is between 55 and 65\u00B0C", "Check that the following restriction sites are absent: EcoRI, SpeI, XbaI, PstI, NotI", "Check out <a href='http://openwetware.org/wiki/Synthetic_Biology:BioBricks/Part_fabrication'>OpenWetWare's reference page</a>"],
   validate: function(primer1, primer2, dna) {
     if (dna.containsRS(["EcoRI", "SpeI", "XbaI", "PstI", "NotI"])) {
       return "One of the following restriction sites is present (and shouldn't be): EcoRI, SpeI, XbaI, PstI, NotI";
     }
     return;
   }
 }

 __hasProp = Object.prototype.hasOwnProperty,
 __extends = function(child, parent) { for (var key in parent) { if (__hasProp.call(parent, key)) child[key] = parent[key]; } function ctor() { this.constructor = child; } ctor.prototype = parent.prototype; child.prototype = new ctor; child.__super__ = parent.prototype; return child; };

 Output.i = 0;

 Output.j = 0;

 function Output(template) {
   this.template = template;
   this.id = "output-" + Output.i++;
   this.fields = {};
   this.matches = {};
   this.displays = {};
   this.parsedTemplate = this.parseTemplate(this.template);
 }

 Output.prototype.attach = function(elem) {
   var displayClass, displayObj, k, v, _ref, _results;
   this.matches = {};
   $(elem).html(this.parsedTemplate);
   _ref = this.displays;
   _results = [];
   for (k in _ref) {
     v = _ref[k];
     _results.push((function() {
       var _i, _len, _ref2, _results2;
       _results2 = [];
       for (_i = 0, _len = v.length; _i < _len; _i++) {
         _ref2 = v[_i], displayClass = _ref2.displayClass, displayObj = _ref2.displayObj;
         _results2.push(displayObj.attach("." + displayClass));
       }
       return _results2;
     })());
   }
   return _results;
 };

 Output.prototype.setMessages = function(messages) {
   var output;
   output = messages;
   if (messages.length === 0) output = ["No messages"];

 };

 Output.prototype.wipe = function() {
   var k, v, _ref;
   _ref = this.fields;
   for (k in _ref) {
     v = _ref[k];
     this.updateValue(k, void 0);
   }
   return this.fields = {};
 };

 Output.prototype.set = function(values) {
   var k, v;
   for (k in values) {
     v = values[k];
     this.updateValue(k, v);
   }
   this.updateValue("__all__", this.fields);
   return this.fields;
 };

 Output.prototype.updateValue = function(k, v) {
   var displayObj, _i, _len, _ref, _results;
   if (this.fields[k] !== v) {
     this.fields[k] = v;
     if (v != null) {
       this.getFields(k).html(v.toString());
     } else {
       this.getFields(k).html("");
     }
   }
   if (this.displays[k] != null) {
     _ref = this.displays[k];
     _results = [];
     for (_i = 0, _len = _ref.length; _i < _len; _i++) {
       displayObj = _ref[_i].displayObj;
       _results.push(displayObj.set(v));
     }
     return _results;
   }
 };

 Output.prototype.getFields = function(name) {
   if (!this.matches[name]) {
     this.matches[name] = $("." + this.id + "-match-" + name);
   }
   return this.matches[name];
 };

 Output.prototype.parseTemplate = function(template) {
   var c1, c2, display, displayClass, displayObj, displayPart, i, inName, key, name, output, skipNext, started, _ref;
   c1 = template[0];
   c2 = template[1];
   output = template + "";
   skipNext = false;
   inName = false;
   started = -1;
   name = "";
   for (i = 1, _ref = template.length - 1; 1 <= _ref ? i <= _ref : i >= _ref; 1 <= _ref ? i++ : i--) {
     c2 = template[i];
     if (!skipNext) {
       if (c1 === "{" && c2 === "{") {
         if (inName) {
           throw new Error("Invalid template, opened brackets in an already opened context");
         }
         name = "";
         started = i;
         skipNext = true;
         inName = true;
       } else if (c1 === "}" && c2 === "}") {
         if (!inName) {
           throw new Error("Invalid template, closed unopened brackets");
         }
         displayPart = name.indexOf(":");
         if (displayPart >= 0) {
           display = name.substr(0, displayPart);
           key = name.substr(displayPart + 1);
           if (key === "") key = "__all__";
           displayClass = this.id + "-display-" + display + "-" + key;
           output = output.replace("Template:" + name + "", "");
           displayObj = new window[display](key);
           if (!(this.displays[key] != null)) this.displays[key] = [];
           this.displays[key].push({
             displayClass: displayClass,
             displayObj: displayObj
           });
         } else {
           output = output.replace("Template:" + name + "", "");
         }
         skipNext = true;
         inName = false;
       } else {
         if (inName) name += c1;
       }
     } else {
       skipNext = false;
     }
     c1 = c2;
   }
   return output;
 };

 return Output;

 function Display(key) {
   this.key = key;
   this.value = void 0;
 }

 Display.prototype.attach = function(id) {
   throw new Error("Not implemented");
 };

 Display.prototype.set = function(values) {
   return this.value = values[this.key];
 };

 Display.prototype.pad = function(str, width, padLeft) {
   var length;
   if (str == null) str = "";
   if (width == null) width = 5;
   if (padLeft == null) padLeft = false;
   str = str.toString();
   length = str.length;
   while (length < width) {
     if (padLeft) {
       str = " " + str;
     } else {
       str += " ";
     }
     length++;
   }
   return str;
 };

 Display.prototype.wrap = function(str, width) {
   var i, length, output;
   if (str == null) str = "";
   if (width == null) width = 40;
   str = str.toString();
   length = str.length;
   output = [];
   i = 0;
   while (length >= width) {
     output.push(str.substr(i, width));
     length -= width;
     i += width;
   }
   if (length > 0) output.push(str.substr(i));
   return output;
 };

 return Display;

 __extends(DNADisplay, _super);

 DNADisplay.i = 0;

 function DNADisplay(key) {
   var that,
     _this = this;
   DNADisplay.__super__.constructor.apply(this, arguments);
   this["class"] = "dnadisplay-" + DNADisplay.i++;
   this.objects = [];
   that = this;

").attr("class", this["class"]).append($("<label>").append($("<input>").attr("class", this["class"] + "-toggleLines").attr("type", "checkbox").attr("checked", "on").on("change", function() {

     if ($("." + _this["class"] + "-toggleLines").attr("checked")) {
       $("." + _this["class"] + "-lines").hide();
       $("." + _this["class"] + "-numberedLines").show();
     } else {
       $("." + _this["class"] + "-lines").show();
       $("." + _this["class"] + "-numberedLines").hide();
     }
     return;

})).append(" Line Numbers")).append($("

").attr("class", this["class"] + "-lines product").hide()).append($("<pre>").attr("class", this["class"] + "-numberedLines product"));
  }

  DNADisplay.prototype.attach = function(elem) {
    $(elem).append(this.dom);
    return this.objects = $("." + this["class"]);
  };

  DNADisplay.prototype.set = function(value) {
    var i, line, lines, numberWidth, numberedLines, outputLines, width, widthNumbered, _len;
    width = 60;
    numberWidth = 6;
    widthNumbered = 40;
    lines = this.wrap(value, width);
    numberedLines = this.wrap(value, widthNumbered);
    outputLines = [];
    for (i = 0, _len = numberedLines.length; i < _len; i++) {
      line = numberedLines[i];
      if (line.length > 0) {
        outputLines[i] = this.pad(i * widthNumbered + 1, numberWidth, true) + " - " + this.pad((i + 1) * widthNumbered, numberWidth) + "  " + line;
      }
    }
    this.full = lines.join("\n");
    this.fullNumbered = outputLines.join("\n");
    $("." + this["class"] + "-lines").text(this.full);
    return $("." + this["class"] + "-numberedLines").text(this.fullNumbered);
  };

  return DNADisplay;

})(Display);

RSDisplay = (function(_super) {

  __extends(RSDisplay, _super);

  RSDisplay.i = 0;

  function RSDisplay(key) {
    var that;
    RSDisplay.__super__.constructor.apply(this, arguments);
    this["class"] = "rsdisplay-" + RSDisplay.i++;
    this.objects = [];
    that = this;
    this.dom = $("<div>").attr("class", this["class"]).append($("<pre>").attr("class", this["class"] + "-pre"));
  }

  RSDisplay.prototype.attach = function(elem) {
    $(elem).append(this.dom);
    return this.objects = $("." + this["class"]);
  };

  RSDisplay.prototype.set = function(_arg) {
    var c, complement, full, left, leftCompStr, leftCut, leftRS, leftRSInput, leftStr, overhang, randomBases, right, rightCompStr, rightCut, rightRS, rightRSInput, rightStr, rs, text, type, _i, _j, _len, _len2, _ref, _ref2;
    rs = _arg.rs, type = _arg.type, leftRS = _arg.leftRS, rightRS = _arg.rightRS;
    if (!type.rs) {
      $("." + this["class"] + "-pre").html("Not applicable");
      return;
    }
    leftRSInput = leftRS.rs;
    rightRSInput = rightRS.rs;
    left = rs.left, right = rs.right, full = rs.full, randomBases = rs.randomBases;
    leftCut = DNA.getCutPosition(leftRSInput);
    if (leftCut < 0) {
      leftRS = DNA.fromString(left).findRS(true);
      leftCut = DNA.getCutPosition(leftRS);
    } else {
      leftRS = leftRSInput;
    }
    if (leftRS.length === 0) leftRS = "?";
    rightCut = DNA.getCutPosition(rightRSInput);
    if (rightCut < 0) {
      rightRS = DNA.fromString(right).findRS(true);
      rightCut = DNA.getCutPosition(rightRS);
    } else {
      rightRS = rightRSInput;
    }
    if (rightRS.length === 0) rightRS = "?";
    leftStr = full.substr(0, randomBases + left.length + 10);
    rightStr = full.substr(full.length - (randomBases + right.length + 10));
    if (randomBases > 6) {
      leftStr = "..." + leftStr.substr(randomBases - 3);
      rightStr = rightStr.substr(0, rightStr.length - (randomBases - 3)) + "...";
      randomBases = 6;
    }
    leftCompStr = "";
    rightCompStr = "";
    complement = function(c) {
      switch (c) {
        case "A":
          return "T";
        case "T":
          return "A";
        case "C":
          return "G";
        case "G":
          return "C";
        default:
          return c;
      }
    };
    _ref = leftStr.split("");
    for (_i = 0, _len = _ref.length; _i < _len; _i++) {
      c = _ref[_i];
      leftCompStr += complement(c);
    }
    _ref2 = rightStr.split("");
    for (_j = 0, _len2 = _ref2.length; _j < _len2; _j++) {
      c = _ref2[_j];
      rightCompStr += complement(c);
    }
    if (leftCut >= 0) {
      overhang = Math.ceil(Math.abs(left.length / 2 - leftCut)) + 1;
      leftStr = leftStr.substr(0, randomBases + leftCut) + this.pad("", overhang + 1) + leftStr.substr(randomBases + leftCut);
      leftCompStr = leftCompStr.substr(0, randomBases + left.length - leftCut) + this.pad("", overhang + 1) + leftCompStr.substr(randomBases + left.length - leftCut);
    } else {
      leftStr = leftStr.substr(0, randomBases) + "  " + leftStr.substr(randomBases, left.length) + "  " + leftStr.substr(randomBases + left.length);
      leftCompStr = leftCompStr.substr(0, randomBases) + "  " + leftCompStr.substr(randomBases, left.length) + "  " + leftCompStr.substr(randomBases + left.length);
    }
    if (rightCut >= 0) {
      overhang = Math.ceil(Math.abs(right.length / 2 - rightCut)) + 1;
      rightStr = rightStr.substr(0, rightStr.length - (randomBases + right.length - rightCut)) + this.pad("", overhang + 1) + rightStr.substr(rightStr.length - (randomBases + right.length - rightCut));
      rightCompStr = rightCompStr.substr(0, rightCompStr.length - (randomBases + rightCut)) + this.pad("", overhang + 1) + rightCompStr.substr(rightCompStr.length - (randomBases + rightCut));
    } else {
      rightStr = rightStr.substr(0, rightStr.length - (randomBases + right.length)) + "  " + rightStr.substr(rightStr.length - (randomBases + right.length), right.length) + "  " + rightStr.substr(rightStr.length - randomBases);
      rightCompStr = rightCompStr.substr(0, rightCompStr.length - (randomBases + right.length)) + "  " + rightCompStr.substr(rightCompStr.length - (randomBases + right.length), right.length) + "  " + rightCompStr.substr(rightCompStr.length - randomBases);
    }
    text = [];
    text.push("Left restriction site: " + leftRS + (leftCut < 0 ? " (cutting site unknown)" : ""));
    text.push("Right restriction site: " + rightRS + (rightCut < 0 ? " (cutting site unknown)" : ""));
    text.push("");
    text.push("5'" + this.pad("3'", leftStr.length + rightStr.length + 1, true));
    text.push(leftStr + "..." + rightStr);
    text.push(leftCompStr + "..." + rightCompStr);
    text.push("3'" + this.pad("5'", leftStr.length + rightStr.length + 1, true));
    return $("." + this["class"] + "-pre").text(text.join("\n"));
  };

  return RSDisplay;

})(Display);

SelfDimerDisplay = (function(_super) {

  __extends(SelfDimerDisplay, _super);

  SelfDimerDisplay.i = 0;

  function SelfDimerDisplay(key) {
    var that,
      _this = this;
    SelfDimerDisplay.__super__.constructor.apply(this, arguments);
    this["class"] = "selfdimerdisplay-" + RSDisplay.i++;
    this.objects = [];
    that = this;
    this.dom = $("<div>").attr("class", this["class"]).append($("<span>").text("This calculation is quite heavy and is done on demand. Press on the button to start the calculations:")).append("<br>").append($("<input>").attr("type", "button").attr("value", "Calculate").attr("class", "btn").click(function() {
      return _this.click();
    })).append("<br>").append("<br>").append($("<pre>").attr("class", this["class"] + "-pre").html("Press the calculate button to update this data"));
  }

  SelfDimerDisplay.prototype.attach = function(elem) {
    $(elem).append(this.dom);
    return this.objects = $("." + this["class"] + "-pre");
  };

  SelfDimerDisplay.prototype.set = function(_arg) {
    var primer1, primer2;
    primer1 = _arg.primer1, primer2 = _arg.primer2;
    if (primer1 !== this.primer1 || primer2 !== this.primer2) {
      this.primer1 = primer1;
      this.primer2 = primer2;
      return this.objects.html("Press the calculate button to update this data");
    }
  };

  SelfDimerDisplay.prototype.click = function() {
    var report;
    report = this.generateReport("Primer 1", this.primer1) + "\n\n" + this.generateReport("Primer 2", this.primer2);
    return this.objects.html(report);
  };

  SelfDimerDisplay.prototype.generateReport = function(name, primer) {
    var character, folds, lineC, lineN, lines, matches, number, p, pairs, rna, _i, _j, _len, _ref, _ref2, _results;
    lines = [];
    lines.push(name + ":");
    rna = RNA.fromString(primer);
    _ref = rna.findKnots(), matches = _ref.matches, folds = _ref.folds;
    lines.push("Amount of matches: " + matches);
    pairs = _.zip((function() {
      _results = [];
      for (var _i = 1, _ref2 = primer.length; 1 <= _ref2 ? _i <= _ref2 : _i >= _ref2; 1 <= _ref2 ? _i++ : _i--){ _results.push(_i); }
      return _results;
    }).apply(this), primer.split(""));
    lineC = "";
    lineN = "";
    for (_j = 0, _len = pairs.length; _j < _len; _j++) {
      p = pairs[_j];
      number = p[0] + " ";
      character = this.pad(p[1], number.length - 1, true) + " ";
      if (lineC.length + number.length > 60) {
        lines.push(lineC);
        lines.push(lineN);
        lines.push("");
        lineC = "";
        lineN = "";
      }
      lineC += character;
      lineN += number;
    }
    if (lineC.length > 0) {
      lines.push(lineC);
      lines.push(lineN);
      lines.push("");
    }
    return lines.join("\n");
  };

  return SelfDimerDisplay;

})(Display);
var Primer;

Primer = (function() {

  Primer.minLength = 8;

  Primer.maxLength = 50;

  Primer.maxDiff = 8;

  Primer.lastData = "";

  Primer.lastTail1 = "";

  Primer.lastTail2 = "";

  Primer.lastTm = 0;

  Primer.lastRandEdgeSize = -1;

  Primer.reset = function() {
    this.lastData = "";
    this.lastTm = 0;
    this.lastTail1 = "";
    this.lastTail2 = "";
    return this.lastRandEdgeSize = -1;
  };

  function Primer(data) {
    if (data instanceof DNA) {
      this.seq = data.clone();
    } else {
      this.seq = DNA.fromString(data);
    }
    this.tail1 = new DNA([]);
    this.tail2 = new DNA([]);
    this.randEdgeSize = 0;
  }

  Primer.prototype.setTails = function(tail1, tail2) {
    this.tail1 = tail1;
    this.tail2 = tail2;
  };

  Primer.prototype.addRandomEdges = function(randEdgeSize) {
    this.randEdgeSize = randEdgeSize;
  };

  Primer.prototype.isSameAsLast = function(data, tm) {
    return Primer.lastTail1.toString() === this.tail1.toString() && Primer.lastTail2.toString() === this.tail2.toString() && Primer.lastData === DNA.fromString(data).toString() && Primer.lastTm === tm && Primer.lastRandEdgeSize === this.randEdgeSize;
  };

  Primer.prototype.generate = function(goal) {
    var diff, l1, l2, maxLength, primer1Length, primer1Temp, primer2Length, primer2Temp, rand1, rand2, revCompl, temp, _ref, _ref2;
    if (2 * Primer.minLength > this.seq.length()) {
      throw new Error("The given sequence is too short");
    }
    Primer.lastData = this.seq.toString();
    Primer.lastTm = goal;
    Primer.lastTail1 = this.tail1;
    Primer.lastTail2 = this.tail2;
    Primer.lastRandEdgeSize = this.randEdgeSize;
    maxLength = Math.min(Math.floor(this.seq.length() / 2), Primer.maxLength);
    revCompl = this.seq.reverseComplement();
    primer1Length = -1;
    primer1Temp = 0;
    primer2Length = -1;
    primer2Temp = 0;
    for (l1 = _ref = Primer.minLength; _ref <= maxLength ? l1 <= maxLength : l1 >= maxLength; _ref <= maxLength ? l1++ : l1--) {
      temp = this.seq.snip(l1).tm();
      diff = Math.abs(temp - goal);
      if (diff <= Primer.maxDiff && (primer1Length === -1 || Math.abs(primer1Temp - goal) > diff)) {
        primer1Length = l1;
        primer1Temp = temp;
      }
      if (temp >= goal) break;
    }
    for (l2 = _ref2 = Primer.minLength; _ref2 <= maxLength ? l2 <= maxLength : l2 >= maxLength; _ref2 <= maxLength ? l2++ : l2--) {
      temp = revCompl.snip(l2).tm();
      diff = Math.abs(temp - goal);
      if (diff <= Primer.maxDiff && (primer2Length === -1 || Math.abs(primer2Temp - goal) > diff)) {
        primer2Length = l2;
        primer2Temp = temp;
      }
      if (temp >= goal) break;
    }
    if (primer1Length < 0 || primer2Length < 0) {
      throw new Error("Couldn't find a primer of correct length that satisfies the conditions");
    }
    rand1 = DNA.fromRandom(this.randEdgeSize);
    rand2 = DNA.fromRandom(this.randEdgeSize);
    return {
      rs: {
        left: this.tail1.toString(),
        right: this.tail2.toString(),
        randomBases: this.randEdgeSize,
        full: rand1.toString() + this.tail1.toString() + this.seq.toString() + this.tail2.reverseComplement().toString() + rand2.reverseComplement().toString()
      },
      primer1: rand1.toString() + " " + this.tail1.toString() + " " + this.seq.snip(primer1Length).toString(),
      primers: {
        primer1: rand1.toString() + this.tail1.toString() + this.seq.snip(primer1Length).toString(),
        primer2: rand2.toString() + this.tail2.toString() + revCompl.snip(primer2Length).toString()
      },
      primer1NoTail: this.seq.snip(primer1Length).toString(),
      primer1Tm: primer1Temp,
      primer1Length: primer1Length,
      primer1TailLength: rand1.length() + this.tail1.length(),
      primer2: rand2.toString() + " " + this.tail2.toString() + " " + revCompl.snip(primer2Length).toString(),
      primer2NoTail: revCompl.snip(primer2Length).toString(),
      primer2Tm: primer2Temp,
      primer2Length: primer2Length,
      primer2TailLength: rand2.length() + this.tail2.length(),
      full: rand1.toString() + this.tail1.toString() + this.seq.toString() + this.tail2.reverseComplement().toString() + rand2.reverseComplement().toString()
    };
  };

  return Primer;

})();
var PrimerFinder;

PrimerFinder = (function() {

  function PrimerFinder(_arg) {
    this.output = _arg.output;
    this.defaults = {
      primer1: "No data",
      primer1Tm: "?",
      primer1Length: 0,
      primer2: "No data",
      primer2Tm: "?",
      primer2Length: 0,
      annealingTm: "?"
    };
  }

  PrimerFinder.prototype.calc = function(data, messages, error) {
    var k, match1, match2, p, primers, result, tail, tail1, tail2, v, validate, _i, _len, _ref, _ref2;
    if (error) {
      messages = ["A fatal error occured:"].concat(messages);
      this.output(data, messages);
      return;
    }
    _ref = this.defaults;
    for (k in _ref) {
      v = _ref[k];
      if (!(data[k] != null)) data[k] = v;
    }
    try {
      p = new Primer(data.dna);
      validate = function(primer1, primer2, dna) {};
      if (data.type.custom) p.setTails(data.leftTail, data.rightTail);
      if (data.type.rs) {
        match1 = data.leftRS.dna.findRS();
        match2 = data.rightRS.dna.findRS();
        if ((match1 != null) && match1.length > 0) {
          messages.push("The left restriction site is " + match1);
        } else {
          messages.push("The left restriction site wasn't recognized");
        }
        if ((match2 != null) && match2.length > 0) {
          messages.push("The right restriction site is " + match2);
        } else {
          messages.push("The right restriction site wasn't recognized");
        }
        p.setTails(data.leftRS.dna, data.rightRS.dna.reverseComplement());
        p.addRandomEdges(data.randomBases);
        messages.push("Click the 'Generate' button to regenerate the random bases added on the end of the primers.");
        messages.push("In the case of a plasmid where the piece between A and B is cut out, and A is used for the primer 1 RS (and B for the second).\nThe generated primers will put the RS such that the given DNA starts at the A side and ends at the B side (in short,\nit will probably work as you expected, but still check what happens with some other tool).");
      }
      if (data.type.known) {
        tail1 = "";
        tail2 = "";
        _ref2 = window.tails;
        for (_i = 0, _len = _ref2.length; _i < _len; _i++) {
          tail = _ref2[_i];
          if (tail.value === data.standardTail) {
            tail1 = tail.primer1Tail;
            tail2 = tail.primer2Tail;
            if (tail.messages != null) messages = [].concat(tail.messages);
            if (tail.validate != null) validate = tail.validate;
          }
        }
        p.setTails(DNA.fromString(tail1), DNA.fromString(tail2));
      }
      primers = p.generate(data.tm);
      result = validate(primers.primer1NoTail, primers.primer2NoTail, data.dna);
      if (result != null) messages.push(result);
      for (k in primers) {
        v = primers[k];
        data[k] = v;
      }
      messages = messages;
    } catch (e) {
      messages = [e.message];
    }
    data.annealingTm = Math.min(data.primer1Tm, data.primer2Tm);
    if (Math.abs(data.primer1Tm - data.primer2Tm) > 5) {
      messages.push("The difference between the primer's Tm is more than 5\u00B0C");
    }
    if (data.annealingTm > 70) {
      messages.push("Consider using the two-step PCR protocol");
    }
    if (data.annealingTm > 72) {
      messages.push("Annealing temperature shouldn't exceed 72\u00B0C");
      data.annealingTm = 72;
    }
    if (data.annealingTm < 45) {
      messages.push("The annealing temperature should be more than 45\u00B0C");
    }
    return this.output(data, messages);
  };

  return PrimerFinder;

})();
var RNA;

RNA = (function() {

  RNA.fromDNA = function(dna) {
    return new RNA(dna.data.map(function(x) {
      switch (x) {
        case "T":
          return "U";
        default:
          return x;
      }
    }));
  };

  RNA.fromString = function(data) {
    return RNA.fromDNA(DNA.fromString(data));
  };

  /*
    Note: Just like for the DNA class, you probably didn't want to use the constructor. Use fromDNA or fromString instead!
  */

  function RNA(data) {
    this.data = data;
    this.n = this.data.length;
    this.knots = void 0;
  }

  RNA.prototype.P = function(i, j) {
    if ((this.data[i] === "A" && this.data[j] === "U") || (this.data[i] === "U" && this.data[j] === "C")) {
      return 1;
    } else if ((this.data[i] === "G" && this.data[j] === "C") || (this.data[i] === "C" && this.data[j] === "G")) {
      return 1;
    } else {
      return 0;
    }
  };

  RNA.prototype.isTooSelfComplementary = function() {
    var fold, folds, i, matches, seq, _i, _len, _ref, _ref2;
    _ref = this.findKnots(), matches = _ref.matches, folds = _ref.folds;
    for (_i = 0, _len = folds.length; _i < _len; _i++) {
      fold = folds[_i];
      seq = [];
      console.log(fold);
      for (i = 0, _ref2 = fold.length - 1; 0 <= _ref2 ? i <= _ref2 : i >= _ref2; 0 <= _ref2 ? i++ : i--) {
        if (fold[i] === "(") {
          if (i > 0 && fold[i - 1] === "(") {
            seq[seq.length - 1] += this.data[i];
          } else {
            seq[seq.length] = this.data[i];
          }
        }
      }
      console.log(seq);
    }
    return false;
  };

  RNA.prototype.findKnots = function(minSize) {
    var HM, M, a, a1, a2, createSolution, hashSet, hm, hs, i, j, k, l, m, max, output, p, sol, str, tmp, _i, _j, _k, _l, _len, _len2, _len3, _len4, _ref, _ref10, _ref2, _ref3, _ref4, _ref5, _ref6, _ref7, _ref8, _ref9,
      _this = this;
    if (minSize == null) minSize = 2;
    if (this.knots !== void 0) return this.knots;
    createSolution = function() {
      var i, _ref, _results;
      _results = [];
      for (i = 1, _ref = _this.n; 1 <= _ref ? i <= _ref : i >= _ref; 1 <= _ref ? i++ : i--) {
        _results.push(".");
      }
      return _results;
    };
    HM = [];
    for (l = 0, _ref = this.n - 1; 0 <= _ref ? l <= _ref : l >= _ref; 0 <= _ref ? l++ : l--) {
      hm = [];
      for (m = 0, _ref2 = this.n - 1; 0 <= _ref2 ? m <= _ref2 : m >= _ref2; 0 <= _ref2 ? m++ : m--) {
        hm[m] = [createSolution()];
      }
      HM[l] = hm;
    }
    M = (function() {
      var _ref3, _results;
      _results = [];
      for (i = 1, _ref3 = this.n; 1 <= _ref3 ? i <= _ref3 : i >= _ref3; 1 <= _ref3 ? i++ : i--) {
        _results.push((function() {
          var _ref4, _results2;
          _results2 = [];
          for (j = 1, _ref4 = this.n; 1 <= _ref4 ? j <= _ref4 : j >= _ref4; 1 <= _ref4 ? j++ : j--) {
            _results2.push(0);
          }
          return _results2;
        }).call(this));
      }
      return _results;
    }).call(this);
    for (i = _ref3 = this.n - 1; _ref3 <= 0 ? i <= 0 : i >= 0; _ref3 <= 0 ? i++ : i--) {
      for (j = i, _ref4 = this.n - 1; i <= _ref4 ? j <= _ref4 : j >= _ref4; i <= _ref4 ? j++ : j--) {
        max = 0;
        if (i < j - minSize) {
          max = M[i + 1][j - 1] + this.P(i, j);
          hs = [];
          _ref5 = HM[i + 1][j - 1];
          for (_i = 0, _len = _ref5.length; _i < _len; _i++) {
            sol = _ref5[_i];
            if (this.P(i, j) === 1) {
              sol[i] = "(";
              sol[j] = ")";
            } else {
              sol[i] = ".";
              sol[j] = ".";
            }
            if (hs.length < 50) hs.push(sol);
          }
          for (k = i, _ref6 = j - 1; i <= _ref6 ? k <= _ref6 : k >= _ref6; i <= _ref6 ? k++ : k--) {
            tmp = M[i][k] + M[k + 1][j];
            if (tmp > max) {
              max = tmp;
              hs = [];
            }
            if (tmp >= max) {
              _ref7 = HM[i][k];
              for (_j = 0, _len2 = _ref7.length; _j < _len2; _j++) {
                a1 = _ref7[_j];
                _ref8 = HM[k + 1][j];
                for (_k = 0, _len3 = _ref8.length; _k < _len3; _k++) {
                  a2 = _ref8[_k];
                  a = createSolution(this.n);
                  for (p = 0; 0 <= k ? p <= k : p >= k; 0 <= k ? p++ : p--) {
                    a[p] = a1[p];
                  }
                  for (p = _ref9 = k + 1; _ref9 <= j ? p <= j : p >= j; _ref9 <= j ? p++ : p--) {
                    a[p] = a2[p];
                  }
                  if (hs.length < 50) hs.push(a);
                }
              }
            }
          }
          M[i][j] = max;
          HM[i][j] = hs;
        }
      }
    }
    output = [];
    hashSet = {};
    _ref10 = HM[0][this.n - 1];
    for (_l = 0, _len4 = _ref10.length; _l < _len4; _l++) {
      sol = _ref10[_l];
      str = sol.join("");
      if (hashSet[str] === void 0) {
        hashSet[str] = true;
        output.push(str);
      }
    }
    return this.knots = {
      matches: M[0][this.n - 1],
      folds: output
    };
  };

  return RNA;

})();
/*
Container class that helps with Tm calculations. It has been seperated to enable easy improvements to the
algorithm.
*/
var TmCalc;

TmCalc = (function() {

  function TmCalc() {}

  TmCalc.maxCacheSize = 500;

  TmCalc.cache = {};

  TmCalc.calc = function(data) {
    var key, keys, result;
    if (!this.cache[data]) {
      result = Math.round(this.calcFull(data) * 10) / 10;
      if (this.cache.length >= this.maxCacheSize) {
        keys = Object.keys(TmCalc.cache);
        key = keys[Math.floor(Math.random() * keys.length)];
        delete TmCalc.cache[key];
      }
      this.cache[data] = result;
    }
    return this.cache[data];
  };

  TmCalc.complement = function(n) {
    switch (n) {
      case "A":
        return "T";
      case "T":
        return "A";
      case "C":
        return "G";
      case "G":
        return "C";
      default:
        throw new Error("Invalid character encountered (" + n + ")");
    }
  };

  TmCalc.neighborH = {
    AA: 9.1,
    AT: 8.6,
    TA: 6.0,
    CA: 5.8,
    GT: 6.5,
    CT: 7.8,
    GA: 5.6,
    CG: 11.9,
    GC: 11.1,
    GG: 11.0
  };

  TmCalc.getH = function(n1, n2) {
    return this.get(this.neighborH, n1, n2);
  };

  TmCalc.neighborG = {
    AA: 1.9,
    AT: 1.5,
    TA: 0.9,
    CA: 1.9,
    GT: 1.3,
    CT: 1.6,
    GA: 1.6,
    CG: 3.6,
    GC: 3.1,
    GG: 3.1
  };

  TmCalc.getG = function(n1, n2) {
    return this.get(this.neighborG, n1, n2);
  };

  TmCalc.neighborS = {
    AA: 24.0,
    AT: 23.9,
    TA: 16.9,
    CA: 12.9,
    GT: 17.3,
    CT: 20.8,
    GA: 13.5,
    CG: 27.8,
    GC: 26.7,
    GG: 26.6
  };

  TmCalc.getS = function(n1, n2) {
    return this.get(this.neighborS, n1, n2);
  };

  TmCalc.get = function(searchVar, n1, n2) {
    switch (n1 + n2) {
      case "AA":
        return searchVar["AA"];
      case "TT":
        return searchVar["AA"];
      case "AT":
        return searchVar["AT"];
      case "TA":
        return searchVar["TA"];
      case "TT":
        return searchVar["TA"];
      case "CA":
        return searchVar["CA"];
      case "TG":
        return searchVar["CA"];
      case "GT":
        return searchVar["GT"];
      case "AC":
        return searchVar["GT"];
      case "CT":
        return searchVar["CT"];
      case "AG":
        return searchVar["CT"];
      case "GA":
        return searchVar["GA"];
      case "TC":
        return searchVar["GA"];
      case "CG":
        return searchVar["CG"];
      case "TC":
        return searchVar["CG"];
      case "GC":
        return searchVar["GC"];
      case "TC":
        return searchVar["GC"];
      case "GG":
        return searchVar["GG"];
      case "CC":
        return searchVar["GG"];
      default:
        throw new Error("No idea what happened... (tried getting " + n1 + n2 + ")");
    }
  };

  TmCalc.calcFull = function(data) {
    /* See (Breslauer et al. 1986): http://www.pnas.org/content/83/11/3746.full.pdf
    */
    var R, dh, ds, dsinit, i, n1, n2, naConc, predG, predH, predS, primerConc, primerc_local, _ref;
    predH = 0;
    predG = -(5 + 0.4);
    predS = 0;
    primerConc = 500 * 10e-3;
    naConc = 50 * 10e-3;
    R = 1.987;
    n1 = data[0];
    for (i = 1, _ref = data.length - 1; 1 <= _ref ? i <= _ref : i >= _ref; 1 <= _ref ? i++ : i--) {
      n2 = data[i];
      predH -= this.getH(n1, n2);
      predG -= this.getG(n1, n2);
      predS -= this.getS(n1, n2);
      n1 = n2;
    }
    dh = 1000 * predH;
    ds = predS;
    dsinit = -10.8;
    primerc_local = primerConc / 4 * 1e-6;
    return dh / (dsinit + ds + R * Math.log(primerc_local / 10)) - 273.15 + 16.6 * Math.log(naConc / 10) / Math.LN10;
  };

  /* Again, old
  @calcFull: (data, options) ->
    ##
    For more details see: http://www.basic.northwestern.edu/biotools/oligocalc.html
    ##
    freq = @calcFrequencies(data)
    
    if not options
      options = {}
    
    if not options.Na
      options.Na = 0.05
    
    GC = freq["G"] + freq["C"]
    AT = freq["A"] + freq["T"]
    N = data.length
    
    if N < 14
      AT*2 + GC*4 - 16.6*Math.log(0.050)/Math.log(10) + 16.6*Math.log(options.Na)/Math.log(10)
    else if N < 50 #18
      100.5 + (41 * GC/N) - (820/N) + 16.6*Math.log(options.Na)/Math.log(10)
    #else if N < 50
    #  81.5 + (41 * GC/N) - (500/N) + 16.6*Math.log(options.Na) - 0.62*options.F
    else
      79.8 + 18.5*Math.log(options.Na)/Math.log(10) + (58.4 * GC/N) + (11.8 * (GC/N) * (GC/N)) - (820/N) 
    
    
  
  @calcFrequencies: (data) ->
    freq = {A: 0, C: 0, G: 0, T: 0}
    data.forEach (x) ->
      freq[x]++
    freq
  */

  return TmCalc;

})();

/* Old version (not very accurate):
  @calc: (data) ->
    Math.round(@calcFull(data)*100)/100
  
  @calcFull: (data) ->
    freq = @calcFrequencies(data)
    if data.length < 14
      4 * (freq["G"] + freq["C"]) + 2 * (freq["A"] + freq["T"])
    else
      64.9 + 41 * (freq["G"] + freq["C"] - 16.4)/data.length
  
  @calcFrequencies: (data) ->
    freq = {A: 0, C: 0, G: 0, T: 0}
    data.forEach (x) ->
      freq[x]++
    freq
*/
// Underscore.js 1.3.3
// (c) 2009-2012 Jeremy Ashkenas, DocumentCloud Inc.
// Underscore is freely distributable under the MIT license.
// Portions of Underscore are inspired or borrowed from Prototype,
// Oliver Steele's Functional, and John Resig's Micro-Templating.
// For all details and documentation:
// http://documentcloud.github.com/underscore
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