VCF to TileDB Import Design

Functionality

The VCF import process performs:

1. Registration of MetaDB related items from a list of VCF files.

2. Optional sorting, compression, and indexing of input VCF files using bcftools.

3. Construction of required configs for GenomicsDB import

4. Optional loading of TileDB array

Config File

See utils/example_configs/vcf_import.config for an example.

Field	Mandatory	Description
workspace	Yes	Full path to TileDB workspace where the array will exist.
array	Yes	Name of array to import VCFs into.
assembly	Yes	Name of assembly. This can be an existing assembly in MetaDB or new assembly to be registered from VCF contig tags.
dburi	Yes	MetaDB Instance to make a connection to, as defined in alembic.ini: driver://user:pass@localhost/dbname
vcf_type	No	Defaults to TN, but overrides if sample size is less than 2. Important to keep track of tumor and normal in metadb.
sort_compress	No	Defaults to True. Will sort and compress files with bcftools.
index	No	Defaults to True. Will index files with bcftools.
source_idx	No	Defaults to 0. Used to specify the ordering of normal sample in the VCF file.
target_idx	No	Defaults to 1. Used to specify the ordering of tumor sample in the VCF file.
sample_name	No	A map of how to read sample information. Defaults to empty {}.
sample_name / derive_sample	No	Defaults to header. header read the samples from header, tag read samples from the sample tag, file read samples from file name. Set split_by and split_index appropriately for tag and file, or see defaults below.
sample_name / split_by	No	Defaults to None. If tag this says what field to grab the sample name from in the sample tag. If file this will split the file name by this.
sample_name / split_index	No	Defaults to 0, set for splitting by file.

GenomicsDB vcf2tiledb Executable

Unlike the MAF importer, the VCF import process does not require an intermediate CSV before passing to the GenomicsDB loading process. The VCF import process for GenomicsDB requires that the VCFs are sorted, blocked compressed, and indexed (addressed by step 2 above). The import process also requires three import configuration files for the GenomicsDB vcf2tiledb import binary (much like the MAF/CSV import process): i) callset_mapping, ii) vid_mapping iii) loader config (addressed by step 3 and 4 above).

Understanding the VCF Format

The main use case for the VCF import process is designed to import VCFs produced from a somatic variant calling pipeline. These VCFs contain two sample columns, one from the NORMAL sample and one from the TUMOR sample. These columns will each be represented as a CallSet in the variant store - meaning each VCF will have two callsets associated with it. The VCF importer is designed to read from a config to understand how to retrieve sample information from the VCF - required because there are two ways a sample name can be labeled in a VCF. These two types are addressed below: i) sample in header and ii) sample tag identifiers. See information about the config section for more on fields related to sample information handling. Note that tumor and normal samples are inferred based on the presense of normal, or target and primary in the sample name.

The secondary use case for the VCF import process is to import single sample, or composite VCF files (no sample). The type of VCF file is assumed based on the number of samples available.

Sample in Header

In the most simple case, the sample information is available in the header line, ie. sample1N and sample1T below.

#CHROM    POS    ID    REF    ALT    QUAL    FILTER    INFO    FORMAT    sample1N    sample1T

Sample Tag Identifiers

Often, the sample information in the header is something more generic and cannot be used to uniquely identify the sample, ie. NORMAL and TUMOR below.

#CHROM    POS    ID    REF    ALT    QUAL    FILTER    INFO    FORMAT    NORMAL    TUMOR

If this is the case, sample tag(s) must be provided in the header for the sample, and the config file sample_map field should specify how to retrieve this information. For example, below would require "split_by": "SampleName".

##SAMPLE=<ID=NORMAL,Description="Wild type",Platform=ILLUMINA,Protocol=WGS,SampleName=sample1N>'
##SAMPLE=<ID=TUMOR,Description="Mutant",Platform=ILLUMINA,Protocol=WGS,SampleName=sample1T>'

ReferenceSet and References

ReferenceSet and Reference registration will be derived from the contig tags of the first VCF file. This section (truncated) is required for proper VCF import:

##contig=<ID=1,assembly=b37,length=249250621>
##contig=<ID=2,assembly=b37,length=243199373>
...
##contig=<ID=MT,assembly=b37,length=16569>
##contig=<ID=X,assembly=b37,length=155270560>
##contig=<ID=Y,assembly=b37,length=59373566>

Usage

See the usage section for examples.

python vcf2tile.py --help
usage: vcf2tile.py [-h] -c CONFIG -d OUTPUTDIR -i INPUTS [INPUTS ...]
                   [-a APPEND_CALLSETS] [-l LOADER]

Register VCF with MetaDB and create TileDB JSON.

optional arguments:
  -h, --help            show this help message and exit
  -c CONFIG, --config CONFIG
                        input configuration file for VCF import
  -d OUTPUTDIR, --outputdir OUTPUTDIR
                        Output directory where the outputs need to be stored
  -i INPUTS [INPUTS ...], --inputs INPUTS [INPUTS ...]
                        VCF files to be imported.
  -a APPEND_CALLSETS, --append_callsets APPEND_CALLSETS
                        CallSet mapping file to append.
  -l LOADER, --loader LOADER
                        Loader JSON to load data into Tile DB.