private static IEnumerable <ProteinGroup> CombinedProteins(IList <ProteinGroup> proteins, Dictionary <IAminoAcidSequence, int> sharedPeptides, int minPeptidesPerProtein = 1)
{
// A list of protein groups that, at the end of this method, will have distinct protein groups.
List <ProteinGroup> proteinGroups = new List <ProteinGroup>();
// 1) Find Indistinguishable Proteins and group them together into Protein Groups
// If they are not indistinguishable, then they are still converted to Protein Groups
// but only contain one protein.
// A 1 2 3 4
// B 1 2 3 4
// C 1 3 4
// Proteins A and B are indistinguisable (have same set of peptides 1,2,3,4), and thus would become a Protein Group (PG1 [a,b])
// C is distinguishable and would become a Protein Group (PG2 [c]).
#region Indistinguishable
// Loop over each protein
int p1 = 0;
while (p1 < proteins.Count)
{
// Grab the next protein and its associated peptides from the list of all proteins
ProteinGroup proteinGroup = proteins[p1];
HashSet <IAminoAcidSequence> peptides = proteinGroup.Peptides;
// Start looking at the next protein in the list
int p2 = p1 + 1;
// Loop over each other protein skipping the one you just made into the PG
while (p2 < proteins.Count)
{
// Does the next protein contain the same set of peptides as the protein group?
if (proteins[p2].Peptides.SetEquals(peptides))
{
// Yes they are indistinguishable (i.e. proteins A and B from above), so add this protein to the protein group
foreach (var protein in proteins[p2].Proteins)
{
proteinGroup.AddProtein(protein);
}
// Then remove this protein from the list of all proteins as not to make it into its own PG later
proteins.RemoveAt(p2);
}
else
{
// Go to next protein in question
p2++;
}
}
// We have gone through every protein possible and thus have completed the grouping of this PG
proteinGroups.Add(proteinGroup);
p1++;
}
//if (printMessages)
// Log("{0:N0} protein groups are left after combining indistinguishable proteins (having the exact same set of peptides)", proteinGroups.Count);
#endregion Indistinguishable
// 2) Find Subsumable Proteins
// Sort proteins from worst to best to remove the worst scoring groups first (note well, lower p-values mean better scores)
// Case Example: P-Value, Protein Group, Peptides
// 0.1 A 1 2
// 0.05 B 1 3
// 0.01 C 2 3
// These are subsumable and we remove the worst scoring protein group (in this case, Protein Group A at p-value of 0.1) first. This would leave:
// 0.05 B 1 3
// 0.01 C 2 3
// Which would mean Protein Group B and C are distinct groups, but share a common peptide (3), peptides 1 and 2 would remain unshared.
// Protein Group A is removed, as it its peptides can be explained by groups B and C.
#region Subsumable
// First, make sure all the peptides know which protein groups they belong too, so we can determined shared peptides
// and thus get correct p-value for the PGs.
//MappedPeptidesToProteinGroups(proteinGroups);
//// First update each protein's p-value
//foreach (ProteinGroup proteinGroup in proteinGroups)
//{
// proteinGroup.UpdatePValue(PScoreCalculationMethod, UseConservativePScore);
//}
//// Then sort the groups on decreasing p-values
//proteinGroups.Sort(ProteinGroup.CompareDecreasing);
p1 = 0;
while (p1 < proteinGroups.Count)
{
// Get the peptides in the protein group
ProteinGroup proteinGroup = proteinGroups[p1];
HashSet <IAminoAcidSequence> referencePeptides = proteinGroup.Peptides;
// Check if all the peptides are shared, if they are then the protein group is subsumable and should be removed
if (referencePeptides.All(p => sharedPeptides[p] > 1))
{
// Since this protein group is being eliminated, remove its reference from all the peptides
foreach (Peptide pep in referencePeptides)
{
int value = sharedPeptides[pep];
sharedPeptides[pep] = value - 1;
}
// Remove the protein group from the master list
proteinGroups.RemoveAt(p1);
}
else
{
p1++;
}
}
#endregion Subsumable
// 3) Remove protein groups that do not have enough peptides within them
#region MinimumGroupSize
// No need to filter if this is one or less
if (minPeptidesPerProtein > 1)
{
p1 = 0;
while (p1 < proteinGroups.Count)
{
ProteinGroup proteinGroup = proteinGroups[p1];
// Check to see if this protein has enough peptides to be considered indentified
if (proteinGroup.Peptides.Count < minPeptidesPerProtein)
{
//// Since this protein group is being eliminated, remove its reference from all the peptides
//foreach (Peptide pep in proteinGroup.Peptides)
//{
// pep.ProteinGroups.Remove(proteinGroup);
//}
// This protein didn't have enough peptides, so remove it from future consideration
proteinGroups.RemoveAt(p1);
}
else
{
p1++;
}
}
}
#endregion MinimumGroupSize
//// 4) Apply false discovery filtering at the protein level
#region FDR filtering
//proteinGroups.Sort();
//// Mark each protein group that passes fdr filtering
//int count = 0;
//foreach (ProteinGroup proteinGroup in FalseDiscoveryRate<ProteinGroup, double>.Filter(proteinGroups, MaxFdr / 100, true))
//{
// proteinGroup.PassesFDR = true;
// count++;
//}
#endregion FDR filtering
return(proteinGroups);
}
public bool Equals(ProteinGroup other)
{
return(Proteins.SetEquals(other.Proteins));
}
public static IEnumerable <ProteinGroup> GroupProteins(IEnumerable <Protein> proteins, IList <IProtease> proteases, IEnumerable <IAminoAcidSequence> observeredSequences, IEqualityComparer <IAminoAcidSequence> peptideComparer, int MaxMissedCleavages = 3, int minPepPerProtein = 1)
{
var proteinGroups = new List <ProteinGroup>();
// Get all the unique peptides defined by the comparere passed in
HashSet <IAminoAcidSequence> peptideSequences = new HashSet <IAminoAcidSequence>(observeredSequences, peptideComparer);
// Peptides that were mapped to proteins, for error checking
var mappedSequences = new Dictionary <IAminoAcidSequence, int>(peptideComparer);
// Find smallest and largest peptide
int smallestPeptide = int.MaxValue;
int largestPeptide = 0;
foreach (var peptideSequence in peptideSequences)
{
int length = peptideSequence.Length;
if (length > largestPeptide)
{
largestPeptide = length;
}
if (length < smallestPeptide)
{
smallestPeptide = length;
}
}
foreach (Protein protein in proteins)
{
HashSet <IAminoAcidSequence> proteinSequences = new HashSet <IAminoAcidSequence>();
foreach (Protease protease in proteases)
{
foreach (Peptide peptide in protein.Digest(protease, MaxMissedCleavages, smallestPeptide, largestPeptide))
{
if (!peptideSequences.Contains(peptide))
{
continue;
}
if (proteinSequences.Add(peptide))
{
int proteinCount;
if (mappedSequences.TryGetValue(peptide, out proteinCount))
{
mappedSequences[peptide] = proteinCount + 1;
}
else
{
mappedSequences.Add(peptide, 1);
}
}
}
}
if (proteinSequences.Count > 0)
{
var proteinGroup = new ProteinGroup(protein, proteinSequences, peptideComparer);
proteinGroups.Add(proteinGroup);
}
}
if (mappedSequences.Count != peptideSequences.Count)
{
throw new Exception("All peptides were not mapped to a protein!");
}
return(CombinedProteins(proteinGroups, mappedSequences, minPepPerProtein));
}