//Global variables
var DatOut,WinOut,WinCount=0; //Simulated output data (array and window), number of windows
var cDNA, Details; //Boolean var to create log2 ratios as output
function simchip3_input(){
//Creates a user form to enter simchip input data
var text="Simulation of malignant transformation<\/h3><\/p>"
+"
"
+"Preliminary publication (in German)
"
+"Simplified source code example";;
document.getElementById("divTxt").innerHTML=text;
}//end of run_simchip
function simchip3_help(){
var WinHelp;
WinHelp=window.open("","","width=500,height=250,left=10,top=10,resizable=yes,scrollbars=yes,menubar=no");
WinHelp.document.writeln("SimChip 3\n");
WinHelp.document.writeln("Simulating malignant transformation
");
WinHelp.document.writeln("Each time you click on GO, SimChip3 creates a formatted table with simulated gene expression data.");
WinHelp.document.writeln("The first column shows a normal expression profile like that in Sim'Chip2, the others show progressive differential expression patterns like those observed in cancer.
");
WinHelp.document.writeln("If you check the cDNA arrays box, the program will generate relative rather than absolute signals, so-called P/R ratios (patient/reference).
");
WinHelp.document.writeln("If you check Stages, the columns will be rearranged into two clusters of early and advanced cancer stages.");
WinHelp.document.writeln("Background: Malignant transformation of gene expression is assumed to be caused by a gradual loss of control of genetic integrity. ");
WinHelp.document.writeln("As a consequence differential gene expression increases from cell cycle to cell cycle, while the overall distribution pattern remains constant. ");
WinHelp.document.writeln("This gradual loss is simulated with a stochastic Brownian fractal for S and D (see SimChip1).");
WinHelp.document.writeln("This algorithm generates a sequence of virtual biochip experiments with increasing malignancy from left to right.");
WinHelp.document.writeln("\n<\/body><\/html>");
WinHelp.document.close();
}//end of simchip2_help
function simchip3_main(){
//Input: reads number of columns and rows and creates a two-dimensional array with experimental results
//Output: creates a coloured table in a new window
//Calls brown(), hexColor() and hex()
var m=parseInt(document.f_inp3.nPrbs.value); //m = number of rows (without head line)
var n=parseInt(document.f_inp3.nExp.value); //n = number of columns (without names and reference)
var Stages=document.f_inp3.Stages.checked; //confuses time sequence of experiments to make patterns less obvious
cDNA=document.f_inp3.cDNA.checked; //calculates P/R ratios
Details=document.f_inp3.Details.checked; //Describes experiment on top of output table
var i,j,k; //index variables
var a,b,tx,pos1,pos2,tmp; //for explanations see below
var min, max,cal; //smallest random number, largest observable signal, calibration factor
min=0.01; //corresponds to realistic mRNA half-lives of 5 to 1000 min
max=30000; //maximal microarray signal
cal=max*min //calibration factor
var co=new Array(4); //coordinates for fractal Brownian movement
DatOut=new Array(m); //array with m rows of experimental output data
//Simulation
for(i=0;iSimChip 3<\/title><\/head>\n<body>");
if (Details==true) {
WinOut.document.writeln("Simulation of " + n + " experiments demonstrating differential expression of " + m + " gene expression signals in cancer samples. Experiment 0 represents a normal sample.<br>");
WinOut.document.writeln("Blue = underexpression, red = overexpression.<br>");
if (cDNA==true) WinOut.document.writeln("Signals are expressed as ratios (experiment \/ reference).<br>");
if (Stages==true) WinOut.document.writeln("Malignant transformation proceeds from left to right.<br>");
}
WinOut.document.writeln("<table border=\'1 \'>");
WinOut.document.write("<tr bgColor=\'#CCCCCC\'><td>SimChip<\/td><td>Exp0<\/td>");
for(i=1;i<=n;i++)
WinOut.document.write("<td>Exp"+i+"<\/td>");
for(i=0;i<m;i++)
WinOut.document.writeln(parseTab(i));
WinOut.document.writeln("<\/table>");//end of formatted table
WinOut.document.writeln("<\/body><\/html>");
WinOut.document.close();
}//end of simchip3_main
function check_Exp(tx){
with (document.f_inp3.nExp) {
value = parseInt(tx);
if(isNaN(value)) value="15";
if(value<0) value="0";
if(value>50) value="50";
}
}
function check_Prbs(tx){
with (document.f_inp3.nPrbs) {
value = parseInt(tx);
if(isNaN(value)) value="150";
if(value<0) value="0";
if(value>1000) value="1000";
}
}
function parseTab(index){
//Converts array row into a string with tab tags, row index and colors
//Adds some noise to each value
//Creates P/R ratios if requested
var a,b,i,x,y,z;
var ret="<tr align=\'center\'><td bgColor=\'#CCCCCC\'>Prb"+(index+1)+"<\/td>";
for(i in DatOut[index]){
x = DatOut[index][i]; //ideal values without analytical errors
if(i>0) {
a=(Math.random()-0.5)*10; //background noise -5 to +5
b=(Math.random()-0.5)/10; //signal noise x+-5%
y=Math.round(x+a+b*x);
if (y<1) y=1;}
else {y=Math.round(x);}
z=y/DatOut[index][0]; //ratio
if (cDNA==true) y=Math.round(z*100)/100; //ratio with two decimals
ret+="<td bgColor=\'"+hexColor(z)+"\'>"+y+"<\/td>";
}
ret+="</td></tr>";
return ret;
}
function brown(pos,wid,min,max){
//Mandelbrot algorithm for fractal Brownian movement
//Changes the position of the reference signal randomly within a given space
//wid=width of individual Brownian movements, min and max = range limits
var ret;
ret = pos + wid*(Math.random()-0.5);
if (ret<min) ret=min;
if (ret>max) ret=max;
return ret;
}
function hexColor(ratio){
//Converts a P/R ratio into a hexadecimal RGB code
//Ratios below 1.0 become increasingly blue, ratios above 1.0 become increasingly red
var logRatio, ret;
var R=255, G=255, B=255, f=50;
if (ratio>16) ratio=16;
if (ratio<1/16) ratio=1/16;
logRatio=f*Math.log(ratio)/Math.LN2;
G-=Math.round(Math.abs(logRatio)-0.5); //Decreases green
if (logRatio>0){
B-=Math.round(logRatio-0.5); //Decreases blue
}
else{
R+=Math.round(logRatio-0.5); //Decreases red
}
ret="#"+hex(R)+hex(G)+hex(B);
return ret;
}
function hex(dec){
//converts decimal into hexadecimal numbers
var ret = "";
var hex="0123456789ABCDEF";
while(dec != 0) {
ret=hex.charAt(dec%16)+ret;
dec=dec >> 4;
}
if (ret=="") ret="00";
return ret;
}