private static void Main(string[] args)
{
Console.WriteLine("Welcome to TransferModifications!");
var p = new FluentCommandLineParser <ApplicationArguments>();
p.Setup(arg => arg.UniProtXml)
.As('x', "uniprot_xml")
.Required()
.WithDescription("UniProt protein XML file.");
p.Setup(arg => arg.SpritzXml)
.As('y', "spritz_xml")
.WithDescription("Custom protein XML file, e.g. from Spritz.");
p.Setup(arg => arg.FusionCodingEffects)
.As('f', "fusion_coding_effect")
.WithDescription("Coding effects from STAR-Fusion, comma separated");
p.SetupHelp("h", "help")
.Callback(text => Console.WriteLine(text));
var result = p.Parse(args);
TransferModifications(p.Object.UniProtXml, p.Object.SpritzXml ?? ProteinAnnotation.ParseCodingEffectsToXml(p.Object.FusionCodingEffects));
DatabaseSummary(p.Object.UniProtXml, p.Object.SpritzXml);
}
private static void Main(string[] args)
{
Console.WriteLine("Welcome to TransferModifications!");
var p = new FluentCommandLineParser <ApplicationArguments>();
p.Setup(arg => arg.UniProtXml)
.As('x', "uniprot_xml")
.WithDescription("UniProt protein XML file.");
p.Setup(arg => arg.SpritzXml)
.As('y', "spritz_xml")
.WithDescription("Custom protein XML file, e.g. from Spritz.");
p.Setup(arg => arg.FusionCodingEffects)
.As('f', "fusion_coding_effect")
.WithDescription("Coding effects from STAR-Fusion, comma separated");
p.Setup(arg => arg.SpritzModXml)
.As('z', "spritz_mod_xml")
.WithDescription("Custom protein XML withmods file, e.g. from Spritz.");
p.Setup(arg => arg.Setup)
.As('s', "setup")
.WithDescription("Perform setup for machines without internet connection.");
p.SetupHelp("h", "help")
.Callback(text => Console.WriteLine(text));
var result = p.Parse(args);
if (p.Object.Setup)
{
Console.WriteLine("Downloading files for TransferUniProtModifications.");
var uniprotPtms = ProteinAnnotation.GetUniProtMods(Environment.CurrentDirectory);
return;
}
Console.WriteLine($"Analyzing UniProt database {p.Object.UniProtXml} and {p.Object.SpritzXml ?? p.Object.SpritzModXml ?? p.Object.FusionCodingEffects}");
if (p.Object.SpritzModXml == null)
{
TransferModifications(p.Object.UniProtXml, p.Object.SpritzXml ?? ProteinAnnotation.ParseCodingEffectsToXml(p.Object.FusionCodingEffects));
}
DatabaseSummary(p.Object.UniProtXml, Path.Combine(Path.GetDirectoryName(p.Object.SpritzXml), Path.GetFileNameWithoutExtension(p.Object.SpritzXml) + ".withmods.xml"),
Path.Combine(Path.GetDirectoryName(p.Object.SpritzXml), Path.GetFileNameWithoutExtension(p.Object.SpritzXml) + ".accname.tsv"),
Path.Combine(Path.GetDirectoryName(p.Object.SpritzXml), Path.GetFileNameWithoutExtension(p.Object.SpritzXml) + ".vardesc.tsv"), true);
DatabaseSummary(p.Object.UniProtXml, Path.Combine(Path.GetDirectoryName(p.Object.SpritzXml), Path.GetFileNameWithoutExtension(p.Object.SpritzXml) + ".withmods.xml"),
Path.Combine(Path.GetDirectoryName(p.Object.SpritzXml), Path.GetFileNameWithoutExtension(p.Object.SpritzXml) + ".accname.decoy.tsv"),
Path.Combine(Path.GetDirectoryName(p.Object.SpritzXml), Path.GetFileNameWithoutExtension(p.Object.SpritzXml) + ".vardesc.decoy.tsv"), false);
}
public static string TransferModifications(string sourceXmlPath, string destinationXmlPath)
{
var uniprotPtms = ProteinAnnotation.GetUniProtMods(Environment.CurrentDirectory);
var uniprot = ProteinDbLoader.LoadProteinXML(sourceXmlPath, true, DecoyType.None, uniprotPtms, false, null, out var un);
string outxml = Path.Combine(Path.GetDirectoryName(destinationXmlPath), Path.GetFileNameWithoutExtension(destinationXmlPath) + ".withmods.xml");
var nonVariantProts = ProteinDbLoader.LoadProteinXML(destinationXmlPath, true, DecoyType.None, uniprotPtms, false, null, out un).Select(p => p.NonVariantProtein).Distinct();
var newProts = ProteinAnnotation.CombineAndAnnotateProteins(uniprot, nonVariantProts.ToList());
ProteinDbWriter.WriteXmlDatabase(null, newProts, outxml);
string outfasta = Path.Combine(Path.GetDirectoryName(destinationXmlPath), Path.GetFileNameWithoutExtension(destinationXmlPath) + ".fasta");
var prot = newProts.FirstOrDefault(p => p.Accession.Contains("_"));
ProteinDbWriter.WriteFastaDatabase(newProts.SelectMany(p => p.GetVariantProteins()).ToList(), outfasta, "|");
return(outxml);
}
public static string TransferModifications(string sourceXmlPath, string destinationXmlPath)
{
var uniprotPtms = ProteinAnnotation.GetUniProtMods(Environment.CurrentDirectory);
var uniprot = ProteinDbLoader.LoadProteinXML(sourceXmlPath, true, DecoyType.None, uniprotPtms, false, null, out var un);
string outxml = Path.Combine(Path.GetDirectoryName(destinationXmlPath), Path.GetFileNameWithoutExtension(destinationXmlPath) + ".withmods.xml");
var nonVariantProts = destinationXmlPath.EndsWith(".xml") | destinationXmlPath.EndsWith(".xml.gz") ?
ProteinDbLoader.LoadProteinXML(destinationXmlPath, true, DecoyType.None, uniprotPtms, false, null, out un).Select(p => p.NonVariantProtein).Distinct() :
ProteinDbLoader.LoadProteinFasta(destinationXmlPath, true, DecoyType.None, false, ProteinDbLoader.UniprotAccessionRegex, PgmNameRegex, PgmNameRegex, ProteinDbLoader.UniprotGeneNameRegex, ProteinDbLoader.UniprotOrganismRegex, out var un2).Select(p => p.NonVariantProtein).Distinct();
var newProts = ProteinAnnotation.CombineAndAnnotateProteins(uniprot, nonVariantProts.ToList());
ProteinDbWriter.WriteXmlDatabase(null, newProts, outxml);
string outfasta = Path.Combine(Path.GetDirectoryName(destinationXmlPath), Path.GetFileNameWithoutExtension(destinationXmlPath) + ".fasta");
string outfastaWithDecoys = Path.Combine(Path.GetDirectoryName(destinationXmlPath), Path.GetFileNameWithoutExtension(destinationXmlPath) + ".withdecoys.fasta");
var prot = newProts.FirstOrDefault(p => p.Accession.Contains("_"));
var protsForFasta = newProts.SelectMany(p => p.GetVariantProteins()).Where(p => !p.BaseSequence.EndsWith('?')).ToList();
var decoyProtsForFasta = ProteinDbLoader.LoadProteinXML(destinationXmlPath, true, DecoyType.Reverse, uniprotPtms, false, null, out un).Where(p => !p.BaseSequence.EndsWith('?')).ToList();
ProteinDbWriter.WriteFastaDatabase(protsForFasta, outfasta, "|");
ProteinDbWriter.WriteFastaDatabase(decoyProtsForFasta, outfastaWithDecoys, "|");
File.WriteAllLines(outfastaWithDecoys, File.ReadAllLines(outfastaWithDecoys).Select(line => line.Replace("mz|DECOY_", "rev_mz|")));
return(outxml);
}
public static void DatabaseSummary(string sourceXmlPath, string destinationXmlPath)
{
var culture = CultureInfo.CurrentCulture;
var uniprotPtms = ProteinAnnotation.GetUniProtMods(Environment.CurrentDirectory);
var uniprot = ProteinDbLoader.LoadProteinXML(sourceXmlPath, true, DecoyType.None, uniprotPtms, false, null, out var un);
var spritz = ProteinDbLoader.LoadProteinXML(destinationXmlPath, true, DecoyType.None, uniprotPtms, false, null, out un);
var spritzCanonical = spritz.Select(p => p.NonVariantProtein).Distinct().ToList();
int numberOfCanonicalProteinEntries = spritzCanonical.Count;
int numberOfVariantProteinEntries = spritz.Count - spritzCanonical.Count;
int synonymousCount = 0;
int totalVariants = 0;
int missenseSnvCount = 0;
int missenseMnvCount = 0;
int insertionCount = 0;
int deletionCount = 0;
int frameshiftCount = 0;
int stopGainCount = 0;
int stopLossCount = 0;
Dictionary <string, List <SequenceVariation> > allVariants = new Dictionary <string, List <SequenceVariation> >();
foreach (var spritzEntry in spritz)
{
if (spritzEntry.AppliedSequenceVariations.Count != 0)
{
if (allVariants.ContainsKey(spritzEntry.NonVariantProtein.Accession))
{
foreach (var variant in spritzEntry.AppliedSequenceVariations)
{
if (!allVariants[spritzEntry.NonVariantProtein.Accession].Contains(variant))
{
allVariants[spritzEntry.NonVariantProtein.Accession].Add(variant);
}
}
}
else
{
allVariants.Add(spritzEntry.NonVariantProtein.Accession, spritzEntry.AppliedSequenceVariations);
}
}
}
foreach (var entry in allVariants)
{
foreach (var variant in entry.Value)
{
if (culture.CompareInfo.IndexOf(variant.Description.Description, "synonymous_variant", CompareOptions.IgnoreCase) >= 0)
{
synonymousCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "missense_variant", CompareOptions.IgnoreCase) >= 0 &&
variant.Description.ReferenceAlleleString.Length == 1 && variant.Description.AlternateAlleleString.Length == 1)
{
missenseSnvCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "missense_variant", CompareOptions.IgnoreCase) >= 0)
{
missenseMnvCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "frameshift_variant", CompareOptions.IgnoreCase) >= 0)
{
frameshiftCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "stop_gained", CompareOptions.IgnoreCase) >= 0)
{
stopGainCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "conservative_inframe_insertion", CompareOptions.IgnoreCase) >= 0 || culture.CompareInfo.IndexOf(variant.Description.Description, "disruptive_inframe_insertion", CompareOptions.IgnoreCase) >= 0)
{
insertionCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "conservative_inframe_deletion", CompareOptions.IgnoreCase) >= 0 || culture.CompareInfo.IndexOf(variant.Description.Description, "disruptive_inframe_deletion", CompareOptions.IgnoreCase) >= 0)
{
deletionCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "stop_loss", CompareOptions.IgnoreCase) >= 0)
{
stopLossCount++;
totalVariants++;
}
}
}
Console.WriteLine($"Spritz Database Summary");
Console.WriteLine($"--------------------------------------------------------------");
Console.WriteLine($"{numberOfCanonicalProteinEntries}\tTotal number of canonical protein entries (before applying variations)");
Console.WriteLine($"{spritz.Count}\tTotal number of protein entries");
Console.WriteLine($"{numberOfVariantProteinEntries}\tTotal number of variant containing protein entries");
Console.WriteLine($"{totalVariants}\tTotal number of unique variants");
Console.WriteLine($"{synonymousCount}\tTotal number of unique synonymous variants");
Console.WriteLine($"{(totalVariants - synonymousCount)}\tTotal number of unique nonsynonymous variants");
Console.WriteLine($"{missenseSnvCount}\tNumber of unique SNV missense variants");
Console.WriteLine($"{missenseMnvCount}\tNumber of unique MNV missense variants");
Console.WriteLine($"{frameshiftCount}\tNumber of unique frameshift variants");
Console.WriteLine($"{insertionCount}\tNumber of unique insertion variants");
Console.WriteLine($"{deletionCount}\tNumber of unique deletion variants");
Console.WriteLine($"{stopGainCount}\tNumber of unique stop gain variants");
Console.WriteLine($"{stopLossCount}\tNumber of unique stop loss variants");
}
public static void DatabaseSummary(string sourceXmlPath, string destinationXmlPath, string destinationAccessionToNameTable, string variantDescriptionTable, bool target)
{
var culture = CultureInfo.CurrentCulture;
var uniprotPtms = ProteinAnnotation.GetUniProtMods(Environment.CurrentDirectory);
var uniprot = ProteinDbLoader.LoadProteinXML(sourceXmlPath, true, target ? DecoyType.None : DecoyType.Reverse, uniprotPtms, false, null, out var un);
var spritz = ProteinDbLoader.LoadProteinXML(destinationXmlPath, true, target ? DecoyType.None : DecoyType.Reverse, uniprotPtms, false, null, out un);
var spritzCanonical = spritz.Select(p => p.NonVariantProtein).Distinct().ToList();
int numberOfCanonicalProteinEntries = spritzCanonical.Count;
int numberOfVariantProteinEntries = spritz.Count - spritzCanonical.Count;
int synonymousCount = 0;
int totalVariants = 0;
int missenseSnvCount = 0;
int missenseMnvCount = 0;
int insertionCount = 0;
int deletionCount = 0;
int frameshiftCount = 0;
int stopGainCount = 0;
int stopLossCount = 0;
List <string> accessionNameList = new List <string>();
List <string> variantDescList = new List <string>();
List <string> accessionSequenceList = new List <string>();
Dictionary <string, List <SequenceVariation> > allVariants = new Dictionary <string, List <SequenceVariation> >();
foreach (var spritzEntry in spritz)
{
if (spritzEntry.AppliedSequenceVariations.Count != 0)
{
// Make pivot tables
accessionNameList.Add($"{spritzEntry.Accession}\t{spritzEntry.FullName}\t{spritzEntry.BaseSequence}");
foreach (SequenceVariation variant in spritzEntry.AppliedSequenceVariations)
{
variantDescList.Add($"{spritzEntry.Accession}\t{variant.SimpleString()}\t{variant.Description}");
}
if (allVariants.ContainsKey(spritzEntry.NonVariantProtein.Accession))
{
foreach (SequenceVariation variant in spritzEntry.AppliedSequenceVariations)
{
if (!allVariants[spritzEntry.NonVariantProtein.Accession].Contains(variant))
{
allVariants[spritzEntry.NonVariantProtein.Accession].Add(variant);
}
}
}
else
{
allVariants.Add(spritzEntry.NonVariantProtein.Accession, spritzEntry.AppliedSequenceVariations);
}
}
}
File.WriteAllLines(destinationAccessionToNameTable, accessionNameList);
File.WriteAllLines(variantDescriptionTable, variantDescList);
foreach (var entry in allVariants)
{
foreach (var variant in entry.Value)
{
variantDescList.Add($"{entry.Key}\t{variant.SimpleString()}\t{variant.Description}");
if (culture.CompareInfo.IndexOf(variant.Description.Description, "synonymous_variant", CompareOptions.IgnoreCase) >= 0)
{
synonymousCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "missense_variant", CompareOptions.IgnoreCase) >= 0 &&
variant.Description.ReferenceAlleleString.Length == 1 && variant.Description.AlternateAlleleString.Length == 1)
{
missenseSnvCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "missense_variant", CompareOptions.IgnoreCase) >= 0)
{
missenseMnvCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "frameshift_variant", CompareOptions.IgnoreCase) >= 0)
{
frameshiftCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "stop_gained", CompareOptions.IgnoreCase) >= 0)
{
stopGainCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "conservative_inframe_insertion", CompareOptions.IgnoreCase) >= 0 || culture.CompareInfo.IndexOf(variant.Description.Description, "disruptive_inframe_insertion", CompareOptions.IgnoreCase) >= 0)
{
insertionCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "conservative_inframe_deletion", CompareOptions.IgnoreCase) >= 0 || culture.CompareInfo.IndexOf(variant.Description.Description, "disruptive_inframe_deletion", CompareOptions.IgnoreCase) >= 0)
{
deletionCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "stop_lost", CompareOptions.IgnoreCase) >= 0)
{
stopLossCount++;
totalVariants++;
}
}
}
Console.WriteLine($"Spritz Database Summary");
Console.WriteLine($"--------------------------------------------------------------");
Console.WriteLine($"{numberOfCanonicalProteinEntries}\tTotal number of canonical protein entries (before applying variations)");
Console.WriteLine($"{spritz.Count}\tTotal number of protein entries");
Console.WriteLine($"{spritzCanonical.Sum(p => p.OneBasedPossibleLocalizedModifications.Values.Sum(b => b.Count))}\tTotal modifications appended from UniProt out of {uniprot.Sum(p => p.OneBasedPossibleLocalizedModifications.Values.Sum(b => b.Count))}");
Console.WriteLine($"{numberOfVariantProteinEntries}\tTotal number of variant containing protein entries");
Console.WriteLine($"{totalVariants}\tTotal number of unique variants");
Console.WriteLine($"{synonymousCount}\tTotal number of unique synonymous variants");
Console.WriteLine($"{(totalVariants - synonymousCount)}\tTotal number of unique nonsynonymous variants");
Console.WriteLine($"{missenseSnvCount}\tNumber of unique SNV missense variants");
Console.WriteLine($"{missenseMnvCount}\tNumber of unique MNV missense variants");
Console.WriteLine($"{frameshiftCount}\tNumber of unique frameshift variants");
Console.WriteLine($"{insertionCount}\tNumber of unique insertion variants");
Console.WriteLine($"{deletionCount}\tNumber of unique deletion variants");
Console.WriteLine($"{stopGainCount}\tNumber of unique stop gain variants");
Console.WriteLine($"{stopLossCount}\tNumber of unique stop loss variants");
}
public static void DatabaseSummary(string sourceXmlPath, string destinationXmlPath)
{
var culture = CultureInfo.CurrentCulture;
var uniprotPtms = ProteinAnnotation.GetUniProtMods(Environment.CurrentDirectory);
var uniprot = ProteinDbLoader.LoadProteinXML(sourceXmlPath, true, DecoyType.None, uniprotPtms, false, null, out var un);
var spritz = ProteinDbLoader.LoadProteinXML(destinationXmlPath, true, DecoyType.None, uniprotPtms, false, null, out un);
var spritzCanonical = spritz.Select(p => p.NonVariantProtein).Distinct().ToList();
int numberOfCanonicalProteinEntries = spritzCanonical.Count;
int numberOfVariantProteinEntries = spritz.Count - spritzCanonical.Count;
int synonymousCount = 0;
int totalVariants = 0;
int missenseCount = 0;
int insertionCount = 0;
int deletionCount = 0;
int frameshiftCount = 0;
int stopGainCount = 0;
int stopLossCount = 0;
Dictionary <string, List <SequenceVariation> > allVariants = new Dictionary <string, List <SequenceVariation> >();
foreach (var spritzEntry in spritz)
{
if (spritzEntry.AppliedSequenceVariations.Count != 0)
{
if (allVariants.ContainsKey(spritzEntry.NonVariantProtein.Accession))
{
foreach (var variant in spritzEntry.AppliedSequenceVariations)
{
if (!allVariants[spritzEntry.NonVariantProtein.Accession].Contains(variant))
{
allVariants[spritzEntry.NonVariantProtein.Accession].Add(variant);
}
}
}
else
{
allVariants.Add(spritzEntry.NonVariantProtein.Accession, spritzEntry.AppliedSequenceVariations);
}
}
}
foreach (var entry in allVariants)
{
foreach (var variant in entry.Value)
{
if (culture.CompareInfo.IndexOf(variant.Description.Description, "synonymous_variant", CompareOptions.IgnoreCase) >= 0)
{
synonymousCount++;
totalVariants++;
}
if (culture.CompareInfo.IndexOf(variant.Description.Description, "missense_variant", CompareOptions.IgnoreCase) >= 0)
{
missenseCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "frameshift_variant", CompareOptions.IgnoreCase) >= 0)
{
frameshiftCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "stop_gained", CompareOptions.IgnoreCase) >= 0)
{
stopGainCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "conservative_inframe_insertion", CompareOptions.IgnoreCase) >= 0 || culture.CompareInfo.IndexOf(variant.Description.Description, "disruptive_inframe_insertion", CompareOptions.IgnoreCase) >= 0)
{
insertionCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "conservative_inframe_deletion", CompareOptions.IgnoreCase) >= 0 || culture.CompareInfo.IndexOf(variant.Description.Description, "disruptive_inframe_deletion", CompareOptions.IgnoreCase) >= 0)
{
deletionCount++;
totalVariants++;
}
else if (culture.CompareInfo.IndexOf(variant.Description.Description, "stop_loss", CompareOptions.IgnoreCase) >= 0)
{
stopLossCount++;
totalVariants++;
}
}
}
string[] summary = new string[20];
summary[0] = $"Spritz Database Summary";
summary[1] = $"--------------------------------------------------------------";
summary[2] = $"Total number of protein entries in the database: {spritz.Count}";
summary[3] = $"Total number of canonical protein entries in the database: {numberOfCanonicalProteinEntries}";
summary[4] = $"Total number of variant containing protein entries in the database: {numberOfVariantProteinEntries}";
summary[5] = $" Total number of unique variants in the database: {totalVariants}";
summary[6] = $" Total number of unique synonymous variants in the database: {synonymousCount}";
summary[7] = $" Total number of unique nonsynonymous variants in the database: {(totalVariants - synonymousCount)}";
summary[8] = $" Number of unique missense variants in the database: {missenseCount}";
summary[9] = $" Number of unique frameshift variants in the database: {frameshiftCount}";
summary[10] = $" Number of unique insertion variants in the database: {insertionCount}";
summary[11] = $" Number of unique deletion variants in the database: {deletionCount}";
summary[12] = $" Number of unique stop gain variants in the database: {stopGainCount}";
summary[13] = $" Number of unique stop loss variants in the database: {stopLossCount}";
File.WriteAllLines(Path.Combine(Path.GetDirectoryName(destinationXmlPath), "SpritzDatabaseSummary.txt"), summary);
}