public Result RunSimulations(int numRuns, int numCuts, double probabilityEvent, String modelDatabase = "", bool extendedOutput = false)
{
SimulationId = DateTime.Now.ToString("yyyyMMddhhmmss");
Result res = new Result();
res.SimulationId = SimulationId;
res.ChromosomeName = Source.Name;
res.Runs = numRuns;
res.Cuts = numCuts;
res.Probability = probabilityEvent;
res.Hmm = modelDatabase;
ExtendedOutput = extendedOutput;
App.Log("<div id='chromoDiv" + SimulationId + "'><b>Chromothripsis Simulation ID " + SimulationId + " on Chromosome " + Source.Name + " - " + numRuns.ToString() + " runs " +
"- Simulating " + numCuts.ToString() + " cuts, " + probabilityEvent.ToString() + " probability</b></div>");
App.LogScroll();
DateTime tStart = DateTime.Now;
NumGenes = 0;
NumOrf = 0;
FusionSequences = new List <FusionSequence>();
Hmmer = new Hmmer();
Hmmer.Debug = false;
if (modelDatabase != "")
{
Hmmer.SetDatabase(modelDatabase);
}
if (ExtendedOutput)
{
App.HideLog();
}
for (int i = 0; i < numRuns; i++)
{
Simulate(numCuts, probabilityEvent);
if ((i % 10) == 0)
{
int percent = (int)(((double)i / (double)numRuns) * 100);
App.Status("Simulation Progress: " + percent.ToString() + "%");
}
}
App.Status();
if (ExtendedOutput)
{
App.ShowLog();
}
if (ExtendedOutput)
{
App.Log("");
}
App.Log("Found a total of " + NumGenes.ToString() + " fusion genes<");
if (ExtendedOutput)
{
App.Log("<b>Performing Hmmer Scan...</b>");
App.LogScroll();
}
//App.HideLog();
double totalScore = Hmmer.DoScan();
App.Log("Total Hmmer Score: " + totalScore.ToString("#0.00") + "");
// App.ShowLog();
List <Hmmer.Result> results = Hmmer.GetResults();
int NumHitOrfs = 0;
String resultTable = "";
if (ExtendedOutput)
{
resultTable = "<br/><div id='chromoResults" + SimulationId + "'><table>" +
"<tr><th>Simulation Id</th><th>Sequence ID</th><th>Score</th><th>Target Name</th><th>Accession</th><th>Exon 1</th>" +
"<th>Start 1</th><th>Length 1</th><th>Exon 2</th><th>Start 2</th><th>Length 2</th><th>ORF</th><th>Sequence</th></tr>";
}
foreach (Hmmer.Result result in results)
{
int seqId = Convert.ToInt32(result.SequenceName);
FusionSequence fs = FusionSequences[seqId];
if (!fs.IsHit)
{
fs.IsHit = true;
FusionSequences[seqId] = fs;
NumHitOrfs++;
}
if (ExtendedOutput)
{
resultTable += "<tr><td>" + SimulationId + "</td><td>" + fs.SequenceId + "</td><td>" + result.Score.ToString("#0.00") + "</td><td>" + result.Name + "</td><td>" + result.Accession
+ "</td><td>" + fs.Exon1.Name + "</td><td>" + fs.Range1.Start + "</td><td>" + fs.Range1.Length
+ "</td><td>" + fs.Exon2.Name + "</td><td>" + fs.Range2.Start + "</td><td>" + fs.Range2.Length
+ "</td><td>" + fs.OrfName + "</td><td>" + fs.Sequence +
"</tr>";
}
}
if (ExtendedOutput)
{
resultTable += "</table></div>";
}
App.Log("Number of fusion sequences that produced hits: " + NumHitOrfs + "");
if (ExtendedOutput)
{
App.Log(resultTable);
}
if (ExtendedOutput)
{
App.Log("");
}
DateTime tEnd = DateTime.Now;
TimeSpan tDiff = tEnd - tStart;
double perSecond = ((double)numRuns / (tDiff.TotalMilliseconds / (double)1000));
res.NumHits = results.Count;
res.NumGenes = NumGenes;
res.NumHitOrfs = NumHitOrfs;
res.NumOrfs = NumOrf;
res.TotalScore = totalScore;
res.RunsPerSecond = perSecond;
App.Log("Finished. " + perSecond.ToString("#0") + " runs per second, time elapsed: " + tDiff.ToString(@"mm\:ss"));
App.Log("<br/>");
App.LogScroll();
UpdateOverview(res);
return(res);
}
protected void OnFusionEvent(Range fragment1, Range fragment2)
{
Exon ex1 = Source.WithinExon(fragment1.End);
Exon ex2 = Source.WithinExon(fragment2.Start);
// 10371808
// 103718617
if ((ex1 != null) && (ex2 != null))
{
// Both sides of the cut are within exons
if (ex1.Strand == ex2.Strand)
{
// Both exons are on same strand
int bpExon1 = (int)(fragment1.End - ex1.Start);
int bpExon2 = (int)(ex2.End - fragment2.Start);
int percentExon1 = (int)(((double)bpExon1 / ex1.Length) * 100);
int percentExon2 = (int)(((double)bpExon2 / ex2.Length) * 100);
if ((bpExon1 > 100) && (bpExon2 > 100))
{
String seqFusion, seq1, seq2;
Range rangeLeft = new Range(ex1.Start, fragment1.End);
Range rangeRight = new Range(fragment2.Start, ex2.End);
seq1 = Source.Read(rangeLeft.Start, (int)rangeLeft.Length);
seq2 = Source.Read(rangeRight.Start, (int)rangeRight.Length);
seqFusion = seq1 + seq2;
Dictionary <String, String> orfs = new Dictionary <string, string>();
orfs.Add("Forward 0", Sequencer.GetORF(seqFusion, 0));
orfs.Add("Forward 1", Sequencer.GetORF(seqFusion, 1));
orfs.Add("Forward 2", Sequencer.GetORF(seqFusion, 2));
String seqInv = Sequencer.Invert(Sequencer.Complement(seqFusion));
orfs.Add("Reverse 0", Sequencer.GetORF(seqInv, 0));
orfs.Add("Reverse 1", Sequencer.GetORF(seqInv, 1));
orfs.Add("Reverse 2", Sequencer.GetORF(seqInv, 2));
Dictionary <String, String> peptides = new Dictionary <string, string>();
bool bSignificantPeptides = false;
foreach (String key in orfs.Keys)
{
if (orfs[key].Length >= 120)
{
String pep = Sequencer.Translate(orfs[key]);
peptides.Add(key, pep);
bSignificantPeptides = true;
}
}
if (bSignificantPeptides)
{
NumGenes++;
String htmlEx1 = "<a href='http://www.ensembl.org/Homo_sapiens/Search/Details?species=Homo_sapiens;idx=Transcript;end=1;q=" + ex1.Name +
"' target='_blank'>" + ex1.Name + "</a> " + bpExon1.ToString() + "bp (" + percentExon1.ToString() + "%)";
String htmlEx2 = "<a href='http://www.ensembl.org/Homo_sapiens/Search/Details?species=Homo_sapiens;idx=Transcript;end=1;q=" + ex2.Name +
"' target='_blank'>" + ex2.Name + "</a> " + bpExon2.ToString() + "bp (" + percentExon2.ToString() + "%)";
if (ExtendedOutput)
{
App.Log("<b>Found Fusion Gene #" + NumGenes + ": </b>" + htmlEx1 + " <b>&</b> " + htmlEx2 + "");
}
// App.Log("Fusion Sequence: " + seqFusion);
foreach (String key in peptides.Keys)
{
String pep = peptides[key];
if (ExtendedOutput)
{
App.Log(key + ": " + pep);
}
FusionSequence fs = new FusionSequence();
fs.SequenceId = NumOrf.ToString();
fs.IsHit = false;
fs.Exon1 = ex1;
fs.Exon2 = ex2;
fs.OrfName = key;
fs.Range1 = rangeLeft;
fs.Range2 = rangeRight;
fs.Sequence = pep;
FusionSequences.Insert(NumOrf, fs);
Hmmer.AddSequence(pep, fs.SequenceId);
//String sequenceName = "#" + NumGenes+" "+ex1.Name + " " + percentExon1.ToString() + "% & " + ex2.Name + " " + percentExon2.ToString() + "% ORF " + key;
NumOrf++;
}
} // if (bSignificantPeptides)
} // if ((bpExon1 > 100) && (bpExon2 > 100))
} // if (ex1.Strand == ex2.Strand)
} // if ((ex1 != null) && (ex2 != null))
else
{
//App.Log("No Fusion Gene :(");
}
}
