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Variant merging

You can use Variant Transforms to load multiple files at once by providing a pattern like --input_pattern gs://mybucket/*.vcf. This will create a merged BigQuery schema that contains all variants from all matching files. Note that the VCF fields must be compatible across files (e.g. INFO and FORMAT fields with the same key have compatible types and numbers across files).

However, by default, calls between files will not be merged. For instance, consider the following VCF files:

gs://mybucket/a.vcf:

## <headers omitted>
#CHROM  POS   ID    REF   ALT   QUAL  FILTER  INFO    FORMAT  S1      S2
1       100   rs1   A     T     29    PASS    DP=14   GT:GQ   0|1:48  0/0:30

gs://mybucket/b.vcf:

## <headers omitted>
#CHROM  POS   ID    REF   ALT   QUAL  FILTER  INFO         FORMAT  S3
1       100   rs1   A     T     7     q10     DP=11;AA=G   GT:GQ   1/1:2

If you load both files together (i.e. by specifying --input_pattern gs://mybucket/*.vcf), you would end up with 2 rows in BigQuery. One with calls S1 and S2, and another with just call S3 even though all calls have the same variant.

Variant merging can be used to merge calls across files. There are different merging strategies and you can specify any of the following strategies by adding --variant_merge_strategy <merge_strategy> to the arguments.

MOVE_TO_CALLS strategy

This strategy merges calls that have the same reference_name, start_position, end_position, reference_bases, and all alternate_bases across files. By default, the variant fields are merged as follows:

  • Calls are merged together in no particular order.
  • The highest quality value is chosen among all variants being merged.
  • All filter values are merged and deduplicated.
  • All names (ID column in the VCF spec) are merged and deduplicated.
  • For each INFO field, one is chosen as representative for the entire merged variant record in no particular order. Note that for repeated fields, a single set is chosen as representative for that particular field.

Depending on your use case, you may customize the merge strategy as follows:

  • Adding --copy_quality_to_calls and/or --copy_filter_to_calls to the arguments will copy the quality and/or filter values in each file to the set of calls specified in that file. This option is useful when merging single-call VCF files as quality and filter values usually correspond to call-level quality/filter. Note that the variant-level quality and filter values will still be merged according to the above logic.
  • Adding --info_keys_to_move_to_calls_regex <regex> will move INFO fields that match the provided regular expression to the associated calls. This is useful to ensure all INFO fields are kept when merging variants. For instance, specifying .* will move all INFO keys to calls, or specifying ^(AA|AF)$ will only move AA and AF fields to calls. See here for more details on the regular expression specifications. Note that if a key is the same in both INFO and FORMAT, then such a key cannot be moved to calls and an error will be raised.

The examples below help with illustrating the details of the above options. You may also read the code and documentation in move_to_calls_strategy.py. Particularly the get_merged_variants method implements the merging logic.

Examples

The following examples illustrate the merging outcome using the example files gs://mybucket/a.vcf and gs://mybucket/b.vcf that are defined above.

  • Default (i.e. just adding --variant_merge_strategy MOVE_TO_CALLS):
reference_name: "1"
start_position: 100
end_position: 101
reference_bases: "A"
alternate_bases: {alt: "T"}
names: ["rs1"]
quality: 29
filter: ["PASS", "q10"]
call: {
  [
    name: "S3",
    genotype: [1, 1]
    phaseset: null
    GQ: 2
  ],
  [
    name: "S1",
    genotype: [0, 1]
    phaseset: "*"
    GQ: 48
  ],
  [
    name: "S2",
    genotype: [0, 0]
    phaseset: null
    GQ: 30
  ]
}
DP: 14  # This can also be 11.
AA: "G"
  • With --copy_quality_to_calls and --copy_filter_to_calls:
reference_name: "1"
start_position: 100
end_position: 101
reference_bases: "A"
alternate_bases: {alt: "T"}
names: ["rs1"]
quality: 29
filter: ["PASS", "q10"]
call: {
  [
    name: "S3",
    genotype: [1, 1]
    phaseset: null
    GQ: 2
    quality: 7
    filter: ["q10"]
  ],
  [
    name: "S1",
    genotype: [0, 1]
    phaseset: "*"
    GQ: 48
    quality: 29
    filter: ["PASS"]
  ],
  [
    name: "S2",
    genotype: [0, 0]
    phaseset: null
    GQ: 30
    quality: 29
    filter: ["PASS"]
  ]
}
DP: 14  # This can also be 11.
AA: "G"
  • With --info_keys_to_move_to_calls_regex ^DP$, --copy_quality_to_calls, --copy_filter_to_calls:
reference_name: "1"
start_position: 100
end_position: 101
reference_bases: "A"
alternate_bases: {alt: "T"}
names: ["rs1"]
quality: 29
filter: ["PASS", "q10"]
call: {
  [
    name: "S3",
    genotype: [1, 1]
    phaseset: null
    GQ: 2
    quality: 7
    filter: ["q10"]
    DP: 11
  ],
  [
    name: "S1",
    genotype: [0, 1]
    phaseset: "*"
    GQ: 48
    quality: 29
    filter: ["PASS"]
    DP: 14
  ],
  [
    name: "S2",
    genotype: [0, 0]
    phaseset: null
    GQ: 30
    quality: 29
    filter: ["PASS"]
    DP: 14
  ]
}
AA: "G"

MERGE_WITH_NON_VARIANTS strategy [EXPERIMENTAL]

This strategy is not yet production ready and can't be used by users. This section is included here to provide more context about our ongoing work (Issue #80 and Issue #88).

The MOVE_TO_CALLS strategy is effective for merging calls that have exactly the same reference and alternate bases. However, this strategy is not effective for merging gVCF files since non-variants are represented as intervals in the genome.

Consider the following VCF file:

gs://mybucket/c.g.vcf:

## <headers omitted>
#CHROM  POS   ID    REF   ALT        QUAL  FILTER  INFO     FORMAT  S4
1       50    .     T     <NON_REF>  .     .       END=150  GT:GQ   0/0:40

If you specify --input_pattern gs://mybucket/*.vcf with MOVE_TO_CALLS merge strategy, the non-variant region from call S4 will not be merged with calls S1, S2, and S3. However, we know that call S4 has genotype 0/0 in chr1:100 since it matches the reference from position 50-150 in chr1. The MERGE_WITH_NON_VARIANTS strategy will infer 0/0 for call S4 at chr1:100 so that the resulting BigQuery table has a single row with all calls S1-4.

Our initial work is focused on correctly calling SNPs (Issue #80). We will then attempt to merge insertions/deletions (Issue #88).