import static org.testng.AssertJUnit.assertSame;
import static org.testng.AssertJUnit.assertTrue;
+import jalview.analysis.AlignmentUtils.DnaVariant;
import jalview.datamodel.AlignedCodonFrame;
import jalview.datamodel.Alignment;
import jalview.datamodel.AlignmentAnnotation;
import java.util.LinkedHashMap;
import java.util.List;
import java.util.Map;
+import java.util.TreeMap;
import org.testng.annotations.Test;
/*
* first with no variants on dna
*/
- LinkedHashMap<Integer, String[][]> variantsMap = AlignmentUtils
+ LinkedHashMap<Integer, List<DnaVariant>[]> variantsMap = AlignmentUtils
.buildDnaVariantsMap(dna, map);
assertTrue(variantsMap.isEmpty());
- // single allele codon 1, on base 1
- SequenceFeature sf = new SequenceFeature("sequence_variant", "", 1, 1,
+ /*
+ * 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);
- sf.setValue("alleles", "T");
- dna.addSequenceFeature(sf);
-
- // two alleles codon 2, on bases 2 and 3
- sf = new SequenceFeature("sequence_variant", "", 5, 5, 0f, null);
- sf.setValue("alleles", "T");
- dna.addSequenceFeature(sf);
- sf = new SequenceFeature("sequence_variant", "", 6, 6, 0f, null);
- sf.setValue("alleles", "G");
- dna.addSequenceFeature(sf);
-
- // two alleles codon 3, both on base 2
- sf = new SequenceFeature("sequence_variant", "", 8, 8, 0f, null);
- sf.setValue("alleles", "C, G");
- dna.addSequenceFeature(sf);
+ 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
- sf = new SequenceFeature("sequence_variant", "", 13, 13, 0f, null);
- sf.setValue("alleles", "C, G"); // (C duplicates given base value)
- dna.addSequenceFeature(sf);
- sf = new SequenceFeature("sequence_variant", "", 14, 14, 0f, null);
- sf.setValue("alleles", "g, a"); // should force to upper-case
- dna.addSequenceFeature(sf);
- sf = new SequenceFeature("sequence_variant", "", 15, 15, 0f, null);
- sf.setValue("alleles", "A, T");
- dna.addSequenceFeature(sf);
+ /*
+ * 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());
- assertTrue(Arrays.deepEquals(new String[][] { { "A", "T" }, { "T" },
- { "G" } }, variantsMap.get(1)));
- assertTrue(Arrays.deepEquals(new String[][] { { "A" }, { "A", "T" },
- { "A", "G" } }, variantsMap.get(2)));
- assertTrue(Arrays.deepEquals(new String[][] { { "T" },
- { "T", "C", "G" }, { "T" } }, variantsMap.get(3)));
- // duplicated bases are not removed here, handled in computePeptideVariants
- assertTrue(Arrays.deepEquals(new String[][] { { "C", "C", "G" },
- { "C", "G", "A" }, { "C", "A", "T" } }, variantsMap.get(5)));
+
+ /*
+ * 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
}
/**
@Test(groups = "Functional")
public void testComputePeptideVariants()
{
- String[][] codonVariants = new String[][] { { "A" }, { "G" }, { "T" } };
-
- /*
- * AGT codes for S - this is not included in the variants returned
- */
- List<String> variants = AlignmentUtils.computePeptideVariants(codonVariants, "S");
- assertEquals("[]", variants.toString());
-
- // S is reported if it differs from the current value (A):
- variants = AlignmentUtils.computePeptideVariants(codonVariants, "A");
- assertEquals("[S]", variants.toString());
-
/*
- * synonymous variant is not reported
+ * scenario: AAATTTCCC codes for KFP, with variants
+ * GAA -> E
+ * CAA -> Q
+ * AAG synonymous
+ * AAT -> N
+ * TTC synonymous
+ * CAC,CGC -> H,R (as one variant)
*/
- codonVariants = new String[][] { { "A" }, { "G" }, { "C", "T" } };
- // AGC and AGT both code for S
- variants = AlignmentUtils.computePeptideVariants(codonVariants, "s");
- assertEquals("[]", variants.toString());
-
+ SequenceI peptide = new Sequence("pep/10-12", "KFP");
+
/*
- * equivalent variants are only reported once
+ * two distinct variants for codon 1 position 1
+ * second one has clinical significance
*/
- codonVariants = new String[][] { { "C" }, { "T" },
- { "A", "C", "G", "T" } };
- // CTA CTC CTG CTT all code for L
- variants = AlignmentUtils.computePeptideVariants(codonVariants, "S");
- assertEquals("[L]", variants.toString());
-
+ SequenceFeature sf1 = new SequenceFeature("sequence_variant", "", 1, 1,
+ 0f, null);
+ sf1.setValue("alleles", "A,G"); // GAA -> E
+ sf1.setValue("ID", "var1.125A>G");
+ SequenceFeature sf2 = new SequenceFeature("sequence_variant", "", 1, 1,
+ 0f, null);
+ sf2.setValue("alleles", "A,C"); // CAA -> Q
+ sf2.setValue("ID", "var2");
+ sf2.setValue("clinical_significance", "Dodgy");
+ SequenceFeature sf3 = new SequenceFeature("sequence_variant", "", 3, 3,
+ 0f, null);
+ sf3.setValue("alleles", "A,G"); // synonymous
+ sf3.setValue("ID", "var3");
+ sf3.setValue("clinical_significance", "None");
+ SequenceFeature sf4 = new SequenceFeature("sequence_variant", "", 3, 3,
+ 0f, null);
+ sf4.setValue("alleles", "A,T"); // AAT -> N
+ sf4.setValue("ID", "sequence_variant:var4"); // prefix gets stripped off
+ sf4.setValue("clinical_significance", "Benign");
+ SequenceFeature sf5 = new SequenceFeature("sequence_variant", "", 6, 6,
+ 0f, null);
+ sf5.setValue("alleles", "T,C"); // synonymous
+ sf5.setValue("ID", "var5");
+ sf5.setValue("clinical_significance", "Bad");
+ SequenceFeature sf6 = new SequenceFeature("sequence_variant", "", 8, 8,
+ 0f, null);
+ sf6.setValue("alleles", "C,A,G"); // CAC,CGC -> H,R
+ sf6.setValue("ID", "var6");
+ sf6.setValue("clinical_significance", "Good");
+
+ List<DnaVariant> codon1Variants = new ArrayList<DnaVariant>();
+ List<DnaVariant> codon2Variants = new ArrayList<DnaVariant>();
+ List<DnaVariant> codon3Variants = new ArrayList<DnaVariant>();
+ List<DnaVariant> codonVariants[] = new ArrayList[3];
+ codonVariants[0] = codon1Variants;
+ codonVariants[1] = codon2Variants;
+ codonVariants[2] = codon3Variants;
+
/*
- * vary codons 1 and 2; variant products are sorted and non-redundant
+ * compute variants for protein position 1
*/
- codonVariants = new String[][] { { "a", "C" }, { "g", "T" }, { "A" } };
- // aga ata cga cta code for R, I, R, L
- variants = AlignmentUtils.computePeptideVariants(codonVariants, "S");
- assertEquals("[I, L, R]", variants.toString());
-
+ codon1Variants.add(new DnaVariant("A", sf1));
+ codon1Variants.add(new DnaVariant("A", sf2));
+ codon2Variants.add(new DnaVariant("A"));
+ codon2Variants.add(new DnaVariant("A"));
+ codon3Variants.add(new DnaVariant("A", sf3));
+ codon3Variants.add(new DnaVariant("A", sf4));
+ AlignmentUtils.computePeptideVariants(peptide, 1, codonVariants);
+
/*
- * vary codons 2 and 3
+ * compute variants for protein position 2
*/
- codonVariants = new String[][] { { "a" }, { "g", "T" }, { "A", "c" } };
- // aga agc ata atc code for R, S, I, I
- variants = AlignmentUtils.computePeptideVariants(codonVariants, "S");
- assertEquals("[I, R]", variants.toString());
-
+ codon1Variants.clear();
+ codon2Variants.clear();
+ codon3Variants.clear();
+ codon1Variants.add(new DnaVariant("T"));
+ codon2Variants.add(new DnaVariant("T"));
+ codon3Variants.add(new DnaVariant("T", sf5));
+ AlignmentUtils.computePeptideVariants(peptide, 2, codonVariants);
+
/*
- * vary codons 1 and 3
+ * compute variants for protein position 3
*/
- codonVariants = new String[][] { { "a", "t" }, { "a" }, { "t", "g" } };
- // aat aag tat tag code for N, K, Y, STOP - STOP sorted to end
- variants = AlignmentUtils.computePeptideVariants(codonVariants, "S");
- assertEquals("[K, N, Y, STOP]", variants.toString());
-
+ codon1Variants.clear();
+ codon2Variants.clear();
+ codon3Variants.clear();
+ codon1Variants.add(new DnaVariant("C"));
+ codon2Variants.add(new DnaVariant("C", sf6));
+ codon3Variants.add(new DnaVariant("C"));
+ AlignmentUtils.computePeptideVariants(peptide, 3, codonVariants);
+
/*
- * vary codons 1, 2 and 3
+ * verify added sequence features for
+ * var1 K -> E
+ * var2 K -> Q
+ * var4 K -> N
+ * var6 P -> H
+ * var6 P -> R
*/
- codonVariants = new String[][] { { "a", "t" }, { "G", "C" },
- { "t", "g" } };
- // agt agg act acg tgt tgg tct tcg code for S, R, T, T, C, W, S, S
- variants = AlignmentUtils.computePeptideVariants(codonVariants, "S");
- assertEquals("[C, R, T, W]", variants.toString());
+ SequenceFeature[] sfs = peptide.getSequenceFeatures();
+ assertEquals(5, sfs.length);
+ SequenceFeature sf = sfs[0];
+ assertEquals(1, sf.getBegin());
+ assertEquals(1, sf.getEnd());
+ assertEquals("K->E", sf.getDescription());
+ assertEquals("var1.125A>G", sf.getValue("ID"));
+ assertNull(sf.getValue("clinical_significance"));
+ assertEquals(1, sf.links.size());
+ // link to variation is urlencoded
+ assertEquals(
+ "K->E var1.125A>G|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var1.125A%3EG",
+ sf.links.get(0));
+ sf = sfs[1];
+ assertEquals(1, sf.getBegin());
+ assertEquals(1, sf.getEnd());
+ assertEquals("K->Q", sf.getDescription());
+ assertEquals("var2", sf.getValue("ID"));
+ assertEquals("Dodgy", sf.getValue("clinical_significance"));
+ assertEquals(1, sf.links.size());
+ assertEquals(
+ "K->Q var2|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var2",
+ sf.links.get(0));
+ sf = sfs[2];
+ assertEquals(1, sf.getBegin());
+ assertEquals(1, sf.getEnd());
+ assertEquals("K->N", sf.getDescription());
+ assertEquals("var4", sf.getValue("ID"));
+ assertEquals("Benign", sf.getValue("clinical_significance"));
+ assertEquals(1, sf.links.size());
+ assertEquals(
+ "K->N var4|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var4",
+ sf.links.get(0));
+ sf = sfs[3];
+ assertEquals(3, sf.getBegin());
+ assertEquals(3, sf.getEnd());
+ assertEquals("P->H", sf.getDescription());
+ assertEquals("var6", sf.getValue("ID"));
+ assertEquals("Good", sf.getValue("clinical_significance"));
+ assertEquals(1, sf.links.size());
+ assertEquals(
+ "P->H var6|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var6",
+ sf.links.get(0));
+ // var5 generates two distinct protein variant features
+ sf = sfs[4];
+ assertEquals(3, sf.getBegin());
+ assertEquals(3, sf.getEnd());
+ assertEquals("P->R", sf.getDescription());
+ assertEquals("var6", sf.getValue("ID"));
+ assertEquals("Good", sf.getValue("clinical_significance"));
+ assertEquals(1, sf.links.size());
+ assertEquals(
+ "P->R var6|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=var6",
+ sf.links.get(0));
}
/**
*/
dna.addCodonFrame(acf);
AlignmentUtils.alignAs(cds, dna);
- assertEquals("---GGGTTT---", cds.getSequenceAt(0).getSequenceAsString());
+ 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<Integer, Map<SequenceI, Character>>();
+ 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<Integer, Map<SequenceI, Character>>();
+ 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());
+ }
}