//Global variables
var WinOut,WinCount=0; //Simulated output data (array and window), number of windows
var S_min=0, S_max=50, D_min=0.05, D_max=25; //limits for user-defined variables
function simchip1_main(){
//reads user-defined variables from input form f_inp
var s0=Math.round(parseFloat(document.f_inp1.S_old.value)*10)/10; //initial synthesis constant (molecules per min per cell)
var d0=Math.round(parseFloat(document.f_inp1.D_old.value)*100)/10000; //initial decay constant (per min, derived from a percentage)
var c0=Math.round(s0/d0); //initial steady-state concentration (molecules per cell)
var s=Math.round(parseFloat(document.f_inp1.S_new.value)*10)/10; //new synthesis constant
var d=Math.round(parseFloat(document.f_inp1.D_new.value)*100)/10000; //new decay constant
var c=Math.round(s/d); //new steady-state concentration
var hl=Math.round(10*(0-Math.log(0.5))/d)/10; //new half-life
if (hl>10) hl=Math.round(hl);
var net=Math.round(Math.log(Math.abs(c0-c))/d); //near-equilibrium time
var e=Math.exp(1); //Euler's constant
var ct, t; //concentration at time t, time t
var graph,graph1; //graphical elements
var a,f1,f2; //constants to rescale the graph
var x,x1,y,y1; //coordinates
var tx; //descriptive text
if (c0>c) tx="Downregulation from " + c0 + " to " + c;
if (c0";
if (c0!=c) tx+="The process is completed within " + Math.round(net/hl*10)/10 + " half-lifes (" + net + " minutes).
";
tx+="
";
//generates grafics
tx+="Time
(min) | mRNA
(molecules/cell) |
";
//finds best y-axis (ordinate)
a=375; //length of ordinate
f1=a/100000;
graph='![](\"./images/ordinate100000.gif\")
';
if(c<10001){
f1=a/10000;
graph='![](\"./images/ordinate10000.gif\")
';}
if(c<1001 && c0<1001){
f1=a/1000;
graph='![](\"./images/ordinate1000.gif\")
';}
if(c<101 && c0<101){
f1=a/100;
graph='![](\"./images/ordinate100.gif\")
';}
//finds best x-axis (abszissa)
f2=100;
graph1='![](\"./images/abscissa10000.gif\")
';
if(hl<=100){
f2=10;
graph1='![](\"./images/abscissa1000.gif\")
';}
if(hl<=10){
f2=1;
graph1='![](\"./images/abscissa100.gif\")
';}
//calculates xy-positions for maximum 100 data points with ct<100000 according to y=a-f1*ct
for(t=0;t<=100;t++){
ct=c+Math.pow(e,(0-d*f2*t))*(c0-c);
tx+="| "+t*f2+" | "+Math.round(ct)+" |
";
if(c<100001){
y=a-f1*ct;
if (t!=Math.ceil(hl/f2))
{graph+='![](\"./images/blue_dot.gif\")
';}
else {graph+='![](\"./images/red_dot.gif\")
';
x1=-10;y1=y-30;
graph+='![](\"./images/arrow.gif\")
';
x=-12;}
}
}
tx+="
";
graph = graph + "
" + graph1 + "" + tx + "
";
//Creates output window
WinCount++;
WinOut=window.open("",WinCount,"width=800,height=600,left=10,top=10,resizable=yes,scrollbars=yes,menubar=yes");
WinOut.document.writeln("SimChip 1<\/title><\/head>\n<body>");
WinOut.document.writeln(graph);
WinOut.document.writeln("<\/body><\/html>");
WinOut.document.close();
}//end of simchip_main
function simchip1_help(){
var WinHelp;
WinHelp=window.open("","","width=500,height=250,left=10,top=10,resizable=yes,scrollbars=yes,menubar=no");
WinHelp.document.writeln("<html><head><title>SimChip 1<\/title><\/head>\n<body>");
WinHelp.document.writeln("<h3>Up- and down-regulation of individual genes<\/h3>");
WinHelp.document.writeln("<p>For a first try just click on GO. Then click on NEW for the next experiment and again on GO. ");
WinHelp.document.writeln("mRNA steady-state concentrations before and after any change of synthesis and decay will be recalculated. ");
WinHelp.document.writeln("Each time you click on GO, a new window will pop up, ");
WinHelp.document.writeln("which visualizes the time course of genetic up- or down-regulation.<\/p>");
WinHelp.document.writeln("You will find that the majority of expression levels is between 10<sup>1</sup> and 10<sup>3</sup> molecules per cell.");
WinHelp.document.writeln("Extreme values are only observed when S or D are close to zero. ");
WinHelp.document.writeln("Decay rates are inversely correlated with mRNA levels, according to the equation c=S/D.");
WinHelp.document.writeln("<h4>Mathematical Background<\/h4>");
WinHelp.document.writeln("<i>SimChip<\/i> is based on the well accepted assumption ");
WinHelp.document.writeln("that observed gene expression is largely reflected by mRNA concentrations ");
WinHelp.document.writeln("that are in a steady-state of linear synthesis and non-linear decay. ");
WinHelp.document.writeln("The underlying differential equation is:<br>");
WinHelp.document.writeln("<a href=\"./downloads/mathematical_background.pdf\" target=\"SimChip 1\">");
WinHelp.document.writeln("<img style=\"border:none\" src=\"./images/formula.jpg\"></a><br>");
WinHelp.document.writeln("where c is the mRNA concentration, S and D are synthesis and decay constants and t is the time.<br> ");
WinHelp.document.writeln("Theoretically, the steady-state is reached at infinity, but in practice the process is completed, ");
WinHelp.document.writeln("when the difference is less than one molecule per cell (so-called near-equilibrium time).<br>");
WinHelp.document.writeln("For further details please click on the formula.");
WinHelp.document.writeln("\n<\/body><\/html>");
WinHelp.document.close();
}//end of simchip1_help
function simchip1_input(){
//Creates a user form to enter simchip input data
var text="<h3>Up- and downregulation of individual genes</h3>"
+"<form name=\'f_inp1\' action=\'\'>"
+"<table style=\'font-size:9pt\'; border=\'1\'; text-align: left; cellpadding=\'2\' cellspacing=\'2\'>"
+"<tr bgcolor=\'080880\' style=\'color: white\'>"
+"<td style=\'width: 180px\'><b>mRNA</b></td>"
+"<td style=\'text-align: center; width: 135px;\'><b>Current Status</b></td>"
+"<td style=\'text-align: center; width: 135px;\'><b>New Status</b></td>"
+"</tr><tr>"
+"<td>Synthesis (molecules/minute)</td>"
+"<td style=\'text-align: center\'><input name=\'S_old\' value=\'2.5\'type=\'text\' title=\'0-50\' size=\'5\' onblur=\'check_S_old(this.value)\'></td>"
+"<td style=\'text-align: center\'><input name=\'S_new\' value=\'8.5\'type=\'text\' title=\'0-50\' size=\'5\' onblur=\'check_S_new(this.value)\'></td>"
+"</tr><tr>"
+"<td>Decay (percent/minute)</td>"
+"<td style=\'text-align: center\'><input name=\'D_old\' value=\'10\'type=\'text\' title=\'0.05-25\' size=\'5\' onblur=\'check_D_old(this.value)\'></td>"
+"<td style=\'text-align: center\'><input name=\'D_new\' value=\'10\'type=\'text\' title=\'0.05-25\' size=\'5\' onblur=\'check_D_new(this.value)\'></td>"
+"</tr></table>"
+"<table style=\'font-size:9pt\'; border=\'1\'; bgColor=\'BBBBBB\'; text-align: left; cellpadding=\'2\' cellspacing=\'2\'>"
+"<tr>"
+"<td style=\'width: 180px;\'>Steady-state (molecules/cell)</td>"
+"<td style=\'text-align: center; width: 135px;\'><input name=\'Ss_old\' type=\'text\' title=\'read only\' size=\'5\' readonly></td>"
+"<td style=\'text-align: center; width: 135px;\'><input name=\'Ss_new\' type=\'text\' title=\'read only\' size=\'5\' readonly></td>"
+"</tr><tr>"
+"<td>Half-life (minutes)</td>"
+"<td style=\'text-align: center\'><input name=\'Hl_old\' type=\'text\' title=\'read only\' size=\'5\' readonly></td>"
+"<td style=\'text-align: center\'><input name=\'Hl_new\' type=\'text\' title=\'read only\' size=\'5\' readonly></td>"
+"</tr></table><br>"
+"<table style=\'font-size:9pt\'; border=\'0\'; text-align: left; cellpadding=\'2\' cellspacing=\'2\'>"
+"<tr>"
+"<td style=\'width: 50px\'><input type=\'button\' value=\'GO\' onClick=\'simchip1_main()\'></td>"
+"<td style=\'width: 250px\'><input type=\'button\' value=\'NEW\' onClick=\'simchip1_rand()\'></td>"
+"<td style=\'width: 50px\'><input type=\'button\' value=\'HELP\' onClick=\'simchip1_help()\'></td>"
+"</tr></table>"
+"</form><br>"
+"<a href=\"./downloads/hoffmann_2008.pdf\" target=\"Literature\">Original publication (Hoffmann et al. 2008)</a><br>"
+"<a href=\"./downloads/simchip1_shortcode.html\" target=\"Source Code\">Simplified source code example</a><br>"
+"<a href=\"./downloads/mathematical_background.pdf\" target=\"Background\">Mathematical background</a><br>";
document.getElementById("divTxt").innerHTML=text;
calculate();
}//end of simchip1_input
function check_S_old(tx){
//replaces decimal komma by decimal point
tx=tx.replace(/,/, ".");
with (document.f_inp1.S_old) {
value = parseFloat(tx);
if(isNaN(value)) value="1";
if(value<S_min) value=S_min;
if(value>S_max) value=S_max;
}
calculate();
}
function check_S_new(tx){
tx=tx.replace(/,/, ".");
with (document.f_inp1.S_new) {
value = parseFloat(tx);
if(isNaN(value)) value="1";
if(value<S_min) value=S_min;
if(value>S_max) value=S_max;
}
calculate();
}
function check_D_old(tx){
tx=tx.replace(/,/, ".");
with (document.f_inp1.D_old) {
value = Math.round(parseFloat(tx)*100)/100;
if(isNaN(value)) value="1";
if(value<D_min) value=D_min;
if(value>D_max) value=D_max;
}
calculate();
}
function check_D_new(tx){
tx=tx.replace(/,/, ".");
with (document.f_inp1.D_new) {
value = Math.round(parseFloat(tx)*100)/100;
if(isNaN(value)) value="1";
if(value<D_min) value=D_min;
if(value>D_max) value=D_max;
}
calculate();
}
function calculate() {
var s1, s2, d1, d2;
with (document.f_inp1) {
s1=S_old.value;
s2=S_new.value;
d1=D_old.value/100;
d2=D_new.value/100;
Ss_old.value=Math.round(s1/d1);
Ss_new.value=Math.round(s2/d2);
Hl_old.value=Math.round(10*(0-Math.log(0.5))/d1)/10;
Hl_new.value=Math.round(10*(0-Math.log(0.5))/d2)/10;
if (Hl_old.value>10) Hl_old.value=Math.round(Hl_old.value);
if (Hl_new.value>10) Hl_new.value=Math.round(Hl_new.value);
}
}
function simchip1_rand(){
with (document.f_inp1) {
S_old.value=S_new.value;
S_new.value=Math.round((Math.random()*Math.random()*Math.random()*(S_max-S_min)+S_min)*10)/10;
D_old.value=D_new.value;
D_new.value=Math.round((Math.random()*Math.random()*Math.random()*(D_max-D_min)+D_min)*100)/100;
}
calculate();
}