static public bool?HasHla(Hla hlaGoal, Dictionary <string, string> row, HlaResolution hlaResolution)
{
bool hasNull = false;
for (int i = 1; i <= 2; ++i)
{
string column = hlaGoal.ToString().Substring(0, 1) + i.ToString();
HlaToLength hlaToLengthOrNull = HlaAssignmentParams.GetHlaToLengthValueOrNull(row, column, hlaResolution);
if (hlaToLengthOrNull == null || hlaToLengthOrNull.HlaNumberToLength >= 9000)
{
hasNull = true;
continue;
}
if (hlaGoal.ToString() == hlaToLengthOrNull.ToString())
{
return(true);
}
}
if (hasNull)
{
return(null);
}
else
{
return(false);
}
}
public static void SearchHlaAssignmentsRelaxation(string fileName, string header, string solutionFileName, string solutionHeader, double causePrior, double linkProbability, double leakProbability, int howManyBest, string outputFilename, HlaResolution hlaResolution)
{
Debug.Assert(Math.Exp(double.NegativeInfinity) == 0);
//Create the structure of patients and their HLAs
Quickscore <Hla, int> quickscore = HlaAssignmentParams.CreateQuickscore(fileName, header, causePrior, linkProbability, leakProbability, hlaResolution);
// Get the list of patients, Hlas, and patient weights
List <int> patientList = quickscore.EffectList();
IEnumerable <Hla> hlaList = quickscore.CauseList();
//The structure file can contain a "weight" column. If it does, weight the patients, otherwise give them all weight 1.0
Dictionary <int, double> patientWeightTable = HlaAssignmentParams.CreatePatientWeightTable(fileName, header);
//The cause assignment table is a mapping from
// peptide to HLA assignments for that peptide
Dictionary <string, List <Dictionary <string, string> > > causeAssignmentTable = CreateCauseAssignmentTable(solutionFileName, solutionHeader);
//We start the report
using (StreamWriter streamwriterOutputFile = File.CreateText(outputFilename))
{
//The report is the same as the input "solution" except that we now list new HLA, a note, and a p(assignment)
streamwriterOutputFile.WriteLine(SpecialFunctions.CreateTabString(solutionHeader,
"newHLA", "rank", "p(assignment)", "note", "Peptide", "LogLikelihood", "TrueHlas.Count", "TrueHlas", "TrueHlasAndRespondingPatients", "UnexplainedPatients.Count"));
//Now we go through the model file, one peptide at a time. For each peptide, we know the patientID (did) of
// every patient who responded. (It also tells the HLAs of the patient, but we already have that info in the structure)
/*
* peptide did a1 a2 b1 b2 c1 c2
*
* ACQGVGGPGHK 10 2 11 38 44 12 16
* ACQGVGGPGHK 14 2 24 1517 58 3 7
* ACQGVGGPGHK 41 11 33 35 40 6 7
* ACQGVGGPGHK 102 2 11 35 44 4 5
*
* AENLWVTVY 25 24 66 35 39 4 12
* AENLWVTVY 36 23 32 8 44 7 7
* AENLWVTVY 45 3 31 39 44 5 12
* AENLWVTVY 46 2 29 41 52 16 16
* AENLWVTVY 59 2 33 7 44 3 15
*
* [...]
*/
foreach (List <Dictionary <string, string> > tableByPeptide in HlaAssignmentParams.QuickScoreOptimalsGroupByPeptide(fileName, header))
{
Debug.Assert(tableByPeptide.Count > 0); // real assert
string peptide = tableByPeptide[0]["peptide"];
//Create lists of patients who responded and assume everyone else didn't.
List <int> patientsWhoRespond;
List <int> patientsWhoDoNotRespond;
FindPatientsWhoRespondAndWhoDoNot(patientList, tableByPeptide, out patientsWhoRespond, out patientsWhoDoNotRespond);
//If we get a peptide with no row in the solution file, skip it.
if (!causeAssignmentTable.ContainsKey(peptide))
{
streamwriterOutputFile.WriteLine("{0}\t\t{1}", peptide, "explained by noise");
continue;
}
//We assign every HLA mentioned by the solution file with this peptide to TRUE and all others to FALSE
//An assignment of TRUE means that this HLA is a cause of this response.
List <Dictionary <string, string> > rowsOfThisPeptide = causeAssignmentTable[peptide];
HlaAssignmentWithResponses hlaAssignmentBase = CreateHlaAssignment(rowsOfThisPeptide, hlaList, hlaResolution, quickscore, patientsWhoRespond);
//Find the likelihood of this structure, with these patient responses, and the solution's HLA assignment.
double baseLogLikelihood = quickscore.LogLikelihoodOfModelWithCompleteAssignments(patientsWhoRespond, patientsWhoDoNotRespond, hlaAssignmentBase.AsDictionary, patientWeightTable);
//Consider each HLA assigned to TRUE (for this peptide) by the solution
foreach (Dictionary <string, string> row in rowsOfThisPeptide)
{
Hla hla = GetHlaFromRow(row, hlaResolution);
//If we already really know that this HLA is a cause of this reponse, just report that.
if (IsKnown(row))
{
streamwriterOutputFile.WriteLine("{0}\t{1}\t{2}", row[""], hla, "known");
continue;
}
//Set it to false as a way to see measure the probability that it is true.
HlaAssignmentWithResponses hlaAssignmentL0 = CreateHlaAssignment(rowsOfThisPeptide, hlaList, hlaResolution, quickscore, patientsWhoRespond, hla, null);
double logL0 = quickscore.LogLikelihoodOfModelWithCompleteAssignments(patientsWhoRespond, patientsWhoDoNotRespond, hlaAssignmentL0.AsDictionary, patientWeightTable);
Debug.Assert(hlaAssignmentL0.TrueCount + 1 == hlaAssignmentBase.TrueCount); // real assert
string noteNote = "";
if (logL0 > baseLogLikelihood)
{
noteNote = string.Format("\tlogL0 > baseLogLikelihood ({0}>{1})", logL0, baseLogLikelihood);
}
double probability = Math.Exp(baseLogLikelihood - SpecialFunctions.LogSum(baseLogLikelihood, logL0));
streamwriterOutputFile.WriteLine(SpecialFunctions.CreateTabString(
row[""], hla, "1 best", probability, noteNote,
peptide, baseLogLikelihood, hlaAssignmentBase.TrueCount, hlaAssignmentBase.TrueToString(), hlaAssignmentBase.TrueToListString(), hlaAssignmentBase.UnexplainedPatients.Count));
streamwriterOutputFile.WriteLine(SpecialFunctions.CreateTabString(
row[""], hla, "remove 1 best", "", noteNote,
peptide, logL0, hlaAssignmentL0.TrueCount, hlaAssignmentL0.TrueToString(), hlaAssignmentL0.TrueToListString(), hlaAssignmentL0.UnexplainedPatients.Count));
//Also, while we're in the world were it is false, let's measure how well each of the currently-set-to-false HLAs would do instead.
//!!!should this be one dictionary to a new class instead of three dictionaries?
List <KeyValuePair <Hla, double> > listOfhla1AndProbability1 = new List <KeyValuePair <Hla, double> >();
Dictionary <Hla, double> loglikelihoodCollection = new Dictionary <Hla, double>();
Dictionary <Hla, HlaAssignmentWithResponses> hla1ToHlaAssignment = new Dictionary <Hla, HlaAssignmentWithResponses>();
foreach (Hla hla1 in hlaList)
{
if (hla1 == hla || hlaAssignmentBase.AsDictionary[hla1])
{
continue;
}
HlaAssignmentWithResponses hlaAssignmentL1 = CreateHlaAssignment(rowsOfThisPeptide, hlaList, hlaResolution, quickscore, patientsWhoRespond, hla, hla1);
if (hlaAssignmentL1.TrueCount == hlaAssignmentBase.TrueCount)
{
double logL1 = quickscore.LogLikelihoodOfModelWithCompleteAssignments(patientsWhoRespond, patientsWhoDoNotRespond, hlaAssignmentL1.AsDictionary, patientWeightTable);
double probability1 = Math.Exp(logL1 - SpecialFunctions.LogSum(logL1, logL0));
loglikelihoodCollection[hla1] = logL1;
hla1ToHlaAssignment.Add(hla1, hlaAssignmentL1);
listOfhla1AndProbability1.Add(new KeyValuePair <Hla, double>(hla1, probability1));
}
}
//Report on the best of these
listOfhla1AndProbability1.Sort(delegate(KeyValuePair <Hla, double> x, KeyValuePair <Hla, double> y) { return(y.Value.CompareTo(x.Value)); });
for (int i = 0; i < howManyBest - 1; ++i)
{
Hla hla1 = listOfhla1AndProbability1[i].Key;
streamwriterOutputFile.WriteLine(SpecialFunctions.CreateTabString(
row[""], hla1, string.Format("{0} best", i + 2), listOfhla1AndProbability1[i].Value,
"", peptide, loglikelihoodCollection[hla1], hla1ToHlaAssignment[hla1].TrueCount, hla1ToHlaAssignment[hla1].TrueToString(), hla1ToHlaAssignment[hla1].TrueToListString(), hla1ToHlaAssignment[hla1].UnexplainedPatients.Count));
}
}
}
}
}
static public IEnumerable <Hla> FindAllHla(List <Dictionary <string, string> > expandedTable, HlaResolution hlaResolution, string header)
{
Qmrr.HlaFactory hlaFactory = Qmrr.HlaFactory.GetFactory("noConstraint");
Dictionary <Hla, bool> seenIt = new Dictionary <Hla, bool>();
foreach (Dictionary <string, string> row in expandedTable)
{
foreach (string column in HlaAssignmentParams.CreateHlaColumns(header))
{
HlaToLength hlaToLengthOrNull = HlaAssignmentParams.GetHlaToLengthValueOrNull(row, column, hlaResolution);
if (hlaToLengthOrNull == null || hlaToLengthOrNull.HlaNumberToLength >= 9000)
{
continue;
}
Hla hla = hlaFactory.GetGroundInstance(hlaToLengthOrNull.ToString());
if (!seenIt.ContainsKey(hla))
{
seenIt.Add(hla, true);
yield return(hla);
}
}
}
}
public static Dictionary <string, Dictionary <Hla, bool> > CreatePatientToHlaToYesNoDontKnow(HlaResolution hlaResolution, List <Dictionary <string, string> > expandedTable, string header, IEnumerable <Hla> hlaList)
{
Dictionary <string, Dictionary <Hla, bool> > patientToHlaToYesNoDontKnow = new Dictionary <string, Dictionary <Hla, bool> >();
foreach (Hla hla in hlaList)
{
Dictionary <string, Set <bool> > patientToSetOfHasHlaValues = new Dictionary <string, Set <bool> >();
foreach (Dictionary <string, string> row in expandedTable)
{
bool?hasHlaOrNull = HasHla(hla, row, hlaResolution);
if (hasHlaOrNull != null)
{
string patient = row["patient"];
Set <bool> setOfHasHlaValues = SpecialFunctions.GetValueOrDefault(patientToSetOfHasHlaValues, patient);
setOfHasHlaValues.AddNewOrOld((bool)hasHlaOrNull);
}
else
{
SpecialFunctions.CheckCondition(!row.ContainsKey("weight") || double.Parse(row["weight"]) == 1);
}
}
foreach (string patient in patientToSetOfHasHlaValues.Keys)
{
Set <bool> setOfHasHlaValues = patientToSetOfHasHlaValues[patient];
if (setOfHasHlaValues.Count == 1)
{
foreach (bool hasHlaOrNull in setOfHasHlaValues)
{
Dictionary <Hla, bool> hlaToYesNoDontKnow = SpecialFunctions.GetValueOrDefault(patientToHlaToYesNoDontKnow, patient);
hlaToYesNoDontKnow.Add(hla, (bool)hasHlaOrNull);
}
}
else
{
//Debug.WriteLine(string.Format("For patient {0} and hla {1}, skipping because of ambiguious data", patient, hla));
}
}
}
return(patientToHlaToYesNoDontKnow);
}
public static Dictionary <bool, List <KeyValuePair <double, double> > > CreateListsWithWeights(HlaResolution hlaResolution, List <Dictionary <string, string> > expandedTable, Dictionary <string, double> logViralLoadTable, Hla hla)
{
Dictionary <bool, List <KeyValuePair <double, double> > > patientListList = new Dictionary <bool, List <KeyValuePair <double, double> > >();
patientListList[false] = new List <KeyValuePair <double, double> >();
patientListList[true] = new List <KeyValuePair <double, double> >();
foreach (Dictionary <string, string> row in expandedTable)
{
bool?hasHlaOrNull = QmrAlgorithms.HasHla(hla, row, hlaResolution);
if (hasHlaOrNull != null)
{
double weight = row.ContainsKey("weight")?double.Parse(row["weight"]):1.0;
string patient = row["patient"];
if (logViralLoadTable.ContainsKey(patient))
{
double logViralLoad = logViralLoadTable[patient];
KeyValuePair <double, double> weightAndLogViralLoad = new KeyValuePair <double, double>(weight, logViralLoad);
patientListList[(bool)hasHlaOrNull].Add(weightAndLogViralLoad);
}
else
{
Debug.WriteLine(string.Format("Can't find patient '{0}' in viralload list", patient));
}
}
}
return(patientListList);
}
private static Hla GetHlaFromRow(Dictionary <string, string> causeAssignmentRow, HlaResolution hlaResolution)
{
Qmrr.HlaFactory hlaFactory = Qmrr.HlaFactory.GetFactory("noConstraint");
string hla = causeAssignmentRow["HLA"];
if (hla.Length == 4 || hla.Length == 2) //!!!should this be moved to GetHlaLengthInstance so doesn't appear twice?
{
hla = hla.Substring(0, 1) + "0" + hla.Substring(1);
}
HlaToLength hlaToLength = hlaResolution.GetHlaLengthInstance(hla);
SpecialFunctions.CheckCondition(hlaToLength != null);
return(hlaFactory.GetGroundInstance(hlaToLength.ToString()));
}
//!!!Yikes tons of repeated code and stuff re-run
public static HlaAssignmentWithResponses CreateHlaAssignment(List <Dictionary <string, string> > rowsOfThisPeptide, IEnumerable <Hla> hlaList, HlaResolution hlaResolution, Quickscore <Hla, int> quickscore, List <int> patientsWhoRespond, Hla hlaToReplace, Hla hlaWithWhichToReplaceItOrNull)
{
//!!!this code is repeated elsewhere
Dictionary <Hla, List <int> > hlaToRespondingPatientsUnfiltered = quickscore.CreateCauseToSubsetOfEffects(patientsWhoRespond);
Dictionary <Hla, List <int> > hlaToRespondingPatients = Filter9xs(hlaToRespondingPatientsUnfiltered);
List <Hla> hlaListFromRepondingPatients = new List <Hla>(hlaToRespondingPatients.Keys);
Dictionary <Hla, bool> hlaAssignmentDicationary = new Dictionary <Hla, bool>();
foreach (Dictionary <string, string> causeAssignmentRow in rowsOfThisPeptide)
{
Hla hla = GetHlaFromRow(causeAssignmentRow, hlaResolution);
hlaAssignmentDicationary[hla] = true;
}
hlaAssignmentDicationary.Remove(hlaToReplace);
if (hlaWithWhichToReplaceItOrNull != null)
{
hlaAssignmentDicationary.Add(hlaWithWhichToReplaceItOrNull, true);
}
List <int> indexCollection = new List <int>();
for (int hlaIndex = 0; hlaIndex < hlaListFromRepondingPatients.Count; ++hlaIndex)
{
Hla hla = hlaListFromRepondingPatients[hlaIndex];
if (hlaAssignmentDicationary.ContainsKey(hla))
{
indexCollection.Add(hlaIndex);
}
}
HlaAssignmentWithResponses hlaAssignment = HlaAssignmentWithResponses.GetInstance(quickscore, hlaListFromRepondingPatients,
indexCollection, hlaToRespondingPatients);
return(hlaAssignment);
}
//private Dictionary<string, bool> GetAList(Dictionary<string, string> row)
//{
// Dictionary<string, bool> alist = new Dictionary<string, bool>();
// string alistValue = row["HLA In Fixed List"];
// foreach (string hla in alistValue.Split(' '))
// {
// Debug.Assert((hla.Length == 3 && !hla.StartsWith("B15")) || (hla.Length == 5 && hla.StartsWith("B15")));
// alist.Add(hla, true);
// }
// return alist;
//}
public static HlaAssignmentWithResponses CreateHlaAssignment(List <Dictionary <string, string> > rowsOfThisPeptide, IEnumerable <Hla> hlaList, HlaResolution hlaResolution, Quickscore <Hla, int> quickscore, List <int> patientsWhoRespond)
{
//!!!this code is repeated elsewhere
Dictionary <Hla, List <int> > hlaToRespondingPatientsUnfiltered = quickscore.CreateCauseToSubsetOfEffects(patientsWhoRespond);
Dictionary <Hla, List <int> > hlaToRespondingPatients = Filter9xs(hlaToRespondingPatientsUnfiltered);
List <Hla> hlaListFromRepondingPatients = new List <Hla>(hlaToRespondingPatients.Keys);
Dictionary <Hla, bool> hlaAssignmentDicationary = new Dictionary <Hla, bool>();
foreach (Dictionary <string, string> causeAssignmentRow in rowsOfThisPeptide)
{
Hla hla = GetHlaFromRow(causeAssignmentRow, hlaResolution);
hlaAssignmentDicationary[hla] = true;
}
HlaAssignmentWithResponses hlaAssignment = HlaAssignmentWithResponses.GetInstance(hlaAssignmentDicationary.Keys, quickscore, hlaListFromRepondingPatients,
hlaToRespondingPatients);
return(hlaAssignment);
}
internal static HlaToLength GetHlaToLengthValueOrNull(Dictionary <string, string> row, string column, HlaResolution hlaResolution)
{
string hlaValue = row[column].ToString();
if (hlaValue.StartsWith("A") || hlaValue.StartsWith("B") || hlaValue.StartsWith("C"))
{
HlaToLength hlaToLength = hlaResolution.GetHlaLengthInstance(hlaValue);
return(hlaToLength);
}
else
{
if (hlaValue.Length == 3 || hlaValue.Length == 1)
{
hlaValue = "0" + hlaValue;
}
string hla = (column[0].ToString() + hlaValue).ToUpper();
HlaToLength hlaToLength = hlaResolution.GetHlaLengthInstance(hla);
return(hlaToLength);
}
}
public static Hla GetHlaValue(Dictionary <string, string> row, string column, HlaResolution hlaResolution)
{
HlaToLength hlaToLength = GetHlaToLengthValueOrNull(row, column, hlaResolution);
SpecialFunctions.CheckCondition(hlaToLength != null);
return(HlaFactory.GetGroundInstance(hlaToLength.ToString()));
}
public static Quickscore <Hla, int> CreateQuickscore(string fileName, string header, double causePrior, double linkProbability, double leakProbability, HlaResolution hlaResolution)
{
Qmrr.HlaFactory hlaFactory = Qmrr.HlaFactory.GetFactory("noConstraint");
Quickscore <Hla, int> quickscore = Quickscore <Hla, int> .GetInstance(hlaFactory.GetGroundInstance(""));
foreach (Dictionary <string, string> row in QuickScoreOptimalsTable(fileName, header))
{
foreach (string column in CreateHlaColumns(header))
{
Hla hla = GetHlaValue(row, column, hlaResolution);
int patient = GetPatient(row);
quickscore.SetCause(hla, causePrior);
quickscore.SetLeak(patient, leakProbability);
quickscore.SetLink(hla, patient, linkProbability);
}
}
return(quickscore);
}
