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/**
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* Copyright (C) 2007 EDIT
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* European Distributed Institute of Taxonomy
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* http://www.e-taxonomy.eu
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*
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* The contents of this file are subject to the Mozilla Public License Version 1.1
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* See LICENSE.TXT at the top of this package for the full license terms.
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*/
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package eu.etaxonomy.cdm.model.molecular;
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import java.net.URI;
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import java.net.URISyntaxException;
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import java.util.HashSet;
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import java.util.Set;
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import javax.persistence.Column;
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import javax.persistence.Entity;
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import javax.persistence.FetchType;
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import javax.persistence.ManyToMany;
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import javax.persistence.ManyToOne;
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import javax.persistence.OneToMany;
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import javax.persistence.Transient;
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import javax.xml.bind.annotation.XmlAccessType;
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import javax.xml.bind.annotation.XmlAccessorType;
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import javax.xml.bind.annotation.XmlAttribute;
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import javax.xml.bind.annotation.XmlElement;
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import javax.xml.bind.annotation.XmlElementWrapper;
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import javax.xml.bind.annotation.XmlIDREF;
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import javax.xml.bind.annotation.XmlRootElement;
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import javax.xml.bind.annotation.XmlSchemaType;
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import javax.xml.bind.annotation.XmlTransient;
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import javax.xml.bind.annotation.XmlType;
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import org.apache.log4j.Logger;
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import org.hibernate.annotations.Cascade;
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import org.hibernate.annotations.CascadeType;
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import org.hibernate.envers.Audited;
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import org.hibernate.search.annotations.IndexedEmbedded;
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import org.springframework.beans.factory.annotation.Configurable;
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import eu.etaxonomy.cdm.common.CdmUtils;
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import eu.etaxonomy.cdm.model.common.AnnotatableEntity;
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import eu.etaxonomy.cdm.model.common.DefinedTerm;
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import eu.etaxonomy.cdm.model.common.TermType;
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import eu.etaxonomy.cdm.model.media.Media;
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import eu.etaxonomy.cdm.model.reference.Reference;
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/**
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* Alignment of multiple {@link SingleRead single sequences} to a consensus sequence.
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* This sequence is a part of (or the complete) DNA sequences of the related {@link DnaSample DNA Sample},
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* while
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*
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* <BR>This class holds information about both the combining process of
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* {@link SingleRead single sequences} to one consensus sequence
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* ({@link #getSingleReads() singleReads} , {@link #getContigFile() contigFile} )
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* as well as sequence related information.
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* The later includes the {@link #getConsensusSequence() sequence string} itself,
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* important genetic information about the DNA that has been sequenced
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* ({@link #getDnaMarker() marker} , {@link #getHaplotype()} haplotype) as well as
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* registration information ({@link #getGeneticAccessionNumber() genetic accession number} ),
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* citations, and barcoding information ({@link #getBoldProcessId() BOLD-id},
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* {@link #getBarcodeSequencePart() barcode sequence}, ...).
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*
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* @author m.doering
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* @since 08-Nov-2007 13:06:51
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* @author a.mueller
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* @updated 11-Jul-2013
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*/
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@XmlAccessorType(XmlAccessType.FIELD)
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@XmlType(name = "Sequence", propOrder = {
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"dnaSample",
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"consensusSequence",
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"isBarcode",
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"barcodeSequencePart",
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"dnaMarker",
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"geneticAccessionNumber",
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"boldProcessId",
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"haplotype",
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"contigFile",
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"singleReadAlignments",
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"citations"
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})
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@XmlRootElement(name = "Sequencing")
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@Entity
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@Audited
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@Configurable
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//@Table(appliesTo="Sequence", indexes = { @Index(name = "sequenceTitleCacheIndex", columnNames = { "titleCache" }) })
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public class Sequence extends AnnotatableEntity implements Cloneable{
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private static final long serialVersionUID = 8298983152731241775L;
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private static final Logger logger = Logger.getLogger(Sequence.class);
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//TODO move to cdmlib-ext?
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private static final String GENBANK_BASE_URI = "http://www.ncbi.nlm.nih.gov/nuccore/%s";
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private static final String EMBL_BASE_URI = "http://www.ebi.ac.uk/ena/data/view/%s";
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private static final String DDBJ_BASE_URI = "http://getentry.ddbj.nig.ac.jp/getentry/na/%s/?filetype=html";
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private static final String BOLD_BASE_URI = "http://www.boldsystems.org/index.php/Public_RecordView?processid=%s";
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@XmlElement( name = "DnaSample")
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@XmlIDREF
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@XmlSchemaType(name = "IDREF")
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@ManyToOne(fetch = FetchType.LAZY)
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@IndexedEmbedded
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private DnaSample dnaSample;
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/** @see #getContigFile() */
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@XmlElement(name = "ContigFile")
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@XmlIDREF
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@XmlSchemaType(name = "IDREF")
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@ManyToOne(fetch = FetchType.LAZY)
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@Cascade({CascadeType.SAVE_UPDATE,CascadeType.MERGE})
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private Media contigFile;
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/** @see #getConsensusSequence() */
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@XmlElement(name = "ConsensusSequence")
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private SequenceString consensusSequence = SequenceString.NewInstance();
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@XmlAttribute(name = "isBarcode")
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private Boolean isBarcode = null;
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/** @see #getBarcodeSequence()*/
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@XmlElement(name = "BarcodeSequencePart")
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private SequenceString barcodeSequencePart = SequenceString.NewInstance();
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/** @see #getGeneticAccessionNumber()*/
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@XmlElement(name = "GeneticAccessionNumber")
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@Column(length=20)
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private String geneticAccessionNumber;
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/** @see #getBoldProcessId() */
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@XmlElement(name = "BoldProcessId")
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@Column(length=20)
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private String boldProcessId;
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@XmlElementWrapper(name = "SingleReadAlignments")
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@XmlElement(name = "SingleReadAlignment")
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@XmlIDREF
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@XmlSchemaType(name = "IDREF")
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@OneToMany(mappedBy="consensusAlignment", fetch = FetchType.LAZY, orphanRemoval=true)
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@Cascade({CascadeType.SAVE_UPDATE,CascadeType.MERGE})
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private Set<SingleReadAlignment> singleReadAlignments = new HashSet<SingleReadAlignment>();
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/** @see #getDnaMarker() */
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@XmlElement(name = "DnaMarker")
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@XmlIDREF
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@XmlSchemaType(name = "IDREF")
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@ManyToOne(fetch = FetchType.LAZY)
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//no cascade as it is a defined term
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private DefinedTerm dnaMarker;
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/** @see #getHaplotype() */
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@XmlElement(name = "Haplotype")
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@Column(length=100)
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private String haplotype;
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/** @see #getCitations() */
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@XmlElementWrapper(name = "Citations")
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@XmlElement(name = "Citation")
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@XmlIDREF
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@XmlSchemaType(name = "IDREF")
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@ManyToMany(fetch = FetchType.LAZY)
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@Cascade({CascadeType.SAVE_UPDATE,CascadeType.MERGE})
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private Set<Reference> citations = new HashSet<Reference>();
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// //should be calculated in case sequence is set
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// @XmlElement (name = "DateSequenced", type= String.class)
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// @XmlJavaTypeAdapter(DateTimeAdapter.class)
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// @Type(type="dateTimeUserType")
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// @Basic(fetch = FetchType.LAZY)
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// private DateTime dateSequenced;
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//*********************** FACTORY ****************************************************/
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public static Sequence NewInstance(String consensusSequence){
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Sequence result = new Sequence();
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result.setSequenceString(consensusSequence);
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return result;
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}
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public static Sequence NewInstance(String consensusSequence, Integer length){
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Sequence result = NewInstance(consensusSequence);
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result.getConsensusSequence().setLength(length);
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return result;
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}
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public static Sequence NewInstance(DnaSample dnaSample, String consensusSequence, Integer length){
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Sequence result = NewInstance(consensusSequence);
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result.getConsensusSequence().setLength(length);
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dnaSample.addSequence(result);
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return result;
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}
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//*********************** CONSTRUCTOR ****************************************************/
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protected Sequence() {}
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//*********************** GETTER / SETTER ****************************************************/
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/**
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* The {@link DnaSample dna sample} this sequencing belongs too.
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*/
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public DnaSample getDnaSample() {
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return dnaSample;
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}
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/**
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* To be called only from {@link DnaSample#addSequence(Sequence)}
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* @see #getDnaSample()
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*/
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//TODO implement full bidirectionality
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protected void setDnaSample(DnaSample dnaSample) {
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this.dnaSample = dnaSample;
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if (dnaSample != null && !dnaSample.getSequences().contains(this)){
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throw new RuntimeException("Don't use DNA setter");
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}
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}
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/**
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* The resulting consensus sequence represened by this {@link Sequence sequence} .
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* The consensus is usually computed from the {@link SingleRead single reads}.
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* The result of which is stored in a file called {@link #getContigFile() contig file}
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*
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* #see {@link #getContigFile()}
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* #see {@link #getSingleReads()}
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*/
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public SequenceString getConsensusSequence() {
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return consensusSequence;
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}
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/**
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* @see #getConsensusSequence()
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*/
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public void setConsensusSequence(SequenceString sequenceString) {
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if (sequenceString == null){
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sequenceString = SequenceString.NewInstance();
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}
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this.consensusSequence = sequenceString;
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}
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/**
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* The isBarcode flag should be set to true if this (consensus) sequence is or includes
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* a barcoding sequence. If the barcoding sequence is only a part of the consensus sequence
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* this part shall be stored as {@link #getBarcodeSequencePart() barcoding sequence part}.
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* A isBarcode value of <code>null</code> indicates that we do have no knowledge
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* whether the sequence is a barcoding sequence or not.
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*
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* @see #getBarcodeSequencePart()
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* @see #getSequenceString()
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* @returns the isBarcode flag value (tri-state)
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*
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*/
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public Boolean getIsBarcode() {
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return isBarcode;
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}
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/**
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* @see #getIsBarcode()
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* @see #getBarcodeSequencePart()
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*/
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public void setIsBarcode(Boolean isBarcode) {
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this.isBarcode = isBarcode;
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}
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/**
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* If the barcode sequence string does not include 100% of the (consensus) sequence
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* the part used as barcode is provided here. However, the barcode part
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* should be kept empty if consensus sequence string and barcode sequence string are equal.
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*
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* @see #getIsBarcode()
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*/
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public SequenceString getBarcodeSequencePart() {
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return barcodeSequencePart;
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}
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/**
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* @see #getBarcodeSequencePart()
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*/
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public void setBarcodeSequencePart(SequenceString barcodeSequencePart) {
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if (barcodeSequencePart == null){
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barcodeSequencePart = SequenceString.NewInstance();
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}
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this.barcodeSequencePart = barcodeSequencePart;
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}
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/**
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* Sets the {@link TermType#DnaMarker DNA marker} examined and described by this sequencing.
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* The marker should usually be similar to the one used in the according {@link Amplification
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* amplification process}. However, it may slightly differ, or, if multiple amplifications where
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* used to build this consensus sequence it may be the super set of the markers used in amplification.
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*
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* @return
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*/
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public DefinedTerm getDnaMarker(){
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return this.dnaMarker;
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}
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/**
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* @see #getDnaMarker()
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* @param marker
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*/
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public void setDnaMarker(DefinedTerm dnaMarker){
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this.dnaMarker = dnaMarker;
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}
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/**
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* The accession number used in GenBank, EMBL and DDBJ.
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* @return
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*/
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public String getGeneticAccessionNumber() {
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return geneticAccessionNumber;
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}
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/**
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* Sets the genetic accession number.
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* @see #getGeneticAccessionNumber()
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*/
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public void setGeneticAccessionNumber(String geneticAccessionNumber) {
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this.geneticAccessionNumber = geneticAccessionNumber;
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}
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/**
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* The identifier used by the Barcode of Life Data Systems (BOLD, http://www.boldsystems.org/).
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*/
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public String getBoldProcessId() {
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return boldProcessId;
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}
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public void setBoldProcessId(String boldProcessId) {
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this.boldProcessId = boldProcessId;
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}
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/**
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* Returns the name of the haplotype.
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* A haplotype (haploide genotype) is a variant of nucleotide sequences on the same chromosome.
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* A certain haplotype may be specific for an individual, a population or a species.
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* @return
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*/
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public String getHaplotype() {
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return haplotype;
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}
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/**
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* @see #getHaplotype()
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*/
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public void setHaplotype(String haplotype) {
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this.haplotype = haplotype;
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}
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/**
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* The contigFile containing all data and data processing for this sequencing.
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*
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* @see #getConsensusSequence()
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* @see #getSingleReads()
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*/
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public Media getContigFile() {
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return contigFile;
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}
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/**
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* @see #getContigFile()
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*/
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public void setContigFile(Media contigFile) {
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this.contigFile = contigFile;
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}
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/**
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* Citations are the set of references in which this sequence was published.
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* Unlike taxonomic names the first publication of a sequence
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* is not so important (maybe because it is required by publishers
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* that they are all registered at Genbank) therefore we do not have something like an
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* "original reference" attribute.<BR>
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* Links to these references are to be stored within the reference itself.
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* @return the set of references in which this sequence was published.
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*/
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public Set<Reference> getCitations() {
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return citations;
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}
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/**
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* @see #getCitations()
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*/
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protected void setCitations(Set<Reference> citations) {
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this.citations = citations;
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}
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/**
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* @see #getCitations()
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*/
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public void addCitation(Reference citation) {
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this.citations.add(citation);
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}
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/**
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* @see #getCitations()
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*/
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public void removeCitation(Reference citation) {
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this.citations.remove(citation);
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}
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/**
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* The {@link SingleRead single reads} that were used to build this consensus sequence.
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*
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* @see #getConsensusSequence()
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* @see #getContigFile()
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*/
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public Set<SingleReadAlignment> getSingleReadAlignments() {
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return singleReadAlignments;
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}
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/**
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* @see #getSingleReads()
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*/
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public void addSingleReadAlignment(SingleReadAlignment singleReadAlignment) {
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this.singleReadAlignments.add(singleReadAlignment);
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if (! this.equals(singleReadAlignment.getConsensusSequence())){
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singleReadAlignment.setConsensusAlignment(this);
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};
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}
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/**
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* @see #getSingleReads()
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*/
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public void removeSingleReadAlignment(SingleReadAlignment singleReadAlignment) {
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this.singleReadAlignments.remove(singleReadAlignment);
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if (this.equals(singleReadAlignment.getConsensusSequence())){
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singleReadAlignment.setConsensusAlignment(null);
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singleReadAlignment.setSingleRead(null);
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}
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}
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// /**
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// * @see #getSingleReads()
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// */
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// //TODO private as long it is unclear how bidirectionality is handled
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// @SuppressWarnings("unused")
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// private void setSingleReadAlignments(Set<SingleReadAlignment> singleReadAlignments) {
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// this.singleReadAlignments = singleReadAlignments;
|
440
|
// }
|
441
|
|
442
|
// *********************** CONVENIENCE ***********************************/
|
443
|
|
444
|
/**
|
445
|
* Convenience method to add a single read to a consensus sequence
|
446
|
* by creating a {@link SingleReadAlignment}.
|
447
|
* @param singleRead the {@link SingleRead} to add
|
448
|
* @return the created SingleReadAlignment
|
449
|
*/
|
450
|
public SingleReadAlignment addSingleRead(SingleRead singleRead) {
|
451
|
SingleReadAlignment alignment = SingleReadAlignment.NewInstance(this, singleRead);
|
452
|
return alignment;
|
453
|
}
|
454
|
|
455
|
public void removeSingleRead(SingleRead singleRead) {
|
456
|
Set<SingleReadAlignment> toRemove = new HashSet<SingleReadAlignment>();
|
457
|
for (SingleReadAlignment align : this.singleReadAlignments){
|
458
|
if (align.getSingleRead() != null && align.getSingleRead().equals(singleRead)){
|
459
|
toRemove.add(align);
|
460
|
}
|
461
|
}
|
462
|
for (SingleReadAlignment align : toRemove){
|
463
|
removeSingleReadAlignment(align);
|
464
|
}
|
465
|
return;
|
466
|
}
|
467
|
|
468
|
/**
|
469
|
* Convenience method that returns all single reads this consensus sequence
|
470
|
* is based on via {@link SingleReadAlignment}s.
|
471
|
* @return set of related single reads
|
472
|
*/
|
473
|
@XmlTransient
|
474
|
@Transient
|
475
|
public Set<SingleRead> getSingleReads(){
|
476
|
Set<SingleRead> singleReads = new HashSet<SingleRead>();
|
477
|
for (SingleReadAlignment align : this.singleReadAlignments){
|
478
|
if (align.getSingleRead() != null){ // == null should not happen
|
479
|
singleReads.add(align.getSingleRead());
|
480
|
}
|
481
|
}
|
482
|
return singleReads;
|
483
|
}
|
484
|
|
485
|
|
486
|
//*************************** Transient GETTER /SETTER *****************************/
|
487
|
|
488
|
/**
|
489
|
* Delegate method to get the text representation of the consensus sequence
|
490
|
* @see #setSequenceString(String)
|
491
|
*/
|
492
|
@Transient
|
493
|
public String getSequenceString() {
|
494
|
return consensusSequence.getString();
|
495
|
}
|
496
|
|
497
|
/**
|
498
|
* Delegate method to set the text representation of the {@link #getConsensusSequence()
|
499
|
* consensus sequence}.
|
500
|
*/
|
501
|
@Transient
|
502
|
public void setSequenceString(String sequence) {
|
503
|
consensusSequence.setString(sequence);
|
504
|
}
|
505
|
|
506
|
/**
|
507
|
* Convenience method which computes the set of all related pherograms
|
508
|
* @return the set of pherograms.
|
509
|
*/
|
510
|
@Transient
|
511
|
public Set<Media> getPherograms(){
|
512
|
Set<Media> result = new HashSet<Media>();
|
513
|
for (SingleReadAlignment singleReadAlign : singleReadAlignments){
|
514
|
if (singleReadAlign.getSingleRead() != null && singleReadAlign.getSingleRead().getPherogram() != null){
|
515
|
result.add(singleReadAlign.getSingleRead().getPherogram());
|
516
|
}
|
517
|
}
|
518
|
return result;
|
519
|
}
|
520
|
|
521
|
|
522
|
//***** Registrations ************/
|
523
|
/**
|
524
|
* Returns the computed genBank uri.
|
525
|
* @return the uri composed of {@link #GENBANK_BASE_URI} and {@link #geneticAccessionNumber}
|
526
|
* @throws URISyntaxException when URI could not be created with {@link #geneticAccessionNumber}
|
527
|
*/
|
528
|
@Transient
|
529
|
public URI getGenBankUri() throws URISyntaxException {
|
530
|
return createExternalUri(GENBANK_BASE_URI, geneticAccessionNumber);
|
531
|
}
|
532
|
|
533
|
/**
|
534
|
* Returns the computed EMBL uri.
|
535
|
* @return the uri composed of {@link #EMBL_BASE_URI} and {@link #geneticAccessionNumber}
|
536
|
* @throws URISyntaxException when URI could not be created with {@link #geneticAccessionNumber}
|
537
|
*/
|
538
|
@Transient
|
539
|
public URI getEmblUri() throws URISyntaxException {
|
540
|
return createExternalUri(EMBL_BASE_URI, geneticAccessionNumber);
|
541
|
}
|
542
|
|
543
|
/**
|
544
|
* Returns the computed DDBJ uri.
|
545
|
* @return the uri composed of {@link #DDBJ_BASE_URI} and {@link #geneticAccessionNumber}
|
546
|
* @throws URISyntaxException when URI could not be created with {@link #geneticAccessionNumber}
|
547
|
*/
|
548
|
@Transient
|
549
|
public URI getDdbjUri() throws URISyntaxException {
|
550
|
return createExternalUri(DDBJ_BASE_URI, geneticAccessionNumber);
|
551
|
}
|
552
|
|
553
|
/**
|
554
|
* Returns the URI for the BOLD entry.
|
555
|
* @return the uri composed of {@link #BOLD_BASE_URI} and {@link #boldProcessId}
|
556
|
* @throws URISyntaxException when URI could not be created with {@link #boldProcessId}
|
557
|
* @see #getBoldProcessId()
|
558
|
*/
|
559
|
@Transient
|
560
|
public URI getBoldUri() throws URISyntaxException {
|
561
|
return createExternalUri(BOLD_BASE_URI, boldProcessId);
|
562
|
}
|
563
|
|
564
|
private URI createExternalUri(String baseUri, String id) throws URISyntaxException{
|
565
|
if (CdmUtils.isNotBlank(id)){
|
566
|
return new URI(String.format(baseUri, id.trim()));
|
567
|
}else{
|
568
|
return null;
|
569
|
}
|
570
|
}
|
571
|
|
572
|
|
573
|
|
574
|
|
575
|
//*********************** CLONE ********************************************************/
|
576
|
/**
|
577
|
* Clones <i>this</i> sequence. This is a shortcut that enables to create
|
578
|
* a new instance that differs only slightly from <i>this</i> sequencing by
|
579
|
* modifying only some of the attributes.<BR><BR>
|
580
|
*
|
581
|
*
|
582
|
* @see eu.etaxonomy.cdm.model.media.IdentifiableEntity#clone()
|
583
|
* @see java.lang.Object#clone()
|
584
|
*/
|
585
|
@Override
|
586
|
public Object clone() {
|
587
|
try{
|
588
|
Sequence result = (Sequence)super.clone();
|
589
|
|
590
|
//sequences
|
591
|
result.consensusSequence = (SequenceString)this.consensusSequence.clone();
|
592
|
result.barcodeSequencePart = (SequenceString)this.barcodeSequencePart.clone();
|
593
|
|
594
|
|
595
|
//single sequences
|
596
|
result.singleReadAlignments = new HashSet<SingleReadAlignment>();
|
597
|
for (SingleReadAlignment singleReadAlign: this.singleReadAlignments){
|
598
|
SingleReadAlignment newAlignment = (SingleReadAlignment)singleReadAlign.clone();
|
599
|
result.singleReadAlignments.add(newAlignment);
|
600
|
}
|
601
|
|
602
|
//citations //TODO do we really want to copy these ??
|
603
|
result.citations = new HashSet<Reference>();
|
604
|
for (Reference ref: this.citations){
|
605
|
result.citations.add(ref);
|
606
|
}
|
607
|
|
608
|
|
609
|
|
610
|
return result;
|
611
|
}catch (CloneNotSupportedException e) {
|
612
|
logger.warn("Object does not implement cloneable");
|
613
|
e.printStackTrace();
|
614
|
return null;
|
615
|
}
|
616
|
}
|
617
|
|
618
|
|
619
|
}
|