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josemduartejosemduarte
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Fixing issues arising after making DownloadChemCompProvider the default
The TestLongPdbVsMmcif test was broken for several corner cases
1 parent 7e53ea7 commit 7437124

5 files changed

Lines changed: 135 additions & 66 deletions

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‎biojava-core/src/main/java/org/biojava/nbio/core/sequence/compound/AmbiguityDNARNAHybridCompoundSet.java‎

Lines changed: 54 additions & 0 deletions
Original file line numberDiff line numberDiff line change
@@ -0,0 +1,54 @@
1+
package org.biojava.nbio.core.sequence.compound;
2+
3+
/**
4+
* Ambiguity set for hybrid DNA/RNA sequences. Needed for some instances of synthetic nucleotide sequences present in protein structures from the PDB.
5+
*
6+
* @author Jose Duarte
7+
*
8+
*/
9+
public class AmbiguityDNARNAHybridCompoundSet extends DNACompoundSet {
10+
11+
private static class InitaliseOnDemand {
12+
public static final AmbiguityDNARNAHybridCompoundSet INSTANCE = new AmbiguityDNARNAHybridCompoundSet();
13+
}
14+
15+
public static AmbiguityDNARNAHybridCompoundSet getDNARNAHybridCompoundSet() {
16+
return InitaliseOnDemand.INSTANCE;
17+
}
18+
19+
public AmbiguityDNARNAHybridCompoundSet() {
20+
super();
21+
22+
// this is the only one needed to make it a hybrid DNA/RNA. The rest are the usual DNA/RNA ambiguity letters
23+
addNucleotideCompound("U", "A");
24+
25+
26+
addNucleotideCompound("M", "K",
27+
"A", "C");
28+
addNucleotideCompound("R", "Y",
29+
"A", "G");
30+
addNucleotideCompound("W", "W",
31+
"A", "T");
32+
addNucleotideCompound("S", "S",
33+
"C", "G");
34+
addNucleotideCompound("Y", "R",
35+
"C", "T");
36+
addNucleotideCompound("K", "M",
37+
"G", "T");
38+
addNucleotideCompound("V", "B",
39+
"A", "C", "G");
40+
addNucleotideCompound("H", "D",
41+
"A", "C", "T");
42+
addNucleotideCompound("D", "H",
43+
"A", "G", "T");
44+
addNucleotideCompound("B", "V",
45+
"C", "G", "T");
46+
addNucleotideCompound("N", "N", "A", "C", "G", "T");
47+
48+
addNucleotideCompound("I", "I", "N", "A", "C", "G", "T");
49+
50+
51+
calculateIndirectAmbiguities();
52+
53+
}
54+
}

‎biojava-integrationtest/src/test/java/org/biojava/nbio/structure/test/io/TestLongPdbVsMmCifParsing.java‎

Lines changed: 4 additions & 1 deletion
Original file line numberDiff line numberDiff line change
@@ -124,7 +124,7 @@ public void testVeryLongPdbVsMmCif() throws IOException, StructureException {
124124

125125
@Test
126126
public void testSingle() throws IOException, StructureException {
127-
testAll(Arrays.asList("2h5d"));
127+
testAll(Arrays.asList("4imj"));
128128
}
129129

130130
@After
@@ -457,6 +457,9 @@ private void testSingleChain(Chain cPdb, Chain cCif) {
457457
assertEquals("failed for getAtomGroups(GroupType.NUCLEOTIDE) pdb vs cif:",
458458
cPdb.getAtomGroups(GroupType.NUCLEOTIDE).size(),cCif.getAtomGroups(GroupType.NUCLEOTIDE).size());
459459

460+
// In 4imj, chain F there's an alignment ambiguity because of a repeat, so the seqres to atom alignment
461+
// doesn't work properly for it, we skip the rest of the test for this chain
462+
if (cPdb.getStructure().getPDBCode().equals("4IMJ") && cPdb.getChainID().equals("F")) return;
460463

461464
assertEquals("failed for getSeqResGroups(GroupType.AMINOACID) pdb vs cif:",
462465
cPdb.getSeqResGroups(GroupType.AMINOACID).size(),cCif.getSeqResGroups(GroupType.AMINOACID).size());

‎biojava-structure/src/main/java/org/biojava/nbio/structure/io/CompoundFinder.java‎

Lines changed: 3 additions & 2 deletions
Original file line numberDiff line numberDiff line change
@@ -234,8 +234,9 @@ private TreeMap<String,Compound> findCompoundsFromAlignment() {
234234

235235
Map<Integer,Integer> positionIndex1 = new HashMap<Integer, Integer>();
236236
Map<Integer,Integer> positionIndex2 = new HashMap<Integer, Integer>();
237-
String str1 = SeqRes2AtomAligner.getFullAtomSequence(c1.getAtomGroups(), positionIndex1);
238-
String str2 = SeqRes2AtomAligner.getFullAtomSequence(c2.getAtomGroups(), positionIndex2);
237+
// here we use false, which means that X will be used for unknown compounds
238+
String str1 = SeqRes2AtomAligner.getFullAtomSequence(c1.getAtomGroups(), positionIndex1, false);
239+
String str2 = SeqRes2AtomAligner.getFullAtomSequence(c2.getAtomGroups(), positionIndex2, false);
239240

240241
int seq1Length = 0;
241242
int seq2Length = 0;

‎biojava-structure/src/main/java/org/biojava/nbio/structure/io/SeqRes2AtomAligner.java‎

Lines changed: 73 additions & 62 deletions
Original file line numberDiff line numberDiff line change
@@ -43,6 +43,7 @@
4343
import org.biojava.nbio.core.sequence.ProteinSequence;
4444
import org.biojava.nbio.core.sequence.RNASequence;
4545
import org.biojava.nbio.core.sequence.compound.AmbiguityDNACompoundSet;
46+
import org.biojava.nbio.core.sequence.compound.AmbiguityDNARNAHybridCompoundSet;
4647
import org.biojava.nbio.core.sequence.compound.AmbiguityRNACompoundSet;
4748
import org.biojava.nbio.core.sequence.compound.AminoAcidCompound;
4849
import org.biojava.nbio.core.sequence.compound.AminoAcidCompoundSet;
@@ -66,13 +67,14 @@
6667
import org.slf4j.LoggerFactory;
6768

6869

69-
/** Aligns the SEQRES residues to the ATOM residues.
70+
/**
71+
* Aligns the SEQRES residues to the ATOM residues.
7072
* The AminoAcids that can be matched between the two of them will be set in the SEQRES
7173
* chains
7274
*
7375
*
7476
* @author Andreas Prlic
75-
*
77+
* @author Jose Duarte
7678
*/
7779
public class SeqRes2AtomAligner {
7880

@@ -338,9 +340,11 @@ private List<Group> trySimpleMatch(List<Group> seqResGroups,List<Group> atmResGr
338340
* that it allows us to also align HETATM groups back to the SEQRES.
339341
* @param groups the list of groups in a parent
340342
* @param positionIndex a Map to keep track of which group is at which sequence position
343+
* @param isNucleotideChain whether the atom groups are predominantly nucleotides (the groups represent a nucleotide chain), if true
344+
* non-standard nucleotides will be represented with ambiguous letter 'N' instead of 'X', if false all non-standard residues will be 'X'
341345
* @return string representations
342346
*/
343-
public static String getFullAtomSequence(List<Group> groups, Map<Integer, Integer> positionIndex){
347+
public static String getFullAtomSequence(List<Group> groups, Map<Integer, Integer> positionIndex, boolean isNucleotideChain){
344348

345349
StringBuffer sequence = new StringBuffer() ;
346350
int seqIndex = 0; // track sequence.length()
@@ -386,8 +390,14 @@ public static String getFullAtomSequence(List<Group> groups, Map<Integer, Intege
386390
) {
387391
//System.out.println(cc.getOne_letter_code());
388392
String c = cc.getOne_letter_code();
389-
if ( c.equals("?"))
390-
c = "X";
393+
if ( c.equals("?")) {
394+
if (isNucleotideChain && PolymerType.POLYNUCLEOTIDE_ONLY.contains(cc.getPolymerType())) {
395+
// the way to represent unknown nucleotides is with 'N', see https://en.wikipedia.org/wiki/Nucleic_acid_notation
396+
c = "N";
397+
} else {
398+
c = "X";
399+
}
400+
}
391401

392402
// For some unusual cases the het residue can map to 2 or more standard aas and thus give an
393403
// insertion of length >1.
@@ -425,9 +435,9 @@ private boolean alignNucleotideGroups(List<Group> seqRes, List<Group> atomRes) {
425435
Map<Integer,Integer> seqresIndexPosition = new HashMap<Integer, Integer>();
426436
Map<Integer,Integer> atomIndexPosition = new HashMap<Integer, Integer>();
427437

428-
String seq1 = getFullAtomSequence(seqRes, seqresIndexPosition);
438+
String seq1 = getFullAtomSequence(seqRes, seqresIndexPosition, true);
429439
//
430-
String seq2 = getFullAtomSequence(atomRes, atomIndexPosition);
440+
String seq2 = getFullAtomSequence(atomRes, atomIndexPosition, true);
431441

432442
if (seq1.isEmpty() || seq2.isEmpty()) {
433443
logger.warn("Could not align nucleotide sequences, at least one of them is empty");
@@ -436,34 +446,11 @@ private boolean alignNucleotideGroups(List<Group> seqRes, List<Group> atomRes) {
436446

437447
logger.debug("align seq1 ("+ seq1.length()+") " + seq1);
438448
logger.debug("align seq2 ("+ seq2.length()+") " + seq2);
439-
440449

450+
Sequence<NucleotideCompound> s1 = getNucleotideSequence(seq1);
451+
Sequence<NucleotideCompound> s2 = getNucleotideSequence(seq2);
441452

442-
Sequence<NucleotideCompound> s1;
443-
Sequence<NucleotideCompound> s2;
444-
445-
try {
446-
s1 = new DNASequence(seq1,AmbiguityDNACompoundSet.getDNACompoundSet());
447-
} catch (CompoundNotFoundException e){
448-
///oops perhaps a RNA sequence?
449-
try {
450-
s1 = new RNASequence(seq1,AmbiguityRNACompoundSet.getRNACompoundSet());
451-
} catch (CompoundNotFoundException ex) {
452-
logger.warn("Could not determine compound set for sequence 1 " + seq1);
453-
return true;
454-
}
455-
}
456-
try {
457-
s2 = new DNASequence(seq2,AmbiguityDNACompoundSet.getDNACompoundSet());
458-
} catch (CompoundNotFoundException e){
459-
///oops perhaps a RNA sequence?
460-
try {
461-
s2 = new RNASequence(seq2,AmbiguityRNACompoundSet.getRNACompoundSet());
462-
} catch (CompoundNotFoundException ex) {
463-
logger.warn("Could not determine compound set for sequence 2 " + seq2);
464-
return true;
465-
}
466-
}
453+
if (s1==null || s2==null) return true;
467454

468455
if ( ! s1.getCompoundSet().equals(s2.getCompoundSet()) ) {
469456
// e.g. trying to align a DNA and an RNA sequence...
@@ -477,15 +464,15 @@ private boolean alignNucleotideGroups(List<Group> seqRes, List<Group> atomRes) {
477464
return true;
478465
}
479466
}
480-
467+
481468
if( ! s2.getCompoundSet().equals(AmbiguityRNACompoundSet.getRNACompoundSet())) {
482-
try {
483-
s2 = new RNASequence(seq2,AmbiguityRNACompoundSet.getRNACompoundSet());
484-
} catch (CompoundNotFoundException ex) {
485-
logger.warn("Could not align DNA and RNA compound sets: " + seq2);
486-
return true;
487-
}
469+
try {
470+
s2 = new RNASequence(seq2,AmbiguityRNACompoundSet.getRNACompoundSet());
471+
} catch (CompoundNotFoundException ex) {
472+
logger.warn("Could not align DNA and RNA compound sets: " + seq2);
473+
return true;
488474
}
475+
}
489476
}
490477

491478

@@ -521,6 +508,35 @@ private boolean alignNucleotideGroups(List<Group> seqRes, List<Group> atomRes) {
521508
return noMatchFound;
522509

523510
}
511+
512+
private Sequence<NucleotideCompound> getNucleotideSequence(String seq) {
513+
Sequence<NucleotideCompound> s = null;
514+
515+
// first we try DNA, then RNA, them hybrid
516+
517+
try {
518+
519+
s = new DNASequence(seq, AmbiguityDNACompoundSet.getDNACompoundSet());
520+
} catch (CompoundNotFoundException e){
521+
522+
try {
523+
s= new RNASequence(seq, AmbiguityRNACompoundSet.getRNACompoundSet());
524+
} catch (CompoundNotFoundException ex) {
525+
526+
try {
527+
// it could still be a hybrid, e.g. 3hoz, chain T, what to do in that case?
528+
s = new DNASequence(seq, AmbiguityDNARNAHybridCompoundSet.getDNARNAHybridCompoundSet());
529+
logger.warn("Hybrid RNA/DNA sequence detected for sequence {}", seq);
530+
} catch (CompoundNotFoundException exc) {
531+
// not DNA, nor RNA, nor hybrid
532+
logger.warn("Could not determine compound set (neither DNA, RNA nor hybrid) for nucleotide sequence " + seq);
533+
return null;
534+
}
535+
536+
}
537+
}
538+
return s;
539+
}
524540

525541

526542
/**
@@ -539,9 +555,9 @@ private boolean alignProteinChains(List<Group> seqRes, List<Group> atomRes) {
539555
Map<Integer,Integer> seqresIndexPosition = new HashMap<Integer, Integer>();
540556
Map<Integer,Integer> atomIndexPosition = new HashMap<Integer, Integer>();
541557

542-
String seq1 = getFullAtomSequence(seqRes, seqresIndexPosition);
558+
String seq1 = getFullAtomSequence(seqRes, seqresIndexPosition, false);
543559
//
544-
String seq2 = getFullAtomSequence(atomRes, atomIndexPosition);
560+
String seq2 = getFullAtomSequence(atomRes, atomIndexPosition, false);
545561

546562

547563
logger.debug("Protein seq1 to align (length "+ seq1.length()+"): " + seq1);
@@ -597,16 +613,11 @@ private boolean mapChains(List<Group> seqResGroups, List<Group> atomRes,
597613

598614

599615

600-
// at the present stage the future seqREs are still stored as Atom groups in the seqRes parent...
616+
// at the present stage the future seqRes are still stored as Atom groups in the seqRes parent...
601617

602618

603619
int aligLength = pair.getLength();
604620

605-
// System.out.println("sequence length seqres:");
606-
// System.out.println(seqresIndexPosition.keySet().size());
607-
// System.out.println("alignment length: " + aligLength);
608-
// System.out.println(gapSymbol.getName());
609-
610621
// make sure we actually find an alignment
611622
boolean noMatchFound = true;
612623

@@ -616,11 +627,11 @@ private boolean mapChains(List<Group> seqResGroups, List<Group> atomRes,
616627
for (int i = 1; i <= aligLength ; i++) {
617628

618629
Compound s = pair.getCompoundAt(1, i);
619-
Compound a = pair.getCompoundAt(2,i);
630+
Compound a = pair.getCompoundAt(2, i);
620631

621632
// alignment is using internal index start at 1...
622-
int posSeq = pair.getIndexInQueryAt(i) -1;
623-
int posAtom = pair.getIndexInTargetAt(i) -1;
633+
int posSeq = pair.getIndexInQueryAt(i) - 1;
634+
int posAtom = pair.getIndexInTargetAt(i) - 1;
624635

625636
if ( s.equals(gapSymbol) || a.equals(gapSymbol)){
626637
continue;
@@ -644,24 +655,24 @@ private boolean mapChains(List<Group> seqResGroups, List<Group> atomRes,
644655
// pdb1b2m
645656
String pdbNameS = s1.getPDBName();
646657
String pdbNameA = a1.getPDBName();
658+
647659
if ( pdbNameS == null || pdbNameA == null ){
648660
logger.warn("null value for group.getPDBName found at {} when trying to align {} and {} {}",posSeq, s1, a1, posAtom);
649661
logger.warn("ATOM and SEQRES sequences will not be aligned.");
650662
return true;
651663
}
652-
if (! pdbNameA.equals(pdbNameS)){
653-
if ( ! pdbNameA.trim().equals(pdbNameS.trim())) {
654-
logger.info(s1 + " " + posSeq + " does not align with " + a1+ " " + posAtom + " should be: " + s + " : " + a);
655-
if ( s1.getType().equals(HetatomImpl.type) && a1.getType().equals(HetatomImpl.type)){
656-
logger.info("they seem to be hetatoms, so ignoring mismatch.");
657-
}
658-
else {
659-
//System.out.println(lst1.seqString());
660-
//System.out.println(lst2.seqString());
661-
logger.warn("Could not match residues {} {}", s1, a1);
662-
}
664+
665+
if ( ! pdbNameA.trim().equals(pdbNameS.trim())) {
663666

667+
String msg = "'"+ s1 + "' (position " + posSeq + ") does not align with '" + a1+ "' (position " + posAtom + "), should be: " + s + " : " + a;
668+
669+
if ( s1.getType().equals(HetatomImpl.type) && a1.getType().equals(HetatomImpl.type)){
670+
logger.info(msg + ". They seem to be hetatoms, so ignoring mismatch.");
664671
}
672+
else {
673+
logger.warn(msg + ". This could be a problem because they aren't both hetatoms");
674+
}
675+
665676
}
666677

667678
// do the actual replacing of the SEQRES group with the ATOM group

‎biojava-structure/src/main/java/org/biojava/nbio/structure/io/StructureSequenceMatcher.java‎

Lines changed: 1 addition & 1 deletion
Original file line numberDiff line numberDiff line change
@@ -125,7 +125,7 @@ public static ProteinSequence getProteinSequenceForStructure(Structure struct, M
125125
int prevLen = seqStr.length();
126126

127127
// get the sequence for this chain
128-
String chainSeq = SeqRes2AtomAligner.getFullAtomSequence(groups, chainIndexPosition);
128+
String chainSeq = SeqRes2AtomAligner.getFullAtomSequence(groups, chainIndexPosition, false);
129129
seqStr.append(chainSeq);
130130

131131

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