print STDERR "RUNNING VB COORD MAPPING\n";
my ( $mapper, $do_upload ) = @_;
my $xref_db = $mapper->xref();
my $core_db = $mapper->core();
my $species = $core_db->species();
my $species_id =
$species );
# We only do coordinate mapping for mouse and human for now.
if ( !( $species eq 'mus_musculus' || $species eq 'homo_sapiens' ) ) {
# return;
}
my $output_dir = $core_db->dir();
my $xref_filename = catfile( $output_dir, 'xref_coord.txt' );
my $object_xref_filename =
catfile( $output_dir, 'object_xref_coord.txt' );
my $unmapped_reason_filename =
catfile( $output_dir, 'unmapped_reason_coord.txt' );
my $unmapped_object_filename =
catfile( $output_dir, 'unmapped_object_coord.txt' );
my $xref_dbh = $xref_db->dbc()->db_handle();
my $core_dbh = $core_db->dbc()->db_handle();
######################################################################
# Figure out the last used 'xref_id', 'object_xref_id', #
# 'unmapped_object_id', and 'unmapped_reason_id' from the Core #
# database. #
######################################################################
my $xref_id =
$core_dbh->selectall_arrayref('SELECT MAX(xref_id) FROM xref')
->[0][0];
my $object_xref_id = $core_dbh->selectall_arrayref(
'SELECT MAX(object_xref_id) FROM object_xref')->[0][0];
my $unmapped_object_id = $core_dbh->selectall_arrayref(
'SELECT MAX(unmapped_object_id) FROM unmapped_object')->[0][0];
my $unmapped_reason_id = $core_dbh->selectall_arrayref(
'SELECT MAX(unmapped_reason_id) FROM unmapped_reason')->[0][0];
$object_xref_id );
$unmapped_object_id );
$unmapped_reason_id );
######################################################################
# Get an 'analysis_id', or discover that we need to add our analysis #
# to the 'analyis' table later. #
######################################################################
my $analysis_params =
sprintf( "weights(coding,ensembl)="
. "%.2f,%.2f;"
. "transcript_score_threshold=" . "%.2f",
$coding_weight, $ens_weight, $transcript_score_threshold );
my $analysis_sql = qq(
SELECT analysis_id
FROM analysis
WHERE logic_name = 'xrefcoordinatemapping'
AND parameters = ?
);
my $analysis_sth = $core_dbh->prepare($analysis_sql);
$analysis_sth->execute($analysis_params);
my $analysis_id = $analysis_sth->fetchall_arrayref()->[0][0];
if ( !defined($analysis_id) ) {
$analysis_id =
$core_dbh->selectall_arrayref( "SELECT analysis_id FROM analysis "
. "WHERE logic_name = 'xrefcoordinatemapping'" )->[0][0];
if ( defined($analysis_id) && $do_upload ) {
. "with new parameter settings\n" );
#-----------------------------------------------------------------
# Update an existing analysis.
#-----------------------------------------------------------------
my $sql = qq(
UPDATE analysis
SET created = now(), parameters = ?
WHERE analysis_id = ?
);
$core_dbh->do( $sql, undef, $analysis_params, $analysis_id );
} else {
log_progress(
"Can not find analysis ID for this analysis:\n");
if ($do_upload) {
#---------------------------------------------------------------
# Store a new analysis.
#---------------------------------------------------------------
$analysis_id = $core_dbh->selectall_arrayref(
'SELECT MAX(analysis_id) FROM analysis')->[0][0];
log_progress(
"Last used analysis_id is %d\n", $analysis_id );
my $sql = 'INSERT INTO analysis '
. 'VALUES(?, now(), ?, \N, \N, \N, ?, \N, \N, ?, ?, \N, \N, \N)';
my $sth = $core_dbh->prepare($sql);
$sth->execute( ++$analysis_id, 'xrefcoordinatemapping',
'CoordinateMapper.pm', $analysis_params,
'CoordinateMapper.pm' );
}
} ## end else [ if ( defined($analysis_id...
} ## end if ( !defined($analysis_id...
if ( defined($analysis_id) ) {
$analysis_id );
}
######################################################################
# Read and store available Xrefs from the Xref database. #
######################################################################
my %unmapped;
my %mapped;
my $xref_sql = qq(
FROM coordinate_xref
WHERE species_id = ?
);
my $xref_sth = $xref_dbh->prepare($xref_sql);
$xref_sth->execute($species_id);
while ( my $xref = $xref_sth->fetchrow_hashref() ) {
$unmapped{ $xref->{'coord_xref_id'} } = {
'external_db_id' =>
$XrefMapper::BasicMapper::source_to_external_db{ $xref->{
'source_id'} }
|| 11000, # FIXME (11000 is 'UCSC')
'accession' => $xref->{'accession'},
'reason' => 'No overlap',
'reason_full' =>
'No coordinate overlap with any Ensembl transcript' };
}
$xref_sth->finish();
######################################################################
# Do coordinate matching. #
######################################################################
my $core_db_adaptor =
-host => $core_db->dbc()->host(),
-port => $core_db->dbc()->port(),
-user => $core_db->dbc()->username(),
-pass => $core_db->dbc()->password(),
-dbname => $core_db->dbc()->dbname(),
);
my $slice_adaptor = $core_db_adaptor->get_SliceAdaptor();
my @chromosomes = @{ $slice_adaptor->fetch_all('Chromosome') };
my $sql = qq(
txStart, txEnd,
cdsStart, cdsEnd,
exonStarts, exonEnds
FROM coordinate_xref
WHERE species_id = ?
AND chromosome = ? AND strand = ?
AND ((txStart >= ? AND txStart <= ?) -- txStart in region
OR (txEnd >= ? AND txEnd <= ?) -- txEnd in region
OR (txStart <= ? AND txEnd >= ?)) -- region is contained
);
foreach my $chromosome (@chromosomes) {
my $chr_name = $chromosome->seq_region_name();
my @genes = @{ $chromosome->get_all_Genes( undef, undef, 1 ) };
scalar(@genes), $chr_name );
while ( my $gene = shift(@genes) ) {
my @transcripts = @{ $gene->get_all_Transcripts() };
my %gene_result;
foreach my $transcript ( sort { $a->start() <=> $b->start() }
@transcripts )
{
################################################################
# For each Ensembl transcript: #
# 1. Register all Ensembl exons in a RangeRegistry. #
# #
# 2. Find all transcripts in the external database that are #
# within the range of this Ensembl transcript. #
# #
# For each of those external transcripts: #
# 3. Calculate the overlap of the exons of the external #
# transcript with the Ensembl exons using the #
# overlap_size() method in the RangeRegistry. #
# #
# 4. Register the external exons in their own RangeRegistry. #
# #
# 5. Calculate the overlap of the Ensembl exons with the #
# external exons as in step 3. #
# #
# 6. Calculate the match score. #
# #
# 7. Decide whether or not to keep the match. #
################################################################
my @exons = @{ $transcript->get_all_Exons() };
my %transcript_result;
# '$rr1' is the RangeRegistry holding Ensembl exons for one
# transcript at a time.
my $coding_transcript;
if ( defined( $transcript->translation() ) ) {
$coding_transcript = 1;
} else {
$coding_transcript = 0;
}
foreach my $exon (@exons) {
#-------------------------------------------------------------
# Register each exon in the RangeRegistry. Register both the
# total length of the exon and the coding range of the exon.
#-------------------------------------------------------------
$exon->end() );
if ( $coding_transcript
&& defined( $exon->coding_region_start($transcript) )
&& defined( $exon->coding_region_end($transcript) ) )
{
$rr1->check_and_register(
'coding',
$exon->coding_region_start($transcript),
$exon->coding_region_end($transcript) );
}
}
#---------------------------------------------------------------
# Get hold of all transcripts from the external database that
# overlaps with this Ensembl transcript.
#---------------------------------------------------------------
my $sth = $xref_dbh->prepare_cached($sql);
$sth->execute( $species_id, $chr_name,
$gene->strand(), $transcript->start(),
$transcript->end(), $transcript->start(),
$transcript->end(), $transcript->start(),
$transcript->end() );
my ( $coord_xref_id, $accession, $txStart, $txEnd, $cdsStart,
$cdsEnd, $exonStarts, $exonEnds );
$sth->bind_columns(
\( $coord_xref_id, $accession, $txStart, $txEnd,
$cdsStart, $cdsEnd, $exonStarts, $exonEnds
) );
while ( $sth->fetch() ) {
my @exonStarts = split( /,\s*/, $exonStarts );
my @exonEnds = split( /,\s*/, $exonEnds );
my $exonCount = scalar(@exonStarts);
# '$rr2' is the RangeRegistry holding exons from the external
# transcript, for one transcript at a time.
my $exon_match = 0;
my $coding_match = 0;
my $coding_count = 0;
for ( my $i = 0 ; $i < $exonCount ; ++$i ) {
#-----------------------------------------------------------
# Register the exons from the external database in the same
# was as with the Ensembl exons, and calculate the overlap
# of the external exons with the previously registered
# Ensembl exons.
#-----------------------------------------------------------
my $overlap =
$exonEnds[$i] );
$exon_match +=
$overlap/( $exonEnds[$i] - $exonStarts[$i] + 1 );
$rr2->check_and_register( 'exon', $exonStarts[$i],
$exonEnds[$i] );
if ( !defined($cdsStart) || !defined($cdsEnd) ) {
# Non-coding transcript.
} else {
my $codingStart = ( $exonStarts[$i] > $cdsStart
? $exonStarts[$i]
: $cdsStart );
my $codingEnd =
( $exonEnds[$i] < $cdsEnd ? $exonEnds[$i] : $cdsEnd );
if ( $codingStart < $codingEnd ) {
my $coding_overlap =
$rr1->overlap_size( 'coding', $codingStart,
$codingEnd );
$coding_match +=
$coding_overlap/( $codingEnd - $codingStart + 1 );
$rr2->check_and_register( 'coding', $codingStart,
$codingEnd );
++$coding_count;
}
}
} ## end for ( my $i = 0 ; $i < ...
my $rexon_match = 0;
my $rcoding_match = 0;
my $rcoding_count = 0;
foreach my $exon (@exons) {
#-----------------------------------------------------------
# Calculate the overlap of the Ensembl exons with the
# external exons.
#-----------------------------------------------------------
my $overlap =
$rr2->overlap_size( 'exon', $exon->start(),
$exon->end() );
$rexon_match +=
$overlap/( $exon->end() - $exon->start() + 1 );
if ( $coding_transcript
&& defined( $exon->coding_region_start($transcript) )
&& defined( $exon->coding_region_end($transcript) ) )
{
my $coding_overlap =
$rr2->overlap_size( 'coding',
$exon->coding_region_start(
$transcript),
$exon->coding_region_end(
$transcript)
);
$rcoding_match +=
$coding_overlap/
( $exon->coding_region_end($transcript) -
$exon->coding_region_start($transcript) +
1 );
++$rcoding_count;
}
} ## end foreach my $exon (@exons)
#-------------------------------------------------------------
# Calculate the match score.
#-------------------------------------------------------------
my $score = ( ( $exon_match + $ens_weight*$rexon_match ) +
$coding_weight*(
$coding_match + $ens_weight*$rcoding_match
)
)/( ( $exonCount + $ens_weight*scalar(@exons) ) +
$coding_weight*(
$coding_count + $ens_weight*$rcoding_count
) );
if ( !defined( $transcript_result{$coord_xref_id} )
|| $transcript_result{$coord_xref_id} < $score )
{
$transcript_result{$coord_xref_id} = $score;
}
} ## end while ( $sth->fetch() )
$sth->finish();
#---------------------------------------------------------------
# Apply transcript threshold and pick the best match(es) for
# this transcript.
#---------------------------------------------------------------
my $best_score;
foreach my $coord_xref_id (
sort( { $transcript_result{$b} <=> $transcript_result{$a} }
keys(%transcript_result) ) )
{
# my $score = $transcript_result{$coord_xref_id};
#
# if ( $score > $transcript_score_threshold ) {
# $best_score ||= $score;
#
# if ( sprintf( "%.3f", $score ) eq
# sprintf( "%.3f", $best_score ) )
# {
if ( exists( $unmapped{$coord_xref_id} ) ) {
$mapped{$coord_xref_id} = $unmapped{$coord_xref_id};
delete( $unmapped{$coord_xref_id} );
$mapped{$coord_xref_id}{'reason'} = undef;
$mapped{$coord_xref_id}{'reason_full'} = undef;
}
push( @{ $mapped{$coord_xref_id}{'mapped_to'} }, {
'ensembl_id' => $transcript->dbID(),
'ensembl_object_type' => 'Transcript'
} );
# # This is now a candidate Xref for the gene.
# if ( !defined( $gene_result{$coord_xref_id} )
# || $gene_result{$coord_xref_id} < $score )
# {
# $gene_result{$coord_xref_id} = $score;
# }
#
# } elsif ( exists( $unmapped{$coord_xref_id} ) ) {
# $unmapped{$coord_xref_id}{'reason'} =
# 'Was not best match';
# $unmapped{$coord_xref_id}{'reason_full'} =
# sprintf(
# "Did not top best transcript match score (%.2f)",
# $best_score );
# if ( !defined( $unmapped{$coord_xref_id}{'score'} )
# || $score > $unmapped{$coord_xref_id}{'score'} )
# {
# $unmapped{$coord_xref_id}{'score'} = $score;
# $unmapped{$coord_xref_id}{'ensembl_id'} =
# $transcript->dbID();
# }
# }
#
# } elsif ( exists( $unmapped{$coord_xref_id} )
# && $unmapped{$coord_xref_id}{'reason'} ne
# 'Was not best match' )
# {
# $unmapped{$coord_xref_id}{'reason'} =
# 'Did not meet threshold';
# $unmapped{$coord_xref_id}{'reason_full'} =
# sprintf( "Match score for transcript "
# . "lower than threshold (%.2f)",
# $transcript_score_threshold );
# if ( !defined( $unmapped{$coord_xref_id}{'score'} )
# || $score > $unmapped{$coord_xref_id}{'score'} )
# {
# $unmapped{$coord_xref_id}{'score'} = $score;
# $unmapped{$coord_xref_id}{'ensembl_id'} =
# $transcript->dbID();
# }
# }
} ## end foreach my $coord_xref_id (...
} ## end foreach my $transcript ( sort...
#-----------------------------------------------------------------
# Pick the best match(es) for this gene.
#-----------------------------------------------------------------
my $best_score;
foreach my $coord_xref_id (
sort( { $gene_result{$b} <=> $gene_result{$a} }
keys(%gene_result) ) )
{
# my $score = $gene_result{$coord_xref_id};
#
# $best_score ||= $score;
#
# if (
# sprintf( "%.3f", $score ) eq sprintf( "%.3f", $best_score ) )
# {
push( @{ $mapped{$coord_xref_id}{'mapped_to'} }, {
'ensembl_id' => $gene->dbID(),
'ensembl_object_type' => 'Gene'
} );
# }
}
} ## end while ( my $gene = shift(...
} ## end foreach my $chromosome (@chromosomes)
# Make all dumps. Order is important.
dump_xref( $xref_filename, $xref_id, \%mapped, \%unmapped );
\%unmapped );
$analysis_id, \%unmapped );
if ($do_upload) {
upload_data(
'object_xref', $object_xref_filename, $core_dbh );
upload_data(
'unmapped_reason', $unmapped_reason_filename,
$core_dbh );
upload_data(
'unmapped_object', $unmapped_object_filename,
$core_dbh );
}