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package org.labkey.sequenceanalysis;
import htsjdk.samtools.util.FileExtensions;
import htsjdk.tribble.index.Index;
import htsjdk.tribble.index.IndexFactory;
import htsjdk.variant.vcf.VCFCodec;
import org.apache.commons.lang3.StringUtils;
import org.apache.commons.lang3.SystemUtils;
import org.apache.logging.log4j.LogManager;
import org.apache.logging.log4j.Logger;
import org.jetbrains.annotations.Nullable;
import org.labkey.api.collections.CaseInsensitiveHashSet;
import org.labkey.api.data.CompareType;
import org.labkey.api.data.Container;
import org.labkey.api.data.ContainerManager;
import org.labkey.api.data.SimpleFilter;
import org.labkey.api.data.TableInfo;
import org.labkey.api.data.TableSelector;
import org.labkey.api.exp.api.ExpData;
import org.labkey.api.exp.api.ExperimentService;
import org.labkey.api.laboratory.DemographicsProvider;
import org.labkey.api.laboratory.NavItem;
import org.labkey.api.module.Module;
import org.labkey.api.module.ModuleLoader;
import org.labkey.api.pipeline.PipelineJob;
import org.labkey.api.pipeline.PipelineJobException;
import org.labkey.api.query.FieldKey;
import org.labkey.api.query.QueryService;
import org.labkey.api.resource.FileResource;
import org.labkey.api.resource.Resource;
import org.labkey.api.security.User;
import org.labkey.api.security.permissions.ReadPermission;
import org.labkey.api.sequenceanalysis.GenomeTrigger;
import org.labkey.api.sequenceanalysis.PedigreeRecord;
import org.labkey.api.sequenceanalysis.ReferenceLibraryHelper;
import org.labkey.api.sequenceanalysis.SequenceAnalysisService;
import org.labkey.api.sequenceanalysis.SequenceDataProvider;
import org.labkey.api.sequenceanalysis.model.Readset;
import org.labkey.api.sequenceanalysis.pipeline.BcftoolsRunner;
import org.labkey.api.sequenceanalysis.pipeline.ReferenceGenome;
import org.labkey.api.sequenceanalysis.pipeline.SamtoolsCramConverter;
import org.labkey.api.sequenceanalysis.pipeline.SequenceOutputHandler;
import org.labkey.api.util.FileType;
import org.labkey.api.util.PageFlowUtil;
import org.labkey.api.util.Path;
import org.labkey.api.view.UnauthorizedException;
import org.labkey.sequenceanalysis.pipeline.ProcessVariantsHandler;
import org.labkey.sequenceanalysis.pipeline.ReferenceGenomeImpl;
import org.labkey.sequenceanalysis.pipeline.ReferenceLibraryPipelineJob;
import org.labkey.sequenceanalysis.pipeline.SequenceTaskHelper;
import org.labkey.sequenceanalysis.run.util.BuildBamIndexWrapper;
import org.labkey.sequenceanalysis.run.util.FastaIndexer;
import org.labkey.sequenceanalysis.run.util.GxfSorter;
import org.labkey.sequenceanalysis.run.util.IndexFeatureFileWrapper;
import org.labkey.sequenceanalysis.run.util.TabixRunner;
import org.labkey.sequenceanalysis.util.FastqMerger;
import org.labkey.sequenceanalysis.util.ReferenceLibraryHelperImpl;
import org.labkey.sequenceanalysis.util.SequenceUtil;
import java.io.File;
import java.io.IOException;
import java.util.ArrayList;
import java.util.Collection;
import java.util.Collections;
import java.util.HashMap;
import java.util.HashSet;
import java.util.List;
import java.util.Map;
import java.util.Set;
import java.util.function.Function;
/**
* User: bimber
* Date: 10/27/13
* Time: 9:21 PM
*/
public class SequenceAnalysisServiceImpl extends SequenceAnalysisService
{
private static final SequenceAnalysisServiceImpl _instance = new SequenceAnalysisServiceImpl();
private final Logger _log = LogManager.getLogger(SequenceAnalysisServiceImpl.class);
private final Set<GenomeTrigger> _genomeTriggers = new HashSet<>();
private final Set<SequenceOutputHandler<SequenceOutputHandler.SequenceOutputProcessor>> _fileHandlers = new HashSet<>();
private final Set<SequenceOutputHandler<SequenceOutputHandler.SequenceReadsetProcessor>> _readsetHandlers = new HashSet<>();
private final Map<String, SequenceDataProvider> _dataProviders = new HashMap<>();
private final List<ReadsetListener> _readsetListeners = new ArrayList<>();
private SequenceAnalysisServiceImpl()
{
}
public static SequenceAnalysisServiceImpl get()
{
return _instance;
}
@Override
public ReferenceLibraryHelper getLibraryHelper(File refFasta)
{
return new ReferenceLibraryHelperImpl(refFasta, _log);
}
@Override
public void registerGenomeTrigger(GenomeTrigger trigger)
{
_genomeTriggers.add(trigger);
}
public Set<GenomeTrigger> getGenomeTriggers()
{
return Collections.unmodifiableSet(_genomeTriggers);
}
@Override
public void registerFileHandler(SequenceOutputHandler<SequenceOutputHandler.SequenceOutputProcessor> handler)
{
_fileHandlers.add(handler);
}
@Override
public void registerReadsetHandler(SequenceOutputHandler<SequenceOutputHandler.SequenceReadsetProcessor> handler)
{
_readsetHandlers.add(handler);
}
// @Override
// public File createTabixIndex(File input, @Nullable Logger log) throws PipelineJobException
// {
// return new TabixRunner(log).execute(input);
// }
public Set<SequenceOutputHandler<?>> getFileHandlers(Container c, SequenceOutputHandler.TYPE type)
{
Set<SequenceOutputHandler<?>> ret = new HashSet<>();
for (SequenceOutputHandler<?> h : getFileHandlers(type))
{
if (c.getActiveModules().contains(h.getOwningModule()))
{
ret.add(h);
}
}
return Collections.unmodifiableSet(ret);
}
public Set<SequenceOutputHandler<?>> getFileHandlers(SequenceOutputHandler.TYPE type)
{
return Collections.unmodifiableSet(type == SequenceOutputHandler.TYPE.OutputFile ? _fileHandlers : _readsetHandlers);
}
@Override
public void registerDataProvider(SequenceDataProvider p)
{
if (_dataProviders.containsKey(p.getKey()))
{
_log.error("A SequenceDataProvider with the name: " + p.getName() + " has already been registered");
}
_dataProviders.put(p.getName(), p);
}
@Override
public List<NavItem> getNavItems(Container c, User u, SequenceDataProvider.SequenceNavItemCategory category)
{
List<NavItem> ret = new ArrayList<>();
for (SequenceDataProvider p : _dataProviders.values())
{
ret.addAll(p.getSequenceNavItems(c, u, category));
}
return ret;
}
@Override
public ReadDataImpl getReadData(int rowId, User u)
{
TableInfo ti = SequenceAnalysisSchema.getTable(SequenceAnalysisSchema.TABLE_READ_DATA);
SimpleFilter filter = new SimpleFilter(FieldKey.fromString("rowid"), rowId);
ReadDataImpl model = new TableSelector(ti, filter, null).getObject(ReadDataImpl.class);
if (model == null)
{
return null;
}
Container c = ContainerManager.getForId(model.getContainer());
if (!c.hasPermission(u, ReadPermission.class))
{
throw new UnauthorizedException("Cannot read data in container: " + c.getPath());
}
return model;
}
@Override
public SequenceReadsetImpl getReadset(int readsetId, User u)
{
TableInfo ti = SequenceAnalysisSchema.getTable(SequenceAnalysisSchema.TABLE_READSETS);
SimpleFilter filter = new SimpleFilter(FieldKey.fromString("rowid"), readsetId);
SequenceReadsetImpl model = new TableSelector(ti, filter, null).getObject(SequenceReadsetImpl.class);
if (model == null)
{
return null;
}
Container c = ContainerManager.getForId(model.getContainer());
if (!c.hasPermission(u, ReadPermission.class))
{
throw new UnauthorizedException("Cannot read data in container: " + c.getPath());
}
return model;
}
@Override
public ReferenceGenomeImpl getReferenceGenome(int genomeId, User u) throws PipelineJobException
{
TableInfo ti = SequenceAnalysisSchema.getInstance().getSchema().getTable(SequenceAnalysisSchema.TABLE_REF_LIBRARIES);
SimpleFilter filter = new SimpleFilter(FieldKey.fromString("rowid"), genomeId);
Map<String, Object> map = new TableSelector(ti, PageFlowUtil.set("rowid", "fasta_file", "container", "name"), filter, null).getMap();
if (map == null)
{
return null;
}
Container c = ContainerManager.getForId((String)map.get("container"));
if (!c.hasPermission(u, ReadPermission.class))
{
throw new UnauthorizedException("Cannot read data in container: " + c.getPath());
}
ExpData d = ExperimentService.get().getExpData((Integer)map.get("fasta_file"));
if (d.getFile() == null)
{
throw new PipelineJobException("No FASTA file found for genome: " + genomeId);
}
return new ReferenceGenomeImpl(d.getFile(), d, genomeId, (String)map.get("name"));
}
@Override
public File ensureVcfIndex(File vcf, Logger log) throws IOException
{
return ensureVcfIndex(vcf, log, false);
}
@Override
public File ensureVcfIndex(File vcf, Logger log, boolean forceRecreate) throws IOException
{
if (vcf == null || !vcf.exists())
{
throw new IOException("VCF does not exist: " + (vcf == null ? null : vcf.getPath()));
}
try
{
FileType gz = new FileType(".gz");
File expectedIdx = gz.isType(vcf) ? new File(vcf.getPath() + ".tbi") : new File(vcf.getPath() + FileExtensions.TRIBBLE_INDEX);
if (!forceRecreate && expectedIdx.exists())
{
return expectedIdx;
}
else
{
log.info("creating vcf index: " + vcf.getPath());
//note: there is a bug in htsjdk's index creation with gz inputs
if (gz.isType(vcf) && !SystemUtils.IS_OS_WINDOWS)
{
// preferentially use bcftools since it supports multithreading:
if (BcftoolsRunner.isBcftoolsFound())
{
new BcftoolsRunner(log).doIndex(vcf);
}
else
{
new TabixRunner(log).execute(vcf);
}
if (!expectedIdx.exists())
{
throw new PipelineJobException("Expected index was not created: " + expectedIdx.getPath());
}
return expectedIdx;
}
else
{
Index idx = vcf.getName().toLowerCase().endsWith(".gz") ? IndexFactory.createIndex(vcf, new VCFCodec(), IndexFactory.IndexType.TABIX) : IndexFactory.createDynamicIndex(vcf, new VCFCodec());
idx.writeBasedOnFeatureFile(vcf);
if (!expectedIdx.exists())
{
throw new PipelineJobException("Expected index was not created: " + expectedIdx.getPath());
}
return expectedIdx;
}
}
}
catch (PipelineJobException e)
{
throw new IOException(e);
}
}
@Override
public File getExpectedBamOrCramIndex(File bamOrCram)
{
return SequenceUtil.getExpectedIndex(bamOrCram);
}
@Override
public File ensureBamOrCramIdx(File bamOrCram, Logger log, boolean forceRecreate) throws PipelineJobException
{
File idx = SequenceUtil.getExpectedIndex(bamOrCram);
if (idx.exists())
{
if (forceRecreate)
{
idx.delete();
}
else
{
return null;
}
}
if (SequenceUtil.FILETYPE.bam.getFileType().isType(bamOrCram))
{
idx = new BuildBamIndexWrapper(log).executeCommand(bamOrCram);
}
else if (SequenceUtil.FILETYPE.cram.getFileType().isType(bamOrCram))
{
idx = new SamtoolsCramConverter(log).doIndex(bamOrCram, null);
}
return idx;
}
@Override
public File bgzipFile(File input, Logger log) throws PipelineJobException
{
return SequenceUtil.bgzip(input, log);
}
@Override
public void ensureFastaIndex(File fasta, Logger log) throws PipelineJobException
{
File index = FastaIndexer.getExpectedIndexName(fasta);
if (!index.exists())
{
log.info("creating FASTA index: " + fasta.getName());
FastaIndexer indexer = new FastaIndexer(log);
indexer.execute(fasta);
}
}
@Override
public String getUnzippedBaseName(String filename)
{
return SequenceTaskHelper.getUnzippedBaseName(filename);
}
@Override
public Integer getExpRunIdForJob(PipelineJob job, boolean throwUnlessFound) throws PipelineJobException
{
return SequenceTaskHelper.getExpRunIdForJob(job, throwUnlessFound);
}
@Override
public List<PedigreeRecord> generatePedigree(Collection<String> sampleNames, Container c, User u, DemographicsProvider d)
{
final List<PedigreeRecord> pedigreeRecords = new ArrayList<>();
TableInfo subjectTable = QueryService.get().getUserSchema(u, (c.isWorkbook() ? c.getParent() : c), d.getSchema()).getTable(d.getQuery());
TableSelector ts = new TableSelector(subjectTable, PageFlowUtil.set(d.getSubjectField(), d.getMotherField(), d.getFatherField(), "gender"), new SimpleFilter(FieldKey.fromString(d.getSubjectField()), sampleNames, CompareType.IN), null);
ts.forEach(rs -> {
PedigreeRecord pedigree = new PedigreeRecord();
pedigree.setSubjectName(rs.getString(d.getSubjectField()));
pedigree.setFather(rs.getString(d.getFatherField()));
pedigree.setMother(rs.getString(d.getMotherField()));
pedigree.setGender(rs.getString(d.getSexField()));
if (!StringUtils.isEmpty(pedigree.getSubjectName()))
pedigreeRecords.add(pedigree);
});
//insert record for any missing parents:
Set<String> distinctSubjects = new CaseInsensitiveHashSet();
for (PedigreeRecord p : pedigreeRecords)
{
distinctSubjects.add(p.getSubjectName());
}
List<PedigreeRecord> newRecords = new ArrayList<>();
for (PedigreeRecord p : pedigreeRecords)
{
appendParents(distinctSubjects, p, newRecords);
}
pedigreeRecords.addAll(newRecords);
//if ID only has one parent, add a dummy ID
List<PedigreeRecord> toAdd = new ArrayList<>();
for (PedigreeRecord pd : pedigreeRecords)
{
if (StringUtils.isEmpty(pd.getFather()) && !StringUtils.isEmpty(pd.getMother()))
{
pd.setFather("xf" + pd.getSubjectName());
pd.setPlaceholderFather(true);
PedigreeRecord pr = new PedigreeRecord();
pr.setSubjectName(pd.getFather());
pr.setGender("m");
toAdd.add(pr);
}
else if (!StringUtils.isEmpty(pd.getFather()) && StringUtils.isEmpty(pd.getMother()))
{
pd.setMother("xm" + pd.getSubjectName());
pd.setPlaceholderMother(true);
PedigreeRecord pr = new PedigreeRecord();
pr.setSubjectName(pd.getMother());
pr.setGender("f");
toAdd.add(pr);
}
}
if (!toAdd.isEmpty())
{
//job.getLogger().info("adding " + toAdd.size() + " subjects to handle IDs with only one parent known");
pedigreeRecords.addAll(toAdd);
}
pedigreeRecords.sort((o1, o2) ->
{
boolean o1ParentOfO2 = o1.getSubjectName().equalsIgnoreCase(o2.getFather()) || o1.getSubjectName().equalsIgnoreCase(o2.getMother());
boolean o2ParentOfO1 = o2.getSubjectName().equalsIgnoreCase(o1.getFather()) || o2.getSubjectName().equalsIgnoreCase(o1.getMother());
if (o1ParentOfO2 && o2ParentOfO1)
{
String msg = "Pedigree records are both parents of one another: " + o1.getSubjectName() + "/" + o2.getSubjectName();
_log.error(msg);
throw new IllegalArgumentException(msg);
}
if (o1ParentOfO2)
return -1;
else if (o2ParentOfO1)
return 1;
return o1.getSubjectName().toLowerCase().compareTo(o2.getSubjectName().toLowerCase());
});
return pedigreeRecords;
}
private void appendParents(Set<String> distinctSubjects, PedigreeRecord p, List<PedigreeRecord> newRecords)
{
if (!StringUtils.isEmpty(p.getFather()) && !distinctSubjects.contains(p.getFather()))
{
PedigreeRecord pr = new PedigreeRecord();
pr.setSubjectName(p.getFather());
pr.setGender("m");
newRecords.add(pr);
distinctSubjects.add(p.getFather());
appendParents(distinctSubjects, pr, newRecords);
}
if (!StringUtils.isEmpty(p.getMother()) && !distinctSubjects.contains(p.getMother()))
{
PedigreeRecord pr = new PedigreeRecord();
pr.setSubjectName(p.getMother());
pr.setGender("f");
newRecords.add(pr);
distinctSubjects.add(p.getMother());
appendParents(distinctSubjects, pr, newRecords);
}
}
@Override
public String getVCFLineCount(File vcf, Logger log, boolean passOnly) throws PipelineJobException
{
return passOnly ? ProcessVariantsHandler.getVCFLineCount(vcf, log, passOnly, false) : ProcessVariantsHandler.getVCFLineCount(vcf, log, passOnly, true);
}
@Override
public String getScriptPath(String moduleName, String path) throws PipelineJobException
{
Module module = ModuleLoader.getInstance().getModule(moduleName);
Resource script = module.getModuleResource(Path.parse(path));
if (script == null || !script.exists())
throw new PipelineJobException("Unable to find file: " + path + " in module: " + moduleName);
File f = ((FileResource) script).getFile();
if (!f.exists())
throw new PipelineJobException("Unable to find file: " + f.getPath());
return f.getPath();
}
@Override
public String createReferenceLibrary(List<Integer> sequenceIds, Container c, User u, String name, String assemblyId, String description, boolean skipCacheIndexes, boolean skipTriggers) throws IOException
{
return createReferenceLibrary(sequenceIds, c, u, name, assemblyId, description, skipCacheIndexes, skipTriggers, null);
}
@Override
public String createReferenceLibrary(List<Integer> sequenceIds, Container c, User u, String name, String assemblyId, String description, boolean skipCacheIndexes, boolean skipTriggers, Set<GenomeTrigger> extraTriggers) throws IOException
{
ReferenceLibraryPipelineJob job = SequenceAnalysisManager.get().createReferenceLibrary(sequenceIds, c, u, name, assemblyId, description, skipCacheIndexes, skipTriggers, null, extraTriggers);
return job.getJobGUID();
}
@Override
public File combineVcfs(List<File> files, File outputGz, ReferenceGenome genome, Logger log, boolean multiThreaded, @Nullable Integer compressionLevel) throws PipelineJobException
{
return combineVcfs(files, outputGz, genome, log, multiThreaded, compressionLevel, false);
}
@Override
public File combineVcfs(List<File> files, File outputGz, ReferenceGenome genome, Logger log, boolean multiThreaded, @Nullable Integer compressionLevel, boolean sortAfterMerge) throws PipelineJobException
{
return SequenceUtil.combineVcfs(files, genome, outputGz, log, multiThreaded, compressionLevel, sortAfterMerge);
}
@Override
public void sortGxf(Logger log, File input, @Nullable File output) throws PipelineJobException
{
new GxfSorter(log).sortGxf(input, output);
}
@Override
public void ensureFeatureFileIndex(File input, Logger log) throws PipelineJobException
{
if (SequenceUtil.FILETYPE.bed.getFileType().isType(input))
{
File expected = new File(input.getPath() + FileExtensions.TRIBBLE_INDEX);
if (expected.exists())
{
log.debug("index exists: " + expected.getPath());
}
else
{
new IndexFeatureFileWrapper(log).ensureFeatureFileIndex(input);
}
}
else if (SequenceUtil.FILETYPE.vcf.getFileType().isType(input))
{
try
{
ensureVcfIndex(input, log);
}
catch (IOException e)
{
throw new PipelineJobException(e);
}
}
else
{
throw new IllegalArgumentException("Unexpected input file type, cannot index: " + input.getName());
}
}
@Override
public void mergeFastqFiles(File output, List<File> inputs, Logger log) throws PipelineJobException
{
FastqMerger merger = new FastqMerger(log);
merger.mergeFiles(output, inputs);
}
List<Function<File, List<File>>> _accessoryFileProviders = new ArrayList<>();
@Override
public void registerAccessoryFileProvider(Function<File, List<File>> fn)
{
_accessoryFileProviders.add(fn);
}
public List<Function<File, List<File>>> getAccessoryFileProviders()
{
return Collections.unmodifiableList(_accessoryFileProviders);
}
@Override
public void registerReadsetListener(ReadsetListener listener)
{
_readsetListeners.add(listener);
}
public void onReadsetCreate(User u, Readset rs, @Nullable Readset replacedReadset, @Nullable PipelineJob job)
{
_readsetListeners.forEach(l -> {
Container c = ContainerManager.getForId(rs.getContainer());
if (l.isAvailable(c, u)) {
l.onReadsetCreate(u, rs, replacedReadset, job);
}
});
}
}