- * Maps exon features from dna to protein, and computes variants in peptide
- * product generated by variants in dna, and adds them as sequence_variant
- * features on the protein sequence. Returns the number of variant features
- * added.
- *
- * @param dnaSeq
- * @param peptide
- * @param dnaToProtein
- */
- public static int computeProteinFeatures(SequenceI dnaSeq,
- SequenceI peptide, MapList dnaToProtein)
- {
- while (dnaSeq.getDatasetSequence() != null)
- {
- dnaSeq = dnaSeq.getDatasetSequence();
- }
- while (peptide.getDatasetSequence() != null)
- {
- peptide = peptide.getDatasetSequence();
- }
-
- transferFeatures(dnaSeq, peptide, dnaToProtein, SequenceOntologyI.EXON);
-
- /*
- * compute protein variants from dna variants and codon mappings;
- * NB - alternatively we could retrieve this using the REST service e.g.
- * http://rest.ensembl.org/overlap/translation
- * /ENSP00000288602?feature=transcript_variation;content-type=text/xml
- * which would be a bit slower but possibly more reliable
- */
-
- /*
- * build a map with codon variations for each potentially varying peptide
- */
- LinkedHashMap<Integer, List<DnaVariant>[]> variants = buildDnaVariantsMap(
- dnaSeq, dnaToProtein);
-
- /*
- * scan codon variations, compute peptide variants and add to peptide sequence
- */
- int count = 0;
- for (Entry<Integer, List<DnaVariant>[]> variant : variants.entrySet())
- {
- int peptidePos = variant.getKey();
- List<DnaVariant>[] codonVariants = variant.getValue();
- count += computePeptideVariants(peptide, peptidePos, codonVariants);
- }
-
- /*
- * sort to get sequence features in start position order
- * - would be better to store in Sequence as a TreeSet or NCList?
- */
- if (peptide.getSequenceFeatures() != null)
- {
- Arrays.sort(peptide.getSequenceFeatures(),
- new Comparator<SequenceFeature>()
- {
- @Override
- public int compare(SequenceFeature o1, SequenceFeature o2)
- {
- int c = Integer.compare(o1.getBegin(), o2.getBegin());
- return c == 0 ? Integer.compare(o1.getEnd(), o2.getEnd())
- : c;
- }
- });
- }
- return count;
- }
-
- /**
- * Computes non-synonymous peptide variants from codon variants and adds them
- * as sequence_variant features on the protein sequence (one feature per
- * allele variant). Selected attributes (variant id, clinical significance)
- * are copied over to the new features.
- *
- * @param peptide
- * the protein sequence
- * @param peptidePos
- * the position to compute peptide variants for
- * @param codonVariants
- * a list of dna variants per codon position
- * @return the number of features added
- */
- static int computePeptideVariants(SequenceI peptide, int peptidePos,
- List<DnaVariant>[] codonVariants)
- {
- String residue = String.valueOf(peptide.getCharAt(peptidePos - 1));
- int count = 0;
- String base1 = codonVariants[0].get(0).base;
- String base2 = codonVariants[1].get(0).base;
- String base3 = codonVariants[2].get(0).base;
-
- /*
- * variants in first codon base
- */
- for (DnaVariant var : codonVariants[0])
- {
- if (var.variant != null)
- {
- String alleles = (String) var.variant.getValue("alleles");
- if (alleles != null)
- {
- for (String base : alleles.split(","))
- {
- String codon = base + base2 + base3;
- if (addPeptideVariant(peptide, peptidePos, residue, var, codon))
- {
- count++;
- }
- }
- }
- }
- }
-
- /*
- * variants in second codon base
- */
- for (DnaVariant var : codonVariants[1])
- {
- if (var.variant != null)
- {
- String alleles = (String) var.variant.getValue("alleles");
- if (alleles != null)
- {
- for (String base : alleles.split(","))
- {
- String codon = base1 + base + base3;
- if (addPeptideVariant(peptide, peptidePos, residue, var, codon))
- {
- count++;
- }
- }
- }
- }
- }
-
- /*
- * variants in third codon base
- */
- for (DnaVariant var : codonVariants[2])
- {
- if (var.variant != null)
- {
- String alleles = (String) var.variant.getValue("alleles");
- if (alleles != null)
- {
- for (String base : alleles.split(","))
- {
- String codon = base1 + base2 + base;
- if (addPeptideVariant(peptide, peptidePos, residue, var, codon))
- {
- count++;
- }
- }
- }
- }
- }
-
- return count;
- }
-
- /**
- * Helper method that adds a peptide variant feature, provided the given codon
- * translates to a value different to the current residue (is a non-synonymous
- * variant). ID and clinical_significance attributes of the dna variant (if
- * present) are copied to the new feature.
- *
- * @param peptide
- * @param peptidePos
- * @param residue
- * @param var
- * @param codon
- * @return true if a feature was added, else false
- */
- static boolean addPeptideVariant(SequenceI peptide, int peptidePos,
- String residue, DnaVariant var, String codon)
- {
- /*
- * get peptide translation of codon e.g. GAT -> D
- * note that variants which are not single alleles,
- * e.g. multibase variants or HGMD_MUTATION etc
- * are currently ignored here
- */
- String trans = codon.contains("-") ? "-"
- : (codon.length() > CODON_LENGTH ? null : ResidueProperties
- .codonTranslate(codon));
- if (trans != null && !trans.equals(residue))
- {
- String residue3Char = StringUtils
- .toSentenceCase(ResidueProperties.aa2Triplet.get(residue));
- String trans3Char = StringUtils
- .toSentenceCase(ResidueProperties.aa2Triplet.get(trans));
- String desc = "p." + residue3Char + peptidePos + trans3Char;
- // set score to 0f so 'graduated colour' option is offered! JAL-2060
- SequenceFeature sf = new SequenceFeature(
- SequenceOntologyI.SEQUENCE_VARIANT, desc, peptidePos,
- peptidePos, 0f, var.getSource());
- StringBuilder attributes = new StringBuilder(32);
- String id = (String) var.variant.getValue(ID);
- if (id != null)
- {
- if (id.startsWith(SEQUENCE_VARIANT))
- {
- id = id.substring(SEQUENCE_VARIANT.length());
- }
- sf.setValue(ID, id);
- attributes.append(ID).append("=").append(id);
- // TODO handle other species variants JAL-2064
- StringBuilder link = new StringBuilder(32);
- try
- {
- link.append(desc)
- .append(" ")
- .append(id)
- .append("|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=")
- .append(URLEncoder.encode(id, "UTF-8"));
- sf.addLink(link.toString());
- } catch (UnsupportedEncodingException e)
- {
- // as if
- }
- }
- String clinSig = (String) var.variant.getValue(CLINICAL_SIGNIFICANCE);
- if (clinSig != null)
- {
- sf.setValue(CLINICAL_SIGNIFICANCE, clinSig);
- attributes.append(";").append(CLINICAL_SIGNIFICANCE).append("=")
- .append(clinSig);
- }
- peptide.addSequenceFeature(sf);
- if (attributes.length() > 0)
- {
- sf.setAttributes(attributes.toString());
- }
- return true;
- }
- return false;
- }
-
- /**
- * Builds a map whose key is position in the protein sequence, and value is a
- * list of the base and all variants for each corresponding codon position
- *
- * @param dnaSeq
- * @param dnaToProtein
- * @return
- */
- @SuppressWarnings("unchecked")
- static LinkedHashMap<Integer, List<DnaVariant>[]> buildDnaVariantsMap(
- SequenceI dnaSeq, MapList dnaToProtein)
- {
- /*
- * map from peptide position to all variants of the codon which codes for it
- * LinkedHashMap ensures we keep the peptide features in sequence order
- */
- LinkedHashMap<Integer, List<DnaVariant>[]> variants = new LinkedHashMap<Integer, List<DnaVariant>[]>();
- SequenceOntologyI so = SequenceOntologyFactory.getInstance();
-
- SequenceFeature[] dnaFeatures = dnaSeq.getSequenceFeatures();
- if (dnaFeatures == null)
- {
- return variants;
- }
-
- int dnaStart = dnaSeq.getStart();
- int[] lastCodon = null;
- int lastPeptidePostion = 0;
-
- /*
- * build a map of codon variations for peptides
- */
- for (SequenceFeature sf : dnaFeatures)
- {
- int dnaCol = sf.getBegin();
- if (dnaCol != sf.getEnd())
- {
- // not handling multi-locus variant features
- continue;
- }
- if (so.isA(sf.getType(), SequenceOntologyI.SEQUENCE_VARIANT))
- {
- int[] mapsTo = dnaToProtein.locateInTo(dnaCol, dnaCol);
- if (mapsTo == null)
- {
- // feature doesn't lie within coding region
- continue;
- }
- int peptidePosition = mapsTo[0];
- List<DnaVariant>[] codonVariants = variants.get(peptidePosition);
- if (codonVariants == null)
- {
- codonVariants = new ArrayList[CODON_LENGTH];
- codonVariants[0] = new ArrayList<DnaVariant>();
- codonVariants[1] = new ArrayList<DnaVariant>();
- codonVariants[2] = new ArrayList<DnaVariant>();
- variants.put(peptidePosition, codonVariants);
- }
-
- /*
- * extract dna variants to a string array
- */
- String alls = (String) sf.getValue("alleles");
- if (alls == null)
- {
- continue;
- }
- String[] alleles = alls.toUpperCase().split(",");
- int i = 0;
- for (String allele : alleles)
- {
- alleles[i++] = allele.trim(); // lose any space characters "A, G"
- }
-
- /*
- * get this peptide's codon positions e.g. [3, 4, 5] or [4, 7, 10]
- */
- int[] codon = peptidePosition == lastPeptidePostion ? lastCodon
- : MappingUtils.flattenRanges(dnaToProtein.locateInFrom(
- peptidePosition, peptidePosition));
- lastPeptidePostion = peptidePosition;
- lastCodon = codon;
-
- /*
- * save nucleotide (and any variant) for each codon position
- */
- for (int codonPos = 0; codonPos < CODON_LENGTH; codonPos++)
- {
- String nucleotide = String.valueOf(
- dnaSeq.getCharAt(codon[codonPos] - dnaStart))
- .toUpperCase();
- List<DnaVariant> codonVariant = codonVariants[codonPos];
- if (codon[codonPos] == dnaCol)
- {
- if (!codonVariant.isEmpty()
- && codonVariant.get(0).variant == null)
- {
- /*
- * already recorded base value, add this variant
- */
- codonVariant.get(0).variant = sf;
- }
- else
- {
- /*
- * add variant with base value
- */
- codonVariant.add(new DnaVariant(nucleotide, sf));
- }
- }
- else if (codonVariant.isEmpty())
- {
- /*
- * record (possibly non-varying) base value
- */
- codonVariant.add(new DnaVariant(nucleotide));
- }
- }
- }
- }
- return variants;
- }
-
- /**