Update ClinVar script to import somatic classifications + patch db schema 115

modules/Bio/EnsEMBL/Variation/DBSQL/PhenotypeFeatureAdaptor.pm

@@ -117,6 +117,41 @@ sub _is_significant_constraint {
 }
 
 
+=head2 _filter_dna_type
+
+  Arg [1]    : string $constraint
+  Arg [1]    : string $dna_type
+  Example    : $self->_filter_dna_type($constraint, $dna_type)
+  Description: Internal method to add a constraint on the column "DNA_type".
+               Phenotype features from ClinVar have DNA_type 'Germline' or 'Somatic'.
+               For non-human or other human sources DNA_type is NULL.
+               This method add a constraint to return a specific type of DNA and/or null.
+  Returntype : string
+  Exceptions : none
+  Caller     : internal
+  Status     : stable
+
+=cut
+
+sub _filter_dna_type {
+  my $self = shift;
+  my $constraint = shift;
+  my $dna_type = shift;
+
+  my $dna_constraint;
+
+  if($dna_type eq "Germline") {
+    $dna_constraint = qq{ (pf.DNA_type='$dna_type' OR pf.DNA_type is NULL) };
+  }
+  else {
+    $dna_constraint = qq{ pf.DNA_type='$dna_type' };
+  }
+
+  $constraint .= (defined($constraint)) ? " AND$dna_constraint" : $dna_constraint;
+
+  return $constraint;
+}
+
 =head2 _is_class_constraint
 
   Arg [1]    : string $constraint
@@ -153,7 +188,8 @@ sub _fetch_all_by_object {
   my $self   = shift;
   my $object = shift;
   my $type   = shift;
-
+  my $dna_type = shift; # dna_type to include
+
   $type ||= (split '::', ref($object))[-1];
   throw("$type is not a valid object type, valid types are: ".(join ", ", sort keys %TYPES)) unless defined $type and defined($TYPES{$type});
 
@@ -163,7 +199,12 @@ sub _fetch_all_by_object {
   $constraint = $self->_is_significant_constraint($constraint);
   # Add the constraint for phenotype class
   $constraint = $self->_is_class_constraint($constraint);
-
+
+  # Filter phenotype features by their DNA_type (when searching for germline also includes null DNA_type)
+  if(defined $dna_type) {
+    $constraint = $self->_filter_dna_type($constraint, $dna_type);
+  }
+
   return $self->generic_fetch($constraint);
 }
 
@@ -400,7 +441,7 @@ sub fetch_all_by_Slice_with_ontology_accession {
 
   Arg [1]    : Bio::EnsEMBL::Variation::Variation $var
   Example    : my @pfs = @{$pfa->fetch_all_by_Variation($var)};
-  Description: Retrieves all PhenotypeFeatures for a given variation.
+  Description: Retrieves all PhenotypeFeatures with 'Germline' DNA type for a given variation.
   Returntype : reference to list Bio::EnsEMBL::Variation::PhenotypeFeature
   Exceptions : throw on bad argument
   Caller     : general
@@ -416,7 +457,32 @@ sub fetch_all_by_Variation {
     throw('Bio::EnsEMBL::Variation::Variation arg expected');
   }
 
-  return $self->_fetch_all_by_object($var, 'Variation');
+  # Only include phenotype features with DNA_type 'Germline' or null
+  return $self->_fetch_all_by_object($var, 'Variation', 'Germline');
+}
+
+=head2 fetch_all_somatic_by_Variation
+
+  Arg [1]    : Bio::EnsEMBL::Variation::Variation $var
+  Example    : my @pfs = @{$pfa->fetch_all_somatic_by_Variation($var)};
+  Description: Retrieves all PhenotypeFeatures with 'Somatic' DNA type for a given variation.
+  Returntype : reference to list Bio::EnsEMBL::Variation::PhenotypeFeature
+  Exceptions : throw on bad argument
+  Caller     : general
+  Status     : stable
+
+=cut
+
+sub fetch_all_somatic_by_Variation {
+  my $self = shift;
+  my $var  = shift;
+
+  if(!ref($var) || !$var->isa('Bio::EnsEMBL::Variation::Variation')) {
+    throw('Bio::EnsEMBL::Variation::Variation arg expected');
+  }
+
+  # Only include phenotype features with DNA_type 'Somatic'
+  return $self->_fetch_all_by_object($var, 'Variation', 'Somatic');
 }
 
 
@@ -1183,7 +1249,8 @@ sub get_clinsig_alleles_by_location {
       AND pf.seq_region_id = ?
       AND pf.seq_region_start >= ?
       AND pf.seq_region_end <= ?
-      AND pf.source_id = ? 
+      AND pf.source_id = ?
+      AND (DNA_type = 'Germline' OR DNA_type is NULL)
       AND EXISTS(select value from phenotype_feature_attrib where phenotype_feature_id = pf.phenotype_feature_id && attrib_type_id = 483)
 
       GROUP BY pf.phenotype_feature_id
@@ -1215,6 +1282,76 @@ sub get_clinsig_alleles_by_location {
   return $hash;
 }
 
+sub get_somatic_clin_impact_by_location {
+  my $self = shift;
+  my $seq_region_id = shift;
+  my $seq_region_start = shift;
+  my $seq_region_end = shift;
+  my $source_id = shift;
+  throw("Cannot fetch attributes without seq region information") unless defined($seq_region_id) && defined($seq_region_start) && defined($seq_region_end);
+
+  my $extra_sql = $self->_is_significant_constraint();
+  # Add the constraint for phenotype class
+  $extra_sql = $self->_is_class_constraint($extra_sql);
+
+  my $sth = $self->dbc->prepare(qq{
+    SELECT
+      CONCAT(pf.seq_region_id, ':', pf.seq_region_start, '-', pf.seq_region_end),
+      CONCAT_WS('; ',
+        CONCAT('id=', pf.object_id), CONCAT('pf_id=', pf.phenotype_feature_id),
+        GROUP_CONCAT(IF(at.code in ('somatic_clin_sig', 'oncogenic_clin_sig'), at.code, NULL), "=", concat('', pfa.value, '') SEPARATOR '; '),
+        CONCAT('phenotype=', p.description)
+      ) AS attribute
+
+      FROM
+        phenotype p,
+        phenotype_feature pf
+
+      LEFT JOIN phenotype_feature_attrib pfa
+        ON pf.phenotype_feature_id = pfa.phenotype_feature_id
+      LEFT JOIN attrib_type `at`
+          ON pfa.attrib_type_id = at.attrib_type_id
+
+      WHERE pf.phenotype_id = p.phenotype_id
+      AND pf.seq_region_id = ?
+      AND pf.seq_region_start >= ?
+      AND pf.seq_region_end <= ?
+      AND pf.source_id = ?
+      AND pf.DNA_type = 'Somatic'
+
+      GROUP BY pf.phenotype_feature_id
+      ORDER BY pf.seq_region_id, pf.seq_region_start, pf.seq_region_end
+  });
+
+  $sth->bind_param(1, $seq_region_id, SQL_VARCHAR);
+  $sth->bind_param(2, $seq_region_start, SQL_VARCHAR);
+  $sth->bind_param(3, $seq_region_end, SQL_VARCHAR);
+  $sth->bind_param(4, $source_id, SQL_VARCHAR);
+  $sth->execute();
+
+  my $pf_id;
+  my $output_string;
+  my $hash;
+  $sth->bind_columns(\$pf_id, \$output_string);
+
+  while ($sth->fetch){
+    $hash->{$pf_id} = [] if !defined($hash->{$pf_id});
+    my $internal_hash;
+
+    # Example: $output_string => "id=rs1555760738; pf_id=266451087; somatic_clin_sig=Tier III - Unknown"
+    foreach my $id (split/\;/,$output_string){
+      my ($key, $value) = split /\=/, $id;
+      $key =~ s/^\s+|\s+$//g;
+
+      $internal_hash->{$key} = $value;
+    }
+    push(@{$hash->{$pf_id}}, $internal_hash);
+  }
+
+  $sth->finish();
+
+  return $hash;
+}
 
 
 # stub method used by web
@@ -1530,6 +1667,7 @@ sub _obj_from_row {
         '_source_id'     => $row->{source_id},
         '_source_name'   => $row->{name}, 
         'is_significant' => $row->{is_significant},
+        'dna_type'       => $row->{dna_type},
       }
     );
 
@@ -1591,8 +1729,9 @@ sub store{
             seq_region_id,
             seq_region_start,
             seq_region_end,
-            seq_region_strand            
-        ) VALUES (?,?,?,?,?,?,?,?,?,?)
+            seq_region_strand,
+            dna_type
+        ) VALUES (?,?,?,?,?,?,?,?,?,?,?)
     });
 
     $sth->execute(
@@ -1605,7 +1744,8 @@ sub store{
         defined($pf->{slice}) ? $pf->slice()->get_seq_region_id() : undef,
         defined($pf->{start}) ? $pf->{start} :undef,
         defined($pf->{end})   ? $pf->{end} : undef,
-        defined($pf->{strand})? $pf->{strand} : undef         
+        defined($pf->{strand})? $pf->{strand} : undef,
+        defined($pf->{dna_type})? $pf->{dna_type} : undef
     );
 
    $sth->finish;

modules/Bio/EnsEMBL/Variation/PhenotypeFeature.pm

@@ -82,7 +82,7 @@ use Exporter;
 use vars qw(@EXPORT_OK @ISA);
 
 our @ISA = ('Bio::EnsEMBL::Feature', 'Exporter');
-@EXPORT_OK = qw(%TYPES);
+@EXPORT_OK = qw(%TYPES %DNA_TYPES);
 
 # define valid object types
 # this must correspond to the types defined in the type column of
@@ -96,6 +96,11 @@ our %TYPES = (
   'RegulatoryFeature'             => 1,
 );
 
+our %DNA_TYPES = (
+  'Germline' => 1,
+  'Somatic'  => 1
+);
+
 =head2 new
 
   Arg [-dbID] :
@@ -157,12 +162,12 @@ sub new {
   my $class = ref($caller) || $caller;
   my $self = $class->SUPER::new(@_);
 
-  my ($dbID,$adaptor,$phenotype_id,$phenotype,$type,$object,$object_id,$source_name,$source_id,$source,$study,$study_id,$is_significant,$attribs, $ontology_accessions) =
+  my ($dbID,$adaptor,$phenotype_id,$phenotype,$type,$object,$object_id,$source_name,$source_id,$source,$study,$study_id,$is_significant,$dna_type,$attribs, $ontology_accessions) =
     rearrange([qw(
       dbID ADAPTOR _PHENOTYPE_ID PHENOTYPE
       TYPE OBJECT _OBJECT_ID
       SOURCE_NAME _SOURCE_ID SOURCE STUDY _STUDY_ID
-      IS_SIGNIFICANT
+      IS_SIGNIFICANT DNA_TYPE
       ATTRIBS ONTOLOGY_ACCESSIONS
     )], @_);
 
@@ -207,6 +212,7 @@ sub new {
 
   $self->{type}                = $type;
   $self->{is_significant}      = $is_significant;
+  $self->{dna_type}            = $dna_type || undef;
   $self->{attribs}             = $attribs || {};
   $self->{ontology_accessions} = $ontology_accessions || undef;
 
@@ -510,6 +516,30 @@ sub type {
   return $self->{'type'};
 }
 
+=head2 dna_type
+
+  Arg [1]    : string $type (optional)
+               The new value to set the clinical significance type attribute to
+  Example    : $type = $obj->dna_type()
+  Description: Getter/Setter for the object dna_type of the PhenotypeFeature.
+  Returntype : string
+  Exceptions : none
+  Caller     : general
+  Status     : Stable
+
+=cut
+
+sub dna_type {
+  my $self = shift;
+  my $type = shift;
+
+  if(defined($type)) {
+    throw("$type is not a valid object type, valid types are: ".(join ", ", sort %DNA_TYPES)) unless defined($DNA_TYPES{$type});
+    $self->{'dna_type'} = $type;
+  }
+
+  return $self->{'dna_type'};
+}
 
 =head2 is_significant
 
@@ -938,6 +968,48 @@ sub clinical_significance {
   return defined($self->get_all_attributes->{'clinvar_clin_sig'}) ? $self->get_all_attributes->{'clinvar_clin_sig'} : undef;
 }
 
+=head2 somatic_classification
+
+  Example    : $somatic_classification = $obj->somatic_classification()
+  Description: Getter for the somatic_clin_sig attribute.
+  Returntype : string
+  Exceptions : none
+  Caller     : general
+  Status     : Stable
+
+=cut
+
+sub somatic_classification {
+  my $self = shift;
+
+  my $classification = undef;
+
+  if(defined $self->get_all_attributes->{'somatic_clin_sig'}) {
+    $classification = $self->get_all_attributes->{'somatic_clin_sig'};
+  }
+
+  return $classification;
+}
+
+=head2 oncogenicity_classification
+
+  Example    : $oncogenicity = $obj->oncogenicity_classification()
+  Description: Getter/setter for the oncogenic_clin_sig attribute.
+  Returntype : string
+  Exceptions : none
+  Caller     : general
+  Status     : Stable
+
+=cut
+
+sub oncogenicity_classification {
+  my $self = shift;
+  my $new  = shift;
+
+  $self->_set_attribute('oncogenic_clin_sig', $new) if defined($new);
+
+  return defined($self->get_all_attributes->{'oncogenic_clin_sig'}) ? $self->get_all_attributes->{'oncogenic_clin_sig'} : undef;
+}
 
 =head2 external_id
 

modules/Bio/EnsEMBL/Variation/Utils/Config.pm

@@ -87,6 +87,18 @@ our @clinvar_clinical_significance_types = (
     'established risk allele'
 );
 
+our @clinvar_clinical_significance_somatic = (
+    'Tier I - Strong',
+    'Tier II - Potential',
+    'Tier III - Uncertain significance',
+    'Tier IV - Benign/likely benign',
+    'Oncogenic',
+    'Likely oncogenic',
+    'Uncertain significance',
+    'Likely benign ',
+    'Benign'
+);
+
 our @dgva_clinical_significance_types = (
     'Not tested',
     'Benign',
@@ -1243,6 +1255,16 @@ our @ATTRIB_TYPES = (
          name => 'ClinVar clinical significance',
          description => 'The clinical significance of a variant as reported by ClinVar',
     },
+    {
+         code => 'somatic_clin_sig',
+         name => 'ClinVar somatic significance',
+         description => 'The somatic classification of a variant as reported by ClinVar',
+    },
+    {
+         code => 'oncogenic_clin_sig',
+         name => 'ClinVar somatic classification of oncogenicity',
+         description => 'The somatic classification of oncogenicity of a variant as reported by ClinVar',
+    },
     {
         code => 'prot_func_analysis',
         name => 'Protein function analysis ',
@@ -1363,6 +1385,7 @@ our %ATTRIBS = (
    'dbsnp_clin_sig'      => \@dbsnp_clinical_significance_types,
    'dgva_clin_sig'       => \@dgva_clinical_significance_types,
    'clinvar_clin_sig'    => \@clinvar_clinical_significance_types,
+   'clinvar_somatic'    => \@clinvar_clinical_significance_somatic,
    'polyphen_prediction' => ['probably damaging', 'possibly damaging', 'benign', 'unknown'],
    'sift_prediction'     => ['tolerated', 'deleterious', 'tolerated - low confidence', 'deleterious - low confidence'],
    'prot_func_analysis'  => [qw(sift polyphen_humvar polyphen_humdiv)],