+
+ /**
+ * Test for the alignSequenceAs method where we have protein mapped to protein
+ */
+ @Test(groups = { "Functional" })
+ public void testAlignSequenceAs_mappedProteinProtein()
+ {
+
+ SequenceI alignMe = new Sequence("Match", "MGAASEV");
+ alignMe.createDatasetSequence();
+ SequenceI alignFrom = new Sequence("Query", "LQTGYMGAASEVMFSPTRR");
+ alignFrom.createDatasetSequence();
+
+ AlignedCodonFrame acf = new AlignedCodonFrame();
+ // this is like a domain or motif match of part of a peptide sequence
+ MapList map = new MapList(new int[] { 6, 12 }, new int[] { 1, 7 }, 1, 1);
+ acf.addMap(alignFrom.getDatasetSequence(),
+ alignMe.getDatasetSequence(), map);
+
+ AlignmentUtils.alignSequenceAs(alignMe, alignFrom, acf, "-", '-', true,
+ true);
+ assertEquals("-----MGAASEV-------", alignMe.getSequenceAsString());
+ }
+
+ /**
+ * Test for the alignSequenceAs method where there are trailing unmapped
+ * residues in the model sequence
+ */
+ @Test(groups = { "Functional" })
+ public void testAlignSequenceAs_withTrailingPeptide()
+ {
+ // map first 3 codons to KPF; G is a trailing unmapped residue
+ MapList map = new MapList(new int[] { 1, 9 }, new int[] { 1, 3 }, 3, 1);
+
+ checkAlignSequenceAs("AAACCCTTT", "K-PFG", true, true, map,
+ "AAA---CCCTTT---");
+ }
+
+ /**
+ * Tests for transferring features between mapped sequences
+ */
+ @Test(groups = { "Functional" })
+ public void testTransferFeatures()
+ {
+ SequenceI dna = new Sequence("dna/20-34", "acgTAGcaaGCCcgt");
+ SequenceI cds = new Sequence("cds/10-15", "TAGGCC");
+
+ // no overlap
+ dna.addSequenceFeature(new SequenceFeature("type1", "desc1", 1, 2, 1f,
+ null));
+ // partial overlap - to [1, 1]
+ dna.addSequenceFeature(new SequenceFeature("type2", "desc2", 3, 4, 2f,
+ null));
+ // exact overlap - to [1, 3]
+ dna.addSequenceFeature(new SequenceFeature("type3", "desc3", 4, 6, 3f,
+ null));
+ // spanning overlap - to [2, 5]
+ dna.addSequenceFeature(new SequenceFeature("type4", "desc4", 5, 11, 4f,
+ null));
+ // exactly overlaps whole mapped range [1, 6]
+ dna.addSequenceFeature(new SequenceFeature("type5", "desc5", 4, 12, 5f,
+ null));
+ // no overlap (internal)
+ dna.addSequenceFeature(new SequenceFeature("type6", "desc6", 7, 9, 6f,
+ null));
+ // no overlap (3' end)
+ dna.addSequenceFeature(new SequenceFeature("type7", "desc7", 13, 15,
+ 7f, null));
+ // overlap (3' end) - to [6, 6]
+ dna.addSequenceFeature(new SequenceFeature("type8", "desc8", 12, 12,
+ 8f, null));
+ // extended overlap - to [6, +]
+ dna.addSequenceFeature(new SequenceFeature("type9", "desc9", 12, 13,
+ 9f, null));
+
+ MapList map = new MapList(new int[] { 4, 6, 10, 12 },
+ new int[] { 1, 6 }, 1, 1);
+
+ /*
+ * transferFeatures() will build 'partial overlap' for regions
+ * that partially overlap 5' or 3' (start or end) of target sequence
+ */
+ AlignmentUtils.transferFeatures(dna, cds, map, null);
+ List<SequenceFeature> sfs = cds.getSequenceFeatures();
+ assertEquals(6, sfs.size());
+
+ SequenceFeature sf = sfs.get(0);
+ assertEquals("type2", sf.getType());
+ assertEquals("desc2", sf.getDescription());
+ assertEquals(2f, sf.getScore());
+ assertEquals(1, sf.getBegin());
+ assertEquals(1, sf.getEnd());
+
+ sf = sfs.get(1);
+ assertEquals("type3", sf.getType());
+ assertEquals("desc3", sf.getDescription());
+ assertEquals(3f, sf.getScore());
+ assertEquals(1, sf.getBegin());
+ assertEquals(3, sf.getEnd());
+
+ sf = sfs.get(2);
+ assertEquals("type4", sf.getType());
+ assertEquals(2, sf.getBegin());
+ assertEquals(5, sf.getEnd());
+
+ sf = sfs.get(3);
+ assertEquals("type5", sf.getType());
+ assertEquals(1, sf.getBegin());
+ assertEquals(6, sf.getEnd());
+
+ sf = sfs.get(4);
+ assertEquals("type8", sf.getType());
+ assertEquals(6, sf.getBegin());
+ assertEquals(6, sf.getEnd());
+
+ sf = sfs.get(5);
+ assertEquals("type9", sf.getType());
+ assertEquals(6, sf.getBegin());
+ assertEquals(6, sf.getEnd());
+ }
+
+ /**
+ * Tests for transferring features between mapped sequences
+ */
+ @Test(groups = { "Functional" })
+ public void testTransferFeatures_withOmit()
+ {
+ SequenceI dna = new Sequence("dna/20-34", "acgTAGcaaGCCcgt");
+ SequenceI cds = new Sequence("cds/10-15", "TAGGCC");
+
+ MapList map = new MapList(new int[] { 4, 6, 10, 12 },
+ new int[] { 1, 6 }, 1, 1);
+
+ // [5, 11] maps to [2, 5]
+ dna.addSequenceFeature(new SequenceFeature("type4", "desc4", 5, 11, 4f,
+ null));
+ // [4, 12] maps to [1, 6]
+ dna.addSequenceFeature(new SequenceFeature("type5", "desc5", 4, 12, 5f,
+ null));
+ // [12, 12] maps to [6, 6]
+ dna.addSequenceFeature(new SequenceFeature("type8", "desc8", 12, 12,
+ 8f, null));
+
+ // desc4 and desc8 are the 'omit these' varargs
+ AlignmentUtils.transferFeatures(dna, cds, map, null, "type4", "type8");
+ List<SequenceFeature> sfs = cds.getSequenceFeatures();
+ assertEquals(1, sfs.size());
+
+ SequenceFeature sf = sfs.get(0);
+ assertEquals("type5", sf.getType());
+ assertEquals(1, sf.getBegin());
+ assertEquals(6, sf.getEnd());
+ }
+
+ /**
+ * Tests for transferring features between mapped sequences
+ */
+ @Test(groups = { "Functional" })
+ public void testTransferFeatures_withSelect()
+ {
+ SequenceI dna = new Sequence("dna/20-34", "acgTAGcaaGCCcgt");
+ SequenceI cds = new Sequence("cds/10-15", "TAGGCC");
+
+ MapList map = new MapList(new int[] { 4, 6, 10, 12 },
+ new int[] { 1, 6 }, 1, 1);
+
+ // [5, 11] maps to [2, 5]
+ dna.addSequenceFeature(new SequenceFeature("type4", "desc4", 5, 11, 4f,
+ null));
+ // [4, 12] maps to [1, 6]
+ dna.addSequenceFeature(new SequenceFeature("type5", "desc5", 4, 12, 5f,
+ null));
+ // [12, 12] maps to [6, 6]
+ dna.addSequenceFeature(new SequenceFeature("type8", "desc8", 12, 12,
+ 8f, null));
+
+ // "type5" is the 'select this type' argument
+ AlignmentUtils.transferFeatures(dna, cds, map, "type5");
+ List<SequenceFeature> sfs = cds.getSequenceFeatures();
+ assertEquals(1, sfs.size());
+
+ SequenceFeature sf = sfs.get(0);
+ assertEquals("type5", sf.getType());
+ assertEquals(1, sf.getBegin());
+ assertEquals(6, sf.getEnd());
+ }
+
+ /**
+ * Test the method that extracts the cds-only part of a dna alignment, for the
+ * case where the cds should be aligned to match its nucleotide sequence.
+ */
+ @Test(groups = { "Functional" })
+ public void testMakeCdsAlignment_alternativeTranscripts()
+ {
+ SequenceI dna1 = new Sequence("dna1", "aaaGGGCC-----CTTTaaaGGG");
+ // alternative transcript of same dna skips CCC codon
+ SequenceI dna2 = new Sequence("dna2", "aaaGGGCC-----cttTaaaGGG");
+ // dna3 has no mapping (protein product) so should be ignored here
+ SequenceI dna3 = new Sequence("dna3", "aaaGGGCCCCCGGGcttTaaaGGG");
+ SequenceI pep1 = new Sequence("pep1", "GPFG");
+ SequenceI pep2 = new Sequence("pep2", "GPG");
+ dna1.createDatasetSequence();
+ dna2.createDatasetSequence();
+ dna3.createDatasetSequence();
+ pep1.createDatasetSequence();
+ pep2.createDatasetSequence();
+
+ AlignmentI dna = new Alignment(new SequenceI[] { dna1, dna2, dna3 });
+ dna.setDataset(null);
+
+ MapList map = new MapList(new int[] { 4, 12, 16, 18 },
+ new int[] { 1, 4 }, 3, 1);
+ AlignedCodonFrame acf = new AlignedCodonFrame();
+ acf.addMap(dna1.getDatasetSequence(), pep1.getDatasetSequence(), map);
+ dna.addCodonFrame(acf);
+ map = new MapList(new int[] { 4, 8, 12, 12, 16, 18 },
+ new int[] { 1, 3 }, 3, 1);
+ acf = new AlignedCodonFrame();
+ acf.addMap(dna2.getDatasetSequence(), pep2.getDatasetSequence(), map);
+ dna.addCodonFrame(acf);
+
+ AlignmentI cds = AlignmentUtils.makeCdsAlignment(new SequenceI[] {
+ dna1, dna2, dna3 }, dna.getDataset(), null);
+ List<SequenceI> cdsSeqs = cds.getSequences();
+ assertEquals(2, cdsSeqs.size());
+ assertEquals("GGGCCCTTTGGG", cdsSeqs.get(0).getSequenceAsString());
+ assertEquals("GGGCCTGGG", cdsSeqs.get(1).getSequenceAsString());
+
+ /*
+ * verify shared, extended alignment dataset
+ */
+ assertSame(dna.getDataset(), cds.getDataset());
+ assertTrue(dna.getDataset().getSequences()
+ .contains(cdsSeqs.get(0).getDatasetSequence()));
+ assertTrue(dna.getDataset().getSequences()
+ .contains(cdsSeqs.get(1).getDatasetSequence()));
+
+ /*
+ * Verify 6 mappings: dna1 to cds1, cds1 to pep1, dna1 to pep1
+ * and the same for dna2/cds2/pep2
+ */
+ List<AlignedCodonFrame> mappings = cds.getCodonFrames();
+ assertEquals(6, mappings.size());
+
+ /*
+ * 2 mappings involve pep1
+ */
+ List<AlignedCodonFrame> pep1Mappings = MappingUtils
+ .findMappingsForSequence(pep1, mappings);
+ assertEquals(2, pep1Mappings.size());
+
+ /*
+ * Get mapping of pep1 to cds1 and verify it
+ * maps GPFG to 1-3,4-6,7-9,10-12
+ */
+ List<AlignedCodonFrame> pep1CdsMappings = MappingUtils
+ .findMappingsForSequence(cds.getSequenceAt(0), pep1Mappings);
+ assertEquals(1, pep1CdsMappings.size());
+ SearchResultsI sr = MappingUtils.buildSearchResults(pep1, 1,
+ pep1CdsMappings);
+ assertEquals(1, sr.getResults().size());
+ SearchResultMatchI m = sr.getResults().get(0);
+ assertEquals(cds.getSequenceAt(0).getDatasetSequence(), m.getSequence());
+ assertEquals(1, m.getStart());
+ assertEquals(3, m.getEnd());
+ sr = MappingUtils.buildSearchResults(pep1, 2, pep1CdsMappings);
+ m = sr.getResults().get(0);
+ assertEquals(4, m.getStart());
+ assertEquals(6, m.getEnd());
+ sr = MappingUtils.buildSearchResults(pep1, 3, pep1CdsMappings);
+ m = sr.getResults().get(0);
+ assertEquals(7, m.getStart());
+ assertEquals(9, m.getEnd());
+ sr = MappingUtils.buildSearchResults(pep1, 4, pep1CdsMappings);
+ m = sr.getResults().get(0);
+ assertEquals(10, m.getStart());
+ assertEquals(12, m.getEnd());
+
+ /*
+ * Get mapping of pep2 to cds2 and verify it
+ * maps GPG in pep2 to 1-3,4-6,7-9 in second CDS sequence
+ */
+ List<AlignedCodonFrame> pep2Mappings = MappingUtils
+ .findMappingsForSequence(pep2, mappings);
+ assertEquals(2, pep2Mappings.size());
+ List<AlignedCodonFrame> pep2CdsMappings = MappingUtils
+ .findMappingsForSequence(cds.getSequenceAt(1), pep2Mappings);
+ assertEquals(1, pep2CdsMappings.size());
+ sr = MappingUtils.buildSearchResults(pep2, 1, pep2CdsMappings);
+ assertEquals(1, sr.getResults().size());
+ m = sr.getResults().get(0);
+ assertEquals(cds.getSequenceAt(1).getDatasetSequence(), m.getSequence());
+ assertEquals(1, m.getStart());
+ assertEquals(3, m.getEnd());
+ sr = MappingUtils.buildSearchResults(pep2, 2, pep2CdsMappings);
+ m = sr.getResults().get(0);
+ assertEquals(4, m.getStart());
+ assertEquals(6, m.getEnd());
+ sr = MappingUtils.buildSearchResults(pep2, 3, pep2CdsMappings);
+ m = sr.getResults().get(0);
+ assertEquals(7, m.getStart());
+ assertEquals(9, m.getEnd());
+ }
+
+ /**
+ * Test the method that realigns protein to match mapped codon alignment.
+ */
+ @Test(groups = { "Functional" })
+ public void testAlignProteinAsDna_incompleteStartCodon()
+ {
+ // seq1: incomplete start codon (not mapped), then [3, 11]
+ SequenceI dna1 = new Sequence("Seq1", "ccAAA-TTT-GGG-");
+ // seq2 codons are [4, 5], [8, 11]
+ SequenceI dna2 = new Sequence("Seq2", "ccaAA-ttT-GGG-");
+ // seq3 incomplete start codon at 'tt'
+ SequenceI dna3 = new Sequence("Seq3", "ccaaa-ttt-GGG-");
+ AlignmentI dna = new Alignment(new SequenceI[] { dna1, dna2, dna3 });
+ dna.setDataset(null);
+
+ // prot1 has 'X' for incomplete start codon (not mapped)
+ SequenceI prot1 = new Sequence("Seq1", "XKFG"); // X for incomplete start
+ SequenceI prot2 = new Sequence("Seq2", "NG");
+ SequenceI prot3 = new Sequence("Seq3", "XG"); // X for incomplete start
+ AlignmentI protein = new Alignment(new SequenceI[] { prot1, prot2,
+ prot3 });
+ protein.setDataset(null);
+
+ // map dna1 [3, 11] to prot1 [2, 4] KFG
+ MapList map = new MapList(new int[] { 3, 11 }, new int[] { 2, 4 }, 3, 1);
+ AlignedCodonFrame acf = new AlignedCodonFrame();
+ acf.addMap(dna1.getDatasetSequence(), prot1.getDatasetSequence(), map);
+
+ // map dna2 [4, 5] [8, 11] to prot2 [1, 2] NG
+ map = new MapList(new int[] { 4, 5, 8, 11 }, new int[] { 1, 2 }, 3, 1);
+ acf.addMap(dna2.getDatasetSequence(), prot2.getDatasetSequence(), map);
+
+ // map dna3 [9, 11] to prot3 [2, 2] G
+ map = new MapList(new int[] { 9, 11 }, new int[] { 2, 2 }, 3, 1);
+ acf.addMap(dna3.getDatasetSequence(), prot3.getDatasetSequence(), map);
+
+ ArrayList<AlignedCodonFrame> acfs = new ArrayList<>();
+ acfs.add(acf);
+ protein.setCodonFrames(acfs);
+
+ /*
+ * verify X is included in the aligned proteins, and placed just
+ * before the first mapped residue
+ * CCT is between CCC and TTT
+ */
+ AlignmentUtils.alignProteinAsDna(protein, dna);
+ assertEquals("XK-FG", prot1.getSequenceAsString());
+ assertEquals("--N-G", prot2.getSequenceAsString());
+ assertEquals("---XG", prot3.getSequenceAsString());
+ }
+
+ /**
+ * Tests for the method that maps the subset of a dna sequence that has CDS
+ * (or subtype) feature - case where the start codon is incomplete.
+ */
+ @Test(groups = "Functional")
+ public void testFindCdsPositions_fivePrimeIncomplete()
+ {
+ SequenceI dnaSeq = new Sequence("dna", "aaagGGCCCaaaTTTttt");
+ dnaSeq.createDatasetSequence();
+ SequenceI ds = dnaSeq.getDatasetSequence();
+
+ // CDS for dna 5-6 (incomplete codon), 7-9
+ SequenceFeature sf = new SequenceFeature("CDS", "", 5, 9, 0f, null);
+ sf.setPhase("2"); // skip 2 bases to start of next codon
+ ds.addSequenceFeature(sf);
+ // CDS for dna 13-15
+ sf = new SequenceFeature("CDS_predicted", "", 13, 15, 0f, null);
+ ds.addSequenceFeature(sf);
+
+ List<int[]> ranges = AlignmentUtils.findCdsPositions(dnaSeq);
+
+ /*
+ * check the mapping starts with the first complete codon
+ */
+ assertEquals(6, MappingUtils.getLength(ranges));
+ assertEquals(2, ranges.size());
+ assertEquals(7, ranges.get(0)[0]);
+ assertEquals(9, ranges.get(0)[1]);
+ assertEquals(13, ranges.get(1)[0]);
+ assertEquals(15, ranges.get(1)[1]);
+ }
+
+ /**
+ * Tests for the method that maps the subset of a dna sequence that has CDS
+ * (or subtype) feature.
+ */
+ @Test(groups = "Functional")
+ public void testFindCdsPositions()
+ {
+ SequenceI dnaSeq = new Sequence("dna", "aaaGGGcccAAATTTttt");
+ dnaSeq.createDatasetSequence();
+ SequenceI ds = dnaSeq.getDatasetSequence();
+
+ // CDS for dna 10-12
+ SequenceFeature sf = new SequenceFeature("CDS_predicted", "", 10, 12,
+ 0f, null);
+ sf.setStrand("+");
+ ds.addSequenceFeature(sf);
+ // CDS for dna 4-6
+ sf = new SequenceFeature("CDS", "", 4, 6, 0f, null);
+ sf.setStrand("+");
+ ds.addSequenceFeature(sf);
+ // exon feature should be ignored here
+ sf = new SequenceFeature("exon", "", 7, 9, 0f, null);
+ ds.addSequenceFeature(sf);
+
+ List<int[]> ranges = AlignmentUtils.findCdsPositions(dnaSeq);
+ /*
+ * verify ranges { [4-6], [12-10] }
+ * note CDS ranges are ordered ascending even if the CDS
+ * features are not
+ */
+ assertEquals(6, MappingUtils.getLength(ranges));
+ assertEquals(2, ranges.size());
+ assertEquals(4, ranges.get(0)[0]);
+ assertEquals(6, ranges.get(0)[1]);
+ assertEquals(10, ranges.get(1)[0]);
+ assertEquals(12, ranges.get(1)[1]);
+ }
+
+ /**
+ * Test the method that computes a map of codon variants for each protein
+ * position from "sequence_variant" features on dna
+ */
+ @Test(groups = "Functional")
+ public void testBuildDnaVariantsMap()
+ {
+ SequenceI dna = new Sequence("dna", "atgAAATTTGGGCCCtag");
+ MapList map = new MapList(new int[] { 1, 18 }, new int[] { 1, 5 }, 3, 1);
+
+ /*
+ * first with no variants on dna
+ */
+ LinkedHashMap<Integer, List<DnaVariant>[]> variantsMap = AlignmentUtils
+ .buildDnaVariantsMap(dna, map);
+ assertTrue(variantsMap.isEmpty());
+
+ /*
+ * single allele codon 1, on base 1
+ */
+ SequenceFeature sf1 = new SequenceFeature("sequence_variant", "", 1, 1,
+ 0f, null);
+ sf1.setValue("alleles", "T");
+ sf1.setValue("ID", "sequence_variant:rs758803211");
+ dna.addSequenceFeature(sf1);
+
+ /*
+ * two alleles codon 2, on bases 2 and 3 (distinct variants)
+ */
+ SequenceFeature sf2 = new SequenceFeature("sequence_variant", "", 5, 5,
+ 0f, null);
+ sf2.setValue("alleles", "T");
+ sf2.setValue("ID", "sequence_variant:rs758803212");
+ dna.addSequenceFeature(sf2);
+ SequenceFeature sf3 = new SequenceFeature("sequence_variant", "", 6, 6,
+ 0f, null);
+ sf3.setValue("alleles", "G");
+ sf3.setValue("ID", "sequence_variant:rs758803213");
+ dna.addSequenceFeature(sf3);
+
+ /*
+ * two alleles codon 3, both on base 2 (one variant)
+ */
+ SequenceFeature sf4 = new SequenceFeature("sequence_variant", "", 8, 8,
+ 0f, null);
+ sf4.setValue("alleles", "C, G");
+ sf4.setValue("ID", "sequence_variant:rs758803214");
+ dna.addSequenceFeature(sf4);
+
+ // no alleles on codon 4
+
+ /*
+ * alleles on codon 5 on all 3 bases (distinct variants)
+ */
+ SequenceFeature sf5 = new SequenceFeature("sequence_variant", "", 13,
+ 13, 0f, null);
+ sf5.setValue("alleles", "C, G"); // (C duplicates given base value)
+ sf5.setValue("ID", "sequence_variant:rs758803215");
+ dna.addSequenceFeature(sf5);
+ SequenceFeature sf6 = new SequenceFeature("sequence_variant", "", 14,
+ 14, 0f, null);
+ sf6.setValue("alleles", "g, a"); // should force to upper-case
+ sf6.setValue("ID", "sequence_variant:rs758803216");
+ dna.addSequenceFeature(sf6);
+
+ SequenceFeature sf7 = new SequenceFeature("sequence_variant", "", 15,
+ 15, 0f, null);
+ sf7.setValue("alleles", "A, T");
+ sf7.setValue("ID", "sequence_variant:rs758803217");
+ dna.addSequenceFeature(sf7);
+
+ /*
+ * build map - expect variants on positions 1, 2, 3, 5
+ */
+ variantsMap = AlignmentUtils.buildDnaVariantsMap(dna, map);
+ assertEquals(4, variantsMap.size());
+
+ /*
+ * protein residue 1: variant on codon (ATG) base 1, not on 2 or 3
+ */
+ List<DnaVariant>[] pep1Variants = variantsMap.get(1);
+ assertEquals(3, pep1Variants.length);
+ assertEquals(1, pep1Variants[0].size());
+ assertEquals("A", pep1Variants[0].get(0).base); // codon[1] base
+ assertSame(sf1, pep1Variants[0].get(0).variant); // codon[1] variant
+ assertEquals(1, pep1Variants[1].size());
+ assertEquals("T", pep1Variants[1].get(0).base); // codon[2] base
+ assertNull(pep1Variants[1].get(0).variant); // no variant here
+ assertEquals(1, pep1Variants[2].size());
+ assertEquals("G", pep1Variants[2].get(0).base); // codon[3] base
+ assertNull(pep1Variants[2].get(0).variant); // no variant here
+
+ /*
+ * protein residue 2: variants on codon (AAA) bases 2 and 3
+ */
+ List<DnaVariant>[] pep2Variants = variantsMap.get(2);
+ assertEquals(3, pep2Variants.length);
+ assertEquals(1, pep2Variants[0].size());
+ // codon[1] base recorded while processing variant on codon[2]
+ assertEquals("A", pep2Variants[0].get(0).base);
+ assertNull(pep2Variants[0].get(0).variant); // no variant here
+ // codon[2] base and variant:
+ assertEquals(1, pep2Variants[1].size());
+ assertEquals("A", pep2Variants[1].get(0).base);
+ assertSame(sf2, pep2Variants[1].get(0).variant);
+ // codon[3] base was recorded when processing codon[2] variant
+ // and then the variant for codon[3] added to it
+ assertEquals(1, pep2Variants[2].size());
+ assertEquals("A", pep2Variants[2].get(0).base);
+ assertSame(sf3, pep2Variants[2].get(0).variant);
+
+ /*
+ * protein residue 3: variants on codon (TTT) base 2 only
+ */
+ List<DnaVariant>[] pep3Variants = variantsMap.get(3);
+ assertEquals(3, pep3Variants.length);
+ assertEquals(1, pep3Variants[0].size());
+ assertEquals("T", pep3Variants[0].get(0).base); // codon[1] base
+ assertNull(pep3Variants[0].get(0).variant); // no variant here
+ assertEquals(1, pep3Variants[1].size());
+ assertEquals("T", pep3Variants[1].get(0).base); // codon[2] base
+ assertSame(sf4, pep3Variants[1].get(0).variant); // codon[2] variant
+ assertEquals(1, pep3Variants[2].size());
+ assertEquals("T", pep3Variants[2].get(0).base); // codon[3] base
+ assertNull(pep3Variants[2].get(0).variant); // no variant here
+
+ /*
+ * three variants on protein position 5
+ */
+ List<DnaVariant>[] pep5Variants = variantsMap.get(5);
+ assertEquals(3, pep5Variants.length);
+ assertEquals(1, pep5Variants[0].size());
+ assertEquals("C", pep5Variants[0].get(0).base); // codon[1] base
+ assertSame(sf5, pep5Variants[0].get(0).variant); // codon[1] variant
+ assertEquals(1, pep5Variants[1].size());
+ assertEquals("C", pep5Variants[1].get(0).base); // codon[2] base
+ assertSame(sf6, pep5Variants[1].get(0).variant); // codon[2] variant
+ assertEquals(1, pep5Variants[2].size());
+ assertEquals("C", pep5Variants[2].get(0).base); // codon[3] base
+ assertSame(sf7, pep5Variants[2].get(0).variant); // codon[3] variant
+ }
+
+ /**
+ * Tests for the method that computes all peptide variants given codon
+ * variants
+ */
+ @Test(groups = "Functional")
+ public void testComputePeptideVariants()
+ {
+ /*
+ * scenario: AAATTTCCC codes for KFP
+ * variants:
+ * GAA -> E source: Ensembl
+ * CAA -> Q source: dbSNP
+ * TAA -> STOP source: dnSNP
+ * AAG synonymous source: COSMIC
+ * AAT -> N source: Ensembl
+ * ...TTC synonymous source: dbSNP
+ * ......CAC,CGC -> H,R source: COSMIC
+ * (one variant with two alleles)
+ */
+ SequenceI peptide = new Sequence("pep/10-12", "KFP");
+
+ /*
+ * two distinct variants for codon 1 position 1
+ * second one has clinical significance
+ */
+ String ensembl = "Ensembl";
+ String dbSnp = "dbSNP";
+ String cosmic = "COSMIC";
+
+ /*
+ * NB setting "id" (as returned by Ensembl for features in JSON format);
+ * previously "ID" (as returned for GFF3 format)
+ */
+ SequenceFeature sf1 = new SequenceFeature("sequence_variant", "", 1, 1,
+ 0f, ensembl);
+ sf1.setValue("alleles", "A,G"); // AAA -> GAA -> K/E
+ sf1.setValue("id", "var1.125A>G");
+
+ SequenceFeature sf2 = new SequenceFeature("sequence_variant", "", 1, 1,
+ 0f, dbSnp);
+ sf2.setValue("alleles", "A,C"); // AAA -> CAA -> K/Q
+ sf2.setValue("id", "var2");
+ sf2.setValue("clinical_significance", "Dodgy");
+
+ SequenceFeature sf3 = new SequenceFeature("sequence_variant", "", 1, 1,
+ 0f, dbSnp);
+ sf3.setValue("alleles", "A,T"); // AAA -> TAA -> stop codon
+ sf3.setValue("id", "var3");
+ sf3.setValue("clinical_significance", "Bad");
+
+ SequenceFeature sf4 = new SequenceFeature("sequence_variant", "", 3, 3,
+ 0f, cosmic);
+ sf4.setValue("alleles", "A,G"); // AAA -> AAG synonymous
+ sf4.setValue("id", "var4");
+ sf4.setValue("clinical_significance", "None");
+
+ SequenceFeature sf5 = new SequenceFeature("sequence_variant", "", 3, 3,
+ 0f, ensembl);
+ sf5.setValue("alleles", "A,T"); // AAA -> AAT -> K/N
+ sf5.setValue("id", "sequence_variant:var5"); // prefix gets stripped off
+ sf5.setValue("clinical_significance", "Benign");
+
+ SequenceFeature sf6 = new SequenceFeature("sequence_variant", "", 6, 6,
+ 0f, dbSnp);
+ sf6.setValue("alleles", "T,C"); // TTT -> TTC synonymous
+ sf6.setValue("id", "var6");
+
+ SequenceFeature sf7 = new SequenceFeature("sequence_variant", "", 8, 8,
+ 0f, cosmic);
+ sf7.setValue("alleles", "C,A,G"); // CCC -> CAC,CGC -> P/H/R
+ sf7.setValue("id", "var7");
+ sf7.setValue("clinical_significance", "Good");
+
+ List<DnaVariant> codon1Variants = new ArrayList<>();
+ List<DnaVariant> codon2Variants = new ArrayList<>();
+ List<DnaVariant> codon3Variants = new ArrayList<>();
+
+ List<DnaVariant> codonVariants[] = new ArrayList[3];
+ codonVariants[0] = codon1Variants;
+ codonVariants[1] = codon2Variants;
+ codonVariants[2] = codon3Variants;
+
+ /*
+ * compute variants for protein position 1
+ */
+ codon1Variants.add(new DnaVariant("A", sf1));
+ codon1Variants.add(new DnaVariant("A", sf2));
+ codon1Variants.add(new DnaVariant("A", sf3));
+ codon2Variants.add(new DnaVariant("A"));
+ // codon2Variants.add(new DnaVariant("A"));
+ codon3Variants.add(new DnaVariant("A", sf4));
+ codon3Variants.add(new DnaVariant("A", sf5));
+ AlignmentUtils.computePeptideVariants(peptide, 1, codonVariants);
+
+ /*
+ * compute variants for protein position 2
+ */
+ codon1Variants.clear();
+ codon2Variants.clear();
+ codon3Variants.clear();
+ codon1Variants.add(new DnaVariant("T"));
+ codon2Variants.add(new DnaVariant("T"));
+ codon3Variants.add(new DnaVariant("T", sf6));
+ AlignmentUtils.computePeptideVariants(peptide, 2, codonVariants);
+
+ /*
+ * compute variants for protein position 3
+ */
+ codon1Variants.clear();
+ codon2Variants.clear();
+ codon3Variants.clear();
+ codon1Variants.add(new DnaVariant("C"));
+ codon2Variants.add(new DnaVariant("C", sf7));
+ codon3Variants.add(new DnaVariant("C"));
+ AlignmentUtils.computePeptideVariants(peptide, 3, codonVariants);
+
+ /*
+ * verify added sequence features for
+ * var1 K -> E Ensembl
+ * var2 K -> Q dbSNP
+ * var3 K -> stop
+ * var4 synonymous
+ * var5 K -> N Ensembl
+ * var6 synonymous
+ * var7 P -> H COSMIC
+ * var8 P -> R COSMIC
+ */
+ List<SequenceFeature> sfs = peptide.getSequenceFeatures();
+ SequenceFeatures.sortFeatures(sfs, true);
+ assertEquals(8, sfs.size());
+
+ /*
+ * features are sorted by start position ascending, but in no
+ * particular order where start positions match; asserts here
+ * simply match the data returned (the order is not important)
+ */
+ // AAA -> AAT -> K/N
+ SequenceFeature sf = sfs.get(0);
+ assertEquals(1, sf.getBegin());
+ assertEquals(1, sf.getEnd());
+ assertEquals("nonsynonymous_variant", sf.getType());
+ assertEquals("p.Lys1Asn", sf.getDescription());
+ assertEquals("var5", sf.getValue("id"));
+ assertEquals("Benign", sf.getValue("clinical_significance"));
+ assertEquals("id=var5;clinical_significance=Benign",
+ sf.getAttributes());
+ assertEquals(1, sf.links.size());
+ assertEquals(
+ "p.Lys1Asn var5|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var5",
+ sf.links.get(0));
+ assertEquals(ensembl, sf.getFeatureGroup());
+
+ // AAA -> CAA -> K/Q
+ sf = sfs.get(1);
+ assertEquals(1, sf.getBegin());
+ assertEquals(1, sf.getEnd());
+ assertEquals("nonsynonymous_variant", sf.getType());
+ assertEquals("p.Lys1Gln", sf.getDescription());
+ assertEquals("var2", sf.getValue("id"));
+ assertEquals("Dodgy", sf.getValue("clinical_significance"));
+ assertEquals("id=var2;clinical_significance=Dodgy", sf.getAttributes());
+ assertEquals(1, sf.links.size());
+ assertEquals(
+ "p.Lys1Gln var2|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var2",
+ sf.links.get(0));
+ assertEquals(dbSnp, sf.getFeatureGroup());
+
+ // AAA -> GAA -> K/E
+ sf = sfs.get(2);
+ assertEquals(1, sf.getBegin());
+ assertEquals(1, sf.getEnd());
+ assertEquals("nonsynonymous_variant", sf.getType());
+ assertEquals("p.Lys1Glu", sf.getDescription());
+ assertEquals("var1.125A>G", sf.getValue("id"));
+ assertNull(sf.getValue("clinical_significance"));
+ assertEquals("id=var1.125A>G", sf.getAttributes());
+ assertEquals(1, sf.links.size());
+ // link to variation is urlencoded
+ assertEquals(
+ "p.Lys1Glu var1.125A>G|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var1.125A%3EG",
+ sf.links.get(0));
+ assertEquals(ensembl, sf.getFeatureGroup());
+
+ // AAA -> TAA -> stop codon
+ sf = sfs.get(3);
+ assertEquals(1, sf.getBegin());
+ assertEquals(1, sf.getEnd());
+ assertEquals("stop_gained", sf.getType());
+ assertEquals("Aaa/Taa", sf.getDescription());
+ assertEquals("var3", sf.getValue("id"));
+ assertEquals("Bad", sf.getValue("clinical_significance"));
+ assertEquals("id=var3;clinical_significance=Bad", sf.getAttributes());
+ assertEquals(1, sf.links.size());
+ assertEquals(
+ "Aaa/Taa var3|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var3",
+ sf.links.get(0));
+ assertEquals(dbSnp, sf.getFeatureGroup());
+
+ // AAA -> AAG synonymous
+ sf = sfs.get(4);
+ assertEquals(1, sf.getBegin());
+ assertEquals(1, sf.getEnd());
+ assertEquals("synonymous_variant", sf.getType());
+ assertEquals("aaA/aaG", sf.getDescription());
+ assertEquals("var4", sf.getValue("id"));
+ assertEquals("None", sf.getValue("clinical_significance"));
+ assertEquals("id=var4;clinical_significance=None", sf.getAttributes());
+ assertEquals(1, sf.links.size());
+ assertEquals(
+ "aaA/aaG var4|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var4",
+ sf.links.get(0));
+ assertEquals(cosmic, sf.getFeatureGroup());
+
+ // TTT -> TTC synonymous
+ sf = sfs.get(5);
+ assertEquals(2, sf.getBegin());
+ assertEquals(2, sf.getEnd());
+ assertEquals("synonymous_variant", sf.getType());
+ assertEquals("ttT/ttC", sf.getDescription());
+ assertEquals("var6", sf.getValue("id"));
+ assertNull(sf.getValue("clinical_significance"));
+ assertEquals("id=var6", sf.getAttributes());
+ assertEquals(1, sf.links.size());
+ assertEquals(
+ "ttT/ttC var6|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var6",
+ sf.links.get(0));
+ assertEquals(dbSnp, sf.getFeatureGroup());
+
+ // var7 generates two distinct protein variant features (two alleles)
+ // CCC -> CGC -> P/R
+ sf = sfs.get(6);
+ assertEquals(3, sf.getBegin());
+ assertEquals(3, sf.getEnd());
+ assertEquals("nonsynonymous_variant", sf.getType());
+ assertEquals("p.Pro3Arg", sf.getDescription());
+ assertEquals("var7", sf.getValue("id"));
+ assertEquals("Good", sf.getValue("clinical_significance"));
+ assertEquals("id=var7;clinical_significance=Good", sf.getAttributes());
+ assertEquals(1, sf.links.size());
+ assertEquals(
+ "p.Pro3Arg var7|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var7",
+ sf.links.get(0));
+ assertEquals(cosmic, sf.getFeatureGroup());
+
+ // CCC -> CAC -> P/H
+ sf = sfs.get(7);
+ assertEquals(3, sf.getBegin());
+ assertEquals(3, sf.getEnd());
+ assertEquals("nonsynonymous_variant", sf.getType());
+ assertEquals("p.Pro3His", sf.getDescription());
+ assertEquals("var7", sf.getValue("id"));
+ assertEquals("Good", sf.getValue("clinical_significance"));
+ assertEquals("id=var7;clinical_significance=Good", sf.getAttributes());
+ assertEquals(1, sf.links.size());
+ assertEquals(
+ "p.Pro3His var7|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var7",
+ sf.links.get(0));
+ assertEquals(cosmic, sf.getFeatureGroup());
+ }
+
+ /**
+ * Tests for the method that maps the subset of a dna sequence that has CDS
+ * (or subtype) feature, with CDS strand = '-' (reverse)
+ */
+ // test turned off as currently findCdsPositions is not strand-dependent
+ // left in case it comes around again...
+ @Test(groups = "Functional", enabled = false)
+ public void testFindCdsPositions_reverseStrand()
+ {
+ SequenceI dnaSeq = new Sequence("dna", "aaaGGGcccAAATTTttt");
+ dnaSeq.createDatasetSequence();
+ SequenceI ds = dnaSeq.getDatasetSequence();
+
+ // CDS for dna 4-6
+ SequenceFeature sf = new SequenceFeature("CDS", "", 4, 6, 0f, null);
+ sf.setStrand("-");
+ ds.addSequenceFeature(sf);
+ // exon feature should be ignored here
+ sf = new SequenceFeature("exon", "", 7, 9, 0f, null);
+ ds.addSequenceFeature(sf);
+ // CDS for dna 10-12
+ sf = new SequenceFeature("CDS_predicted", "", 10, 12, 0f, null);
+ sf.setStrand("-");
+ ds.addSequenceFeature(sf);
+
+ List<int[]> ranges = AlignmentUtils.findCdsPositions(dnaSeq);
+ /*
+ * verify ranges { [12-10], [6-4] }
+ */
+ assertEquals(6, MappingUtils.getLength(ranges));
+ assertEquals(2, ranges.size());
+ assertEquals(12, ranges.get(0)[0]);
+ assertEquals(10, ranges.get(0)[1]);
+ assertEquals(6, ranges.get(1)[0]);
+ assertEquals(4, ranges.get(1)[1]);
+ }
+
+ /**
+ * Tests for the method that maps the subset of a dna sequence that has CDS
+ * (or subtype) feature - reverse strand case where the start codon is
+ * incomplete.
+ */
+ @Test(groups = "Functional", enabled = false)
+ // test turned off as currently findCdsPositions is not strand-dependent
+ // left in case it comes around again...
+ public void testFindCdsPositions_reverseStrandThreePrimeIncomplete()
+ {
+ SequenceI dnaSeq = new Sequence("dna", "aaagGGCCCaaaTTTttt");
+ dnaSeq.createDatasetSequence();
+ SequenceI ds = dnaSeq.getDatasetSequence();
+
+ // CDS for dna 5-9
+ SequenceFeature sf = new SequenceFeature("CDS", "", 5, 9, 0f, null);
+ sf.setStrand("-");
+ ds.addSequenceFeature(sf);
+ // CDS for dna 13-15
+ sf = new SequenceFeature("CDS_predicted", "", 13, 15, 0f, null);
+ sf.setStrand("-");
+ sf.setPhase("2"); // skip 2 bases to start of next codon
+ ds.addSequenceFeature(sf);
+
+ List<int[]> ranges = AlignmentUtils.findCdsPositions(dnaSeq);
+
+ /*
+ * check the mapping starts with the first complete codon
+ * expect ranges [13, 13], [9, 5]
+ */
+ assertEquals(6, MappingUtils.getLength(ranges));
+ assertEquals(2, ranges.size());
+ assertEquals(13, ranges.get(0)[0]);
+ assertEquals(13, ranges.get(0)[1]);
+ assertEquals(9, ranges.get(1)[0]);
+ assertEquals(5, ranges.get(1)[1]);
+ }
+
+ @Test(groups = "Functional")
+ public void testAlignAs_alternateTranscriptsUngapped()
+ {
+ SequenceI dna1 = new Sequence("dna1", "cccGGGTTTaaa");
+ SequenceI dna2 = new Sequence("dna2", "CCCgggtttAAA");
+ AlignmentI dna = new Alignment(new SequenceI[] { dna1, dna2 });
+ ((Alignment) dna).createDatasetAlignment();
+ SequenceI cds1 = new Sequence("cds1", "GGGTTT");
+ SequenceI cds2 = new Sequence("cds2", "CCCAAA");
+ AlignmentI cds = new Alignment(new SequenceI[] { cds1, cds2 });
+ ((Alignment) cds).createDatasetAlignment();
+
+ AlignedCodonFrame acf = new AlignedCodonFrame();
+ MapList map = new MapList(new int[] { 4, 9 }, new int[] { 1, 6 }, 1, 1);
+ acf.addMap(dna1.getDatasetSequence(), cds1.getDatasetSequence(), map);
+ map = new MapList(new int[] { 1, 3, 10, 12 }, new int[] { 1, 6 }, 1, 1);
+ acf.addMap(dna2.getDatasetSequence(), cds2.getDatasetSequence(), map);
+
+ /*
+ * verify CDS alignment is as:
+ * cccGGGTTTaaa (cdna)
+ * CCCgggtttAAA (cdna)
+ *
+ * ---GGGTTT--- (cds)
+ * CCC------AAA (cds)
+ */
+ dna.addCodonFrame(acf);
+ AlignmentUtils.alignAs(cds, dna);
+ assertEquals("---GGGTTT", cds.getSequenceAt(0).getSequenceAsString());
+ assertEquals("CCC------AAA", cds.getSequenceAt(1).getSequenceAsString());
+ }
+
+ @Test(groups = { "Functional" })
+ public void testAddMappedPositions()
+ {
+ SequenceI from = new Sequence("dna", "ggAA-ATcc-TT-g");
+ SequenceI seq1 = new Sequence("cds", "AAATTT");
+ from.createDatasetSequence();
+ seq1.createDatasetSequence();
+ Mapping mapping = new Mapping(seq1, new MapList(
+ new int[] { 3, 6, 9, 10 }, new int[] { 1, 6 }, 1, 1));
+ Map<Integer, Map<SequenceI, Character>> map = new TreeMap<>();
+ AlignmentUtils.addMappedPositions(seq1, from, mapping, map);
+
+ /*
+ * verify map has seq1 residues in columns 3,4,6,7,11,12
+ */
+ assertEquals(6, map.size());
+ assertEquals('A', map.get(3).get(seq1).charValue());
+ assertEquals('A', map.get(4).get(seq1).charValue());
+ assertEquals('A', map.get(6).get(seq1).charValue());
+ assertEquals('T', map.get(7).get(seq1).charValue());
+ assertEquals('T', map.get(11).get(seq1).charValue());
+ assertEquals('T', map.get(12).get(seq1).charValue());
+
+ /*
+ *
+ */
+ }
+
+ /**
+ * Test case where the mapping 'from' range includes a stop codon which is
+ * absent in the 'to' range
+ */
+ @Test(groups = { "Functional" })
+ public void testAddMappedPositions_withStopCodon()
+ {
+ SequenceI from = new Sequence("dna", "ggAA-ATcc-TT-g");
+ SequenceI seq1 = new Sequence("cds", "AAATTT");
+ from.createDatasetSequence();
+ seq1.createDatasetSequence();
+ Mapping mapping = new Mapping(seq1, new MapList(
+ new int[] { 3, 6, 9, 10 }, new int[] { 1, 6 }, 1, 1));
+ Map<Integer, Map<SequenceI, Character>> map = new TreeMap<>();
+ AlignmentUtils.addMappedPositions(seq1, from, mapping, map);
+
+ /*
+ * verify map has seq1 residues in columns 3,4,6,7,11,12
+ */
+ assertEquals(6, map.size());
+ assertEquals('A', map.get(3).get(seq1).charValue());
+ assertEquals('A', map.get(4).get(seq1).charValue());
+ assertEquals('A', map.get(6).get(seq1).charValue());
+ assertEquals('T', map.get(7).get(seq1).charValue());
+ assertEquals('T', map.get(11).get(seq1).charValue());
+ assertEquals('T', map.get(12).get(seq1).charValue());
+ }
+
+ /**
+ * Test for the case where the products for which we want CDS are specified.
+ * This is to represent the case where EMBL has CDS mappings to both Uniprot
+ * and EMBLCDSPROTEIN. makeCdsAlignment() should only return the mappings for
+ * the protein sequences specified.
+ */
+ @Test(groups = { "Functional" })
+ public void testMakeCdsAlignment_filterProducts()
+ {
+ SequenceI dna1 = new Sequence("dna1", "aaaGGGcccTTTaaa");
+ SequenceI dna2 = new Sequence("dna2", "GGGcccTTTaaaCCC");
+ SequenceI pep1 = new Sequence("Uniprot|pep1", "GF");
+ SequenceI pep2 = new Sequence("Uniprot|pep2", "GFP");
+ SequenceI pep3 = new Sequence("EMBL|pep3", "GF");
+ SequenceI pep4 = new Sequence("EMBL|pep4", "GFP");
+ dna1.createDatasetSequence();
+ dna2.createDatasetSequence();
+ pep1.createDatasetSequence();
+ pep2.createDatasetSequence();
+ pep3.createDatasetSequence();
+ pep4.createDatasetSequence();
+ AlignmentI dna = new Alignment(new SequenceI[] { dna1, dna2 });
+ dna.setDataset(null);
+ AlignmentI emblPeptides = new Alignment(new SequenceI[] { pep3, pep4 });
+ emblPeptides.setDataset(null);
+
+ AlignedCodonFrame acf = new AlignedCodonFrame();
+ MapList map = new MapList(new int[] { 4, 6, 10, 12 },
+ new int[] { 1, 2 }, 3, 1);
+ acf.addMap(dna1.getDatasetSequence(), pep1.getDatasetSequence(), map);
+ acf.addMap(dna1.getDatasetSequence(), pep3.getDatasetSequence(), map);
+ dna.addCodonFrame(acf);
+
+ acf = new AlignedCodonFrame();
+ map = new MapList(new int[] { 1, 3, 7, 9, 13, 15 }, new int[] { 1, 3 },
+ 3, 1);
+ acf.addMap(dna2.getDatasetSequence(), pep2.getDatasetSequence(), map);
+ acf.addMap(dna2.getDatasetSequence(), pep4.getDatasetSequence(), map);
+ dna.addCodonFrame(acf);
+
+ /*
+ * execute method under test to find CDS for EMBL peptides only
+ */
+ AlignmentI cds = AlignmentUtils.makeCdsAlignment(new SequenceI[] {
+ dna1, dna2 }, dna.getDataset(), emblPeptides.getSequencesArray());
+
+ assertEquals(2, cds.getSequences().size());
+ assertEquals("GGGTTT", cds.getSequenceAt(0).getSequenceAsString());
+ assertEquals("GGGTTTCCC", cds.getSequenceAt(1).getSequenceAsString());
+
+ /*
+ * verify shared, extended alignment dataset
+ */
+ assertSame(dna.getDataset(), cds.getDataset());
+ assertTrue(dna.getDataset().getSequences()
+ .contains(cds.getSequenceAt(0).getDatasetSequence()));
+ assertTrue(dna.getDataset().getSequences()
+ .contains(cds.getSequenceAt(1).getDatasetSequence()));
+
+ /*
+ * Verify mappings from CDS to peptide, cDNA to CDS, and cDNA to peptide
+ * the mappings are on the shared alignment dataset
+ */
+ List<AlignedCodonFrame> cdsMappings = cds.getDataset().getCodonFrames();
+ /*
+ * 6 mappings, 2*(DNA->CDS), 2*(DNA->Pep), 2*(CDS->Pep)
+ */
+ assertEquals(6, cdsMappings.size());
+
+ /*
+ * verify that mapping sets for dna and cds alignments are different
+ * [not current behaviour - all mappings are on the alignment dataset]
+ */
+ // select -> subselect type to test.
+ // Assert.assertNotSame(dna.getCodonFrames(), cds.getCodonFrames());
+ // assertEquals(4, dna.getCodonFrames().size());
+ // assertEquals(4, cds.getCodonFrames().size());
+
+ /*
+ * Two mappings involve pep3 (dna to pep3, cds to pep3)
+ * Mapping from pep3 to GGGTTT in first new exon sequence
+ */
+ List<AlignedCodonFrame> pep3Mappings = MappingUtils
+ .findMappingsForSequence(pep3, cdsMappings);
+ assertEquals(2, pep3Mappings.size());
+ List<AlignedCodonFrame> mappings = MappingUtils
+ .findMappingsForSequence(cds.getSequenceAt(0), pep3Mappings);
+ assertEquals(1, mappings.size());
+
+ // map G to GGG
+ SearchResultsI sr = MappingUtils.buildSearchResults(pep3, 1, mappings);
+ assertEquals(1, sr.getResults().size());
+ SearchResultMatchI m = sr.getResults().get(0);
+ assertSame(cds.getSequenceAt(0).getDatasetSequence(), m.getSequence());
+ assertEquals(1, m.getStart());
+ assertEquals(3, m.getEnd());
+ // map F to TTT
+ sr = MappingUtils.buildSearchResults(pep3, 2, mappings);
+ m = sr.getResults().get(0);
+ assertSame(cds.getSequenceAt(0).getDatasetSequence(), m.getSequence());
+ assertEquals(4, m.getStart());
+ assertEquals(6, m.getEnd());
+
+ /*
+ * Two mappings involve pep4 (dna to pep4, cds to pep4)
+ * Verify mapping from pep4 to GGGTTTCCC in second new exon sequence
+ */
+ List<AlignedCodonFrame> pep4Mappings = MappingUtils
+ .findMappingsForSequence(pep4, cdsMappings);
+ assertEquals(2, pep4Mappings.size());
+ mappings = MappingUtils.findMappingsForSequence(cds.getSequenceAt(1),
+ pep4Mappings);
+ assertEquals(1, mappings.size());
+ // map G to GGG
+ sr = MappingUtils.buildSearchResults(pep4, 1, mappings);
+ assertEquals(1, sr.getResults().size());
+ m = sr.getResults().get(0);
+ assertSame(cds.getSequenceAt(1).getDatasetSequence(), m.getSequence());
+ assertEquals(1, m.getStart());
+ assertEquals(3, m.getEnd());
+ // map F to TTT
+ sr = MappingUtils.buildSearchResults(pep4, 2, mappings);
+ m = sr.getResults().get(0);
+ assertSame(cds.getSequenceAt(1).getDatasetSequence(), m.getSequence());
+ assertEquals(4, m.getStart());
+ assertEquals(6, m.getEnd());
+ // map P to CCC
+ sr = MappingUtils.buildSearchResults(pep4, 3, mappings);
+ m = sr.getResults().get(0);
+ assertSame(cds.getSequenceAt(1).getDatasetSequence(), m.getSequence());
+ assertEquals(7, m.getStart());
+ assertEquals(9, m.getEnd());
+ }
+
+ /**
+ * Test the method that just copies aligned sequences, provided all sequences
+ * to be aligned share the aligned sequence's dataset
+ */
+ @Test(groups = "Functional")
+ public void testAlignAsSameSequences()
+ {
+ SequenceI dna1 = new Sequence("dna1", "cccGGGTTTaaa");
+ SequenceI dna2 = new Sequence("dna2", "CCCgggtttAAA");
+ AlignmentI al1 = new Alignment(new SequenceI[] { dna1, dna2 });
+ ((Alignment) al1).createDatasetAlignment();
+
+ SequenceI dna3 = new Sequence(dna1);
+ SequenceI dna4 = new Sequence(dna2);
+ assertSame(dna3.getDatasetSequence(), dna1.getDatasetSequence());
+ assertSame(dna4.getDatasetSequence(), dna2.getDatasetSequence());
+ String seq1 = "-cc-GG-GT-TT--aaa";
+ dna3.setSequence(seq1);
+ String seq2 = "C--C-Cgg--gtt-tAA-A-";
+ dna4.setSequence(seq2);
+ AlignmentI al2 = new Alignment(new SequenceI[] { dna3, dna4 });
+ ((Alignment) al2).createDatasetAlignment();
+
+ assertTrue(AlignmentUtils.alignAsSameSequences(al1, al2));
+ assertEquals(seq1, al1.getSequenceAt(0).getSequenceAsString());
+ assertEquals(seq2, al1.getSequenceAt(1).getSequenceAsString());
+
+ /*
+ * add another sequence to 'aligned' - should still succeed, since
+ * unaligned sequences still share a dataset with aligned sequences
+ */
+ SequenceI dna5 = new Sequence("dna5", "CCCgggtttAAA");
+ dna5.createDatasetSequence();
+ al2.addSequence(dna5);
+ assertTrue(AlignmentUtils.alignAsSameSequences(al1, al2));
+ assertEquals(seq1, al1.getSequenceAt(0).getSequenceAsString());
+ assertEquals(seq2, al1.getSequenceAt(1).getSequenceAsString());
+
+ /*
+ * add another sequence to 'unaligned' - should fail, since now not
+ * all unaligned sequences share a dataset with aligned sequences
+ */
+ SequenceI dna6 = new Sequence("dna6", "CCCgggtttAAA");
+ dna6.createDatasetSequence();
+ al1.addSequence(dna6);
+ // JAL-2110 JBP Comment: what's the use case for this behaviour ?
+ assertFalse(AlignmentUtils.alignAsSameSequences(al1, al2));
+ }
+
+ @Test(groups = "Functional")
+ public void testAlignAsSameSequencesMultipleSubSeq()
+ {
+ SequenceI dna1 = new Sequence("dna1", "cccGGGTTTaaa");
+ SequenceI dna2 = new Sequence("dna2", "CCCgggtttAAA");
+ SequenceI as1 = dna1.deriveSequence();
+ SequenceI as2 = dna1.deriveSequence().getSubSequence(3, 7);
+ SequenceI as3 = dna2.deriveSequence();
+ as1.insertCharAt(6, 5, '-');
+ String s_as1 = as1.getSequenceAsString();
+ as2.insertCharAt(6, 5, '-');
+ String s_as2 = as2.getSequenceAsString();
+ as3.insertCharAt(6, 5, '-');
+ String s_as3 = as3.getSequenceAsString();
+ AlignmentI aligned = new Alignment(new SequenceI[] { as1, as2, as3 });
+
+ // why do we need to cast this still ?
+ ((Alignment) aligned).createDatasetAlignment();
+ SequenceI uas1 = dna1.deriveSequence();
+ SequenceI uas2 = dna1.deriveSequence().getSubSequence(3, 7);
+ SequenceI uas3 = dna2.deriveSequence();
+ AlignmentI tobealigned = new Alignment(new SequenceI[] { uas1, uas2,
+ uas3 });
+ ((Alignment) tobealigned).createDatasetAlignment();
+
+ assertTrue(AlignmentUtils.alignAsSameSequences(tobealigned, aligned));
+ assertEquals(s_as1, uas1.getSequenceAsString());
+ assertEquals(s_as2, uas2.getSequenceAsString());
+ assertEquals(s_as3, uas3.getSequenceAsString());
+ }
+
+ @Test(groups = { "Functional" })
+ public void testTransferGeneLoci()
+ {
+ SequenceI from = new Sequence("transcript",
+ "aaacccgggTTTAAACCCGGGtttaaacccgggttt");
+ SequenceI to = new Sequence("CDS", "TTTAAACCCGGG");
+ MapList map = new MapList(new int[] { 1, 12 }, new int[] { 10, 21 }, 1,
+ 1);
+
+ /*
+ * first with nothing to transfer
+ */
+ AlignmentUtils.transferGeneLoci(from, map, to);
+ assertNull(to.getGeneLoci());
+
+ /*
+ * next with gene loci set on 'from' sequence
+ */
+ int[] exons = new int[] { 100, 105, 155, 164, 210, 229 };
+ MapList geneMap = new MapList(new int[] { 1, 36 }, exons, 1, 1);
+ from.setGeneLoci("human", "GRCh38", "7", geneMap);
+ AlignmentUtils.transferGeneLoci(from, map, to);
+
+ GeneLociI toLoci = to.getGeneLoci();
+ assertNotNull(toLoci);
+ // DBRefEntry constructor upper-cases 'source'
+ assertEquals("HUMAN", toLoci.getSpeciesId());
+ assertEquals("GRCh38", toLoci.getAssemblyId());
+ assertEquals("7", toLoci.getChromosomeId());
+
+ /*
+ * transcript 'exons' are 1-6, 7-16, 17-36
+ * CDS 1:12 is transcript 10-21
+ * transcript 'CDS' is 10-16, 17-21
+ * which is 'gene' 158-164, 210-214
+ */
+ MapList toMap = toLoci.getMap();
+ assertEquals(1, toMap.getFromRanges().size());
+ assertEquals(2, toMap.getFromRanges().get(0).length);
+ assertEquals(1, toMap.getFromRanges().get(0)[0]);
+ assertEquals(12, toMap.getFromRanges().get(0)[1]);
+ assertEquals(2, toMap.getToRanges().size());
+ assertEquals(2, toMap.getToRanges().get(0).length);
+ assertEquals(158, toMap.getToRanges().get(0)[0]);
+ assertEquals(164, toMap.getToRanges().get(0)[1]);
+ assertEquals(210, toMap.getToRanges().get(1)[0]);
+ assertEquals(214, toMap.getToRanges().get(1)[1]);
+ // or summarised as (but toString might change in future):
+ assertEquals("[ [1, 12] ] 1:1 to [ [158, 164] [210, 214] ]",
+ toMap.toString());
+
+ /*
+ * an existing value is not overridden
+ */
+ geneMap = new MapList(new int[] { 1, 36 }, new int[] { 36, 1 }, 1, 1);
+ from.setGeneLoci("inhuman", "GRCh37", "6", geneMap);
+ AlignmentUtils.transferGeneLoci(from, map, to);
+ assertEquals("GRCh38", toLoci.getAssemblyId());
+ assertEquals("7", toLoci.getChromosomeId());
+ toMap = toLoci.getMap();
+ assertEquals("[ [1, 12] ] 1:1 to [ [158, 164] [210, 214] ]",
+ toMap.toString());
+ }
+
+ /**
+ * Tests for the method that maps nucleotide to protein based on CDS features
+ */
+ @Test(groups = "Functional")
+ public void testMapCdsToProtein()
+ {
+ SequenceI peptide = new Sequence("pep", "KLQ");
+
+ /*
+ * Case 1: CDS 3 times length of peptide
+ * NB method only checks lengths match, not translation
+ */
+ SequenceI dna = new Sequence("dna", "AACGacgtCTCCT");
+ dna.createDatasetSequence();
+ dna.addSequenceFeature(new SequenceFeature("CDS", "", 1, 4, null));
+ dna.addSequenceFeature(new SequenceFeature("CDS", "", 9, 13, null));
+ MapList ml = AlignmentUtils.mapCdsToProtein(dna, peptide);
+ assertEquals(3, ml.getFromRatio());
+ assertEquals(1, ml.getToRatio());
+ assertEquals("[[1, 3]]",
+ Arrays.deepToString(ml.getToRanges().toArray()));
+ assertEquals("[[1, 4], [9, 13]]",
+ Arrays.deepToString(ml.getFromRanges().toArray()));
+
+ /*
+ * Case 2: CDS 3 times length of peptide + stop codon
+ * (note code does not currently check trailing codon is a stop codon)
+ */
+ dna = new Sequence("dna", "AACGacgtCTCCTCCC");
+ dna.createDatasetSequence();
+ dna.addSequenceFeature(new SequenceFeature("CDS", "", 1, 4, null));
+ dna.addSequenceFeature(new SequenceFeature("CDS", "", 9, 16, null));
+ ml = AlignmentUtils.mapCdsToProtein(dna, peptide);
+ assertEquals(3, ml.getFromRatio());
+ assertEquals(1, ml.getToRatio());
+ assertEquals("[[1, 3]]",
+ Arrays.deepToString(ml.getToRanges().toArray()));
+ assertEquals("[[1, 4], [9, 13]]",
+ Arrays.deepToString(ml.getFromRanges().toArray()));
+
+ /*
+ * Case 3: CDS longer than 3 * peptide + stop codon - no mapping is made
+ */
+ dna = new Sequence("dna", "AACGacgtCTCCTTGATCA");
+ dna.createDatasetSequence();
+ dna.addSequenceFeature(new SequenceFeature("CDS", "", 1, 4, null));
+ dna.addSequenceFeature(new SequenceFeature("CDS", "", 9, 19, null));
+ ml = AlignmentUtils.mapCdsToProtein(dna, peptide);
+ assertNull(ml);
+
+ /*
+ * Case 4: CDS shorter than 3 * peptide - no mapping is made
+ */
+ dna = new Sequence("dna", "AACGacgtCTCC");
+ dna.createDatasetSequence();
+ dna.addSequenceFeature(new SequenceFeature("CDS", "", 1, 4, null));
+ dna.addSequenceFeature(new SequenceFeature("CDS", "", 9, 12, null));
+ ml = AlignmentUtils.mapCdsToProtein(dna, peptide);
+ assertNull(ml);
+
+ /*
+ * Case 5: CDS 3 times length of peptide + part codon - mapping is truncated
+ */
+ dna = new Sequence("dna", "AACGacgtCTCCTTG");
+ dna.createDatasetSequence();
+ dna.addSequenceFeature(new SequenceFeature("CDS", "", 1, 4, null));
+ dna.addSequenceFeature(new SequenceFeature("CDS", "", 9, 15, null));
+ ml = AlignmentUtils.mapCdsToProtein(dna, peptide);
+ assertEquals(3, ml.getFromRatio());
+ assertEquals(1, ml.getToRatio());
+ assertEquals("[[1, 3]]",
+ Arrays.deepToString(ml.getToRanges().toArray()));
+ assertEquals("[[1, 4], [9, 13]]",
+ Arrays.deepToString(ml.getFromRanges().toArray()));
+
+ /*
+ * Case 6: incomplete start codon corresponding to X in peptide
+ */
+ dna = new Sequence("dna", "ACGacgtCTCCTTGG");
+ dna.createDatasetSequence();
+ SequenceFeature sf = new SequenceFeature("CDS", "", 1, 3, null);
+ sf.setPhase("2"); // skip 2 positions (AC) to start of next codon (GCT)
+ dna.addSequenceFeature(sf);
+ dna.addSequenceFeature(new SequenceFeature("CDS", "", 8, 15, null));
+ peptide = new Sequence("pep", "XLQ");
+ ml = AlignmentUtils.mapCdsToProtein(dna, peptide);
+ assertEquals("[[2, 3]]",
+ Arrays.deepToString(ml.getToRanges().toArray()));
+ assertEquals("[[3, 3], [8, 12]]",
+ Arrays.deepToString(ml.getFromRanges().toArray()));
+ }
+
+ /**
+ * Tests for the method that locates the CDS sequence that has a mapping to
+ * the given protein. That is, given a transcript-to-peptide mapping, find the
+ * cds-to-peptide mapping that relates to both, and return the CDS sequence.
+ */
+ @Test
+ public void testFindCdsForProtein()
+ {
+ List<AlignedCodonFrame> mappings = new ArrayList<>();
+ AlignedCodonFrame acf1 = new AlignedCodonFrame();
+ mappings.add(acf1);
+
+ SequenceI dna1 = new Sequence("dna1", "cgatATcgGCTATCTATGacg");
+ dna1.createDatasetSequence();
+
+ // NB we currently exclude STOP codon from CDS sequences
+ // the test would need to change if this changes in future
+ SequenceI cds1 = new Sequence("cds1", "ATGCTATCT");
+ cds1.createDatasetSequence();
+
+ SequenceI pep1 = new Sequence("pep1", "MLS");
+ pep1.createDatasetSequence();
+ List<AlignedCodonFrame> seqMappings = new ArrayList<>();
+ MapList mapList = new MapList(
+ new int[]
+ { 5, 6, 9, 15 }, new int[] { 1, 3 }, 3, 1);
+ Mapping dnaToPeptide = new Mapping(pep1.getDatasetSequence(), mapList);
+
+ // add dna to peptide mapping
+ seqMappings.add(acf1);
+ acf1.addMap(dna1.getDatasetSequence(), pep1.getDatasetSequence(),
+ mapList);
+
+ /*
+ * first case - no dna-to-CDS mapping exists - search fails
+ */
+ SequenceI seq = AlignmentUtils.findCdsForProtein(mappings, dna1,
+ seqMappings, dnaToPeptide);
+ assertNull(seq);
+
+ /*
+ * second case - CDS-to-peptide mapping exists but no dna-to-CDS
+ * - search fails
+ */
+ // todo this test fails if the mapping is added to acf1, not acf2
+ // need to tidy up use of lists of mappings in AlignedCodonFrame
+ AlignedCodonFrame acf2 = new AlignedCodonFrame();
+ mappings.add(acf2);
+ MapList cdsToPeptideMapping = new MapList(new int[]
+ { 1, 9 }, new int[] { 1, 3 }, 3, 1);
+ acf2.addMap(cds1.getDatasetSequence(), pep1.getDatasetSequence(),
+ cdsToPeptideMapping);
+ assertNull(AlignmentUtils.findCdsForProtein(mappings, dna1, seqMappings,
+ dnaToPeptide));
+
+ /*
+ * third case - add dna-to-CDS mapping - CDS is now found!
+ */
+ MapList dnaToCdsMapping = new MapList(new int[] { 5, 6, 9, 15 },
+ new int[]
+ { 1, 9 }, 1, 1);
+ acf1.addMap(dna1.getDatasetSequence(), cds1.getDatasetSequence(),
+ dnaToCdsMapping);
+ seq = AlignmentUtils.findCdsForProtein(mappings, dna1, seqMappings,
+ dnaToPeptide);
+ assertSame(seq, cds1.getDatasetSequence());
+ }
+
+ /**
+ * Tests for the method that locates the CDS sequence that has a mapping to
+ * the given protein. That is, given a transcript-to-peptide mapping, find the
+ * cds-to-peptide mapping that relates to both, and return the CDS sequence.
+ * This test is for the case where transcript and CDS are the same length.
+ */
+ @Test
+ public void testFindCdsForProtein_noUTR()
+ {
+ List<AlignedCodonFrame> mappings = new ArrayList<>();
+ AlignedCodonFrame acf1 = new AlignedCodonFrame();
+ mappings.add(acf1);
+
+ SequenceI dna1 = new Sequence("dna1", "ATGCTATCTTAA");
+ dna1.createDatasetSequence();
+
+ // NB we currently exclude STOP codon from CDS sequences
+ // the test would need to change if this changes in future
+ SequenceI cds1 = new Sequence("cds1", "ATGCTATCT");
+ cds1.createDatasetSequence();
+
+ SequenceI pep1 = new Sequence("pep1", "MLS");
+ pep1.createDatasetSequence();
+ List<AlignedCodonFrame> seqMappings = new ArrayList<>();
+ MapList mapList = new MapList(
+ new int[]
+ { 1, 9 }, new int[] { 1, 3 }, 3, 1);
+ Mapping dnaToPeptide = new Mapping(pep1.getDatasetSequence(), mapList);
+
+ // add dna to peptide mapping
+ seqMappings.add(acf1);
+ acf1.addMap(dna1.getDatasetSequence(), pep1.getDatasetSequence(),
+ mapList);
+
+ /*
+ * first case - transcript lacks CDS features - it appears to be
+ * the CDS sequence and is returned
+ */
+ SequenceI seq = AlignmentUtils.findCdsForProtein(mappings, dna1,
+ seqMappings, dnaToPeptide);
+ assertSame(seq, dna1.getDatasetSequence());
+
+ /*
+ * second case - transcript has CDS feature - this means it is
+ * not returned as a match for CDS (CDS sequences don't have CDS features)
+ */
+ dna1.addSequenceFeature(
+ new SequenceFeature(SequenceOntologyI.CDS, "cds", 1, 12, null));
+ seq = AlignmentUtils.findCdsForProtein(mappings, dna1, seqMappings,
+ dnaToPeptide);
+ assertNull(seq);
+
+ /*
+ * third case - CDS-to-peptide mapping exists but no dna-to-CDS
+ * - search fails
+ */
+ // todo this test fails if the mapping is added to acf1, not acf2
+ // need to tidy up use of lists of mappings in AlignedCodonFrame
+ AlignedCodonFrame acf2 = new AlignedCodonFrame();
+ mappings.add(acf2);
+ MapList cdsToPeptideMapping = new MapList(new int[]
+ { 1, 9 }, new int[] { 1, 3 }, 3, 1);
+ acf2.addMap(cds1.getDatasetSequence(), pep1.getDatasetSequence(),
+ cdsToPeptideMapping);
+ assertNull(AlignmentUtils.findCdsForProtein(mappings, dna1, seqMappings,
+ dnaToPeptide));
+
+ /*
+ * fourth case - add dna-to-CDS mapping - CDS is now found!
+ */
+ MapList dnaToCdsMapping = new MapList(new int[] { 1, 9 },
+ new int[]
+ { 1, 9 }, 1, 1);
+ acf1.addMap(dna1.getDatasetSequence(), cds1.getDatasetSequence(),
+ dnaToCdsMapping);
+ seq = AlignmentUtils.findCdsForProtein(mappings, dna1, seqMappings,
+ dnaToPeptide);
+ assertSame(seq, cds1.getDatasetSequence());
+ }