private void ReadPanelFile(string pathToDatabase)
{
using (
StreamReader reader = new StreamReader(pathToDatabase))
//new StreamReader(new EncryptedFileStream(pathToDatabase, passPhrase, FileAccess.Read)))
{
while (!reader.EndOfStream)
{
string line = reader.ReadLine();
if (line == null)
{
break;
}
line = line.Trim();
//check its not a header line or comment.
if (IsItAComment(line))
{
continue;
}
string[] data = line.Split('\t');
//check its not an empty line
if (data.Length > 5)
{
RefPanelEntry entry = new RefPanelEntry();
entry.LoadEntry(data);
AddEntryToTable(entry);
}
}
}
}
public static bool CheckForMatch(RefPanelEntry entry, VcfVariant var)
{
bool match = (entry.Chr == var.ReferenceName) &&
(entry.FwdStandFirstPositionOfMutation == var.ReferencePosition) &&
(entry.FwdStrandRefAllele == var.ReferenceAllele) &&
(entry.FwdStrandAltAllele == var.VariantAlleles[0]);
return(match);
}
private void AddEntryToDictionaries(RefPanelEntry data)
{
string exonName = data.Gene.Substring(0, 1).ToUpper() + data.Exon;
string mutationName = data.Chr + "_" + data.FwdStandFirstPositionOfMutation + "_" + data.FwdStrandRefAllele + "_" +
data.FwdStrandAltAllele;
//add entry to ExonToPositionTable
DetectableMutationList.Add(mutationName);
if (!ExonToPositionTable.ContainsKey(exonName))
{
HashSet <string> setOfMutations = new HashSet <string>()
{
mutationName
};
ExonToPositionTable.Add(exonName, setOfMutations);
}
else
{
ExonToPositionTable[exonName].Add(mutationName);
}
//Add entry to
if (exonName.Equals("K2"))
{
string aminoAcidChangeForTherascreen = data.Gene + "_" + data.AminoAcidPosition + data.AminoAcidAlt.ToUpper();
//Console.WriteLine($"aminoAcidChangeForTherascreen = {aminoAcidChangeForTherascreen}");
if (!AminoAcidToBaseChangeForTherascreenDictionary.ContainsKey(aminoAcidChangeForTherascreen))
{
List <string> newMutationNameList = new List <string>()
{
mutationName
};
AminoAcidToBaseChangeForTherascreenDictionary.Add(aminoAcidChangeForTherascreen, newMutationNameList);
}
else
{
AminoAcidToBaseChangeForTherascreenDictionary[aminoAcidChangeForTherascreen].Add(mutationName);
}
}
else
{
string aminoAcidChangeForSanger = data.Gene.Substring(0, 1).ToUpper() + data.Exon + "_" + data.Codon;
//Console.WriteLine($"aminoAcidChangeForSanger = {aminoAcidChangeForSanger}");
if (!AminoAcidToBaseChangeForSangerDictionary.ContainsKey(aminoAcidChangeForSanger))
{
List <string> newMutationNameList = new List <string>()
{
mutationName
};
AminoAcidToBaseChangeForSangerDictionary.Add(aminoAcidChangeForSanger, newMutationNameList);
}
else
{
AminoAcidToBaseChangeForSangerDictionary[aminoAcidChangeForSanger].Add(mutationName);
}
}
}
private void AddEntryToTable(RefPanelEntry entry)
{
if (!TableDataByChrAndPos.ContainsKey(entry.Chr))
{
TableDataByChrAndPos[entry.Chr] = new Dictionary <int, List <RefPanelEntry> >();
}
if (!TableDataByChrAndPos[entry.Chr].ContainsKey(entry.FwdStandFirstPositionOfMutation))
{
TableDataByChrAndPos[entry.Chr][entry.FwdStandFirstPositionOfMutation] = new List <RefPanelEntry>();
}
TableDataByChrAndPos[entry.Chr][entry.FwdStandFirstPositionOfMutation].Add(entry);
}
//examples of Therascreen detections:
//12ASP detected
//12CYS
//13ASP
//WT
//12VAL detected
//INVALID
public RuleApplier(string mutationDataBase)
{
if (!File.Exists(mutationDataBase))
{
Console.WriteLine($"{mutationDataBase} does not exist");
System.Environment.Exit(1);
}
using (StreamReader mutationDatabaseReader = new StreamReader(mutationDataBase))
{
while (!mutationDatabaseReader.EndOfStream)
{
string line = mutationDatabaseReader.ReadLine();
if (line == null)
{
break;
}
line = line.Trim();
//check its not a header line or comment.
if (IsItAComment(line))
{
continue;
}
string[] data = line.Split('\t');
//check its not an empty line
if (data.Length > 5)
{
RefPanelEntry entry = new RefPanelEntry();
entry.LoadEntry(data);
AddEntryToDictionaries(entry);
DetectableMutationEntries.Add(entry);
}
}
//generate the mutation information
foreach (var mutationEntry in DetectableMutationEntries)
{
string currentMutationSource;
string currentMutationConfirmed;
string mutationID = mutationEntry.Chr + "_" + mutationEntry.FwdStandFirstPositionOfMutation + "_" + mutationEntry.FwdStrandRefAllele + "_" +
mutationEntry.FwdStrandAltAllele;
//check the possible source
if (mutationEntry.Gene.Equals("KRAS") && mutationEntry.Exon.Equals("2"))
{
currentMutationSource = mutationEntry.Gene.Substring(0, 1).ToUpper() + mutationEntry.Exon + "_" + mutationEntry.Codon;
string theraAminoAcidChange = "KRAS_" + mutationEntry.AminoAcidPosition + mutationEntry.AminoAcidAlt.ToUpper();
if (AminoAcidToBaseChangeForTherascreenDictionary[theraAminoAcidChange].Count == 1)
{
currentMutationConfirmed = "confirmed";
}
else if (AminoAcidToBaseChangeForTherascreenDictionary[theraAminoAcidChange].Count > 1)
{
currentMutationConfirmed = "plausible";
}
else
{
Console.WriteLine($"unrecogonized: {theraAminoAcidChange}");
throw new Exception("unregonized mutation in therascreen List, must something wrong");
}
}
else
{
currentMutationSource = mutationEntry.Gene.Substring(0, 1).ToUpper() + mutationEntry.Exon + "_" + mutationEntry.Codon;
if (AminoAcidToBaseChangeForSangerDictionary[currentMutationSource].Count == 1)
{
currentMutationConfirmed = "confirmed";
}
else if (AminoAcidToBaseChangeForSangerDictionary[currentMutationSource].Count > 1)
{
currentMutationConfirmed = "plausible";
}
else
{
throw new Exception("unregonized mutation in sanger List, must something wrong");
}
}
//if (!MutationConfirmedInformationFromAminoAcid.ContainsKey(mutationID))
MutationConfirmedInformationFromAminoAcid.Add(mutationID,
new List <string>()
{
currentMutationSource, currentMutationConfirmed
});
}
}
}
