diff spp/src/BamReader_p.cpp @ 6:ce08b0efa3fd draft

Uploaded

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/spp/src/BamReader_p.cpp	Tue Nov 27 16:11:40 2012 -0500
@@ -0,0 +1,729 @@
+// ***************************************************************************
+// BamReader_p.cpp (c) 2009 Derek Barnett
+// Marth Lab, Department of Biology, Boston College
+// All rights reserved.
+// ---------------------------------------------------------------------------
+// Last modified: 22 November 2010 (DB)
+// ---------------------------------------------------------------------------
+// Provides the basic functionality for reading BAM files
+// ***************************************************************************
+
+#include <BamReader.h>
+#include <BGZF.h>
+#include <BamReader_p.h>
+#include <BamStandardIndex_p.h>
+#include <BamToolsIndex_p.h>
+using namespace BamTools;
+using namespace BamTools::Internal;
+
+#include <algorithm>
+#include <iostream>
+#include <iterator>
+#include <vector>
+using namespace std;
+
+// constructor
+BamReaderPrivate::BamReaderPrivate(BamReader* parent)
+    : HeaderText("")
+    , Index(0)
+    , HasIndex(false)
+    , AlignmentsBeginOffset(0)
+//    , m_header(0)
+    , IndexCacheMode(BamIndex::LimitedIndexCaching)
+    , HasAlignmentsInRegion(true)
+    , Parent(parent)
+    , DNA_LOOKUP("=ACMGRSVTWYHKDBN")
+    , CIGAR_LOOKUP("MIDNSHP")
+{
+    IsBigEndian = SystemIsBigEndian();
+}
+
+// destructor
+BamReaderPrivate::~BamReaderPrivate(void) {
+    Close();
+}
+
+// adjusts requested region if necessary (depending on where data actually begins)
+void BamReaderPrivate::AdjustRegion(BamRegion& region) {
+
+    // check for valid index first
+    if ( Index == 0 ) return;
+
+    // see if any references in region have alignments
+    HasAlignmentsInRegion = false;
+    int currentId = region.LeftRefID;
+
+    const int rightBoundRefId = ( region.isRightBoundSpecified() ? region.RightRefID : References.size() - 1 );
+    while ( currentId <= rightBoundRefId ) {
+	HasAlignmentsInRegion = Index->HasAlignments(currentId);
+	if ( HasAlignmentsInRegion ) break;
+	++currentId;
+    }
+
+    // if no data found on any reference in region
+    if ( !HasAlignmentsInRegion ) return;
+
+    // if left bound of desired region had no data, use first reference that had data
+    // otherwise, leave requested region as-is
+    if ( currentId != region.LeftRefID ) {
+	region.LeftRefID = currentId;
+	region.LeftPosition = 0;
+    }
+}
+
+// fills out character data for BamAlignment data
+bool BamReaderPrivate::BuildCharData(BamAlignment& bAlignment) {
+
+    // calculate character lengths/offsets
+    const unsigned int dataLength     = bAlignment.SupportData.BlockLength - BAM_CORE_SIZE;
+    const unsigned int seqDataOffset  = bAlignment.SupportData.QueryNameLength + (bAlignment.SupportData.NumCigarOperations * 4);
+    const unsigned int qualDataOffset = seqDataOffset + (bAlignment.SupportData.QuerySequenceLength+1)/2;
+    const unsigned int tagDataOffset  = qualDataOffset + bAlignment.SupportData.QuerySequenceLength;
+    const unsigned int tagDataLength  = dataLength - tagDataOffset;
+
+    // check offsets to see what char data exists
+    const bool hasSeqData  = ( seqDataOffset  < dataLength );
+    const bool hasQualData = ( qualDataOffset < dataLength );
+    const bool hasTagData  = ( tagDataOffset  < dataLength );
+
+    // set up char buffers
+    const char* allCharData = bAlignment.SupportData.AllCharData.data();
+    const char* seqData     = ( hasSeqData  ? (((const char*)allCharData) + seqDataOffset)  : (const char*)0 );
+    const char* qualData    = ( hasQualData ? (((const char*)allCharData) + qualDataOffset) : (const char*)0 );
+          char* tagData     = ( hasTagData  ? (((char*)allCharData) + tagDataOffset)        : (char*)0 );
+
+    // store alignment name (relies on null char in name as terminator)
+    bAlignment.Name.assign((const char*)(allCharData));
+
+    // save query sequence
+    bAlignment.QueryBases.clear();
+    if ( hasSeqData ) {
+        bAlignment.QueryBases.reserve(bAlignment.SupportData.QuerySequenceLength);
+        for (unsigned int i = 0; i < bAlignment.SupportData.QuerySequenceLength; ++i) {
+            char singleBase = DNA_LOOKUP[ ( (seqData[(i/2)] >> (4*(1-(i%2)))) & 0xf ) ];
+            bAlignment.QueryBases.append(1, singleBase);
+        }
+    }
+
+    // save qualities, converting from numeric QV to 'FASTQ-style' ASCII character
+    bAlignment.Qualities.clear();
+    if ( hasQualData ) {
+        bAlignment.Qualities.reserve(bAlignment.SupportData.QuerySequenceLength);
+        for (unsigned int i = 0; i < bAlignment.SupportData.QuerySequenceLength; ++i) {
+            char singleQuality = (char)(qualData[i]+33);
+            bAlignment.Qualities.append(1, singleQuality);
+        }
+    }
+
+    // if QueryBases is empty (and this is a allowed case)
+    if ( bAlignment.QueryBases.empty() )
+        bAlignment.AlignedBases = bAlignment.QueryBases;
+
+    // if QueryBases contains data, then build AlignedBases using CIGAR data
+    else {
+
+        // resize AlignedBases
+        bAlignment.AlignedBases.clear();
+        bAlignment.AlignedBases.reserve(bAlignment.SupportData.QuerySequenceLength);
+
+        // iterate over CigarOps
+        int k = 0;
+        vector<CigarOp>::const_iterator cigarIter = bAlignment.CigarData.begin();
+        vector<CigarOp>::const_iterator cigarEnd  = bAlignment.CigarData.end();
+        for ( ; cigarIter != cigarEnd; ++cigarIter ) {
+
+            const CigarOp& op = (*cigarIter);
+            switch(op.Type) {
+
+            case ('M') :
+            case ('I') :
+                bAlignment.AlignedBases.append(bAlignment.QueryBases.substr(k, op.Length)); // for 'M', 'I' - write bases
+                // fall through
+
+            case ('S') :
+                k += op.Length;                                     // for 'S' - soft clip, skip over query bases
+                break;
+
+            case ('D') :
+                bAlignment.AlignedBases.append(op.Length, '-');     // for 'D' - write gap character
+                break;
+
+            case ('P') :
+                bAlignment.AlignedBases.append( op.Length, '*' );   // for 'P' - write padding character
+                break;
+
+            case ('N') :
+                bAlignment.AlignedBases.append( op.Length, 'N' );  // for 'N' - write N's, skip bases in original query sequence
+                break;
+
+            case ('H') :
+                break;  // for 'H' - hard clip, do nothing to AlignedBases, move to next op
+
+            default:
+                fprintf(stderr, "ERROR: Invalid Cigar op type\n"); // shouldn't get here
+                exit(1);
+            }
+        }
+    }
+
+    // save tag data
+    bAlignment.TagData.clear();
+    if ( hasTagData ) {
+        if ( IsBigEndian ) {
+            int i = 0;
+            while ( (unsigned int)i < tagDataLength ) {
+
+                i += 2; // skip tag type (e.g. "RG", "NM", etc)
+                uint8_t type = toupper(tagData[i]);     // lower & upper case letters have same meaning
+                ++i;                                    // skip value type
+
+                switch (type) {
+
+                    case('A') :
+                    case('C') :
+                        ++i;
+                        break;
+
+                    case('S') :
+                        SwapEndian_16p(&tagData[i]);
+                        i += sizeof(uint16_t);
+                        break;
+
+                    case('F') :
+                    case('I') :
+                        SwapEndian_32p(&tagData[i]);
+                        i += sizeof(uint32_t);
+                        break;
+
+                    case('D') :
+                        SwapEndian_64p(&tagData[i]);
+                        i += sizeof(uint64_t);
+                        break;
+
+                    case('H') :
+                    case('Z') :
+                        while (tagData[i]) { ++i; }
+                        ++i; // increment one more for null terminator
+                        break;
+
+                    default :
+                        fprintf(stderr, "ERROR: Invalid tag value type\n"); // shouldn't get here
+                        exit(1);
+                }
+            }
+        }
+
+        // store tagData in alignment
+        bAlignment.TagData.resize(tagDataLength);
+        memcpy((char*)bAlignment.TagData.data(), tagData, tagDataLength);
+    }
+
+    // clear the core-only flag
+    bAlignment.SupportData.HasCoreOnly = false;
+
+    // return success
+    return true;
+}
+
+// clear index data structure
+void BamReaderPrivate::ClearIndex(void) {
+    delete Index;
+    Index = 0;
+    HasIndex = false;
+}
+
+// closes the BAM file
+void BamReaderPrivate::Close(void) {
+
+    // close BGZF file stream
+    mBGZF.Close();
+
+    // clear out index data
+    ClearIndex();
+
+    // clear out header data
+    HeaderText.clear();
+//    if ( m_header ) {
+//	delete m_header;
+//	m_header = 0;
+//    }
+
+    // clear out region flags
+    Region.clear();
+}
+
+// creates index for BAM file, saves to file
+// default behavior is to create the BAM standard index (".bai")
+// set flag to false to create the BamTools-specific index (".bti")
+bool BamReaderPrivate::CreateIndex(bool useStandardIndex) {
+
+    // clear out prior index data
+    ClearIndex();
+
+    // create index based on type requested
+    if ( useStandardIndex )
+	Index = new BamStandardIndex(&mBGZF, Parent);
+    else
+	Index = new BamToolsIndex(&mBGZF, Parent);
+
+    // set index cache mode to full for writing
+    Index->SetCacheMode(BamIndex::FullIndexCaching);
+
+    // build new index
+    bool ok = true;
+    ok &= Index->Build();
+    HasIndex = ok;
+
+    // mark empty references
+    MarkReferences();
+
+    // attempt to save index data to file
+    ok &= Index->Write(Filename);
+
+    // set client's desired index cache mode
+    Index->SetCacheMode(IndexCacheMode);
+
+    // return success/fail of both building & writing index
+    return ok;
+}
+
+const string BamReaderPrivate::GetHeaderText(void) const {
+
+    return HeaderText;
+
+//    if ( m_header )
+//	return m_header->Text();
+//    else
+//	return string("");
+}
+
+// get next alignment (from specified region, if given)
+bool BamReaderPrivate::GetNextAlignment(BamAlignment& bAlignment) {
+
+    // if valid alignment found, attempt to parse char data, and return success/failure
+    if ( GetNextAlignmentCore(bAlignment) )
+	return BuildCharData(bAlignment);
+
+    // no valid alignment found
+    else return false;
+}
+
+// retrieves next available alignment core data (returns success/fail)
+// ** DOES NOT parse any character data (read name, bases, qualities, tag data)
+//    these can be accessed, if necessary, from the supportData
+// useful for operations requiring ONLY positional or other alignment-related information
+bool BamReaderPrivate::GetNextAlignmentCore(BamAlignment& bAlignment) {
+
+    // if region is set but has no alignments
+    if ( !Region.isNull() && !HasAlignmentsInRegion )
+	return false;
+
+    // if valid alignment available
+    if ( LoadNextAlignment(bAlignment) ) {
+
+	// set core-only flag
+	bAlignment.SupportData.HasCoreOnly = true;
+
+	// if region not specified with at least a left boundary, return success
+	if ( !Region.isLeftBoundSpecified() ) return true;
+
+	// determine region state (before, within, after)
+	BamReaderPrivate::RegionState state = IsOverlap(bAlignment);
+
+	// if alignment lies after region, return false
+	if ( state == AFTER_REGION ) return false;
+
+	while ( state != WITHIN_REGION ) {
+	    // if no valid alignment available (likely EOF) return failure
+	    if ( !LoadNextAlignment(bAlignment) ) return false;
+	    // if alignment lies after region, return false (no available read within region)
+	    state = IsOverlap(bAlignment);
+	    if ( state == AFTER_REGION ) return false;
+	}
+
+	// return success (alignment found that overlaps region)
+	return true;
+    }
+
+    // no valid alignment
+    else return false;
+}
+
+// returns RefID for given RefName (returns References.size() if not found)
+int BamReaderPrivate::GetReferenceID(const string& refName) const {
+
+    // retrieve names from reference data
+    vector<string> refNames;
+    RefVector::const_iterator refIter = References.begin();
+    RefVector::const_iterator refEnd  = References.end();
+    for ( ; refIter != refEnd; ++refIter)
+	refNames.push_back( (*refIter).RefName );
+
+    // return 'index-of' refName ( if not found, returns refNames.size() )
+    return distance(refNames.begin(), find(refNames.begin(), refNames.end(), refName));
+}
+
+// returns region state - whether alignment ends before, overlaps, or starts after currently specified region
+// this *internal* method should ONLY called when (at least) IsLeftBoundSpecified == true
+BamReaderPrivate::RegionState BamReaderPrivate::IsOverlap(BamAlignment& bAlignment) {
+
+    // if alignment is on any reference sequence before left bound
+    if ( bAlignment.RefID < Region.LeftRefID ) return BEFORE_REGION;
+
+    // if alignment starts on left bound reference
+    else if ( bAlignment.RefID == Region.LeftRefID ) {
+
+	// if alignment starts at or after left boundary
+	if ( bAlignment.Position >= Region.LeftPosition) {
+
+	    // if right boundary is specified AND
+	    // left/right boundaries are on same reference AND
+	    // alignment starts past right boundary
+	    if ( Region.isRightBoundSpecified() &&
+		 Region.LeftRefID == Region.RightRefID &&
+		 bAlignment.Position > Region.RightPosition )
+		return AFTER_REGION;
+
+	    // otherwise, alignment is within region
+	    return WITHIN_REGION;
+	}
+
+	// alignment starts before left boundary
+	else {
+	    // check if alignment overlaps left boundary
+	    if ( bAlignment.GetEndPosition() >= Region.LeftPosition ) return WITHIN_REGION;
+	    else return BEFORE_REGION;
+	}
+    }
+
+    // alignment starts on a reference after the left bound
+    else {
+
+	// if region has a right boundary
+	if ( Region.isRightBoundSpecified() ) {
+
+	    // alignment is on reference between boundaries
+	    if ( bAlignment.RefID < Region.RightRefID ) return WITHIN_REGION;
+
+	    // alignment is on reference after right boundary
+	    else if ( bAlignment.RefID > Region.RightRefID ) return AFTER_REGION;
+
+	    // alignment is on right bound reference
+	    else {
+		// check if alignment starts before or at right boundary
+		if ( bAlignment.Position <= Region.RightPosition ) return WITHIN_REGION;
+		else return AFTER_REGION;
+	    }
+	}
+
+	// otherwise, alignment is after left bound reference, but there is no right boundary
+	else return WITHIN_REGION;
+    }
+}
+
+// load BAM header data
+void BamReaderPrivate::LoadHeaderData(void) {
+
+//    m_header = new BamHeader(&mBGZF);
+//    bool headerLoadedOk = m_header->Load();
+//    if ( !headerLoadedOk )
+//	cerr << "BamReader could not load header" << endl;
+
+    // check to see if proper BAM header
+    char buffer[4];
+    if (mBGZF.Read(buffer, 4) != 4) {
+	fprintf(stderr, "Could not read header type\n");
+	exit(1);
+    }
+
+    if (strncmp(buffer, "BAM\001", 4)) {
+	fprintf(stderr, "wrong header type!\n");
+	exit(1);
+    }
+
+    // get BAM header text length
+    mBGZF.Read(buffer, 4);
+    unsigned int headerTextLength = BgzfData::UnpackUnsignedInt(buffer);
+    if ( IsBigEndian ) SwapEndian_32(headerTextLength);
+
+    // get BAM header text
+    char* headerText = (char*)calloc(headerTextLength + 1, 1);
+    mBGZF.Read(headerText, headerTextLength);
+    HeaderText = (string)((const char*)headerText);
+
+    // clean up calloc-ed temp variable
+    free(headerText);
+}
+
+// load existing index data from BAM index file (".bti" OR ".bai"), return success/fail
+bool BamReaderPrivate::LoadIndex(const bool lookForIndex, const bool preferStandardIndex) {
+
+    // clear out any existing index data
+    ClearIndex();
+
+    // if no index filename provided, so we need to look for available index files
+    if ( IndexFilename.empty() ) {
+
+	// attempt to load BamIndex based on current Filename provided & preferStandardIndex flag
+	const BamIndex::PreferredIndexType type = (preferStandardIndex ? BamIndex::STANDARD : BamIndex::BAMTOOLS);
+	Index = BamIndex::FromBamFilename(Filename, &mBGZF, Parent, type);
+
+	// if null, return failure
+	if ( Index == 0 ) return false;
+
+	// generate proper IndexFilename based on type of index created
+	IndexFilename = Filename + Index->Extension();
+    }
+
+    else {
+
+	// attempt to load BamIndex based on IndexFilename provided by client
+	Index = BamIndex::FromIndexFilename(IndexFilename, &mBGZF, Parent);
+
+	// if null, return failure
+	if ( Index == 0 ) return false;
+    }
+
+    // set cache mode for BamIndex
+    Index->SetCacheMode(IndexCacheMode);
+
+    // loading the index data from file
+    HasIndex = Index->Load(IndexFilename);
+
+    // mark empty references
+    MarkReferences();
+
+    // return index status
+    return HasIndex;
+}
+
+// populates BamAlignment with alignment data under file pointer, returns success/fail
+bool BamReaderPrivate::LoadNextAlignment(BamAlignment& bAlignment) {
+
+    // read in the 'block length' value, make sure it's not zero
+    char buffer[4];
+    mBGZF.Read(buffer, 4);
+    bAlignment.SupportData.BlockLength = BgzfData::UnpackUnsignedInt(buffer);
+    if ( IsBigEndian ) { SwapEndian_32(bAlignment.SupportData.BlockLength); }
+    if ( bAlignment.SupportData.BlockLength == 0 ) return false;
+
+    // read in core alignment data, make sure the right size of data was read
+    char x[BAM_CORE_SIZE];
+    if ( mBGZF.Read(x, BAM_CORE_SIZE) != BAM_CORE_SIZE ) return false;
+
+    if ( IsBigEndian ) {
+	for ( int i = 0; i < BAM_CORE_SIZE; i+=sizeof(uint32_t) )
+	    SwapEndian_32p(&x[i]);
+    }
+
+    // set BamAlignment 'core' and 'support' data
+    bAlignment.RefID    = BgzfData::UnpackSignedInt(&x[0]);
+    bAlignment.Position = BgzfData::UnpackSignedInt(&x[4]);
+
+    unsigned int tempValue = BgzfData::UnpackUnsignedInt(&x[8]);
+    bAlignment.Bin        = tempValue >> 16;
+    bAlignment.MapQuality = tempValue >> 8 & 0xff;
+    bAlignment.SupportData.QueryNameLength = tempValue & 0xff;
+
+    tempValue = BgzfData::UnpackUnsignedInt(&x[12]);
+    bAlignment.AlignmentFlag = tempValue >> 16;
+    bAlignment.SupportData.NumCigarOperations = tempValue & 0xffff;
+
+    bAlignment.SupportData.QuerySequenceLength = BgzfData::UnpackUnsignedInt(&x[16]);
+    bAlignment.MateRefID    = BgzfData::UnpackSignedInt(&x[20]);
+    bAlignment.MatePosition = BgzfData::UnpackSignedInt(&x[24]);
+    bAlignment.InsertSize   = BgzfData::UnpackSignedInt(&x[28]);
+
+    // set BamAlignment length
+    bAlignment.Length = bAlignment.SupportData.QuerySequenceLength;
+
+    // read in character data - make sure proper data size was read
+    bool readCharDataOK = false;
+    const unsigned int dataLength = bAlignment.SupportData.BlockLength - BAM_CORE_SIZE;
+    char* allCharData = (char*)calloc(sizeof(char), dataLength);
+
+    if ( mBGZF.Read(allCharData, dataLength) == (signed int)dataLength) {
+
+	// store 'allCharData' in supportData structure
+	bAlignment.SupportData.AllCharData.assign((const char*)allCharData, dataLength);
+
+	// set success flag
+	readCharDataOK = true;
+
+	// save CIGAR ops
+	// need to calculate this here so that  BamAlignment::GetEndPosition() performs correctly,
+	// even when GetNextAlignmentCore() is called
+	const unsigned int cigarDataOffset = bAlignment.SupportData.QueryNameLength;
+	uint32_t* cigarData = (uint32_t*)(allCharData + cigarDataOffset);
+	CigarOp op;
+	bAlignment.CigarData.clear();
+	bAlignment.CigarData.reserve(bAlignment.SupportData.NumCigarOperations);
+	for (unsigned int i = 0; i < bAlignment.SupportData.NumCigarOperations; ++i) {
+
+	    // swap if necessary
+	    if ( IsBigEndian ) SwapEndian_32(cigarData[i]);
+
+	    // build CigarOp structure
+	    op.Length = (cigarData[i] >> BAM_CIGAR_SHIFT);
+	    op.Type   = CIGAR_LOOKUP[ (cigarData[i] & BAM_CIGAR_MASK) ];
+
+	    // save CigarOp
+	    bAlignment.CigarData.push_back(op);
+	}
+    }
+
+    free(allCharData);
+    return readCharDataOK;
+}
+
+// loads reference data from BAM file
+void BamReaderPrivate::LoadReferenceData(void) {
+
+    // get number of reference sequences
+    char buffer[4];
+    mBGZF.Read(buffer, 4);
+    unsigned int numberRefSeqs = BgzfData::UnpackUnsignedInt(buffer);
+    if ( IsBigEndian ) SwapEndian_32(numberRefSeqs);
+    if ( numberRefSeqs == 0 ) return;
+    References.reserve((int)numberRefSeqs);
+
+    // iterate over all references in header
+    for (unsigned int i = 0; i != numberRefSeqs; ++i) {
+
+	// get length of reference name
+	mBGZF.Read(buffer, 4);
+	unsigned int refNameLength = BgzfData::UnpackUnsignedInt(buffer);
+	if ( IsBigEndian ) SwapEndian_32(refNameLength);
+	char* refName = (char*)calloc(refNameLength, 1);
+
+	// get reference name and reference sequence length
+	mBGZF.Read(refName, refNameLength);
+	mBGZF.Read(buffer, 4);
+	int refLength = BgzfData::UnpackSignedInt(buffer);
+	if ( IsBigEndian ) SwapEndian_32(refLength);
+
+	// store data for reference
+	RefData aReference;
+	aReference.RefName   = (string)((const char*)refName);
+	aReference.RefLength = refLength;
+	References.push_back(aReference);
+
+	// clean up calloc-ed temp variable
+	free(refName);
+    }
+}
+
+// mark references with no alignment data
+void BamReaderPrivate::MarkReferences(void) {
+
+    // ensure index is available
+    if ( !HasIndex ) return;
+
+    // mark empty references
+    for ( int i = 0; i < (int)References.size(); ++i )
+	References.at(i).RefHasAlignments = Index->HasAlignments(i);
+}
+
+// opens BAM file (and index)
+bool BamReaderPrivate::Open(const string& filename, const string& indexFilename, const bool lookForIndex, const bool preferStandardIndex) {
+
+    // store filenames
+    Filename = filename;
+    IndexFilename = indexFilename;
+
+    // open the BGZF file for reading, return false on failure
+    if ( !mBGZF.Open(filename, "rb") ) return false;
+
+    // retrieve header text & reference data
+    LoadHeaderData();
+    LoadReferenceData();
+
+    // store file offset of first alignment
+    AlignmentsBeginOffset = mBGZF.Tell();
+
+    // if no index filename provided
+    if ( IndexFilename.empty() ) {
+
+	// client did not specify that index SHOULD be found
+	// useful for cases where sequential access is all that is required
+	if ( !lookForIndex ) return true;
+
+	// otherwise, look for index file, return success/fail
+	return LoadIndex(lookForIndex, preferStandardIndex) ;
+    }
+
+    // client supplied an index filename
+    // attempt to load index data, return success/fail
+    return LoadIndex(lookForIndex, preferStandardIndex);
+}
+
+// returns BAM file pointer to beginning of alignment data
+bool BamReaderPrivate::Rewind(void) {
+
+    // rewind to first alignment, return false if unable to seek
+    if ( !mBGZF.Seek(AlignmentsBeginOffset) ) return false;
+
+    // retrieve first alignment data, return false if unable to read
+    BamAlignment al;
+    if ( !LoadNextAlignment(al) ) return false;
+
+    // reset default region info using first alignment in file
+    Region.clear();
+    HasAlignmentsInRegion = true;
+
+    // rewind back to beginning of first alignment
+    // return success/fail of seek
+    return mBGZF.Seek(AlignmentsBeginOffset);
+}
+
+// change the index caching behavior
+void BamReaderPrivate::SetIndexCacheMode(const BamIndex::BamIndexCacheMode mode) {
+    IndexCacheMode = mode;
+    if ( Index == 0 ) return;
+    Index->SetCacheMode(mode);
+}
+
+// asks Index to attempt a Jump() to specified region
+// returns success/failure
+bool BamReaderPrivate::SetRegion(const BamRegion& region) {
+
+    // clear out any prior BamReader region data
+    //
+    // N.B. - this is cleared so that BamIndex now has free reign to call
+    // GetNextAlignmentCore() and do overlap checking without worrying about BamReader
+    // performing any overlap checking of its own and moving on to the next read... Calls
+    // to GetNextAlignmentCore() with no Region set, simply return the next alignment.
+    // This ensures that the Index is able to do just that. (All without exposing
+    // LoadNextAlignment() to the public API, and potentially confusing clients with the nomenclature)
+    Region.clear();
+
+    // check for existing index
+    if ( !HasIndex ) return false;
+
+    // adjust region if necessary to reflect where data actually begins
+    BamRegion adjustedRegion(region);
+    AdjustRegion(adjustedRegion);
+
+    // if no data present, return true
+    // not an error, but BamReader knows that no data is there for future alignment access
+    // (this is useful in a MultiBamReader setting where some BAM files may lack data in regions
+    // that other BAMs have data)
+    if ( !HasAlignmentsInRegion ) {
+	Region = adjustedRegion;
+	return true;
+    }
+
+    // attempt jump to user-specified region return false if jump could not be performed at all
+    // (invalid index, unknown reference, etc)
+    //
+    // Index::Jump() is allowed to modify the HasAlignmentsInRegion flag
+    //  * This covers case where a region is requested that lies beyond the last alignment on a reference
+    //    If this occurs, any subsequent calls to GetNexAlignment[Core] simply return false
+    //    BamMultiReader is then able to successfully pull alignments from a region from multiple files
+    //    even if one or more have no data.
+    if ( !Index->Jump(adjustedRegion, &HasAlignmentsInRegion) ) return false;
+
+    // save region and return success
+    Region = adjustedRegion;
+    return true;
+}