/// <summary>
/// returns the desired JSON transcript given an annotated variant, a transcript ID, and an alt allele
/// </summary>
public static IAnnotatedTranscript GetTranscript(IAnnotatedVariant annotatedVariant, string transcriptId, string altAllele, string refAllele = null)
{
foreach (var variant in annotatedVariant.AnnotatedAlternateAlleles)
{
if (altAllele != null && variant.AltAllele != altAllele)
{
continue;
}
if (refAllele != null && variant.RefAllele != refAllele)
{
continue;
}
foreach (var transcript in
variant.EnsemblTranscripts.Where(
transcript => FormatUtilities.SplitVersion(transcript.TranscriptID).Item1 == transcriptId))
{
return(transcript);
}
foreach (var transcript in
variant.RefSeqTranscripts.Where(
transcript => FormatUtilities.SplitVersion(transcript.TranscriptID).Item1 == transcriptId))
{
return(transcript);
}
}
return(null);
}
private void AddSmallAnnotations(IAnnotatedVariant annotatedVariant)
{
foreach (INsaReader nsaReader in _nsaReaders)
{
var variant = annotatedVariant.Variant;
var annotations = nsaReader.GetAnnotation(variant.Start);
if (annotations == null)
{
continue;
}
if (nsaReader.IsPositional)
{
AddPositionalAnnotation(annotations, annotatedVariant, nsaReader);
continue;
}
if (nsaReader.MatchByAllele)
{
AddAlleleSpecificAnnotation(nsaReader, annotations, annotatedVariant, variant);
}
else
{
AddNonAlleleSpecificAnnotations(annotations, variant, annotatedVariant, nsaReader);
}
}
}
private static string ExtractDbId(IAnnotatedVariant annotatedVariant, string idField)
{
var dbSnp = new VcfField();
var nonDbsnpIds = GetNonDbsnpIds(idField);
if (nonDbsnpIds != null)
{
foreach (var nonDbsnpId in nonDbsnpIds)
{
dbSnp.Add(nonDbsnpId);
}
}
foreach (var altAllele in annotatedVariant.AnnotatedAlternateAlleles)
{
if (altAllele.DbSnpIds == null)
{
continue;
}
foreach (var id in altAllele.DbSnpIds)
{
dbSnp.Add(id);
}
}
return(dbSnp.GetString(""));
}
internal static string GetAllele(IAnnotatedVariant annotatedVariant, int alleleIndex = 0)
{
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.ElementAt(alleleIndex);
Assert.NotNull(altAllele);
return(altAllele.ToString());
}
internal static string GetSampleJson(IAnnotatedVariant annotatedVariant, int sampleIndex)
{
var sample = annotatedVariant.AnnotatedSamples.ElementAt(sampleIndex);
Assert.NotNull(sample);
return(sample.ToString());
}
private void WriteJson(IAnnotatedVariant annotatedVariant, IAnnotatedAlternateAllele firstAllele,
UnifiedJsonWriter writer)
{
if (firstAllele.IsReference && !firstAllele.IsReferenceMinor && !firstAllele.IsReferenceNoCall)
{
return;
}
writer.Write(annotatedVariant.ToString());
}
private void AddRegulatoryRegion(IAnnotatedVariant annotatedVariant)
{
var regulatoryRegion = new RegulatoryRegion(_chromosome, 103, 104, CompactId.Convert("7157"),
RegulatoryRegionType.TF_binding_site);
var consequences = new List <ConsequenceTag> {
ConsequenceTag.regulatory_region_amplification
};
annotatedVariant.RegulatoryRegions.Add(new AnnotatedRegulatoryRegion(regulatoryRegion, consequences));
}
private static void AddTranscript(IAnnotatedVariant annotatedVariant)
{
var annotatedTranscript = new Mock <IAnnotatedTranscript>();
annotatedTranscript.SetupGet(x => x.Transcript.Id).Returns(CompactId.Convert("ENST00000540021"));
annotatedTranscript.SetupGet(x => x.Transcript.Start).Returns(966300);
annotatedTranscript.SetupGet(x => x.Transcript.End).Returns(966405);
annotatedTranscript.SetupGet(x => x.AlternateCodons).Returns("cAt/cGt");
annotatedVariant.EnsemblTranscripts.Add(annotatedTranscript.Object);
}
/// <summary>
/// returns the desired JSON transcript given an annotated variant, a transcript ID, and an alt allele
/// </summary>
private static IRegulatoryRegion GetRegulatoryRegion(IAnnotatedVariant annotatedVariant, string regulatoryRegionId)
{
// ReSharper disable once LoopCanBeConvertedToQuery
foreach (var variant in annotatedVariant.AnnotatedAlternateAlleles)
{
foreach (var regulatoryRegion in variant.RegulatoryRegions.Where(r => r.ID == regulatoryRegionId))
{
return(regulatoryRegion);
}
}
return(null);
}
private static void AddSupplementaryAnnotation(IAnnotatedVariant annotatedVariant)
{
var dataSource = new SaDataSource("clinVar", "clinVar", "C", true, false, null,
new[] { "\"good\":\"result\"" });
var annotatedSaDataSource = new AnnotatedSaDataSource(dataSource, "C");
var dataSource2 = new SaDataSource("exac", "exac", "G", true, true, null,
new[] { "\"bad\":\"temper\"", "\"brutal\":\"kangaroo\"" });
var annotatedSaDataSource2 = new AnnotatedSaDataSource(dataSource2, "G");
annotatedVariant.SupplementaryAnnotations.Add(annotatedSaDataSource);
annotatedVariant.SupplementaryAnnotations.Add(annotatedSaDataSource2);
}
private static void AddSaPositon(ISaPosition saPosition, IAnnotatedVariant annotatedVariant)
{
foreach (var dataSource in saPosition.DataSources)
{
var saAltAllele = SaReaderUtils.GetReducedAllele(annotatedVariant.Variant.RefAllele,
annotatedVariant.Variant.AltAllele);
if (dataSource.MatchByAllele && dataSource.AltAllele != saAltAllele)
{
continue;
}
annotatedVariant.SupplementaryAnnotations.Add(new AnnotatedSaDataSource(dataSource, saAltAllele));
}
}
internal static IAnnotatedVariant[] GetAnnotatedVariants(IVariant[] variants)
{
if (variants?[0].Behavior == null)
{
return(null);
}
var numVariants = variants.Length;
var annotatedVariants = new IAnnotatedVariant[numVariants];
for (var i = 0; i < numVariants; i++)
{
annotatedVariants[i] = new AnnotatedVariant(variants[i]);
}
return(annotatedVariants);
}
private void AddInfoField(string infoField, IAnnotatedVariant annotatedVariant, StringBuilder sb)
{
var infoEntries = new VcfField();
if (!string.IsNullOrEmpty(infoField))
{
infoEntries.Add(infoField);
}
ExtractInfo(annotatedVariant as UnifiedJson, infoEntries);
infoField = infoEntries.GetString("");
// remove .
if (infoField == ".")
{
infoField = "";
}
sb.Append(infoField);
var csqs = new List <CsqEntry>();
ExtractCsqs(annotatedVariant as UnifiedJson, csqs);
if (csqs.Count != 0)
{
if (infoField.Length > 0)
{
sb.Append(";");
}
}
// append CSQ tags using delegate from annotator
sb.Append(GetCsqtAndCsqrVcfInfo(csqs));
if (csqs.Count == 0 && infoField.Length == 0)
{
sb.Append(".");
}
}
public string Convert(IVariant vcfVariant, IAnnotatedVariant annotatedVariant)
{
_sb.Clear();
var fields = vcfVariant.Fields;
// add all of the fields before the info field
for (var vcfIndex = 0; vcfIndex < VcfCommon.IdIndex; vcfIndex++)
{
_sb.Append(fields[vcfIndex]);
_sb.Append('\t');
}
// add dbSNP id
var dbSnpId = ExtractDbId(annotatedVariant, fields[VcfCommon.IdIndex]);
_sb.Append(dbSnpId);
_sb.Append('\t');
for (var vcfIndex = VcfCommon.IdIndex + 1; vcfIndex < VcfCommon.InfoIndex; vcfIndex++)
{
_sb.Append(fields[vcfIndex]);
_sb.Append('\t');
}
var infoField = (annotatedVariant as UnifiedJson)?.InfoFromVcf;
AddInfoField(infoField, annotatedVariant, _sb);
// add all of the fields after the info field
var numColumns = fields.Length;
for (var vcfIndex = VcfCommon.InfoIndex + 1; vcfIndex < numColumns; vcfIndex++)
{
_sb.Append('\t');
_sb.Append(fields[vcfIndex]);
}
return(_sb.ToString());
}
public void AnnotateVariant(IVariantFeature variant, List <Transcript> transcripts,
IAnnotatedVariant annotatedVariant, ICompressedSequence sequence)
{
if (variant.IsStructuralVariant)
{
return;
}
CreateTranscriptDictionary(transcripts);
foreach (var altAllele in annotatedVariant.AnnotatedAlternateAlleles)
{
foreach (var transcript in altAllele.EnsemblTranscripts)
{
var lofteeOut = LofteeAnalysis(transcript, altAllele, sequence);
if (lofteeOut != null)
{
if (transcript.AdditionalInfo == null)
{
transcript.AdditionalInfo = new Dictionary <string, string>();
}
transcript.AdditionalInfo["loftee"] = lofteeOut;
}
}
foreach (var transcript in altAllele.RefSeqTranscripts)
{
var lofteeOut = LofteeAnalysis(transcript, altAllele, sequence);
if (lofteeOut != null)
{
if (transcript.AdditionalInfo == null)
{
transcript.AdditionalInfo = new Dictionary <string, string>();
}
transcript.AdditionalInfo["loftee"] = lofteeOut;
}
}
}
}
private void WriteOutput(string vcfOutput, IAnnotatedVariant annotatedVariant, LiteVcfWriter vcfWriter,
LiteVcfWriter gvcfWriter, UnifiedJsonWriter jsonWriter)
{
if (ConfigurationSettings.Gvcf)
{
WriteGvcf(vcfOutput, gvcfWriter);
}
if (annotatedVariant?.AnnotatedAlternateAlleles == null ||
annotatedVariant.AnnotatedAlternateAlleles.Count == 0)
{
return;
}
var firstAllele = annotatedVariant.AnnotatedAlternateAlleles[0];
WriteJson(annotatedVariant, firstAllele, jsonWriter);
if (ConfigurationSettings.Vcf)
{
WriteVcf(vcfOutput, firstAllele, vcfWriter);
}
}
// ReSharper disable once UnusedParameter.Global
internal static void AlleleContains(IAnnotatedVariant annotatedVariant, string expected, int alleleIndex = 0)
{
var observed = GetAllele(annotatedVariant, alleleIndex);
Assert.Contains(expected, observed);
}
/// <summary> /// returns the first alternate allele in JSON representation /// </summary> internal static string GetFirstAlleleJson(IAnnotatedVariant annotatedVariant) => annotatedVariant.AnnotatedAlternateAlleles.FirstOrDefault()?.ToString();
public void Write(IVariant vcfVariant, IAnnotatedVariant annotatedVariant)
{
_writer.WriteLine(_conversion.Convert(vcfVariant, annotatedVariant));
}
private string GetVcfString(IVariant variant, IAnnotatedVariant annotatedVariant)
{
return(ConfigurationSettings.Vcf || ConfigurationSettings.Gvcf
? _conversion.Convert(variant, annotatedVariant)
: null);
}
// ReSharper disable once UnusedParameter.Global
public static void CheckSampleCount(int expectedCount, IAnnotatedVariant annotatedVariant)
{
var observedCount = annotatedVariant.AnnotatedSamples.Count();
Assert.Equal(expectedCount, observedCount);
}
// ReSharper disable once UnusedParameter.Global
public static void CheckJsonDoesNotContain(string expectedString, IAnnotatedVariant annotatedVariant)
{
var json = annotatedVariant.ToString();
Assert.DoesNotContain(expectedString, json);
}
// ReSharper disable once UnusedParameter.Global
public static void CheckIntervalCount(int expectedCount, IAnnotatedVariant annotatedVariant)
{
var observedCount = annotatedVariant.SupplementaryIntervals.Count();
Assert.Equal(expectedCount, observedCount);
}
// ReSharper disable once UnusedParameter.Global
public static void CheckAlleleCount(int expectedCount, IAnnotatedVariant annotatedVariant)
{
var observedCount = annotatedVariant.AnnotatedAlternateAlleles.Count;
Assert.Equal(expectedCount, observedCount);
}
private static bool IsStructVariant(IAnnotatedVariant annotatedVariant) => annotatedVariant.Variant.Behavior.StructuralVariantConsequence;