package jalview.datamodel; import jalview.io.gff.Gff3Helper; import jalview.schemes.ResidueProperties; import jalview.util.MappingUtils; import jalview.util.StringUtils; import java.util.HashSet; import java.util.List; import java.util.Set; /** * A data bean to hold a list of mapped sequence features (e.g. CDS features * mapped from protein), and the mapping between the sequences. It also provides * a method to derive peptide variants from codon variants. * * @author gmcarstairs */ public class MappedFeatures { private static final String HGV_SP = "HGVSp"; private static final String CSQ = "CSQ"; /* * the mapping from one sequence to another */ public final Mapping mapping; /** * the sequence mapped from */ public final SequenceI fromSeq; /* * features on the sequence mapped to that overlap the mapped positions */ public final List features; /* * the residue position in the sequence mapped to */ private final int toPosition; /* * the residue at toPosition */ private final char toResidue; /* * if the mapping is 3:1 or 1:3 (peptide to CDS), this holds the * mapped positions i.e. codon base positions in CDS; to * support calculation of peptide variants from alleles */ private final int[] codonPos; private final char[] baseCodon; /** * Constructor * * @param theMapping * @param from * the sequence mapped from (e.g. CDS) * @param pos * the residue position in the sequence mapped to * @param res * the residue character at position pos * @param theFeatures * list of mapped features found in the 'from' sequence at * the mapped position(s) */ public MappedFeatures(Mapping theMapping, SequenceI from, int pos, char res, List theFeatures) { mapping = theMapping; fromSeq = from; toPosition = pos; toResidue = res; features = theFeatures; /* * determine codon positions and canonical codon * for a peptide-to-CDS mapping */ int[] codonIntervals = mapping.getMap().locateInFrom(toPosition, toPosition); int[] codonPositions = codonIntervals == null ? null : MappingUtils.flattenRanges(codonIntervals); if (codonPositions != null && codonPositions.length == 3) { codonPos = codonPositions; baseCodon = new char[3]; int cdsStart = fromSeq.getStart(); baseCodon[0] = Character .toUpperCase(fromSeq.getCharAt(codonPos[0] - cdsStart)); baseCodon[1] = Character .toUpperCase(fromSeq.getCharAt(codonPos[1] - cdsStart)); baseCodon[2] = Character .toUpperCase(fromSeq.getCharAt(codonPos[2] - cdsStart)); } else { codonPos = null; baseCodon = null; } } /** * Computes and returns comma-delimited HGVS notation peptide variants derived * from codon allele variants. If no variants are found, answers an empty * string. * * @param sf * a sequence feature (which must be one of those held in this * object) * @return */ public String findProteinVariants(SequenceFeature sf) { if (!features.contains(sf) || baseCodon == null) { return ""; } /* * VCF data may already contain the protein consequence */ String hgvsp = sf.getValueAsString(CSQ, HGV_SP); if (hgvsp != null) { int colonPos = hgvsp.lastIndexOf(':'); if (colonPos >= 0) { String var = hgvsp.substring(colonPos + 1); if (var.contains("p.")) // sanity check { return var; } } } /* * otherwise, compute codon and peptide variant */ int cdsPos = sf.getBegin(); if (cdsPos != sf.getEnd()) { // not handling multi-locus variant features return ""; } if (cdsPos != codonPos[0] && cdsPos != codonPos[1] && cdsPos != codonPos[2]) { // e.g. feature on intron within spliced codon! return ""; } String alls = (String) sf.getValue(Gff3Helper.ALLELES); if (alls == null) { return ""; } String from3 = StringUtils.toSentenceCase( ResidueProperties.aa2Triplet.get(String.valueOf(toResidue))); /* * make a peptide variant for each SNP allele * e.g. C,G,T gives variants G and T for base C */ Set variantPeptides = new HashSet<>(); String[] alleles = alls.toUpperCase().split(","); StringBuilder vars = new StringBuilder(); for (String allele : alleles) { allele = allele.trim().toUpperCase(); if (allele.length() > 1 || "-".equals(allele)) { continue; // multi-locus variant } char[] variantCodon = new char[3]; variantCodon[0] = baseCodon[0]; variantCodon[1] = baseCodon[1]; variantCodon[2] = baseCodon[2]; /* * poke variant base into canonical codon; * ignore first 'allele' (canonical base) */ final int i = cdsPos == codonPos[0] ? 0 : (cdsPos == codonPos[1] ? 1 : 2); variantCodon[i] = allele.toUpperCase().charAt(0); if (variantCodon[i] == baseCodon[i]) { continue; } String codon = new String(variantCodon); String peptide = ResidueProperties.codonTranslate(codon); boolean synonymous = toResidue == peptide.charAt(0); StringBuilder var = new StringBuilder(); if (synonymous) { /* * synonymous variant notation e.g. c.1062C>A(p.=) */ var.append("c.").append(String.valueOf(cdsPos)) .append(String.valueOf(baseCodon[i])).append(">") .append(String.valueOf(variantCodon[i])) .append("(p.=)"); } else { /* * missense variant notation e.g. p.Arg355Met */ String to3 = ResidueProperties.STOP.equals(peptide) ? "Ter" : StringUtils.toSentenceCase( ResidueProperties.aa2Triplet.get(peptide)); var.append("p.").append(from3).append(String.valueOf(toPosition)) .append(to3); } if (!variantPeptides.contains(peptide)) // duplicate consequence { variantPeptides.add(peptide); if (vars.length() > 0) { vars.append(","); } vars.append(var); } } return vars.toString(); } }