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Capture uploaded allele correctly for VCF input #1744

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Capture uploaded allele correctly for VCF input #1744

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439731a
Capture uploaded allele correctly for VCF input
likhitha-surapaneni Aug 20, 2024
11adcb8
Cleanup
likhitha-surapaneni Aug 20, 2024
3538ac4
Cleanup
likhitha-surapaneni Aug 20, 2024
5f1d345
Supporting uploaded allele for multiple alternate alleles
likhitha-surapaneni Aug 20, 2024
6794d24
Return vf after enabling minimised
likhitha-surapaneni Aug 21, 2024
c039ac7
Clearer variable name and comments
likhitha-surapaneni Aug 22, 2024
b7b2013
Renaming conflicting variable names
likhitha-surapaneni Aug 30, 2024
8ad71eb
Fix buffer logic for multi-allelic variants
likhitha-surapaneni Nov 5, 2024
d3d655c
Modify unittests
likhitha-surapaneni Dec 4, 2024
df56c61
Changes in rejoin_vf; Fix unit tests
likhitha-surapaneni Dec 4, 2024
56d965a
Fixed unit tests
likhitha-surapaneni Dec 5, 2024
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6 changes: 3 additions & 3 deletions modules/Bio/EnsEMBL/VEP/InputBuffer.pm
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Expand Up @@ -257,8 +257,7 @@ sub next {
die($error_msg);
}

$self->split_variants() if $self->{minimal};

$self->split_variants() if $self->{minimal} ;
return $buffer;
}

Expand Down Expand Up @@ -664,7 +663,8 @@ sub split_variants {
$first->{original_allele_string} = $original_vf->{allele_string};
$first->{original_start} = $original_vf->{start};
$first->{original_end} = $original_vf->{end};
$first->{minimised} = 1
$first->{minimised} = 1;
$first->{first} = 1;
}

push @tmp, $new_vf;
Expand Down
6 changes: 4 additions & 2 deletions modules/Bio/EnsEMBL/VEP/OutputFactory.pm
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Expand Up @@ -1296,7 +1296,8 @@ sub VariationFeatureOverlapAllele_to_output_hash {

# reference allele
$hash->{REF_ALLELE} = $vf->ref_allele_string if $self->{show_ref_allele};


# Capture uploaded allele
$hash->{UPLOADED_ALLELE} = ($vf->{original_allele_string} || $vf->{allele_string} || $vf->{class_SO_term} || "" ) if $self->param('uploaded_allele');

# picked?
Expand Down Expand Up @@ -2193,7 +2194,8 @@ sub rejoin_variants_in_InputBuffer {
foreach my $vf(@{$buffer->buffer}) {

# reset original one
if(defined($vf->{original_allele_string})) {
# check $vf->{first} to get first $vf in split_variants
if(defined($vf->{first})) {
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# do consequence stuff
$self->get_all_output_hashes_by_VariationFeature($vf);
Expand Down
33 changes: 26 additions & 7 deletions modules/Bio/EnsEMBL/VEP/Parser.pm
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Expand Up @@ -851,13 +851,24 @@ sub post_process_vfs {
$vf->seq_region_start($vf->{start});
$vf->seq_region_end($vf->{end});

# Checks if the allele string is insertion or/and deletion
# Checks if the allele string is non-minimised insertion or/and deletion
my $is_sv = ref($vf) eq 'Bio::EnsEMBL::Variation::StructuralVariationFeature';
if(!$is_sv && defined($vf->{allele_string}) && $vf->{allele_string} =~ /\//){
my $is_indel = 0;
my ($ref_allele_string,$alt_allele_string) = split(/\//, $vf->{allele_string});
$is_indel = 1 unless length($ref_allele_string) == length($alt_allele_string) or $vf->{allele_string} =~ /-/;
$vf = ${$self->minimise_alleles([$vf])}[0] if $is_indel;
my $is_non_minimised_indel = 0;
# For VCF input, the allele_string is trimmed to remove anchor base, so we capture original allele

my $original_allele_string = ($vf->{nontrimmed_allele_string} || $vf->{allele_string});
my @alleles = split(/\//, $original_allele_string);
my $ref_allele_string = shift @alleles;
my $alt_allele_count;

foreach my $alt(@alleles) {
if (length($ref_allele_string) != length($alt) or $original_allele_string =~ /^-/){
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@likhitha-surapaneni , it seems we are checking only if ref allele is - with $original_allele_string =~ /^-/ unlike for any allele like before. Was it intended?

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$original_allele_string contains both ref_allele and alt_alleles in the same string separated by "/"

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true, but with ^ you are only checking - allele for ref and missing deletions?

$is_non_minimised_indel = 1;
last;
}
}
$vf = ${$self->minimise_alleles([$vf])}[0] if $is_non_minimised_indel;
}
}
return $vfs;
Expand Down Expand Up @@ -950,7 +961,15 @@ sub minimise_alleles {

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# skip VFs with more than one alt
# they get taken care of later by split_variants/rejoin_variants
if(!$vf->{allele_string} || $vf->{allele_string} =~ /.+\/.+\/.+/ || $vf->{allele_string} !~ /.+\/.+/) {
if(!$vf->{allele_string} || $vf->{allele_string} !~ /.+\/.+/) {
push @return, $vf;
}

elsif($vf->{allele_string} =~ /.+\/.+\/.+/)
{
# Updating a flag to minimise multi-allelic variants in split_variants/rejoin_variants
$vf->{minimised} = 1;
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Comment on lines +970 to +971
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Multi-allelic is not getting minimised for default format. For example - 1 961320 961324 GCAGG/GCA/GCAG +

But in the output still getting MINIMISED=1, (without the PR they are also not minimised but there is no MINIMISED=1).

$vf->{original_allele_string} = $vf->{nontrimmed_allele_string} || $vf->{allele_string};
push @return, $vf;
}

Expand All @@ -976,7 +995,7 @@ sub minimise_alleles {
$new_vf->{end} = $end;
$new_vf->{seq_region_start} = $start;
$new_vf->{seq_region_end} = $end;
$new_vf->{original_allele_string} = $vf->{allele_string};
$new_vf->{original_allele_string} = $vf->{nontrimmed_allele_string} || $vf->{allele_string};
$new_vf->{original_start} = $vf->{start};
$new_vf->{original_end} = $vf->{end};
$new_vf->{minimised} = 1;
Expand Down
1 change: 1 addition & 0 deletions modules/Bio/EnsEMBL/VEP/Parser/VCF.pm
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Expand Up @@ -340,6 +340,7 @@ sub create_VariationFeatures {
start => $start,
end => $end,
allele_string => $non_variant ? $ref : $ref.'/'.join('/', @$alts),
nontrimmed_allele_string => $non_variant ? $original_alleles[0] : join("/",@original_alleles),
strand => 1,
map_weight => 1,
adaptor => $self->get_adaptor('variation', 'VariationFeature'),
Expand Down
10 changes: 10 additions & 0 deletions t/InputBuffer.t
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Expand Up @@ -72,6 +72,7 @@ is_deeply($vfs->[0], bless( {
'variation_name' => 'rs142513484',
'map_weight' => 1,
'allele_string' => 'C/T',
'nontrimmed_allele_string' => 'C/T',
'end' => 25585733,
'start' => 25585733,
'seq_region_end' => 25585733,
Expand All @@ -90,6 +91,7 @@ is_deeply($vfs->[0], bless( {
'variation_name' => 'rs148490508',
'map_weight' => 1,
'allele_string' => 'A/G',
'nontrimmed_allele_string' => 'A/G',
'end' => 25592911,
'start' => 25592911,
'seq_region_end' => 25592911,
Expand Down Expand Up @@ -418,7 +420,9 @@ is_deeply($ib->buffer, [
'chr' => '1',
'minimised' => 1,
'original_allele_string' => 'CAGAAGAAAG/TAGAAGAAAG/C',
'nontrimmed_allele_string' => 'CAGAAGAAAG/TAGAAGAAAG/C',
'original_end' => 10,
'first' => 1,
'end' => 1,
'original_start' => 1,
'strand' => 1,
Expand All @@ -439,7 +443,10 @@ is_deeply($ib->buffer, [
'variation_name' => '.',
'alt_allele' => '-',
'map_weight' => 1,
'minimised' => 1,
'allele_string' => 'AGAAGAAAG/-',
'original_allele_string' => 'CAGAAGAAAG/TAGAAGAAAG/C',
'nontrimmed_allele_string' => 'CAGAAGAAAG/TAGAAGAAAG/C',
'start' => 2,
'seq_region_start' => 2,
'seq_region_end' => 10,
Expand Down Expand Up @@ -470,7 +477,10 @@ is_deeply(
'strand' => 1,
'variation_name' => '.',
'map_weight' => 1,
'minimised' => 1,
'allele_string' => 'CAG/TAG/T',
'original_allele_string' => 'CAG/TAG/T',
'nontrimmed_allele_string' => 'CAG/TAG/T',
'end' => 3,
'start' => 1,
'seq_region_start' => 1,
Expand Down
4 changes: 3 additions & 1 deletion t/OutputFactory.t
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Expand Up @@ -1678,7 +1678,9 @@ $ib = get_annotated_buffer({

is(scalar @{$ib->buffer}, 2, 'minimal - expanded count');
is($ib->buffer->[0]->allele_string, 'C/T', 'minimal - expanded first allele string');

# print("Before rejoin\n");
# use Data::Dumper;
# print(Dumper($ib->buffer));
Comment on lines +1681 to +1683
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should we remove the comments?

$of->rejoin_variants_in_InputBuffer($ib);

is(scalar @{$ib->buffer}, 1, 'minimal - rejoined count');
Expand Down
2 changes: 1 addition & 1 deletion t/OutputFactory_JSON.t
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Expand Up @@ -532,7 +532,7 @@ SKIP: {
'cdna_start' => 2347,
'transcript_id' => 'NM_000484.3',
'gene_id' => '351',
'uploaded_allele' => '-/A',
'uploaded_allele' => 'G/GA',
'cds_start' => 2147,
'protein_start' => 716,
'refseq_match' => [
Expand Down
4 changes: 4 additions & 0 deletions t/Parser_Region.t
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Expand Up @@ -127,9 +127,13 @@ is_deeply($vf, bless( {
'strand' => '1',
'variation_name' => '21:25587759-25587758:1/A',
'map_weight' => 1,
'minimised' => 1,
'allele_string' => '-/A',
'original_allele_string' => '-/A',
'end' => '25587758',
'start' => '25587759',
'original_start' => '25587759',
'original_end' => '25587758',
'seq_region_end' => '25587758',
'seq_region_start' => '25587759',
'_line' => ['21:25587759-25587758:1/A']
Expand Down
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