public bool same_ptmset(PtmSet that, bool unlocalized)
{
if (unlocalized) //methyl,methyl,methyl = methyl; methyl; methyl, etc
{
string this_ptms = string.Join(", ", ptm_combination.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).OrderBy(m => m));
string that_ptms = string.Join(", ", that.ptm_combination.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).OrderBy(m => m));
return(this_ptms == that_ptms);
}
else
{
List <string> this_ptms = this.ptm_combination.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList();
List <string> that_ptms = that.ptm_combination.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList();
if (this_ptms.Count != that_ptms.Count)
{
return(false);
}
foreach (string m in this_ptms.Distinct())
{
if (that_ptms.Count(s => s == m) != this_ptms.Count(s => s == m))
{
return(false);
}
}
foreach (string m in that_ptms.Distinct())
{
if (that_ptms.Count(s => s == m) != this_ptms.Count(s => s == m))
{
return(false);
}
}
return(true);
}
}
public PtmSet(List <Ptm> unique_ptm_combination)
{
ptm_combination = unique_ptm_combination;
mass = ptm_combination == null ? 0 : ptm_combination.Select(ptm => ptm.modification).Sum(m => (double)m.MonoisotopicMass);
ptm_description = ptm_combination == null ?
"Unknown" :
ptm_combination.Count == 0 ?
"Unmodified" :
string.Join("; ", ptm_combination.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).OrderBy(m => m).ToList());
}
public static bool modification_is_adduct(Modification mod)
{
if (mod.OriginalId == "Sulfate Adduct" ||
mod.OriginalId == "Acetone Artifact (Unconfirmed)" ||
mod.OriginalId == "Hydrogen Dodecyl Sulfate" ||
UnlocalizedModification.LookUpId(mod) == "Oxidation")
{
return(true);
}
return(false);
}
private void calculate_topdown_level()
{
topdown_level_description = "";
if (ambiguous_topdown_hits.Count == 0)
{
topdown_level = 1;
topdown_level_description = "Unambiguous";
}
else
{
var unique_accessions = new List <string>()
{
this.accession.Split('_')[0].Split('-')[0]
}.Concat(ambiguous_topdown_hits.Select(a => a.accession.Split('_')[0].Split('-')[0])).Distinct();
var unique_sequences = new List <string>()
{
sequence
}.Concat(ambiguous_topdown_hits.Select(a => sequence)).Distinct();
var unique_PTM_locations = new List <string>()
{
string.Join(",", topdown_ptm_set.ptm_combination.Select(p => p.position).OrderBy(n => n))
}.Concat(ambiguous_topdown_hits.Select(h => string.Join(",", h.ptm_list.Select(p => p.position).OrderBy(n => n)))).Distinct();
var unique_PTM_IDs = new List <string>()
{
string.Join(",", topdown_ptm_set.ptm_combination.Select(p => UnlocalizedModification.LookUpId(p.modification)).OrderBy(n => n))
}.Concat(ambiguous_topdown_hits.Select(h => string.Join(",", h.ptm_list.Select(p => UnlocalizedModification.LookUpId(p.modification)).OrderBy(n => n)))).Distinct();
int gene_ambiguity = unique_accessions.Count() > 1 ? 1 : 0;
int sequence_ambiguity = unique_sequences.Count() > 1 ? 1 : 0;
int PTM_ambiguity = unique_PTM_IDs.Count() > 1 ? 1 : 0;
int PTM_location = unique_PTM_locations.Count() > 1 ? 1 : 0;
if (gene_ambiguity == 0 && sequence_ambiguity == 0 && PTM_ambiguity == 0 && PTM_location == 0)
{
var unique_PTMs = new List <string>()
{
string.Join(",", topdown_ptm_set.ptm_combination.Select(p => UnlocalizedModification.LookUpId(p.modification) + "@" + p.position).OrderBy(n => n))
}.Concat(ambiguous_topdown_hits.Select(h => string.Join(",", h.ptm_list.Select(p => UnlocalizedModification.LookUpId(p.modification) + "@" + p.position).OrderBy(n => n)))).Distinct();
if (unique_PTMs.Count() > 1)
{
PTM_location = 1;
}
else
{
PTM_ambiguity = 1;
}
}
if (gene_ambiguity > 0)
{
topdown_level_description += "Gene ambiguity; ";
}
if (sequence_ambiguity > 0)
{
topdown_level_description += "Sequence ambiguity; ";
}
if (PTM_ambiguity > 0)
{
topdown_level_description += "PTM identity ambiguity; ";
}
if (PTM_location > 0)
{
topdown_level_description += "PTM localization ambiguity; ";
}
topdown_level = 1 + gene_ambiguity + sequence_ambiguity + PTM_ambiguity + PTM_location;
}
}
private void get_uniprot_mods()
{
var mods = topdown_ptm_set.ptm_combination.Where(p => !Proteoform.modification_is_adduct(p.modification))
.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList().Distinct().OrderBy(m => m).ToList();
topdown_uniprot_mods = "";
string add = "";
if (Sweet.lollipop.theoretical_database.theoreticals_by_accession.ContainsKey(Sweet.lollipop.target_proteoform_community.community_number))
{
Sweet.lollipop.theoretical_database.theoreticals_by_accession[Sweet.lollipop.target_proteoform_community.community_number].TryGetValue(accession.Split('_')[0].Split('-')[0], out var matching_theoretical);
if (matching_theoretical != null)
{
foreach (string mod in mods)
{
// positions with mod
List <int> theo_ptms = matching_theoretical.First().ExpandedProteinList.SelectMany(p => p
.OneBasedPossibleLocalizedModifications)
.Where(p => p.Key >= topdown_begin && p.Key <= topdown_end &&
p.Value.Select(m => UnlocalizedModification.LookUpId(m)).Contains(mod))
.Select(m => m.Key).ToList();
if (theo_ptms.Count > 0)
{
add += mod + " @ " + string.Join(", ", theo_ptms) + "; ";
}
if (topdown_ptm_set.ptm_combination.Where(ptm => !Proteoform.modification_is_adduct(ptm.modification)).Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count)
{
topdown_novel_mods = true;
}
}
topdown_uniprot_mods += add;
if (add.Length == 0)
{
topdown_uniprot_mods += "N/A";
}
foreach (var ambig_id in ambiguous_topdown_hits)
{
Sweet.lollipop.theoretical_database.theoreticals_by_accession[Sweet.lollipop.target_proteoform_community.community_number].TryGetValue(accession.Split('_')[0].Split('-')[0], out var matching_ambig_theoretical);
if (matching_ambig_theoretical != null)
{
var ambig_mods = ambig_id.ptm_list.Where(p => !Proteoform.modification_is_adduct(p.modification))
.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList().Distinct().OrderBy(m => m).ToList();
topdown_uniprot_mods += " | ";
add = "";
foreach (var mod in ambig_mods)
{
// positions with mod
List <int> theo_ptms = matching_ambig_theoretical.First().ExpandedProteinList.SelectMany(p => p
.OneBasedPossibleLocalizedModifications)
.Where(p => p.Key >= ambig_id.begin && p.Key <= ambig_id.end &&
p.Value.Select(m => UnlocalizedModification.LookUpId(m)).Contains(mod))
.Select(m => m.Key).ToList();
if (theo_ptms.Count > 0)
{
add += mod + " @ " + string.Join(", ", theo_ptms) + "; ";
}
if (ambig_id.ptm_list.Where(ptm => !Proteoform.modification_is_adduct(ptm.modification)).Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count)
{
topdown_novel_mods = true;
}
}
}
topdown_uniprot_mods += add;
if (add.Length == 0)
{
topdown_uniprot_mods += "N/A";
}
}
}
}
}
public DeltaMassPeak(ProteoformRelation base_relation, HashSet <ProteoformRelation> relations_to_group)
{
lock (base_relation)
{
base_relation.peak = this;
}
lock (Sweet.lollipop)
{
IncrementInstanceCounter(); //Not thread safe
}
RelationType = base_relation.RelationType;
DeltaMass = base_relation.DeltaMass;
InstanceId = instance_counter;
if (RelationType == ProteoformComparison.ExperimentalExperimental || !Sweet.lollipop.et_use_notch)
{
grouped_relations = find_nearby_relations(relations_to_group);
bool are_positive_candidates =
Sweet.lollipop.theoretical_database.possible_ptmset_dictionary.TryGetValue(Math.Round(DeltaMass, 1),
out List <PtmSet> positive_candidates);
bool are_negative_candidates =
Sweet.lollipop.theoretical_database.possible_ptmset_dictionary.TryGetValue(
Math.Round(-DeltaMass, 1), out List <PtmSet> negative_candidates) &&
(RelationType == ProteoformComparison.ExperimentalExperimental ||
RelationType == ProteoformComparison.ExperimentalFalse);
if (are_positive_candidates || are_negative_candidates)
{
List <PtmSet> candidates = (are_positive_candidates ? positive_candidates : new List <PtmSet>())
.Concat(are_negative_candidates ? negative_candidates : new List <PtmSet>()).ToList();
possiblePeakAssignments = candidates.Where(c =>
RelationType == ProteoformComparison.ExperimentalTheoretical ||
RelationType == ProteoformComparison.ExperimentalDecoy
? Math.Abs(DeltaMass - c.mass) <=
(grouped_relations.First().RelationType == ProteoformComparison.ExperimentalTheoretical
? Sweet.lollipop.peak_width_base_et
: Sweet.lollipop.peak_width_base_ee)
: Math.Abs(Math.Abs(DeltaMass) - Math.Abs(c.mass)) <=
(grouped_relations.First().RelationType == ProteoformComparison.ExperimentalTheoretical
? Sweet.lollipop.peak_width_base_et
: Sweet.lollipop.peak_width_base_ee)).ToList();
}
else
{
possiblePeakAssignments = new List <PtmSet>();
}
}
else
{
grouped_relations = relations_to_group.Where(r => Math.Round(r.candidate_ptmset.mass, 5) == Math.Round(base_relation.candidate_ptmset.mass, 5)).ToList();
possiblePeakAssignments = grouped_relations.Select(r => r.candidate_ptmset).ToList();
DeltaMass = possiblePeakAssignments.First().mass;
}
foreach (ProteoformRelation mass_difference in grouped_relations)
{
foreach (Proteoform p in mass_difference.connected_proteoforms)
{
lock (p) p.relationships.Add(mass_difference);
}
}
possiblePeakAssignments_string = "[" + string.Join("][", possiblePeakAssignments.OrderBy(p => p.ptm_rank_sum).Select(ptmset =>
string.Join(";", ptmset.ptm_combination.Select(ptm =>
UnlocalizedModification.LookUpId(ptm.modification)))).Distinct()) + "]";
Accepted = grouped_relations != null && grouped_relations.Count > 0 && grouped_relations.First().RelationType == ProteoformComparison.ExperimentalTheoretical ?
(peak_relation_group_count >= Sweet.lollipop.min_peak_count_et)
:
(peak_relation_group_count >= Sweet.lollipop.min_peak_count_ee && (!Sweet.lollipop.ee_accept_peaks_based_on_rank || possiblePeakAssignments.Count > 0 && possiblePeakAssignments.Any(p => p.ptm_rank_sum < Sweet.lollipop.mod_rank_first_quartile)));
}
private bool assign_pf_identity(ExperimentalProteoform e, PtmSet set, int begin, int end, ProteoformRelation r, TheoreticalProteoform theoretical_base, List <Proteoform> linked_proteoform_references, bool check_ambiguous_IDs)
{
bool identification_assigned = false;
if (!Sweet.lollipop.id_use_ppm_tolerance || Math.Abs(e.calculate_mass_error(theoretical_base, set, begin, end) * 1e6 / e.modified_mass) < Sweet.lollipop.id_ppm_tolerance)
{
int new_begin = begin;
int new_end = end;
PtmSet new_set = new PtmSet(new List <Ptm>(set.ptm_combination));
List <Ptm> remove = new List <Ptm>();
//do retention of M first
foreach (var mod in new_set.ptm_combination.Where(m => m.modification.ModificationType == "AminoAcid"))
{
new_begin--;
remove.Add(mod);
}
foreach (var mod in new_set.ptm_combination.Where(m => m.modification.ModificationType == "Missing"))
{
if (!new_set.ptm_combination.Any(m => m.modification.ModificationType == "AminoAcid") && begin >= theoretical_base.begin)
{
if (theoretical_base.sequence[begin - theoretical_base.begin].ToString() ==
mod.modification.Target.ToString())
{
new_begin++;
remove.Add(mod); //dont have in ptmset --> change the begin & end
}
}
if (!remove.Contains(mod) && theoretical_base.sequence[end - theoretical_base.begin].ToString() ==
mod.modification.Target.ToString())
{
new_end--;
remove.Add(mod);
}
}
foreach (var ptm in remove)
{
new_set.ptm_combination.Remove(ptm);
}
new_set = new PtmSet(new_set.ptm_combination);
if (e.linked_proteoform_references == null)
{
identification_assigned = true;
if (linked_proteoform_references != null)
{
e.linked_proteoform_references = new List <Proteoform>(linked_proteoform_references);
e.linked_proteoform_references.Add(this);
}
else
{
e.linked_proteoform_references = new List <Proteoform>()
{
theoretical_base
};
}
e.relation_to_id = r;
e.ptm_set = new_set;
e.begin = new_begin;
e.end = new_end;
if (e.gene_name == null)
{
e.gene_name = theoretical_base.gene_name;
}
else
{
e.gene_name.gene_names.Concat(this.gene_name.gene_names);
}
}
else
{
if (linked_proteoform_references != null && !linked_proteoform_references.Contains(e))
{
bool different_id = e.gene_name.get_prefered_name(Lollipop.preferred_gene_label) !=
theoretical_base.gene_name.get_prefered_name(Lollipop.preferred_gene_label) ||
ExperimentalProteoform.get_sequence(e.linked_proteoform_references.First() as TheoreticalProteoform, e.begin, e.end)
!= ExperimentalProteoform.get_sequence(theoretical_base, new_begin, new_end) || !e.ptm_set.same_ptmset(new_set, true);
List <Modification> this_known_mods = theoretical_base.ExpandedProteinList.SelectMany(p => p.OneBasedPossibleLocalizedModifications).SelectMany(kv => kv.Value).Where(v => v.MonoisotopicMass != 0).ToList();
List <Modification> previous_id_known_mods = (e.linked_proteoform_references.First() as TheoreticalProteoform).ExpandedProteinList.SelectMany(p => p.OneBasedPossibleLocalizedModifications).SelectMany(kv => kv.Value).Where(v => v.MonoisotopicMass != 0).ToList();
if (!Sweet.lollipop.topdown_theoretical_reduce_ambiguity || (theoretical_base.topdown_theoretical && !(e.linked_proteoform_references.First() as TheoreticalProteoform).topdown_theoretical))
{
if (!Sweet.lollipop.annotated_PTMs_reduce_ambiguity ||
(new_set.ptm_combination.All(mod1 => modification_is_adduct(mod1.modification) || this_known_mods.Select(mod2 => UnlocalizedModification.LookUpId(mod2)).Contains(UnlocalizedModification.LookUpId(mod1.modification))) &&
!e.ptm_set.ptm_combination.All(mod1 => modification_is_adduct(mod1.modification) || previous_id_known_mods.Select(mod2 => UnlocalizedModification.LookUpId(mod2)).Contains(UnlocalizedModification.LookUpId(mod1.modification)))))
{
if (Sweet.lollipop.topdown_theoretical_reduce_ambiguity || Sweet.lollipop.annotated_PTMs_reduce_ambiguity)
{
if (Sweet.lollipop.remove_bad_connections && different_id) //&& e.relation_to_id != r)
{
e.relation_to_id.Identification = false;
e.relation_to_id.represented_ptmset = null;
}
e.linked_proteoform_references = null;
e.ptm_set = new PtmSet(new List <Ptm>());
e.begin = 0;
e.end = 0;
e.gene_name = null;
e.ambiguous_identifications.Clear();
ProteoformRelation relation = null;
e.relation_to_id = relation;
//reassign the topdown - based ID
return(this.assign_pf_identity(e, set, begin, end, r, theoretical_base, linked_proteoform_references, true));
}
}
}
if (Sweet.lollipop.topdown_theoretical_reduce_ambiguity && (e.linked_proteoform_references.First() as TheoreticalProteoform).topdown_theoretical && !theoretical_base.topdown_theoretical)
{
}
else if (Sweet.lollipop.annotated_PTMs_reduce_ambiguity &&
!new_set.ptm_combination.All(mod1 => modification_is_adduct(mod1.modification) || this_known_mods.Select(mod2 => UnlocalizedModification.LookUpId(mod2)).Contains(UnlocalizedModification.LookUpId(mod1.modification))) &&
e.ptm_set.ptm_combination.All(mod1 => modification_is_adduct(mod1.modification) || previous_id_known_mods.Select(mod2 => UnlocalizedModification.LookUpId(mod2)).Contains(UnlocalizedModification.LookUpId(mod1.modification))))
{
}
else
{
if (different_id)
{
var new_linked_proteoform_references = new List <Proteoform>(linked_proteoform_references);
new_linked_proteoform_references.Add(this);
AmbiguousIdentification new_id =
new AmbiguousIdentification(new_begin, new_end, new_set, r, theoretical_base, new_linked_proteoform_references);
lock (e.ambiguous_identifications)
{
if (!e.ambiguous_identifications.Any(p =>
p.theoretical_base.gene_name.primary ==
new_id.theoretical_base.gene_name.primary &&
ExperimentalProteoform.get_sequence(p.theoretical_base, p.begin, p.end) == ExperimentalProteoform.get_sequence(new_id.theoretical_base, new_id.begin, new_id.end) &&
p.ptm_set.same_ptmset(new_id.ptm_set, true)))
{
e.ambiguous_identifications.Add(new_id);
identification_assigned = true;
}
}
}
}
}
}
}
if (check_ambiguous_IDs)
{
//remove bad relations if using td to reduce ambiguity
if (identification_assigned)
{
List <AmbiguousIdentification> to_remove = new List <AmbiguousIdentification>();
List <Modification> previous_id_known_mods = (e.linked_proteoform_references.First() as TheoreticalProteoform).ExpandedProteinList.SelectMany(p => p.OneBasedPossibleLocalizedModifications).SelectMany(kv => kv.Value).Where(m => m.MonoisotopicMass != 0).ToList();
if (theoretical_base.topdown_theoretical && Sweet.lollipop.topdown_theoretical_reduce_ambiguity)
{
to_remove.AddRange(e.ambiguous_identifications.Where(id => !id.theoretical_base.topdown_theoretical));
}
if (Sweet.lollipop.annotated_PTMs_reduce_ambiguity &&
e.ptm_set.ptm_combination.All(mod1 => modification_is_adduct(mod1.modification) || previous_id_known_mods.Select(mod2 => UnlocalizedModification.LookUpId(mod2)).Contains(UnlocalizedModification.LookUpId(mod1.modification))))
{
foreach (var ambiguous_id in e.ambiguous_identifications)
{
List <Modification> ambiguous_id_known_mods = ambiguous_id.theoretical_base.ExpandedProteinList.SelectMany(p => p.OneBasedPossibleLocalizedModifications).SelectMany(kv => kv.Value).Where(m => m.MonoisotopicMass != 0).ToList();
if (ambiguous_id.ptm_set.ptm_combination.Any(mod1 => !modification_is_adduct(mod1.modification) && !ambiguous_id_known_mods.Select(mod2 => UnlocalizedModification.LookUpId(mod2)).Contains(UnlocalizedModification.LookUpId(mod1.modification))))
{
to_remove.Add(ambiguous_id);
}
}
}
foreach (var x in to_remove)
{
if (e.ambiguous_identifications.Contains(x))
{
e.ambiguous_identifications.Remove(x);
if (Sweet.lollipop.remove_bad_connections)
{
if (e.relation_to_id != x.relation)
{
x.relation.Identification = false;
x.relation.represented_ptmset = null;
}
}
}
}
foreach (var x in e.ambiguous_identifications)
{
x.relation.Identification = true;
}
}
if (this as ExperimentalProteoform != null && (this as ExperimentalProteoform).ambiguous_identifications.Count > 0)
{
lock ((this as ExperimentalProteoform).ambiguous_identifications)
{
int count = (this as ExperimentalProteoform).ambiguous_identifications.Count;
PtmSet[] new_ptm_set = new PtmSet[count];
Parallel.For(0, count, i =>
{
var id = (this as ExperimentalProteoform).ambiguous_identifications[i];
new_ptm_set[i] = determine_mod_change(e, this, id.theoretical_base, r, id.ptm_set, id.begin, id.end);
});
for (int i = 0; i < count; i++)
{
if (new_ptm_set[i] != null)
{
var id = (this as ExperimentalProteoform).ambiguous_identifications[i];
if (assign_pf_identity(e, new_ptm_set[i], id.begin, id.end, r, id.theoretical_base, id.linked_proteoform_references, false))
{
identification_assigned = true;
}
}
}
}
}
}
return(identification_assigned);
}
public static List <SpectrumMatch> get_possible_PSMs(string accession, PtmSet ptm_set, int begin, int end)
{
var bottom_up_PSMs = new List <SpectrumMatch>();
//add BU PSMs
Sweet.lollipop.theoretical_database.bottom_up_psm_by_accession.TryGetValue(accession.Split('_')[0].Split('-')[0], out var psms);
if (psms != null)
{
bottom_up_PSMs.AddRange(psms.Where(s => s.begin >= begin && s.end <= end && s.ptm_list.All(m1 =>
ptm_set.ptm_combination.Count(m2 =>
UnlocalizedModification.LookUpId(m1.modification) ==
UnlocalizedModification.LookUpId(m2.modification)) >=
s.ptm_list.Count(m2 =>
UnlocalizedModification.LookUpId(m1.modification) ==
UnlocalizedModification.LookUpId(m2.modification)))));
}
return(bottom_up_PSMs.OrderByDescending(p => p.ptm_list.Count).ToList());
}
public static List <PtmSet> generate_possible_added_ptmsets(List <PtmSet> possible_peak_assignments, List <Modification> all_mods_with_mass,
TheoreticalProteoform theoretical_base, int begin, int end, PtmSet ptm_set, int additional_ptm_penalty, bool final_assignment)
{
List <Modification> known_mods = theoretical_base.ExpandedProteinList.SelectMany(p => p.OneBasedPossibleLocalizedModifications).SelectMany(kv => kv.Value).ToList();
List <PtmSet> possible_ptmsets = new List <PtmSet>();
foreach (PtmSet set in possible_peak_assignments)
{
List <Modification> mods_in_set = set.ptm_combination.Select(ptm => ptm.modification).ToList();
int rank_sum = additional_ptm_penalty * (set.ptm_combination.Sum(m => Sweet.lollipop.theoretical_database.unlocalized_lookup.TryGetValue(m.modification, out UnlocalizedModification x) ? x.ptm_count : 1) - 1); // penalize additional PTMs
foreach (Modification m in mods_in_set)
{
int mod_rank = Sweet.lollipop.theoretical_database.unlocalized_lookup.TryGetValue(m, out UnlocalizedModification u) ? u.ptm_rank : Sweet.lollipop.modification_ranks.TryGetValue(Math.Round((double)m.MonoisotopicMass, 5), out int x) ? x : Sweet.lollipop.mod_rank_sum_threshold;
bool could_be_m_retention = m.ModificationType == "AminoAcid" && m.Target.ToString() == "M" && theoretical_base.begin == 2 && begin == 2 && !ptm_set.ptm_combination.Any(p => p.modification.Equals(m));
bool motif_matches_n_terminus = begin - theoretical_base.begin >= 0 && begin - theoretical_base.begin < theoretical_base.sequence.Length && m.Target.ToString() == theoretical_base.sequence[begin - theoretical_base.begin].ToString() && !mods_in_set.Any(mod => mod.ModificationType == "AminoAcid" && mod.Target.ToString() == "M");
bool motif_matches_c_terminus = end - theoretical_base.begin >= 0 && end - theoretical_base.begin < theoretical_base.sequence.Length && m.Target.ToString() == theoretical_base.sequence[end - theoretical_base.begin].ToString();
bool cannot_be_degradation = !motif_matches_n_terminus && !motif_matches_c_terminus;
if ((m.ModificationType == "Missing" && cannot_be_degradation) ||
(m.ModificationType == "AminoAcid" && !could_be_m_retention) ||
((u != null ? u.require_proteoform_without_mod : false) && set.ptm_combination.Count > 1))
{
rank_sum = Int32.MaxValue;
break;
}
bool could_be_n_term_degradation = m.ModificationType == "Missing" && motif_matches_n_terminus;
bool could_be_c_term_degradation = m.ModificationType == "Missing" && motif_matches_c_terminus;
//if selected, going to only allow mods in Mods folder (type "Common"), Missing, Missed Monoisotopic, known mods for that protein, or Unmodified
if (Sweet.lollipop.only_assign_common_or_known_mods && final_assignment)
{
if (!(m.MonoisotopicMass == 0 || m.ModificationType == "Common" || could_be_m_retention || could_be_n_term_degradation || could_be_c_term_degradation || m.ModificationType == "Deconvolution Error" || known_mods.Concat(Sweet.lollipop.theoretical_database.variableModifications).Contains(m) ||
known_mods.Select(mod => UnlocalizedModification.LookUpId(mod)).Contains(UnlocalizedModification.LookUpId(m))))
{
rank_sum = Int32.MaxValue;
break;
}
}
// In order of likelihood:
// 1. First, we observe I/L/A cleavage to be the most common, other degradations and methionine cleavage are weighted mid-level
// 2. Missed monoisotopic errors are considered, but weighted towards the bottom. This should allow missed monoisotopics with common modifications like oxidation, but not rare ones. (handled in unlocalized modification)
if (m.MonoisotopicMass == 0)
{
rank_sum += mod_rank;
continue;
}
rank_sum -= Convert.ToInt32(Sweet.lollipop.theoretical_database.variableModifications.Contains(m)); // favor variable modifications over regular modifications of the same mass
if (could_be_m_retention || could_be_n_term_degradation || could_be_c_term_degradation)
{
rank_sum += Sweet.lollipop.mod_rank_first_quartile / 2;
}
else if (m.ModificationType == "Deconvolution Error")
{
rank_sum += Sweet.lollipop.neucode_labeled ?
Sweet.lollipop.mod_rank_third_quartile : //in neucode-labeled data, fewer missed monoisotopics - don't prioritize
1; //in label-free, more missed monoisotoipcs, should prioritize (set to same priority as variable modification)
rank_sum -= additional_ptm_penalty;
}
else
{
//if annotated in DB for this, just add 1?
rank_sum += known_mods.Concat(Sweet.lollipop.theoretical_database.variableModifications).Select(mod => UnlocalizedModification.LookUpId(mod)).Contains(UnlocalizedModification.LookUpId(m))
?
1 : //mod rank
mod_rank + Sweet.lollipop.mod_rank_first_quartile / 2; // Penalize modifications that aren't known for this protein and push really rare ones out of the running if they're not in the protein entry
}
}
if (rank_sum <= Sweet.lollipop.mod_rank_sum_threshold)
{
PtmSet adjusted_ranksum = new PtmSet(set.ptm_combination);
adjusted_ranksum.ptm_rank_sum = rank_sum;
possible_ptmsets.Add(adjusted_ranksum);
}
}
return(possible_ptmsets);
}
private static PtmSet determine_mod_change(ExperimentalProteoform e, Proteoform p,
TheoreticalProteoform theoretical_base, ProteoformRelation r, PtmSet this_ptmset, int begin, int end)
{
double mass_tolerance = p.modified_mass / 1000000 * Sweet.lollipop.mass_tolerance;
int sign = Math.Sign(e.modified_mass - p.modified_mass);
double deltaM =
Math.Sign(r.peak.DeltaMass) < 0
? r.peak.DeltaMass
: sign * r.peak
.DeltaMass; // give EE relations the correct sign, but don't switch negative ET relation deltaM's
List <PtmSet> possible_additions = r.peak.possiblePeakAssignments
.Where(peak => Math.Abs(peak.mass - deltaM) <= 1)
.ToList(); // EE relations have PtmSets around both positive and negative deltaM, so remove the ones around the opposite of the deltaM of interest
PtmSet best_addition = generate_possible_added_ptmsets(possible_additions,
Sweet.lollipop.theoretical_database.all_mods_with_mass, theoretical_base, begin, end,
this_ptmset, 1, true)
.OrderBy(x =>
(double)x.ptm_rank_sum +
Math.Abs(x.mass - deltaM) *
10E-6) // major score: delta rank; tie breaker: deltaM, where it's always less than 1
.FirstOrDefault();
List <PtmSet> best_losses = new List <PtmSet>();
foreach (PtmSet set in r.peak.possiblePeakAssignments)
//Parallel.ForEach(Sweet.lollipop.theoretical_database.all_possible_ptmsets, set =>
{
bool within_loss_tolerance = deltaM >= -set.mass - mass_tolerance && deltaM <= -set.mass + mass_tolerance;
if (within_loss_tolerance)
{
List <Modification> these_mods = this_ptmset.ptm_combination.Select(ptm => ptm.modification).ToList();
List <Modification> those_mods = set.ptm_combination.Select(ptm => ptm.modification).ToList(); // all must be in the current set to remove them
bool can_be_removed = those_mods.All(m1 => these_mods.Count(m2 =>
UnlocalizedModification.LookUpId(m2) ==
UnlocalizedModification.LookUpId(m1)) >=
those_mods.Count(m2 =>
UnlocalizedModification.LookUpId(m2) ==
UnlocalizedModification.LookUpId(m1)));
lock (best_losses)
{
if (can_be_removed && within_loss_tolerance)
{
best_losses.Add(set);
}
}
}
} //);
PtmSet best_loss = best_losses.OrderBy(s => Math.Abs(deltaM - (-s.mass))).FirstOrDefault();
if (best_addition == null && best_loss == null)
{
return(null);
}
// Make the new ptmset with ptms removed or added
PtmSet with_mod_change = null;
if (best_loss == null)
{
with_mod_change = new PtmSet(new List <Ptm>(this_ptmset.ptm_combination
.Concat(best_addition.ptm_combination).Where(ptm => ptm.modification.MonoisotopicMass != 0)
.ToList()));
}
else
{
List <Ptm> new_combo = new List <Ptm>(this_ptmset.ptm_combination);
foreach (Ptm ptm in best_loss.ptm_combination)
{
new_combo.Remove(new_combo.FirstOrDefault(asdf => UnlocalizedModification.LookUpId(asdf.modification) == UnlocalizedModification.LookUpId(ptm.modification)));
}
with_mod_change = new PtmSet(new_combo);
}
if (r.represented_ptmset == null)
{
r.represented_ptmset = best_loss == null ? best_addition : best_loss;
//if (r.RelationType == ProteoformComparison.ExperimentalExperimental)
//{
// r.DeltaMass *= sign;
//}
}
return(with_mod_change);
}
private void assign_pf_identity(ExperimentalProteoform e, PtmSet set, ProteoformRelation r, TheoreticalProteoform theoretical_base)
{
if (e.linked_proteoform_references == null)
{
e.linked_proteoform_references = new List <Proteoform>(this.linked_proteoform_references);
e.linked_proteoform_references.Add(this);
e.ptm_set = set;
e.begin = this.begin;
e.end = this.end;
List <Ptm> remove = new List <Ptm>();
//do retention of M first
foreach (var mod in set.ptm_combination.Where(m => m.modification.ModificationType == "AminoAcid"))
{
e.begin--;
remove.Add(mod);
}
foreach (var mod in set.ptm_combination.Where(m => m.modification.ModificationType == "Missing"))
{
if (theoretical_base.sequence[this.begin - theoretical_base.begin].ToString() == mod.modification.Target.ToString())
{
e.begin++;
remove.Add(mod); //dont have in ptmset --> change the begin & end
}
else if (theoretical_base.sequence[this.end - this.begin].ToString() == mod.modification.Target.ToString())
{
e.end--;
remove.Add(mod);
}
}
foreach (var ptm in remove)
{
e.ptm_set.ptm_combination.Remove(ptm);
}
e.ptm_set = new PtmSet(e.ptm_set.ptm_combination);
if (e.gene_name == null)
{
e.gene_name = this.gene_name;
}
else if (!e.topdown_id)
{
e.gene_name.gene_names.Concat(this.gene_name.gene_names);
}
}
else
{
//check if assign
int begin = this.begin;
int end = this.end;
PtmSet ptm_set = set;
List <Ptm> remove = new List <Ptm>();
//do retention of M first
foreach (var mod in set.ptm_combination.Where(m => m.modification.ModificationType == "AminoAcid"))
{
begin--;
remove.Add(mod);
}
foreach (var mod in set.ptm_combination.Where(m => m.modification.ModificationType == "Missing"))
{
if (theoretical_base.sequence[this.begin - theoretical_base.begin].ToString() ==
mod.modification.Target.ToString())
{
begin++;
remove.Add(mod); //dont have in ptmset --> change the begin & end
}
else if (theoretical_base.sequence[this.end - this.begin].ToString() ==
mod.modification.Target.ToString())
{
end--;
remove.Add(mod);
}
}
foreach (var ptm in remove)
{
ptm_set.ptm_combination.Remove(ptm);
}
ptm_set = new PtmSet(ptm_set.ptm_combination);
if (e.gene_name.get_prefered_name(Lollipop.preferred_gene_label) !=
this.gene_name.get_prefered_name(Lollipop.preferred_gene_label) ||
e.begin != begin || e.end != end || !e.ptm_set.same_ptmset(ptm_set, true))
{
e.ambiguous = true;
Proteoform linked_proteoform_reference =
this.linked_proteoform_references == null || this.linked_proteoform_references.Count == 0
? this
: this.linked_proteoform_references.First();
Tuple <Proteoform, int, int, PtmSet> new_id =
new Tuple <Proteoform, int, int, PtmSet>(linked_proteoform_reference, begin, end, ptm_set);
lock (e.ambiguous_identifications)
{
if (!e.ambiguous_identifications.Any(p =>
p.Item1.gene_name.get_prefered_name(Lollipop.preferred_gene_label) ==
new_id.Item1.gene_name.get_prefered_name(Lollipop.preferred_gene_label) &&
p.Item2 == new_id.Item2 && p.Item3 == new_id.Item3 &&
p.Item4.same_ptmset(new_id.Item4, true)))
{
e.ambiguous_identifications.Add(new_id);
}
}
}
}
if (this as ExperimentalProteoform != null && (this as ExperimentalProteoform).ambiguous)
{
foreach (var id in this.ambiguous_identifications)
{
TheoreticalProteoform id_theoretical_base = id.Item1 as TheoreticalProteoform;
int begin = id.Item2;
int end = id.Item3;
var remove = new List <Ptm>();
var ptm_set = determine_mod_change(e, this, id_theoretical_base, r, id.Item4);
if (ptm_set == null)
{
continue;
}
//do retention of M first
foreach (var mod in ptm_set.ptm_combination.Where(m => m.modification.ModificationType == "AminoAcid"))
{
begin--;
remove.Add(mod);
}
foreach (var mod in ptm_set.ptm_combination.Where(m => m.modification.ModificationType == "Missing"))
{
if (id_theoretical_base.sequence[id.Item2 - id.Item1.begin].ToString() == mod.modification.Target.ToString())
{
begin++;
remove.Add(mod); //dont have in ptmset --> change the begin & end
}
else if (id_theoretical_base.sequence[id.Item3 - id.Item2].ToString() == mod.modification.Target.ToString())
{
end--;
remove.Add(mod);
}
}
foreach (var ptm in remove)
{
ptm_set.ptm_combination.Remove(ptm);
}
ptm_set = new PtmSet(ptm_set.ptm_combination);
lock (e.ambiguous_identifications)
{
var new_id = new Tuple <Proteoform, int, int, PtmSet>(id.Item1, begin, end, ptm_set);
if ((e.gene_name.get_prefered_name(Lollipop.preferred_gene_label) !=
new_id.Item1.gene_name.get_prefered_name(Lollipop.preferred_gene_label) ||
e.begin != new_id.Item2 || e.end != new_id.Item3 || !e.ptm_set.same_ptmset(new_id.Item4, true)) &&
!e.ambiguous_identifications.Any(p =>
p.Item1.gene_name.get_prefered_name(Lollipop.preferred_gene_label) ==
new_id.Item1.gene_name.get_prefered_name(Lollipop.preferred_gene_label) &&
p.Item2 == new_id.Item2 && p.Item3 == new_id.Item3 &&
p.Item4.same_ptmset(new_id.Item4, true)))
{
e.ambiguous_identifications.Add(new_id);
e.ambiguous = true;
}
}
}
}
e.uniprot_mods = "";
foreach (string mod in e.ptm_set.ptm_combination.Concat(e.ambiguous_identifications.SelectMany(i => i.Item4.ptm_combination)).Where(ptm => ptm.modification.ModificationType != "Deconvolution Error").Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList().Distinct().OrderBy(m => m))
{
// positions with mod
List <int> theo_ptms = theoretical_base.ExpandedProteinList.First()
.OneBasedPossibleLocalizedModifications
.Where(p => p.Key >= e.begin && p.Key <= e.end &&
p.Value.Select(m => UnlocalizedModification.LookUpId(m)).Contains(mod))
.Select(m => m.Key).ToList();
if (theo_ptms.Count > 0)
{
e.uniprot_mods += mod + " @ " + string.Join(", ", theo_ptms) + "; ";
}
if (e.ptm_set.ptm_combination.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count ||
e.ambiguous_identifications.Any(i => i.Item4.ptm_combination.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count))
{
e.novel_mods = true;
}
}
//else if (!e.topdown_id && e.gene_name.get_prefered_name(Lollipop.preferred_gene_label) != this.gene_name.get_prefered_name(Lollipop.preferred_gene_label)
// && e.linked_proteoform_references.Count == this.linked_proteoform_references.Count + 1)
//{
// e.ambiguous = true;
//}
}
public void identify_experimentals()
{
HashSet <ExperimentalProteoform> identified_experimentals = new HashSet <ExperimentalProteoform>();
if (Sweet.lollipop.identify_from_td_nodes)
{
foreach (TopDownProteoform topdown in experimental_proteoforms.Where(e => e.topdown_id))
{
Sweet.lollipop.theoretical_database
.theoreticals_by_accession[Sweet.lollipop.target_proteoform_community.community_number]
.TryGetValue(topdown.accession.Split('_')[0].Split('-')[0], out var t);
if (t != null && t.Count > 0)
{
TheoreticalProteoform theoretical =
new TheoreticalProteoform(topdown.accession, topdown.name, topdown.sequence,
t.First().ExpandedProteinList, topdown.modified_mass, topdown.lysine_count,
topdown.topdown_ptm_set, true, false, null);
theoretical.topdown_theoretical = true;
theoretical.new_topdown_proteoform = true;
theoretical.begin = topdown.topdown_begin;
theoretical.end = topdown.topdown_end;
foreach (ExperimentalProteoform e in topdown.identify_connected_experimentals(theoretical, topdown.topdown_begin, topdown.topdown_end,
new PtmSet(topdown.topdown_ptm_set.ptm_combination), null))
{
identified_experimentals.Add(e);
}
}
}
}
foreach (TheoreticalProteoform t in theoretical_proteoforms.OrderBy(t => t.topdown_theoretical))
{
lock (identified_experimentals)
foreach (ExperimentalProteoform e in t.identify_connected_experimentals(t, t.begin, t.end, t.ptm_set, t.linked_proteoform_references))
{
identified_experimentals.Add(e);
}
}
//Continue looking for new experimental identifications until no more remain to be identified
List <ExperimentalProteoform> newly_identified_experimentals = new List <ExperimentalProteoform>(identified_experimentals).OrderBy(p => p.relationships.Count(r => r.candidate_ptmset != null) > 0 ? p.relationships.Where(r => r.candidate_ptmset != null).Min(r => Math.Abs(r.DeltaMass - r.candidate_ptmset.mass)) : 1e6).ThenBy(p => p.modified_mass).ToList();
int last_identified_count = identified_experimentals.Count - 1;
while (newly_identified_experimentals.Count > 0) //&& identified_experimentals.Count > last_identified_count)
{
last_identified_count = identified_experimentals.Count;
HashSet <ExperimentalProteoform> tmp_new_experimentals = new HashSet <ExperimentalProteoform>();
foreach (ExperimentalProteoform id_experimental in newly_identified_experimentals)
{
{
lock (identified_experimentals) lock (tmp_new_experimentals)
foreach (ExperimentalProteoform new_e in id_experimental.identify_connected_experimentals(id_experimental.linked_proteoform_references.First() as TheoreticalProteoform, id_experimental.begin,
id_experimental.end, id_experimental.ptm_set, id_experimental.linked_proteoform_references))
{
identified_experimentals.Add(new_e);
tmp_new_experimentals.Add(new_e);
}
}
}
newly_identified_experimentals = new List <ExperimentalProteoform>(tmp_new_experimentals);
}
List <string> topdown_ids = Sweet.lollipop.topdown_proteoforms
.Select(p => p.accession.Split('_')[0].Split('-')[0] + "_" + p.sequence + "_" + string.Join(", ", p.topdown_ptm_set.ptm_combination.Where(m => m.modification.ModificationType != "Deconvolution Error").Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).OrderBy(m => m))).ToList();
//determine identified experimentals that are adducts
//checks if any experimentals have same mods as e's ptmset, except e has additional adduct only mods.
Parallel.ForEach(experimental_proteoforms, e =>
{
e.adduct =
e.linked_proteoform_references != null &&
e.ptm_set.ptm_combination.Any(m => Proteoform.modification_is_adduct(m.modification)) &&
experimental_proteoforms.Any(l =>
l.linked_proteoform_references != null &&
l.gene_name.get_prefered_name(Lollipop.preferred_gene_label) == e.gene_name.get_prefered_name(Lollipop.preferred_gene_label) &&
l.ptm_set.ptm_combination.Count < e.ptm_set.ptm_combination.Count &&
e.ptm_set.ptm_combination.Where(m => l.ptm_set.ptm_combination.Count(p => UnlocalizedModification.LookUpId(p.modification) == UnlocalizedModification.LookUpId(m.modification)) != e.ptm_set.ptm_combination.Count(p => UnlocalizedModification.LookUpId(p.modification) == UnlocalizedModification.LookUpId(m.modification)))
.Count(p => !Proteoform.modification_is_adduct(p.modification))
== 0
);
if (e as TopDownProteoform != null)
{
(e as TopDownProteoform).set_correct_id();
}
if (e.linked_proteoform_references != null)
{
var mods = e.ptm_set.ptm_combination.Where(p => !Proteoform.modification_is_adduct(p.modification))
.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList().Distinct().OrderBy(m => m).ToList();
e.uniprot_mods = "";
string add = "";
foreach (string mod in mods)
{
// positions with mod
List <int> theo_ptms = (e.linked_proteoform_references.First() as TheoreticalProteoform).ExpandedProteinList.SelectMany(p => p
.OneBasedPossibleLocalizedModifications)
.Where(p => p.Key >= e.begin && p.Key <= e.end &&
p.Value.Select(m => UnlocalizedModification.LookUpId(m)).Contains(mod))
.Select(m => m.Key).ToList();
if (theo_ptms.Count > 0)
{
add += mod + " @ " + string.Join(", ", theo_ptms) + "; ";
}
if (e.ptm_set.ptm_combination.Where(ptm => ptm.modification.ModificationType != "Deconvolution Error" && !Proteoform.modification_is_adduct(ptm.modification)).Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count)
{
e.novel_mods = true;
}
}
e.uniprot_mods += add;
if (add.Length == 0)
{
e.uniprot_mods += "N/A";
}
foreach (var ambig_id in e.ambiguous_identifications)
{
var ambig_mods = ambig_id.ptm_set.ptm_combination.Where(p => !Proteoform.modification_is_adduct(p.modification))
.Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).ToList().Distinct().OrderBy(m => m).ToList();
e.uniprot_mods += " | ";
add = "";
foreach (var mod in ambig_mods)
{
// positions with mod
List <int> theo_ptms = ambig_id.theoretical_base.ExpandedProteinList.SelectMany(p => p
.OneBasedPossibleLocalizedModifications)
.Where(p => p.Key >= ambig_id.begin && p.Key <= ambig_id.end &&
p.Value.Select(m => UnlocalizedModification.LookUpId(m)).Contains(mod))
.Select(m => m.Key).ToList();
if (theo_ptms.Count > 0)
{
add += mod + " @ " + string.Join(", ", theo_ptms) + "; ";
}
if (ambig_id.ptm_set.ptm_combination.Where(ptm => ptm.modification.ModificationType != "Deconvolution Error" && !Proteoform.modification_is_adduct(ptm.modification)).Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))
.Count(m => m == mod) > theo_ptms.Count)
{
e.novel_mods = true;
}
}
e.uniprot_mods += add;
if (add.Length == 0)
{
e.uniprot_mods += "N/A";
}
}
}
//determine level #
e.proteoform_level_description = "";
if (e.linked_proteoform_references == null)
{
e.proteoform_level = 5;
e.proteoform_level_description = "Unidentified";
}
else if (e.ambiguous_identifications.Count == 0)
{
if (e.ptm_set.ptm_combination.Count == 0)
{
e.proteoform_level = 1;
}
else
{
e.proteoform_level = 2;
e.proteoform_level_description += "PTM localization ambiguity; ";
}
//check if accessions had been grouped in constructing the theoretical database
if ((e.linked_proteoform_references.First() as TheoreticalProteoform).ExpandedProteinList.SelectMany(p => p.AccessionList).Select(a => a.Split('_')[0]).Distinct().Count() > 1)
{
e.proteoform_level += 1;
e.proteoform_level_description += "Gene ambiguity; ";
}
}
else
{
var unique_accessions = new List <string>()
{
e.linked_proteoform_references.First().accession.Split('_')[0].Split('-')[0]
}.Concat(e.ambiguous_identifications.Select(a => a.theoretical_base.accession.Split('_')[0].Split('-')[0])).Distinct();
var unique_sequences = new List <string>()
{
ExperimentalProteoform.get_sequence(e.linked_proteoform_references.First() as TheoreticalProteoform, e.begin, e.end)
}.
Concat(e.ambiguous_identifications.Select(a => ExperimentalProteoform.get_sequence(a.theoretical_base, a.begin, a.end))).Distinct();
var unique_PTMs = new List <string>()
{
string.Join(", ", e.ptm_set.ptm_combination.Where(m => m.modification.ModificationType != "Deconvolution Error").Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).OrderBy(m => m))
}.Concat(e.ambiguous_identifications.Select(a => string.Join(", ", a.ptm_set.ptm_combination.Where(m => m.modification.ModificationType != "Deconvolution Error").Select(ptm => UnlocalizedModification.LookUpId(ptm.modification))))).Distinct();
int gene_ambiguity = unique_accessions.Count() > 1 ? 1 : 0;
//check if accessions had been grouped in constructing the theoretical database
if ((e.linked_proteoform_references.First() as TheoreticalProteoform).ExpandedProteinList.SelectMany(p => p.AccessionList).Select(a => a.Split('_')[0]).Distinct().Count() > 1)
{
gene_ambiguity = 1;
}
int sequence_ambiguity = unique_sequences.Count() > 1 ? 1 : 0;
int PTM_ambiguity = unique_PTMs.Count() > 1 ? 1 : 0;
int PTM_location = e.ptm_set.ptm_combination.Count(m => m.modification.ModificationType != "Deconvolution Error") > 0 || e.ambiguous_identifications.Any(a => a.ptm_set.ptm_combination.Count(m => m.modification.ModificationType != "Deconvolution Error") > 0) ? 1 : 0;
e.proteoform_level = 1 + gene_ambiguity + sequence_ambiguity + PTM_ambiguity + PTM_location;
if (gene_ambiguity > 0)
{
e.proteoform_level_description += "Gene ambiguity; ";
}
if (sequence_ambiguity > 0)
{
e.proteoform_level_description += "Sequence ambiguity; ";
}
if (PTM_ambiguity > 0)
{
e.proteoform_level_description += "PTM identity ambiguity; ";
}
if (PTM_location > 0)
{
e.proteoform_level_description += "PTM localization ambiguity; ";
}
}
if (e.proteoform_level == 1)
{
e.proteoform_level_description = "Unambiguous";
}
//determine if new intact-mass ID
e.new_intact_mass_id = false;
if (!e.topdown_id && e.linked_proteoform_references != null && e.ambiguous_identifications.Count == 0)
{
string this_id = string.Join(",", (e.linked_proteoform_references.First() as TheoreticalProteoform).ExpandedProteinList.SelectMany(p => p.AccessionList.Select(a => a.Split('_')[0])).Distinct()) + "_" + ExperimentalProteoform.get_sequence(e.linked_proteoform_references.First() as TheoreticalProteoform, e.begin, e.end) + "_" + string.Join(", ", e.ptm_set.ptm_combination.Where(m => m.modification.ModificationType != "Deconvolution Error").Select(ptm => UnlocalizedModification.LookUpId(ptm.modification)).OrderBy(m => m));
if (!topdown_ids.Any(t => this_id.Split('_')[0].Split(',').Contains(t.Split('_')[0]) &&
this_id.Split('_')[1] == t.Split('_')[1] && this_id.Split('_')[2] == t.Split('_')[2]))
{
e.new_intact_mass_id = true;
}
}
});
if (Sweet.lollipop.remove_bad_connections)
{
if (theoretical_proteoforms.Count > 0 || (Sweet.lollipop.identify_from_td_nodes && experimental_proteoforms.Count(e => e.topdown_id) > 0))
{
Parallel.ForEach(relations, r =>
{
r.Accepted = r.Identification;
});
}
}
}