package jalview.ext.ensembl;
+import jalview.analysis.AlignmentUtils;
+import jalview.datamodel.Alignment;
import jalview.datamodel.AlignmentI;
+import jalview.datamodel.DBRefEntry;
import jalview.datamodel.DBRefSource;
+import jalview.datamodel.Mapping;
+import jalview.datamodel.SequenceFeature;
import jalview.datamodel.SequenceI;
import jalview.exceptions.JalviewException;
-import jalview.ext.ensembl.SeqFetcher.EnsemblSeqType;
import jalview.io.FastaFile;
import jalview.io.FileParse;
+import jalview.io.gff.SequenceOntologyFactory;
+import jalview.io.gff.SequenceOntologyI;
+import jalview.schemes.ResidueProperties;
import jalview.util.DBRefUtils;
-import jalview.ws.seqfetcher.DbSourceProxy;
-import jalview.ws.seqfetcher.DbSourceProxyImpl;
+import jalview.util.MapList;
+import jalview.util.MappingUtils;
+import jalview.util.StringUtils;
+import java.io.IOException;
+import java.net.MalformedURLException;
+import java.net.URL;
import java.util.ArrayList;
import java.util.Arrays;
+import java.util.Collections;
+import java.util.Comparator;
+import java.util.LinkedHashMap;
import java.util.List;
+import java.util.Map.Entry;
-import com.stevesoft.pat.Regex;
-
-public abstract class EnsemblSeqProxy extends DbSourceProxyImpl implements
- DbSourceProxy
+/**
+ * Base class for Ensembl sequence fetchers
+ *
+ * @author gmcarstairs
+ */
+public abstract class EnsemblSeqProxy extends EnsemblRestClient
{
- SeqFetcher sf;
+ private static final List<String> CROSS_REFERENCES = Arrays
+ .asList(new String[] { "CCDS" });
+
+ protected static final String CONSEQUENCE_TYPE = "consequence_type";
+
+ protected static final String PARENT = "Parent";
+
+ protected static final String ID = "ID";
+
+ protected static final String NAME = "Name";
+
+ public enum EnsemblSeqType
+ {
+ /**
+ * type=genomic for the full dna including introns
+ */
+ GENOMIC("genomic"),
+
+ /**
+ * type=cdna for transcribed dna including UTRs
+ */
+ CDNA("cdna"),
+
+ /**
+ * type=cds for coding dna excluding UTRs
+ */
+ CDS("cds"),
+
+ /**
+ * type=protein for the peptide product sequence
+ */
+ PROTEIN("protein");
+
+ /*
+ * the value of the 'type' parameter to fetch this version of
+ * an Ensembl sequence
+ */
+ private String type;
+
+ EnsemblSeqType(String t)
+ {
+ type = t;
+ }
+
+ public String getType()
+ {
+ return type;
+ }
+
+ }
+
+ /**
+ * A comparator to sort ranges into ascending start position order
+ */
+ private class RangeSorter implements Comparator<int[]>
+ {
+ boolean forwards;
+
+ RangeSorter(boolean forward)
+ {
+ forwards = forward;
+ }
- public EnsemblSeqProxy() throws Exception
+ @Override
+ public int compare(int[] o1, int[] o2)
+ {
+ return (forwards ? 1 : -1) * Integer.compare(o1[0], o2[0]);
+ }
+
+ }
+
+ /**
+ * Constructor
+ */
+ public EnsemblSeqProxy()
{
- sf = new SeqFetcher();
- addDbSourceProperty(DBRefSource.MULTIACC);
- addDbSourceProperty(DBRefSource.SEQDB);
- // decide whether these need to be filtered according to return type
- addDbSourceProperty(DBRefSource.PROTSEQDB);
- addDbSourceProperty(DBRefSource.DNACODINGSEQDB);
- addDbSourceProperty(DBRefSource.DNASEQDB);
}
+ /**
+ * Makes the sequence queries to Ensembl's REST service and returns an
+ * alignment consisting of the returned sequences.
+ */
@Override
- public String getDbSource()
+ public AlignmentI getSequenceRecords(String query) throws Exception
+ {
+ // TODO use a String... query vararg instead?
+
+ // danger: accession separator used as a regex here, a string elsewhere
+ // in this case it is ok (it is just a space), but (e.g.) '\' would not be
+ List<String> allIds = Arrays.asList(query
+ .split(getAccessionSeparator()));
+ AlignmentI alignment = null;
+ inProgress = true;
+
+ /*
+ * execute queries, if necessary in batches of the
+ * maximum allowed number of ids
+ */
+ int maxQueryCount = getMaximumQueryCount();
+ for (int v = 0, vSize = allIds.size(); v < vSize; v += maxQueryCount)
+ {
+ int p = Math.min(vSize, v + maxQueryCount);
+ List<String> ids = allIds.subList(v, p);
+ try
+ {
+ alignment = fetchSequences(ids, alignment);
+ } catch (Throwable r)
+ {
+ inProgress = false;
+ String msg = "Aborting ID retrieval after " + v
+ + " chunks. Unexpected problem (" + r.getLocalizedMessage()
+ + ")";
+ System.err.println(msg);
+ break;
+ // if (alignment != null)
+ // {
+ // break; // return what we got
+ // }
+ // else
+ // {
+ // throw new JalviewException(msg, r);
+ // }
+ }
+ }
+
+ /*
+ * fetch and transfer genomic sequence features,
+ * fetch protein product and add as cross-reference
+ */
+ for (String accId : allIds)
+ {
+ addFeaturesAndProduct(accId, alignment);
+ }
+
+ for (SequenceI seq : alignment.getSequences())
+ {
+ getCrossReferences(seq);
+ }
+
+ return alignment;
+ }
+
+ /**
+ * Fetches Ensembl features using the /overlap REST endpoint, and adds them to
+ * the sequence in the alignment. Also fetches the protein product, maps it
+ * from the CDS features of the sequence, and saves it as a cross-reference of
+ * the dna sequence.
+ *
+ * @param accId
+ * @param alignment
+ */
+ protected void addFeaturesAndProduct(String accId, AlignmentI alignment)
{
- return "ENSEMBL";
+ if (alignment == null)
+ {
+ return;
+ }
+
+ try
+ {
+ /*
+ * get 'dummy' genomic sequence with exon, cds and variation features
+ */
+ SequenceI genomicSequence = null;
+ EnsemblOverlap gffFetcher = new EnsemblOverlap();
+ EnsemblFeatureType[] features = getFeaturesToFetch();
+ AlignmentI geneFeatures = gffFetcher.getSequenceRecords(accId,
+ features);
+ if (geneFeatures.getHeight() > 0)
+ {
+ genomicSequence = geneFeatures.getSequenceAt(0);
+ }
+ if (genomicSequence != null)
+ {
+ /*
+ * transfer features to the query sequence
+ */
+ SequenceI querySeq = alignment.findName(accId);
+ if (transferFeatures(accId, genomicSequence, querySeq))
+ {
+
+ /*
+ * fetch and map protein product, and add it as a cross-reference
+ * of the retrieved sequence
+ */
+ addProteinProduct(querySeq);
+ }
+ }
+ } catch (IOException e)
+ {
+ System.err.println("Error transferring Ensembl features: "
+ + e.getMessage());
+ }
}
+ /**
+ * Returns those sequence feature types to fetch from Ensembl. We may want
+ * features either because they are of interest to the user, or as means to
+ * identify the locations of the sequence on the genomic sequence (CDS
+ * features identify CDS, exon features identify cDNA etc).
+ *
+ * @return
+ */
+ protected abstract EnsemblFeatureType[] getFeaturesToFetch();
+
+ /**
+ * Fetches and maps the protein product, and adds it as a cross-reference of
+ * the retrieved sequence
+ */
+ protected void addProteinProduct(SequenceI querySeq)
+ {
+ String accId = querySeq.getName();
+ try
+ {
+ AlignmentI protein = new EnsemblProtein().getSequenceRecords(accId);
+ if (protein == null || protein.getHeight() == 0)
+ {
+ System.out.println("Failed to retrieve protein for " + accId);
+ return;
+ }
+ SequenceI proteinSeq = protein.getSequenceAt(0);
+
+ /*
+ * need dataset sequences (to be the subject of mappings)
+ */
+ proteinSeq.createDatasetSequence();
+ querySeq.createDatasetSequence();
+ MapList mapList = mapCdsToProtein(querySeq, proteinSeq);
+ if (mapList != null)
+ {
+ Mapping map = new Mapping(proteinSeq.getDatasetSequence(), mapList);
+ DBRefEntry dbr = new DBRefEntry(getDbSource(), getDbVersion(),
+ accId, map);
+ querySeq.getDatasetSequence().addDBRef(dbr);
+
+ /*
+ * compute peptide variants from dna variants and add as
+ * sequence features on the protein sequence ta-da
+ */
+ computeProteinFeatures(querySeq, proteinSeq, mapList);
+ }
+ } catch (Exception e)
+ {
+ System.err
+ .println(String.format("Error retrieving protein for %s: %s",
+ accId, e.getMessage()));
+ }
+ }
+
+ /**
+ * Get Uniprot and PDB xrefs from Ensembl, and attach them to the protein
+ * sequence
+ *
+ * @param seq
+ */
+ protected void getCrossReferences(SequenceI seq)
+ {
+ while (seq.getDatasetSequence() != null)
+ {
+ seq = seq.getDatasetSequence();
+ }
+
+ EnsemblXref xrefFetcher = new EnsemblXref();
+ List<DBRefEntry> xrefs = xrefFetcher.getCrossReferences(seq.getName(),
+ getCrossReferenceDatabases());
+ for (DBRefEntry xref : xrefs)
+ {
+ seq.addDBRef(xref);
+ /*
+ * Save any Uniprot xref to be the reference for SIFTS mapping
+ */
+ if (DBRefSource.UNIPROT.equals(xref.getSource()))
+ {
+ seq.setSourceDBRef(xref);
+ }
+ }
+ }
+
+ /**
+ * Returns a list of database names to be used when fetching cross-references.
+ *
+ * @return
+ */
+ protected List<String> getCrossReferenceDatabases()
+ {
+ return CROSS_REFERENCES;
+ }
+
+ /**
+ * Returns a mapping from dna to protein by inspecting sequence features of
+ * type "CDS" on the dna.
+ *
+ * @param dnaSeq
+ * @param proteinSeq
+ * @return
+ */
+ protected MapList mapCdsToProtein(SequenceI dnaSeq, SequenceI proteinSeq)
+ {
+ List<int[]> ranges = new ArrayList<int[]>(50);
+
+ int mappedDnaLength = getCdsRanges(dnaSeq, ranges);
+
+ int proteinLength = proteinSeq.getLength();
+ List<int[]> proteinRange = new ArrayList<int[]>();
+ int proteinStart = 1;
+
+ /*
+ * incomplete start codon may mean X at start of peptide
+ * we ignore both for mapping purposes
+ */
+ if (proteinSeq.getCharAt(0) == 'X')
+ {
+ proteinStart = 2;
+ proteinLength--;
+ }
+ proteinRange.add(new int[] { proteinStart, proteinLength });
+
+ /*
+ * dna length should map to protein (or protein plus stop codon)
+ */
+ int codesForResidues = mappedDnaLength / 3;
+ if (codesForResidues == proteinLength
+ || codesForResidues == (proteinLength + 1))
+ {
+ return new MapList(ranges, proteinRange, 3, 1);
+ }
+ return null;
+ }
+
+ /**
+ * Adds CDS ranges to the ranges list, and returns the total length mapped
+ * from.
+ *
+ * No need to worry about reverse strand dna, here since the retrieved
+ * sequence is as transcribed (reverse complement for reverse strand), i.e in
+ * the same sense as the peptide.
+ *
+ * @param dnaSeq
+ * @param ranges
+ * @return
+ */
+ protected int getCdsRanges(SequenceI dnaSeq, List<int[]> ranges)
+ {
+ SequenceFeature[] sfs = dnaSeq.getSequenceFeatures();
+ if (sfs == null)
+ {
+ return 0;
+ }
+ int mappedDnaLength = 0;
+ for (SequenceFeature sf : sfs)
+ {
+ /*
+ * process a CDS feature (or a sub-type of CDS)
+ */
+ if (SequenceOntologyFactory.getInstance().isA(sf.getType(),
+ SequenceOntologyI.CDS))
+ {
+ int phase = 0;
+ try {
+ phase = Integer.parseInt(sf.getPhase());
+ } catch (NumberFormatException e)
+ {
+ // ignore
+ }
+ /*
+ * phase > 0 on first codon means 5' incomplete - skip to the start
+ * of the next codon; example ENST00000496384
+ */
+ int begin = sf.getBegin();
+ int end = sf.getEnd();
+ if (ranges.isEmpty() && phase > 0)
+ {
+ begin += phase;
+ if (begin > end)
+ {
+ continue; // shouldn't happen?
+ }
+ }
+ ranges.add(new int[] { begin, end });
+ mappedDnaLength += Math.abs(end - begin) + 1;
+ }
+ }
+ return mappedDnaLength;
+ }
+
+ /**
+ * Fetches sequences for the list of accession ids and adds them to the
+ * alignment. Returns the extended (or created) alignment.
+ *
+ * @param ids
+ * @param alignment
+ * @return
+ * @throws JalviewException
+ * @throws IOException
+ */
+ protected AlignmentI fetchSequences(List<String> ids, AlignmentI alignment)
+ throws JalviewException, IOException
+ {
+ if (!isEnsemblAvailable())
+ {
+ inProgress = false;
+ throw new JalviewException("ENSEMBL Rest API not available.");
+ }
+ FileParse fp = getSequenceReader(ids);
+ FastaFile fr = new FastaFile(fp);
+ if (fr.hasWarningMessage())
+ {
+ System.out.println(String.format(
+ "Warning when retrieving %d ids %s\n%s", ids.size(),
+ ids.toString(), fr.getWarningMessage()));
+ }
+ else if (fr.getSeqs().size() != ids.size())
+ {
+ System.out.println(String.format(
+ "Only retrieved %d sequences for %d query strings", fr
+ .getSeqs().size(), ids.size()));
+ }
+
+ if (fr.getSeqs().size() == 1 && fr.getSeqs().get(0).getLength() == 0)
+ {
+ /*
+ * POST request has returned an empty FASTA file e.g. for invalid id
+ */
+ throw new IOException("No data returned for " + ids);
+ }
+
+ if (fr.getSeqs().size() > 0)
+ {
+ AlignmentI seqal = new Alignment(
+ fr.getSeqsAsArray());
+ for (SequenceI sq:seqal.getSequences())
+ {
+ if (sq.getDescription() == null)
+ {
+ sq.setDescription(getDbName());
+ }
+ String name = sq.getName();
+ if (ids.contains(name)
+ || ids.contains(name.replace("ENSP", "ENST")))
+ {
+ DBRefUtils.parseToDbRef(sq, DBRefSource.ENSEMBL, "0", name);
+ }
+ }
+ if (alignment == null)
+ {
+ alignment = seqal;
+ }
+ else
+ {
+ alignment.append(seqal);
+ }
+ }
+ return alignment;
+ }
+
+ /**
+ * Returns the URL for the REST call
+ *
+ * @return
+ * @throws MalformedURLException
+ */
@Override
- public String getDbVersion()
+ protected URL getUrl(List<String> ids) throws MalformedURLException
{
- return "0"; // sf.getVersion();
+ /*
+ * a single id is included in the URL path
+ * multiple ids go in the POST body instead
+ */
+ StringBuffer urlstring = new StringBuffer(128);
+ urlstring.append(SEQUENCE_ID_URL);
+ if (ids.size() == 1)
+ {
+ urlstring.append("/").append(ids.get(0));
+ }
+ // @see https://github.com/Ensembl/ensembl-rest/wiki/Output-formats
+ urlstring.append("?type=").append(getSourceEnsemblType().getType());
+ urlstring.append(("&Accept=text/x-fasta"));
+
+ URL url = new URL(urlstring.toString());
+ return url;
}
+ /**
+ * A sequence/id POST request currently allows up to 50 queries
+ *
+ * @see http://rest.ensembl.org/documentation/info/sequence_id_post
+ */
@Override
- public String getAccessionSeparator()
+ public int getMaximumQueryCount()
{
- return " ";
+ return 50;
}
@Override
- public Regex getAccessionValidator()
+ protected boolean useGetRequest()
{
- return new Regex("((ENSP|ENST|ENSG|CCDS)[0-9.]{3,})");
+ return false;
}
@Override
- public String getTestQuery()
+ protected String getRequestMimeType(boolean multipleIds)
{
- return "ENSP00000288602";
+ return multipleIds ? "application/json" : "text/x-fasta";
}
@Override
- public boolean isValidReference(String accession)
+ protected String getResponseMimeType()
+ {
+ return "text/x-fasta";
+ }
+
+ /**
+ *
+ * @return the configured sequence return type for this source
+ */
+ protected abstract EnsemblSeqType getSourceEnsemblType();
+
+ /**
+ * Returns a list of [start, end] genomic ranges corresponding to the sequence
+ * being retrieved.
+ *
+ * The correspondence between the frames of reference is made by locating
+ * those features on the genomic sequence which identify the retrieved
+ * sequence. Specifically
+ * <ul>
+ * <li>genomic sequence is identified by "transcript" features with
+ * ID=transcript:transcriptId</li>
+ * <li>cdna sequence is identified by "exon" features with
+ * Parent=transcript:transcriptId</li>
+ * <li>cds sequence is identified by "CDS" features with
+ * Parent=transcript:transcriptId</li>
+ * </ul>
+ *
+ * The returned ranges are sorted to run forwards (for positive strand) or
+ * backwards (for negative strand). Aborts and returns null if both positive
+ * and negative strand are found (this should not normally happen).
+ *
+ * @param sourceSequence
+ * @param accId
+ * @param start
+ * the start position of the sequence we are mapping to
+ * @return
+ */
+ protected MapList getGenomicRangesFromFeatures(SequenceI sourceSequence,
+ String accId, int start)
+ {
+ SequenceFeature[] sfs = sourceSequence.getSequenceFeatures();
+ if (sfs == null)
+ {
+ return null;
+ }
+
+ /*
+ * generously initial size for number of cds regions
+ * (worst case titin Q8WZ42 has c. 313 exons)
+ */
+ List<int[]> regions = new ArrayList<int[]>(100);
+ int mappedLength = 0;
+ int direction = 1; // forward
+ boolean directionSet = false;
+
+ for (SequenceFeature sf : sfs)
+ {
+ /*
+ * accept the target feature type or a specialisation of it
+ * (e.g. coding_exon for exon)
+ */
+ if (identifiesSequence(sf, accId))
+ {
+ int strand = sf.getStrand();
+ strand = strand == 0 ? 1 : strand; // treat unknown as forward
+
+ if (directionSet && strand != direction)
+ {
+ // abort - mix of forward and backward
+ System.err.println("Error: forward and backward strand for "
+ + accId);
+ return null;
+ }
+ direction = strand;
+ directionSet = true;
+
+ /*
+ * add to CDS ranges, semi-sorted forwards/backwards
+ */
+ if (strand < 0)
+ {
+ regions.add(0, new int[] { sf.getEnd(), sf.getBegin() });
+ }
+ else
+ {
+ regions.add(new int[] { sf.getBegin(), sf.getEnd() });
+ }
+ mappedLength += Math.abs(sf.getEnd() - sf.getBegin() + 1);
+
+ if (!isSpliceable())
+ {
+ /*
+ * 'gene' sequence is contiguous so we can stop as soon as its
+ * identifying feature has been found
+ */
+ break;
+ }
+ }
+ }
+
+ if (regions.isEmpty())
+ {
+ System.out.println("Failed to identify target sequence for " + accId
+ + " from genomic features");
+ return null;
+ }
+
+ /*
+ * a final sort is needed since Ensembl returns CDS sorted within source
+ * (havana / ensembl_havana)
+ */
+ Collections.sort(regions, new RangeSorter(direction == 1));
+
+ List<int[]> to = Arrays.asList(new int[] { start,
+ start + mappedLength - 1 });
+
+ return new MapList(regions, to, 1, 1);
+ }
+
+ /**
+ * Answers true if the sequence being retrieved may occupy discontiguous
+ * regions on the genomic sequence.
+ */
+ protected boolean isSpliceable()
{
- return getAccessionValidator().search(accession);
+ return true;
}
- private volatile boolean inProgress = false;
+ /**
+ * Returns true if the sequence feature marks positions of the genomic
+ * sequence feature which are within the sequence being retrieved. For
+ * example, an 'exon' feature whose parent is the target transcript marks the
+ * cdna positions of the transcript.
+ *
+ * @param sf
+ * @param accId
+ * @return
+ */
+ protected abstract boolean identifiesSequence(SequenceFeature sf,
+ String accId);
+
+ /**
+ * Transfers the sequence feature to the target sequence, locating its start
+ * and end range based on the mapping. Features which do not overlap the
+ * target sequence are ignored.
+ *
+ * @param sf
+ * @param targetSequence
+ * @param mapping
+ * mapping from the sequence feature's coordinates to the target
+ * sequence
+ */
+ protected void transferFeature(SequenceFeature sf,
+ SequenceI targetSequence, MapList mapping)
+ {
+ int start = sf.getBegin();
+ int end = sf.getEnd();
+ int[] mappedRange = mapping.locateInTo(start, end);
+
+ if (mappedRange != null)
+ {
+ SequenceFeature copy = new SequenceFeature(sf);
+ copy.setBegin(Math.min(mappedRange[0], mappedRange[1]));
+ copy.setEnd(Math.max(mappedRange[0], mappedRange[1]));
+ targetSequence.addSequenceFeature(copy);
+
+ /*
+ * for sequence_variant, make an additional feature with consequence
+ */
+ if (SequenceOntologyFactory.getInstance().isA(sf.getType(),
+ SequenceOntologyI.SEQUENCE_VARIANT))
+ {
+ String consequence = (String) sf.getValue(CONSEQUENCE_TYPE);
+ if (consequence != null)
+ {
+ SequenceFeature sf2 = new SequenceFeature("consequence",
+ consequence, copy.getBegin(), copy.getEnd(), 0f,
+ null);
+ targetSequence.addSequenceFeature(sf2);
+ }
+ }
+ }
+ }
+
+ /**
+ * Transfers features from sourceSequence to targetSequence
+ *
+ * @param accessionId
+ * @param sourceSequence
+ * @param targetSequence
+ * @return true if any features were transferred, else false
+ */
+ protected boolean transferFeatures(String accessionId,
+ SequenceI sourceSequence, SequenceI targetSequence)
+ {
+ if (sourceSequence == null || targetSequence == null)
+ {
+ return false;
+ }
+
+ SequenceFeature[] sfs = sourceSequence.getSequenceFeatures();
+ MapList mapping = getGenomicRangesFromFeatures(sourceSequence, accessionId,
+ targetSequence.getStart());
+ if (mapping == null)
+ {
+ return false;
+ }
+
+ return transferFeatures(sfs, targetSequence, mapping, accessionId);
+ }
+
+ /**
+ * Transfer features to the target sequence. The start/end positions are
+ * converted using the mapping. Features which do not overlap are ignored.
+ * Features whose parent is not the specified identifier are also ignored.
+ *
+ * @param features
+ * @param targetSequence
+ * @param mapping
+ * @param parentId
+ * @return
+ */
+ protected boolean transferFeatures(SequenceFeature[] features,
+ SequenceI targetSequence, MapList mapping, String parentId)
+ {
+ final boolean forwardStrand = mapping.isFromForwardStrand();
+
+ /*
+ * sort features by start position (descending if reverse strand)
+ * before transferring (in forwards order) to the target sequence
+ */
+ Arrays.sort(features, new Comparator<SequenceFeature>()
+ {
+ @Override
+ public int compare(SequenceFeature o1, SequenceFeature o2)
+ {
+ int c = Integer.compare(o1.getBegin(), o2.getBegin());
+ return forwardStrand ? c : -c;
+ }
+ });
+
+ boolean transferred = false;
+ for (SequenceFeature sf : features)
+ {
+ if (retainFeature(sf, parentId))
+ {
+ transferFeature(sf, targetSequence, mapping);
+ transferred = true;
+ }
+ }
+ return transferred;
+ }
+
+ /**
+ * Answers true if the feature type is one we want to keep for the sequence.
+ * Some features are only retrieved in order to identify the sequence range,
+ * and may then be discarded as redundant information (e.g. "CDS" feature for
+ * a CDS sequence).
+ */
+ @SuppressWarnings("unused")
+ protected boolean retainFeature(SequenceFeature sf, String accessionId)
+ {
+ return true; // override as required
+ }
+
+ /**
+ * Answers true if the feature has a Parent which refers to the given
+ * accession id, or if the feature has no parent. Answers false if the
+ * feature's Parent is for a different accession id.
+ *
+ * @param sf
+ * @param identifier
+ * @return
+ */
+ protected boolean featureMayBelong(SequenceFeature sf, String identifier)
+ {
+ String parent = (String) sf.getValue(PARENT);
+ // using contains to allow for prefix "gene:", "transcript:" etc
+ if (parent != null && !parent.contains(identifier))
+ {
+ // this genomic feature belongs to a different transcript
+ return false;
+ }
+ return true;
+ }
@Override
- public AlignmentI getSequenceRecords(String queries) throws Exception
+ public String getDescription()
{
- inProgress = true;
- List<String> tids, ids = new ArrayList<String>();
- tids = Arrays.asList(queries.split(" +"));
- AlignmentI rtn = null;
- for (int v = 0, vSize = tids.size(); v < vSize; v += 50)
+ return "Ensembl " + getSourceEnsemblType().getType()
+ + " sequence with variant features";
+ }
+
+ /**
+ * Returns a (possibly empty) list of features on the sequence which have the
+ * specified sequence ontology type (or a sub-type of it), and the given
+ * identifier as parent
+ *
+ * @param sequence
+ * @param type
+ * @param parentId
+ * @return
+ */
+ protected List<SequenceFeature> findFeatures(SequenceI sequence,
+ String type, String parentId)
+ {
+ List<SequenceFeature> result = new ArrayList<SequenceFeature>();
+
+ SequenceFeature[] sfs = sequence.getSequenceFeatures();
+ if (sfs != null) {
+ SequenceOntologyI so = SequenceOntologyFactory.getInstance();
+ for (SequenceFeature sf :sfs) {
+ if (so.isA(sf.getType(), type))
+ {
+ String parent = (String) sf.getValue(PARENT);
+ if (parent.equals(parentId))
+ {
+ result.add(sf);
+ }
+ }
+ }
+ }
+ return result;
+ }
+
+ /**
+ * 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
+ */
+ static int computeProteinFeatures(SequenceI dnaSeq,
+ SequenceI peptide, MapList dnaToProtein)
+ {
+ while (dnaSeq.getDatasetSequence() != null)
+ {
+ dnaSeq = dnaSeq.getDatasetSequence();
+ }
+ while (peptide.getDatasetSequence() != null)
{
- int p = v + 50;
- if (p > vSize)
+ peptide = peptide.getDatasetSequence();
+ }
+
+ AlignmentUtils.transferFeatures(dnaSeq, peptide, dnaToProtein,
+ SequenceOntologyI.EXON);
+
+ LinkedHashMap<Integer, String[][]> variants = buildDnaVariantsMap(
+ dnaSeq, dnaToProtein);
+
+ /*
+ * scan codon variations, compute peptide variants and add to peptide sequence
+ */
+ int count = 0;
+ for (Entry<Integer, String[][]> variant : variants.entrySet())
+ {
+ int peptidePos = variant.getKey();
+ String[][] codonVariants = variant.getValue();
+ String residue = String.valueOf(peptide.getCharAt(peptidePos - 1)); // 0-based
+ List<String> peptideVariants = computePeptideVariants(codonVariants,
+ residue);
+ if (!peptideVariants.isEmpty())
{
- p = vSize;
+ String desc = StringUtils.listToDelimitedString(peptideVariants,
+ ", ");
+ SequenceFeature sf = new SequenceFeature(
+ SequenceOntologyI.SEQUENCE_VARIANT, desc, peptidePos,
+ peptidePos, 0f, null);
+ peptide.addSequenceFeature(sf);
+ count++;
}
- ;
- ids = tids.subList(v, p);
- try
+ }
+ return count;
+ }
+
+ /**
+ * Builds a map whose key is position in the protein sequence, and value is an
+ * array of all variants for the coding codon positions
+ *
+ * @param dnaSeq
+ * @param dnaToProtein
+ * @return
+ */
+ static LinkedHashMap<Integer, String[][]> buildDnaVariantsMap(
+ SequenceI dnaSeq, MapList dnaToProtein)
+ {
+ /*
+ * map from peptide position to all variant features of the codon for it
+ * LinkedHashMap ensures we add the peptide features in sequence order
+ */
+ LinkedHashMap<Integer, String[][]> variants = new LinkedHashMap<Integer, String[][]>();
+ 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())
{
- if (!sf.isEnsemblAvailable())
+ // not handling multi-locus variant features
+ continue;
+ }
+ if (so.isA(sf.getType(), SequenceOntologyI.SEQUENCE_VARIANT))
+ {
+ int[] mapsTo = dnaToProtein.locateInTo(dnaCol, dnaCol);
+ if (mapsTo == null)
{
- inProgress = false;
- throw new JalviewException("ENSEMBL Rest API not available.");
+ // feature doesn't lie within coding region
+ continue;
}
- FileParse fp = new FileParse(sf.getSequenceReader(
- getSourceEnsemblType(), ids));
- FastaFile fr = new FastaFile(fp);
- if (fr.hasWarningMessage())
+ int peptidePosition = mapsTo[0];
+ String[][] codonVariants = variants.get(peptidePosition);
+ if (codonVariants == null)
{
- System.out
- .println("Warning when retrieving " + ids.size() + " ids"
- + ids.toString() + "\n" + fr.getWarningMessage());
+ codonVariants = new String[3][];
+ variants.put(peptidePosition, codonVariants);
}
- else if (fr.getSeqs().size() != ids.size())
+
+ /*
+ * extract dna variants to a string array
+ */
+ String alls = (String) sf.getValue("alleles");
+ if (alls == null)
{
- System.out.println("Only retrieved " + fr.getSeqs().size()
- + " sequences for " + ids.size() + " query strings.");
+ continue;
}
- if (fr.getSeqs().size() > 0)
+ String[] alleles = alls.split(",");
+
+ /*
+ * get this peptides 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 this variant) for each codon position
+ */
+ for (int codonPos = 0; codonPos < 3; codonPos++)
{
- AlignmentI seqal = new jalview.datamodel.Alignment(
- fr.getSeqsAsArray());
- for (SequenceI sq:seqal.getSequences())
+ String nucleotide = String.valueOf(dnaSeq
+ .getCharAt(codon[codonPos] - dnaStart));
+ if (codon[codonPos] == dnaCol)
{
- if (ids.contains((sq.getName())))
- {
- DBRefUtils.parseToDbRef(sq, "ENSEMBL", "0", sq.getName());
- }
+ /*
+ * record current dna base and its alleles
+ */
+ String[] dnaVariants = new String[alleles.length + 1];
+ dnaVariants[0] = nucleotide;
+ System.arraycopy(alleles, 0, dnaVariants, 1, alleles.length);
+ codonVariants[codonPos] = dnaVariants;
}
- if (rtn == null)
+ else if (codonVariants[codonPos] == null)
{
- rtn = seqal;
+ /*
+ * record current dna base only
+ * (at least until we find any variation and overwrite it)
+ */
+ codonVariants[codonPos] = new String[] { nucleotide };
}
- else
+ }
+ }
+ }
+ return variants;
+ }
+
+ /**
+ * Returns a sorted, non-redundant list of all peptide translations generated
+ * by the given dna variants, excluding the current residue value
+ *
+ * @param codonVariants
+ * an array of base values (acgtACGT) for codon positions 1, 2, 3
+ * @param residue
+ * the current residue translation
+ * @return
+ */
+ static List<String> computePeptideVariants(
+ String[][] codonVariants, String residue)
+ {
+ List<String> result = new ArrayList<String>();
+ for (String base1 : codonVariants[0])
+ {
+ for (String base2 : codonVariants[1])
+ {
+ for (String base3 : codonVariants[2])
+ {
+ String codon = base1 + base2 + base3;
+ // TODO: report frameshift/insertion/deletion
+ // and multiple-base variants?!
+ String peptide = codon.contains("-") ? "-" : ResidueProperties
+ .codonTranslate(codon);
+ if (peptide != null && !result.contains(peptide)
+ && !peptide.equalsIgnoreCase(residue))
{
- rtn.append(seqal);
+ result.add(peptide);
}
}
- } catch (Throwable r)
+ }
+ }
+
+ /*
+ * sort alphabetically with STOP at the end
+ */
+ Collections.sort(result, new Comparator<String>()
+ {
+
+ @Override
+ public int compare(String o1, String o2)
{
- inProgress = false;
- if (rtn != null)
+ if ("STOP".equals(o1))
{
- System.err.println("Aborting ID retrieval after " + v
- + " chunks.");
- r.printStackTrace();
+ return 1;
+ }
+ else if ("STOP".equals(o2))
+ {
+ return -1;
}
else
{
-
- throw new JalviewException("Aborting ID retrieval after " + v
- + " chunks. Unexpected problem ("
- + r.getLocalizedMessage() + ")", r);
+ return o1.compareTo(o2);
}
-
}
- }
- inProgress = false;
- return rtn;
+ });
+ return result;
}
/**
+ * Answers true if the feature type is either 'NMD_transcript_variant' or
+ * 'transcript' or one of its sub-types in the Sequence Ontology. This is
+ * needed because NMD_transcript_variant behaves like 'transcript' in Ensembl
+ * although strictly speaking it is not (it is a sub-type of
+ * sequence_variant).
*
- * @return the configured sequence return type for this source
+ * @param featureType
+ * @return
*/
- protected abstract EnsemblSeqType getSourceEnsemblType();
-
- @Override
- public boolean queryInProgress()
- {
- return inProgress;
- }
-
- @Override
- public StringBuffer getRawRecords()
- {
- return null;
- }
-
- @Override
- public int getTier()
+ public static boolean isTranscript(String featureType)
{
- return 0;
+ return SequenceOntologyI.NMD_TRANSCRIPT_VARIANT.equals(featureType)
+ || SequenceOntologyFactory.getInstance().isA(featureType,
+ SequenceOntologyI.TRANSCRIPT);
}
}
git://source.jalview.org / jalview.git / blobdiff