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code-adVNTR - A tool for genotyping coding VNTRs

code-adVNTR is a tool for genotyping Variable Number Tandem Repeats (VNTR) from sequence data.

code-adVNTR utilizes multiple motif HMMs to identify small variants within motifs and estimate diploid repeat counts for VNTRs. It takes short reads, and a pre-trained HMM model for reference VNTRs as input and outputs either estimated diploid repeat count or small variants within the target VNTRs.

Installation

Currently, you can install code-adVNTR from source install the adVNTR from source with dependencies.

code-adVNTR could be invoked from command line with advntr. In the future, code-adVNTR will be merged into the master branch of adVNTR for easy access.

Here are the instructions to install from source:

  1. Prepare a directory that you want to download code-adVNTR and go to the directory, cd "directory_name"
  2. Download the source code using the following command, git clone https://github.com/mehrdadbakhtiari/adVNTR.git --branch enhanced_hmm
  3. Go to the directory that you downloaded the source code, cd adVNTR
  4. Install adVNTR using the following command, python setup install
  5. Download the reference VNTRs from this link below.
  6. Run adVNTR for a VNTR using the following command, advntr genotype -fs --vntr_id [id] --alignment_file [bam_file] -m [reference_vntr] --working_directory [working_dir] -fs is a parameter for variant detection, --vntr_id option is for specifying the target VNTR. For example 25561 for MUC1 VNTR with hg19 reference VNTRs.

If you encounter an error about muscle, please install the following version. conda install muscle=3.8.1551

Data Requirements

In order to genotype VNTRs, you need to either train models for loci of interest or use pre-trained models (recommended):

  • To run adVNTR on trained VNTR models:
    • Download vntr_data_recommended_loci.zip and extract it inside the project directory. This includes a set of pre-trained VNTR models for Illumina (6719 loci) and Pacbio (8960 loci) sequencing data.
    • You can also download and use vntr_data_genic_loci.zip for 158522 VNTRs that results in having much longer running time.

Alternatively, you can add model for custom VNTR. See Add Custom VNTR for more information about training models for custom VNTRs.

Execution:

Use following command to see the help for running the tool.

advntr --help

The program outputs either the RU count genotypes or small variants of trained VNTRs. To specify a single VNTR by its ID use --vntr_id <id> option. The list of some known VNTRs and their ID is available at Disease-linked-VNTRs page in wiki.

See the demo below or Quickstart page to see an example data set with step-by-step genotyping commands.

Demo input in BAM format

  • --alignment_file specifies the alignment file containing mapped and unmapped reads:
    advntr genotype --alignment_file aligned_illumina_reads.bam --working_directory ./log_dir/
  • Use --frameshift to find the possible frameshifts in VNTR:
    advntr genotype --alignment_file aligned_illumina_reads.bam --working_directory ./log_dir/ --frameshift

Documentation:

Documentation is available at advntr.readthedocs.io.

See Quickstart page to see an example data set with step-by-step genotyping commands.

Citation:

Jonghun Park, Mehrdad Bakhtiari, Bernt Popp, Michael Wiesener, Vineet Bafna. Detecting tandem repeat variants in coding regions using code-adVNTR iScience vol. 25,8 104785. (2022)

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A tool for genotyping Variable Number Tandem Repeats (VNTR) from sequence data

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