//Written by Paul Stothard, University of Alberta, Canada

function primerMap (theDocument) {	

	var newDna = "";
	var title = "";
	var maxInput = 100000;

	if (testScript() == false) {
		return false;
	}

	var restrictionSiteCollection;
	var forwardMatches;
	var reverseMatches;

	var geneticCode = getGeneticCodeString(theDocument.forms[0].elements[7].options[theDocument.forms[0].elements[7].selectedIndex].value);

	var restrictionSites = getRestrictionSiteString("standard");	

	if ((checkFormElement (theDocument.forms[0].elements[0]) == false) || (checkSequenceLength(theDocument.forms[0].elements[0].value, maxInput) == false))	{
		return false;
	}

	geneticCode = geneticCode.split(/,/);

	if (checkGeneticCode(geneticCode) == false)	{
		return false;
	}

	restrictionSites = restrictionSites.split(/,/);
	if (checkRestPatterns(restrictionSites) == false)	{
		return false;
	}

	var primers = theDocument.forms[0].elements[1].value.split(/,/);
	var newPrimers = new Array();
	var primerSeq;
	var primerRe;
	var primerName;
	var matchArray;
	var re = /\(([^\(]+)\)\s*([A-Za-z]+)/;
	for (var i = 0; i < primers.length; i++) {
		//isolate name and seq and check  
		if (matchArray = re.exec(primers[i])) {
			primerName = matchArray[1];
			if (matchArray[2].length < 10) {
				alert("Please enter primer sequences that are at least 10 bases long.");
				return false;
			}
			primerSeq = matchArray[2];
			primerRe = eval("/" + convertDegenerates(primerSeq) + "/gi");
			newPrimers.push(new Primer(primerSeq, primerRe, primerName));		
		}			
	}

	openWindow("Primer Map");	
	if (theDocument.forms[0].elements[8].options[theDocument.forms[0].elements[8].selectedIndex].value == "shown") {
		outputWindow.document.write("<span class=\"one\">" + "cuts once" + "</span><br />\n");
		outputWindow.document.write("<span class=\"two\">" + "cuts twice" + "</span><br />\n");
		outputWindow.document.write("\n");
		outputWindow.document.write("<span class=\"forward_primer\">" + "&gt;&gt;&gt;forward primer" + "</span><br />\n");
		outputWindow.document.write("<span class=\"reverse_primer\">" + "&lt;&lt;&lt;reverse primer" + "</span><br />\n");
		outputWindow.document.write("\n");	
	}			
	var arrayOfFasta = getArrayOfFasta (theDocument.forms[0].elements[0].value);

	for (var i = 0; i < arrayOfFasta.length; i++)	{
		newDna = getSequenceFromFasta (arrayOfFasta[i]);
		title = getTitleFromFasta (arrayOfFasta[i]);

		newDna = removeNonDna(newDna);
		openPre();
		outputWindow.document.write(getInfoFromTitleAndSequenceAndTopology(title, newDna, theDocument.forms[0].elements[9].options[theDocument.forms[0].elements[9].selectedIndex].value));

		if (theDocument.forms[0].elements[8].options[theDocument.forms[0].elements[8].selectedIndex].value == "shown") {
			restrictionSiteCollection = findRestrictionSites(newDna, restrictionSites, theDocument.forms[0].elements[9].options[theDocument.forms[0].elements[9].selectedIndex].value);
			restrictionSiteCollection.sortRestrictionSites();
		}
		
		//create match collections
		forwardMatches = findMatches (newPrimers, newDna, theDocument.forms[0].elements[9].options[theDocument.forms[0].elements[9].selectedIndex].value, false);
		reverseMatches = findMatches (newPrimers, reverse(complement(newDna)), theDocument.forms[0].elements[9].options[theDocument.forms[0].elements[9].selectedIndex].value, true);

		//now adjust forwardMatches for the figure
		for (var j = 0; j < forwardMatches.matches.length; j++) {
			forwardMatches.matches[j].position = forwardMatches.matches[j].position - forwardMatches.matches[j].matchingText.length;
			forwardMatches.matches[j].end = forwardMatches.matches[j].position + forwardMatches.matches[j].matchingText.length;
			if (forwardMatches.matches[j].position < 0) {
				forwardMatches.matches[j].position = forwardMatches.matches[j].position + newDna.length;
			}
			if (forwardMatches.matches[j].end > newDna.length) {
				forwardMatches.matches[j].end = forwardMatches.matches[j].end - newDna.length;
			}
		}		

		//now adjust reverseMatches for the figure
		for (var j = 0; j < reverseMatches.matches.length; j++) {
			reverseMatches.matches[j].position = newDna.length - reverseMatches.matches[j].position;
			reverseMatches.matches[j].end = reverseMatches.matches[j].position + reverseMatches.matches[j].matchingText.length
			if (reverseMatches.matches[j].position < 0) {
				reverseMatches.matches[j].position = reverseMatches.matches[j].position + newDna.length;
			}
			if (reverseMatches.matches[j].end > newDna.length) {
				reverseMatches.matches[j].end = reverseMatches.matches[j].end - newDna.length;
			}
		}

		//sort forwardMatches and reverseMatches.
		forwardMatches.sortMatches();
		reverseMatches.sortMatches();

		layoutPrimerMap (newDna, geneticCode, restrictionSiteCollection, forwardMatches, reverseMatches, theDocument.forms[0].elements[5].options[theDocument.forms[0].elements[5].selectedIndex].value, theDocument.forms[0].elements[6].options[theDocument.forms[0].elements[6].selectedIndex].value);
		
		outputWindow.document.write ('\n');
		closePre();		
		//this is a summary of the sites.
		if (theDocument.forms[0].elements[8].options[theDocument.forms[0].elements[8].selectedIndex].value == "shown") {				
			writeRestrictionSites (newDna, restrictionSites, theDocument.forms[0].elements[9].options[theDocument.forms[0].elements[9].selectedIndex].value);
			outputWindow.document.write ('<br />\n');	
		}
		//write summary of primers
		writePrimerSites(newPrimers);		

		outputWindow.document.write ('<br />\n<br />\n');

		//set primers hasMatch to false
		for (var j = 0; j < newPrimers.length; j++) {
			newPrimers[j].hasForwardMatch = false;
			newPrimers[j].hasReverseMatch = false;
		}	
	}

	closeWindow();
	return true;
}

function writePrimerSites (primers) {
	var backGroundClass;
	outputWindow.document.write ('<table border="1" width="100%" cellspacing="0" cellpadding="2"><tbody>\n');	
	outputWindow.document.write ('<tr><td class="title" width="200px">' + 'Primer:' + '</td><td class="title">' + 'Sequence:' + '</td></tr>\n');	
	for (var i = 0; i < (primers.length); i++)	{
		if ((primers[i].hasForwardMatch) && (primers[i].hasReverseMatch)) {
			backGroundClass = "many";	
		}
		else if (primers[i].hasForwardMatch) {
			backGroundClass = "forward_primer";			
		}
		else if (primers[i].hasReverseMatch) {
			backGroundClass = "reverse_primer";			
		}
		else {
			backGroundClass = "none";
		}		
		outputWindow.document.write ('<tr><td class="' + backGroundClass + '">' + primers[i].name + '</td><td class="' + backGroundClass + '">' + '5\'-' + primers[i].sequence  + '-3\'' + '</td></tr>\n');
	}
	outputWindow.document.write('</tbody></table>\n');
	return true;
}	

function layoutPrimerMap (dnaSequence, geneticCode, restrictionSiteCollection, forwardMatches, reverseMatches, basesPerLine, readingFrame)	{

	basesPerLine = parseInt(basesPerLine);

	var geneticCodeMatchExp = getGeneticCodeMatchExp (geneticCode);
	var geneticCodeMatchResult = getGeneticCodeMatchResult (geneticCode);
	var spaceString = "                                                                                                                                  ";	

	var textLayout = new TextLayout();

	if ((readingFrame == "3") || (readingFrame == "all_three")) {
		var translation = new TranslationComponent();
		translation.setCharacters("  " + translate(dnaSequence.substring(2, dnaSequence.length), geneticCodeMatchExp, geneticCodeMatchResult));
		textLayout.addComponent(translation);
	}

	if ((readingFrame == "2") || (readingFrame == "all_three")) {
		var translation = new TranslationComponent();
		translation.setCharacters(" " + translate(dnaSequence.substring(1, dnaSequence.length), geneticCodeMatchExp, geneticCodeMatchResult));
		textLayout.addComponent(translation);
	}

	if ((readingFrame == "1") || (readingFrame == "all_three")) {
		var translation = new TranslationComponent();
		translation.setCharacters(translate(dnaSequence, geneticCodeMatchExp, geneticCodeMatchResult));
		textLayout.addComponent(translation);
	}

	if (readingFrame == "uppercase") {
		var translation = new UppercaseTranslationComponent();
		translation.setCharacters(uppercaseTranslate(dnaSequence, geneticCodeMatchExp, geneticCodeMatchResult));
		textLayout.addComponent(translation);
	}
		
	var dna = new DnaComponent();
	dna.setCharacters(dnaSequence);
	textLayout.addComponent(dna);

	dna = new DnaComponent();
	dna.setCharacters(complement(dnaSequence));
	textLayout.addComponent(dna);

	var sitesInRange = new Array();

	for (var i = 0; i < dnaSequence.length; i = i + basesPerLine) {

		if (restrictionSiteCollection != null) {
		    //first get restriction sites in this range
		    sitesInRange = restrictionSiteCollection.getSitesInRange(i, i + basesPerLine);

		    //reversing gives better appearance
		    sitesInRange.reverse();

		    for (var j = 0; j < sitesInRange.length; j++) {
			    //9 is added because of indent to dna sequence

			    if (sitesInRange[j].numberOfCuts == 1) {
				    outputWindow.document.write(spaceString.substring(0, sitesInRange[j].position - i + 9) + "<span class=\"one\">" + sitesInRange[j].label + "</span>\n");
			    }

			    else if (sitesInRange[j].numberOfCuts == 2) {
				    outputWindow.document.write(spaceString.substring(0, sitesInRange[j].position - i + 9) + "<span class=\"two\">" + sitesInRange[j].label + "</span>\n");
			    }

			    else if (sitesInRange[j].numberOfCuts == 3) {
				    outputWindow.document.write(spaceString.substring(0, sitesInRange[j].position - i + 9) + "<span class=\"three\">" + sitesInRange[j].label + "</span>\n");
			    }

			    else {
				    outputWindow.document.write(spaceString.substring(0, sitesInRange[j].position - i + 9) + sitesInRange[j].label + "\n");
			    }
		    }
		}

		//get forwardPrimer matches in this range
		sitesInRange = forwardMatches.getMatchesInRange(i, i + basesPerLine);

		sitesInRange.reverse();
		for (var j = 0; j < sitesInRange.length; j++) {
			//9 is added because of indent to dna sequence
			outputWindow.document.write(spaceString.substring(0, sitesInRange[j].position - i + 9) + "<span class=\"forward_primer\">" + "&gt;&gt;&gt;" + sitesInRange[j].primerName + "&gt;&gt;&gt;" + " " + (sitesInRange[j].position + 1) + " to " + sitesInRange[j].end + "</span>\n");
		}

		//get reversePrimer matches in this range
		sitesInRange = reverseMatches.getMatchesInRange(i, i + basesPerLine);

		sitesInRange.reverse();
		for (var j = 0; j < sitesInRange.length; j++) {
			//9 is added because of indent to dna sequence
			outputWindow.document.write(spaceString.substring(0, sitesInRange[j].position - i + 9) + "<span class=\"reverse_primer\">" + "&lt;&lt;&lt;" + sitesInRange[j].primerName + "&lt;&lt;&lt;" + " " + (sitesInRange[j].position + 1) + " to " + sitesInRange[j].end + "</span>\n");
		}		

		textLayout.writeLayout(i, i + basesPerLine);
	}

	return true;
}

function translate (dnaSequence, geneticCodeMatchExp, geneticCodeMatchResult) {

	//don't translate if fewer than three bases
	if (dnaSequence.replace(/[^A-Za-z]/g, "").length < 3) {
		return "";
	}

	dnaSequence = dnaSequence.replace(/(...)/g, 
                    function (str, p1, offset, s) {
                      	return " " + p1 + " ";
                   }
        );	
	
	for (var i = 0; i < geneticCodeMatchExp.length; i++)	{
		dnaSequence = dnaSequence.replace(geneticCodeMatchExp[i], geneticCodeMatchResult[i]);
	}

	dnaSequence = dnaSequence.replace(/\S{3}/g, "X");
	dnaSequence = dnaSequence.replace(/\s\S{1,2}$/, "");
	dnaSequence = dnaSequence.replace(/^\s/, "");
	return dnaSequence;	
}

function uppercaseTranslate (dnaSequence, geneticCodeMatchExp, geneticCodeMatchResult) {

	dnaSequence = dnaSequence.replace(/[a-z]/g, " ");

	//don't translate if fewer than three bases
	if (dnaSequence.replace(/[^A-Za-z]/g, "").length < 3) {
		return "";
	}

	dnaSequence = dnaSequence.replace(/([A-Z])(\s*)([A-Z])(\s*)([A-Z])(\s*)/g, 
                    function (str, p1, p2, p3, p4, p5, p6, offset, s) {
                      	return " " + p1 + p3 + p5 + " " + p2 + p4 + p6;
                   }
        );

	dnaSequence = dnaSequence.replace(/\s\S{1,2}\s/g, "");

	for (var i = 0; i < geneticCodeMatchExp.length; i++)	{
		dnaSequence = dnaSequence.replace(geneticCodeMatchExp[i], geneticCodeMatchResult[i]);
	}

	dnaSequence = dnaSequence.replace(/\S{3}/g, "X");
	dnaSequence = dnaSequence.replace(/^\s/, "");

	return dnaSequence;	
}

function findRestrictionSites (sequence, arrayOfItems, dnaConformation)	{	

	var lookAhead = 50;
	var lowerLimit = 0;
	var upperLimit = sequence.length;
	var shiftValue = 0;
	var cutDistance;
	var matchExp;
	var matchPosition;
	var matchArray;
	var label;
	var timesFound = 0;
	var tempArray = new Array();

	var restrictionSiteCollection = new RestrictionSiteCollection();

	if (dnaConformation == "circular")	{
		shiftValue = (sequence.substring(0, lookAhead)).length;
		sequence = sequence.substring(sequence.length - lookAhead,sequence.length) + sequence + sequence.substring(0,lookAhead);
		lowerLimit = 0 + shiftValue;
		upperLimit = upperLimit + shiftValue;
	}

	for (var i = 0; i < (arrayOfItems.length); i++)	{

		matchExp = arrayOfItems[i].match(/\/.+\//) + "gi";
		matchPosition = 0;
		matchExp = eval(matchExp);
		cutDistance = parseFloat((arrayOfItems[i].match(/\)\D*\d+/)).toString().replace(/\)\D*/,""));
		label = ((arrayOfItems[i].match(/\([^\(]+\)/)).toString()).replace(/\(|\)/g,"");

		while (matchArray = matchExp.exec(sequence)) {
			timesFound++;
			matchPosition = matchExp.lastIndex;
			matchPosition = matchPosition - cutDistance;
			if ((matchPosition >= lowerLimit) && (matchPosition < upperLimit))	{	
				tempArray.push(new RestrictionSite(label + " " + (matchPosition - shiftValue + 1), (matchPosition - shiftValue)));
			}				
		}
		
		
		for (var j = 0; j < tempArray.length; j++) {
			tempArray[j].numberOfCuts = timesFound;
			restrictionSiteCollection.addRestrictionSite(tempArray[j]);
		}
		timesFound = 0;	
		tempArray = new Array();
	}
	
	return restrictionSiteCollection;
}

function findMatches (primers, sequence, topology, isReverseStrand) {
	var matchArray;
	var matchPosition;
	var matchCollection = new MatchCollection();
	var re;
	var originalLength = sequence.length;

	if (topology == "circular")	{
		var lookAhead = 50;
		var shiftValue = (sequence.substring(0, lookAhead)).length;
		var upperLimit = sequence.length + shiftValue;
		sequence = sequence.substring(sequence.length - lookAhead,sequence.length) + sequence + sequence.substring(0,lookAhead);
		var lowerLimit = 0 + shiftValue;
		
		for (var i = 0; i < primers.length; i++)	{
			re = primers[i].re;
			while (matchArray = re.exec(sequence)) {
				matchPosition = re.lastIndex;
				if ((matchPosition >= lowerLimit) && (matchPosition < upperLimit))	{
					matchPosition = matchPosition - shiftValue;
					if (matchPosition == 0) {
						matchPosition = originalLength;
					}
					matchCollection.addMatch(new Match(primers[i].name, matchArray[0], matchPosition));
					if (isReverseStrand) {
						primers[i].hasReverseMatch = true;
					}
					else {
						primers[i].hasForwardMatch = true;
					}
				}		
			}
		}
	}
	else {
		for (var i = 0; i < primers.length; i++)	{
			re = primers[i].re;
			while (matchArray = re.exec(sequence)) {
				matchPosition = re.lastIndex;
				matchCollection.addMatch(new Match(primers[i].name, matchArray[0], matchPosition));
				if (isReverseStrand) {
					primers[i].hasReverseMatch = true;
				}
				else {
					primers[i].hasForwardMatch = true;
				}			
			}
		}
	}
	return matchCollection;
}

//------------------------------------ TextLayout Class
//TextLayout writeLayout method
function writeLayout (start, stop) {
	for (var i = 0; i < this.components.length; i++)	{
		this.components[i].writeLayoutComponent(start, stop);
	}	
}

//TextLayout addComponent method
function addComponent(component) {
	this.components.push(component);
}

//TextLayout class
function TextLayout () {
   	this.components = new Array();
}

//create and throw away a prototype object
new TextLayout();

//define object methods
TextLayout.prototype.writeLayout = writeLayout;
TextLayout.prototype.addComponent = addComponent;
//------------------------------------


//------------------------------------ LayoutComponent Abstract Class
//LayoutComponent writeLayoutComponent method
function writeLayoutComponent(start, stop) {
	//abstract method
}

//LayoutComponent setCharacters method
function setCharacters (text) {
	if (text.search(/./) != -1)	{
		this.characters = text.match(/./g);
	}
}

//LayoutComponent isRoom method
function isRoom (start, stop) {
	//return true if nothing in characters array in this range
	var rangeToCheck = this.characters.slice(start, stop);
	rangeToCheck = rangeToCheck.join("");
	if (rangeToCheck.search(/\w/) == -1) {
		return true;
	}
	else {
		return false;
	}
}

//LayoutComponent class
function LayoutComponent() {
	this.characters = new Array();
	this.positionLabel = 1;
}

//create and throw away a prototype object
new LayoutComponent();

//define object methods
LayoutComponent.prototype.writeLayoutComponent = writeLayoutComponent;
LayoutComponent.prototype.setCharacters = setCharacters;
LayoutComponent.prototype.isRoom = isRoom;
//------------------------------------

//------------------------------------ TranslationComponent Class extend LayoutComponent Class
//constructor
function TranslationComponent () {
	this.characters = new Array();
	this.positionLabel = 1;
}

TranslationComponent.prototype = new LayoutComponent();

//override writeLayoutComponent
TranslationComponent.prototype.writeLayoutComponent = function (start, stop) {
	outputWindow.document.write (rightNum (this.positionLabel, "", 8, ""));
	outputWindow.document.write (this.characters.slice(start, stop).join("") + "\n");
	this.positionLabel = this.positionLabel + (stop - start) / 3;
}

//------------------------------------

//------------------------------------ UppercaseTranslationComponent Class extend LayoutComponent Class
//constructor
function UppercaseTranslationComponent () {
	this.characters = new Array();
	this.positionLabel = 1;
}

UppercaseTranslationComponent.prototype = new LayoutComponent ();

//override writeLayoutComponent
UppercaseTranslationComponent.prototype.writeLayoutComponent = function (start, stop) {
	var textToWrite = this.characters.slice(start, stop).join("") + "\n";
	if (textToWrite.search(/\w/) != -1) {
		outputWindow.document.write (rightNum (this.positionLabel, "", 8, ""));
		this.positionLabel = this.positionLabel + ((textToWrite.match(/[A-Z]/g)).length);
		outputWindow.document.write (textToWrite);
	}
}
//------------------------------------

//------------------------------------ DnaComponent Class extend LayoutComponent Class
//constructor
function DnaComponent () {
	this.characters = new Array();
	this.positionLabel = 1;
}
DnaComponent.prototype = new LayoutComponent ();

//override writeLayoutComponent
DnaComponent.prototype.writeLayoutComponent = function (start, stop) {
	outputWindow.document.write (rightNum (this.positionLabel, "", 8, ""));
	outputWindow.document.write (this.characters.slice(start, stop).join("") + "\n");
	this.positionLabel = this.positionLabel + (stop - start);
}
//------------------------------------

//------------------------------------ RestrictionSite class
//RestrictionSite class
function RestrictionSite(label, position) {
	this.label = label;
	this.position = position;
	this.numberOfCuts;
}
//------------------------------------

//------------------------------------ RestrictionSiteCollection class
//RestrictionSiteCollection addRestrictionSite method
function addRestrictionSite (restrictionSite) {
	this.restrictionSites.push(restrictionSite);	
}

//RestrictionSiteCollection sortRestrictionSites method
function sortRestrictionSites () {
	this.restrictionSites.sort(restrictionSiteSorter);	
}

//RestrictionSiteCollection getSitesInRange method
function getSitesInRange (start, stop) {
	var arrayToReturn = new Array();
	//start at end
	for (var i = this.restrictionSites.length - 1; i >= 0; i--)	{
		if ((this.restrictionSites[i].position >= start) && (this.restrictionSites[i].position < stop)) {
			arrayToReturn.push(this.restrictionSites.pop());
		}
		else {
			break;
		}
	}	
	return arrayToReturn;
}

//RestrictionSiteCollection class
function RestrictionSiteCollection () {
   	this.restrictionSites = new Array();
}

//create and throw away a prototype object
new RestrictionSiteCollection();

//define object methods
RestrictionSiteCollection.prototype.addRestrictionSite = addRestrictionSite;
RestrictionSiteCollection.prototype.sortRestrictionSites = sortRestrictionSites;
RestrictionSiteCollection.prototype.getSitesInRange = getSitesInRange;

//------------------------------------

//sort so first ones at end
function restrictionSiteSorter (a, b) {
   	if (a.position < b.position) {
      		return 1;
	}
   	if (a.position > b.position) {
      		return -1;
	}
	else {
		return 0;
	}
}

//------------------------------------

//Primer class
function Primer (sequence, re, name) {
	this.sequence = sequence;
	this.re = re;
	this.name = name;
	this.hasForwardMatch = false;
	this.hasReverseMatch = false;
}

//------------------------------------

//Match class
function Match (primerName, matchingText, position) {
	this.primerName = primerName;
	this.matchingText = matchingText;
	this.position = position;
	this.end;
}
//------------------------------------ MatchCollection class
//MatchCollection addMatch method
function addMatch (match) {
	this.matches.push(match);	
}

//MatchCollection sortMatches method
function sortMatches () {
	this.matches.sort(matchSorter);	
}

//MatchCollection getMatchesInRange method
function getMatchesInRange (start, stop) {
	var arrayToReturn = new Array();
	//start at end
	for (var i = this.matches.length - 1; i >= 0; i--)	{
		if ((this.matches[i].position >= start) && (this.matches[i].position < stop)) {
			arrayToReturn.push(this.matches.pop());
		}
		else {
			break;
		}
	}	
	return arrayToReturn;
}

//MatchCollection class
function MatchCollection () {
   	this.matches = new Array();
}

//create and throw away a prototype object
new MatchCollection();

//define object methods
MatchCollection.prototype.addMatch = addMatch;
MatchCollection.prototype.sortMatches = sortMatches;
MatchCollection.prototype.getMatchesInRange = getMatchesInRange;

//sort so first ones at end
function matchSorter (a, b) {
   	if (a.position < b.position) {
      		return 1;
	}
   	if (a.position > b.position) {
      		return -1;
	}
	else {
		return 0;
	}
}