public List <ProteinDto> ExtractProteins(double mw, SearchParametersDto parameters)
{
var query = GetQuery(mw, parameters);
var connectionString = GetConnectionString(parameters.ProtDb);
List <SerializedProteinDataDto> prot;
using (var connection = new SqlConnection(connectionString))
{
prot = connection.Query <SerializedProteinDataDto>(query).ToList();
}
var proteins = new List <ProteinDto>();
foreach (var proteinInfo in prot)
{
var insilico = new InsilicoObjectDto()
{
InsilicoMassLeft = proteinInfo.Insilico.Split(',').Select(double.Parse).ToList(),
InsilicoMassRight = proteinInfo.Insilico.Split(',').Select(double.Parse).ToList()
};
var protein = new ProteinDto()
{
Header = proteinInfo.ID,
InsilicoDetails = insilico,
Mw = proteinInfo.MW,
Sequence = proteinInfo.Seq
};
proteins.Add(protein);
}
return(proteins);
}
private double ComputeVariableModificationsScore(ProteinDto protein, List <ProteinDto> shortlisted, List <double> peakList, SearchParametersDto parameters)
{
var filteredSitesA = new List <PostTranslationModificationsSiteDto>();
EvaulateModificationSites(protein.Sequence, filteredSitesA, parameters.PtmCodeVar, parameters.PtmTolerance); // filtered sites is currently empty
var sortedList = filteredSitesA.OrderBy(o => o.Score).ToList();
var combos = new List <string>();
var siteIndices = new List <int>();
for (var j = 1; j <= Constants.MaximumVariableModifications; j++)
{
foreach (var comb in Combinations(j, sortedList.Count))
{
var dummy = string.Empty;
foreach (var t in comb)
{
dummy += t.ToString();
siteIndices.Add(t); // separates indices
}
combos.Add(dummy);
siteIndices.Add(777);
}
}
if (sortedList.Count > 0)
{
GenerateModifiedProteins(filteredSitesA, siteIndices, protein, shortlisted, peakList, parameters);
}
return(0);
}
//STEP 2: Generate theoretical fragments of each protein
private static void MakeAdjustment(ProteinDto prot, double rightOffset, double leftOffset, List <double> specialList, double s, List <double> specialDependecy)
{
for (var seqIndex = 0; seqIndex < prot.Sequence.Length - 1; seqIndex++) //for Fragment
{
prot.InsilicoDetails.InsilicoMassLeft[seqIndex] = prot.InsilicoDetails.InsilicoMassLeft[seqIndex] + leftOffset; // ;
prot.InsilicoDetails.InsilicoMassRight[seqIndex] = prot.InsilicoDetails.InsilicoMassRight[seqIndex] + rightOffset;
specialList.Add(specialDependecy[seqIndex] + s);
}
}
private double[] GetModifiedIonsArray(ProteinDto protein)
{
var modifiedIonsArray = protein.InsilicoDetails.InsilicoMassLeftAo.ToArray();
modifiedIonsArray.AddRange(protein.InsilicoDetails.InsilicoMassLeftAstar);
modifiedIonsArray.AddRange(protein.InsilicoDetails.InsilicoMassLeftBo);
modifiedIonsArray.AddRange(protein.InsilicoDetails.InsilicoMassLeftBstar);
modifiedIonsArray.AddRange(protein.InsilicoDetails.InsilicoMassRightYo);
modifiedIonsArray.AddRange(protein.InsilicoDetails.InsilicoMassRightYstar);
modifiedIonsArray.AddRange(protein.InsilicoDetails.InsilicoMassRightZo);
modifiedIonsArray.AddRange(protein.InsilicoDetails.InsilicoMassRightZoo);
return(modifiedIonsArray);
}
private double ComputeFixedModificationScore(ProteinDto parentPro, List <ProteinDto> modifiedProteins, List <double> peakList, SearchParametersDto parameters)
{
var filteredSites = new List <PostTranslationModificationsSiteDto>();
EvaulateModificationSites(parentPro.Sequence, filteredSites, parameters.PtmCodeFix);
filteredSites = filteredSites.OrderBy(o => o.Score).ToList();
var siteIndices = Enumerable.Range(0, filteredSites.Count).ToList();
siteIndices.Add(777);
if (filteredSites.Count > 0)
{
GenerateModifiedProteins(filteredSites, siteIndices, parentPro, modifiedProteins, peakList, parameters);
}
return(0);
}
private void GenerateModifiedProteins(List <PostTranslationModificationsSiteDto> filteredSites, List <int> combos,
ProteinDto parent, List <ProteinDto> shortProt, List <double> peakList, SearchParametersDto parameters)
{
var dummyMw = parent.Mw; // MW of the original sequence
double dummyPtmScore = 0; // ptm score of the unmodified sequence
var sitesInfo = new List <PostTranslationModificationsSiteDto>();
foreach (var i in combos)
{
if (i != 777)
{
dummyMw += filteredSites.ElementAt(i).ModWeight;
// accumulates the mod weight of all the sites in the current combination
dummyPtmScore += filteredSites.ElementAt(i).Score; //accumlates the ptm score
sitesInfo.Add(filteredSites.ElementAt(i));
}
else if (i == 777)
{
var temProtein = new ProteinDto()
{
Mw = dummyMw,
PtmScore = dummyPtmScore,
Sequence = parent.Sequence,
Header = parent.Header,
PstScore = parent.PstScore,
InsilicoScore = parent.InsilicoScore,
MwScore = parent.MwScore,
Score = parent.Score,
InsilicoDetails = parent.InsilicoDetails,
PtmParticulars = sitesInfo
};
InsilicoFragmentationPtmCpu.insilico_fragmentation(temProtein, parameters.InsilicoFragType, parameters.HandleIons);
// _insilicoFilter.ComputeInsilicoScore(new List<ProteinDto>{temProtein}, peakList, parameters.HopThreshhold);
//temProtein.set_score(parameters.MwSweight, parameters.PstSweight, parameters.InsilicoSweight);
shortProt.Add(temProtein);
dummyMw = parent.Mw;
dummyPtmScore = 0;
sitesInfo = new List <PostTranslationModificationsSiteDto>();
}
}
}
public static void insilico_fragmentation(ProteinDto prot, string clevageType, string ions)
{
Frag1(prot, clevageType, ions);
}
private static void Frag1(ProteinDto prot, string clevageType, string handleIon)
{
const double proton = 1.00727647;
const double h = 1.007825035;
const double c = 12.0000;
const double o = 15.99491463;
const double n = 14.003074;
const double oh = o + h;
const double co = c + o;
const double nh = n + h;
const double nh3 = n + h + h + h;
const double h2O = h + h + o;
var strprotein = prot.Sequence.ToUpper();
var prtlength = strprotein.Length; //Gives length of Protein
for (var seqIndex = 0; seqIndex < prtlength - 1; seqIndex++) //for Fragment
{
if (prot.PtmParticulars == null)
{
continue;
}
if (prot.PtmParticulars.Count == 0)
{
continue;
}
foreach (var ptmSite in prot.PtmParticulars)
{
if (seqIndex >= ptmSite.Index)
{
prot.InsilicoDetails.InsilicoMassLeft[seqIndex] =
prot.InsilicoDetails.InsilicoMassLeft[seqIndex] + ptmSite.ModWeight;
}
else
{
prot.InsilicoDetails.InsilicoMassRight[seqIndex] =
prot.InsilicoDetails.InsilicoMassRight[seqIndex] + ptmSite.ModWeight;
}
}
}
for (var seqIndex = 0; seqIndex < prtlength - 1; seqIndex++) //for Fragment
{
switch (clevageType)
{
case "CID": //WHY CID in caps and in small letters(cid)???
case "cid":
case "bird":
case "BIRD":
case "imd":
case "IMD":
case "HCD":
case "hcd":
case "SID":
case "sid":
prot.InsilicoDetails.InsilicoMassLeft[seqIndex] = prot.InsilicoDetails.InsilicoMassLeft[seqIndex] + proton;
prot.InsilicoDetails.InsilicoMassRight[seqIndex] = prot.InsilicoDetails.InsilicoMassRight[seqIndex] + oh + 2 * h;
switch (handleIon)
{
case "bo":
prot.InsilicoDetails.InsilicoMassLeftBo.Add(prot.InsilicoDetails.InsilicoMassLeft[seqIndex] - h2O);
break;
case "bstar":
prot.InsilicoDetails.InsilicoMassLeftBstar.Add(prot.InsilicoDetails.InsilicoMassLeft[seqIndex] - nh3);
break;
case "ystar":
prot.InsilicoDetails.InsilicoMassRightYstar.Add(prot.InsilicoDetails.InsilicoMassRight[seqIndex] - nh3);
break;
case "yo":
prot.InsilicoDetails.InsilicoMassRightYo.Add(prot.InsilicoDetails.InsilicoMassRight[seqIndex] - h2O);
break;
}
break;
case "ECD":
case "ecd":
case "ETD":
case "etd":
prot.InsilicoDetails.InsilicoMassLeft[seqIndex] = prot.InsilicoDetails.InsilicoMassLeft[seqIndex] + proton + n + 3 * h;
prot.InsilicoDetails.InsilicoMassRight[seqIndex] = prot.InsilicoDetails.InsilicoMassRight[seqIndex] + oh - nh;
switch (handleIon)
{
case "zd":
prot.InsilicoDetails.InsilicoMassRightZo.Add(prot.InsilicoDetails.InsilicoMassRight[seqIndex] + proton);
break;
case "zdd":
prot.InsilicoDetails.InsilicoMassRightZoo.Add(prot.InsilicoDetails.InsilicoMassRight[seqIndex] + 2 * proton);
break;
}
break;
case "EDD":
case "edd":
case "NETD":
case "netd":
prot.InsilicoDetails.InsilicoMassLeft[seqIndex] = prot.InsilicoDetails.InsilicoMassLeft[seqIndex] + proton - co;
prot.InsilicoDetails.InsilicoMassRight[seqIndex] = prot.InsilicoDetails.InsilicoMassRight[seqIndex] + oh + co;
switch (handleIon)
{
case "ao":
prot.InsilicoDetails.InsilicoMassLeftAo.Add(prot.InsilicoDetails.InsilicoMassLeft[seqIndex] - h2O);
break;
case "astar":
prot.InsilicoDetails.InsilicoMassLeftAstar.Add(prot.InsilicoDetails.InsilicoMassLeft[seqIndex] - nh3);
break;
}
break;
}
}
}
private void adjustProteinForFragmentTypeAndSpecialIons(ProteinDto prot, string clevageType, string handleIon)
{
var strprotein = prot.Sequence.ToUpper();
var prtlength = strprotein.Length; //Gives length of Protein
if (prot.PtmParticulars != null && prot.PtmParticulars.Count != 0)
{
for (var seqIndex = 0; seqIndex < prtlength - 1; seqIndex++) //for Fragment
{
foreach (var ptmSite in prot.PtmParticulars)
{
if (seqIndex >= ptmSite.Index)
{
prot.InsilicoDetails.InsilicoMassLeft[seqIndex] =
prot.InsilicoDetails.InsilicoMassLeft[seqIndex] + ptmSite.ModWeight;
}
else
{
prot.InsilicoDetails.InsilicoMassRight[seqIndex] =
prot.InsilicoDetails.InsilicoMassRight[seqIndex] + ptmSite.ModWeight;
}
}
}
}
string[] IndividualHandleIonArray = handleIon.Split(','); // We got string of handle ions with comma separated. So, converting it into (string array) with separated ion
for (int HandleIonIteration = 0; HandleIonIteration < IndividualHandleIonArray.Length; HandleIonIteration++)
{
string IndividualHandleIon = IndividualHandleIonArray[HandleIonIteration];
for (var seqIndex = 0; seqIndex < prtlength - 1; seqIndex++) //for Fragment
{
switch (clevageType.ToUpper())
{
case CleavageTypes.CID:
case CleavageTypes.BIRD:
case CleavageTypes.IMD:
case CleavageTypes.HCD:
case CleavageTypes.SID:
switch (IndividualHandleIon) //(handleIon)
{
case SpecialIons.BO:
MakeAdjustment(prot, MassAdjustment.OH + 2 * MassAdjustment.H, MassAdjustment.Proton, prot.InsilicoDetails.InsilicoMassLeftBo, -MassAdjustment.H2O, prot.InsilicoDetails.InsilicoMassLeft);
break;
case SpecialIons.BSTAR:
MakeAdjustment(prot, MassAdjustment.OH + 2 * MassAdjustment.H, MassAdjustment.Proton, prot.InsilicoDetails.InsilicoMassLeftBstar, -MassAdjustment.NH3, prot.InsilicoDetails.InsilicoMassLeft);
break;
case SpecialIons.YSTAR:
MakeAdjustment(prot, MassAdjustment.OH + 2 * MassAdjustment.H, MassAdjustment.Proton, prot.InsilicoDetails.InsilicoMassRightYstar, -MassAdjustment.NH3, prot.InsilicoDetails.InsilicoMassRight);
break;
case SpecialIons.YO:
MakeAdjustment(prot, MassAdjustment.OH + 2 * MassAdjustment.H, MassAdjustment.Proton, prot.InsilicoDetails.InsilicoMassRightYo, -MassAdjustment.H2O, prot.InsilicoDetails.InsilicoMassRight);
break;
}
break;
case CleavageTypes.ECD:
case CleavageTypes.ETD:
switch (IndividualHandleIon) //(handleIon)
{
case SpecialIons.ZD:
MakeAdjustment(prot, MassAdjustment.OH - MassAdjustment.NH, MassAdjustment.Proton + MassAdjustment.N + 3 * MassAdjustment.H, prot.InsilicoDetails.InsilicoMassRightZo, MassAdjustment.Proton, prot.InsilicoDetails.InsilicoMassRight);
break;
case SpecialIons.ZDD:
MakeAdjustment(prot, MassAdjustment.OH - MassAdjustment.NH, MassAdjustment.Proton + MassAdjustment.N + 3 * MassAdjustment.H, prot.InsilicoDetails.InsilicoMassRightYo, 2 * MassAdjustment.Proton, prot.InsilicoDetails.InsilicoMassRight);
break;
}
break;
case CleavageTypes.EDD:
case CleavageTypes.NETD:
switch (IndividualHandleIon) //(handleIon)
{
case SpecialIons.AO:
MakeAdjustment(prot, MassAdjustment.OH + MassAdjustment.CO, MassAdjustment.Proton - MassAdjustment.CO, prot.InsilicoDetails.InsilicoMassLeftAo, -MassAdjustment.H2O, prot.InsilicoDetails.InsilicoMassLeft);
break;
case SpecialIons.ASTAR:
MakeAdjustment(prot, MassAdjustment.OH + MassAdjustment.CO, MassAdjustment.Proton - MassAdjustment.CO, prot.InsilicoDetails.InsilicoMassLeftAstar, -MassAdjustment.NH3, prot.InsilicoDetails.InsilicoMassLeft);
break;
}
break;
}
}
}
}
private SearchResult GetSearchResultModel(string queryTd, int fileId, string headerTag, ProteinDto protein, Guid resId)
{
var searchResult = new SearchResult
{
QueryId = queryTd,
Sequence = protein.Sequence,
FileId = fileId.ToString(),
Header = headerTag,
InsilicoScore = protein.InsilicoScore,
Mw = protein.Mw,
MwScore = protein.MwScore,
PstScore = protein.PstScore,
PtmScore = protein.PtmScore,
ResultId = resId.ToString(),
Score = protein.Score
};
return(searchResult);
}
