Quickstart

This document is intended for the impatient users who want to quickly setup and prioritize variants with SvAnna.

Prerequisites

SvAnna is written in Java 11 and needs Java 11+ to be present in the runtime environment. Please verify that you are using Java 11+ by running:

$ java -version

If java is present on your $PATH, then the command above will print a message similar to this one:

openjdk version "11" 2018-09-25
OpenJDK Runtime Environment 18.9 (build 11+28)
OpenJDK 64-Bit Server VM 18.9 (build 11+28, mixed mode)

Setup

SvAnna is installed by running the following three steps.

1. Download SvAnna distribution ZIP

Download and extract SvAnna distribution ZIP archive from here. Expand the Assets menu and download the svanna-cli-${project.version}-distribution.zip. Choose the latest stable version, or a release candidate (RC).

After unzipping the distribution archive, run the following command to display the help message:

$ java -jar svanna-cli-${project.version}.jar --help

Note

If things went OK, the command above will print the following help message:

Structural variant prioritization
Usage: svanna-cli.jar [-hV] [COMMAND]
  -h, --help      Show this help message and exit.
  -V, --version   Print version information and exit.
Commands:
  prioritize         Prioritize the variants.
See the full documentation at `https://svanna.readthedocs.io/en/master`

2. Download SvAnna database files

SvAnna database files are available for download in the Downloads section.

After the download, unzip the archive(s) content into a folder of your choice and note down the path:

$ unzip -d svanna-data *.svanna.zip

Prioritize structural variants in VCF file

Let’s annotate a toy VCF file containing eight SVs reported in the SvAnna manuscript. First, let’s download the VCF file from here:

$ wget https://raw.githubusercontent.com/TheJacksonLaboratory/SvAnna/master/svanna-cli/src/examples/example.vcf

The variants were sourced from published clinical case reports and presence of each variant results in a Mendelian disease.

For the purpose of this test run, let’s assume that the VCF file contains SVs identified in a short/long read sequencing run of a patient presenting with the following clinical symptoms:

HP:0011890 - Prolonged bleeding following procedure
HP:0000978 - Bruising susceptibility
HP:0012147 - Reduced quantity of Von Willebrand factor

Now, let’s prioritize the variants:

$ java -jar svanna-cli-${project.version}.jar prioritize -d svanna-data --output-format html,csv,vcf --vcf example.vcf --phenotype-term HP:0011890 --phenotype-term HP:0000978 --phenotype-term HP:0012147

The variant Othman-2010-20696945-VWF-index-FigS7 disrupts a promoter of the von Willenbrand factor (VWF) gene (Othman et al., 2010). The variant receives the highest $PSV$ score of 47.26, and it is ranked first.

SvAnna stores prioritization results in HTML, CSV, and VCF output formats in the current working directory.