###########################################################################################################
# This demo showcases the GAVIN+ Variant Interpretation tool and Genome Report tool for genome diagnostics.
#
# For authorship and licensing information, see https://github.com/molgenis and https://github.com/molgenis/gavin-plus.
# The example data used within this demo is not real patient data, but healthy individuals with artificially introduced pathogenic mutations.
#
# Software disclaimer:
# This SOFTWARE PRODUCT is provided by THE PROVIDER "as is" and "with all faults."
# THE PROVIDER makes no representations or warranties of any kind concerning the safety, suitability, lack of viruses, inaccuracies, typographical errors, or other harmful components of this SOFTWARE PRODUCT.
# There are inherent dangers in the use of any software, and you are solely responsible for determining whether this SOFTWARE PRODUCT is compatible with your equipment and other software installed on your equipment.
# You are also solely responsible for the protection of your equipment and backup of your data, and THE PROVIDER will not be liable for any damages you may suffer in connection with using, modifying, or distributing this SOFTWARE PRODUCT.
###########################################################################################################

## Download GAVIN+ 1.3 beta and data bundle
mkdir gavin-tools
cd gavin-tools
wget http://molgenis.org/downloads/gavin/GAVIN-Plus-1.3beta.jar
wget http://molgenis.org/downloads/gavin/genomereport-1.0.0-SNAPSHOT-jar-with-dependencies.jar
wget https://github.com/joerivandervelde/gavin-plus/raw/master/src/test/resources/bundle_r1.2/CGD_26jun2018.txt.gz
wget https://github.com/joerivandervelde/gavin-plus/raw/master/src/test/resources/bundle_r1.2/FDR_allGenes_r1.2.tsv
wget https://github.com/joerivandervelde/gavin-plus/raw/master/src/test/resources/bundle_r1.2/GAVIN_calibrations_r0.5.tsv
wget https://github.com/joerivandervelde/gavin-plus/raw/master/src/test/resources/bundle_r1.2/clinvar.vkgl.patho.26june2018.vcf.gz
cd ..

## Download demo files (note that the VCF has been annotated by SnpEff, ExAC, GoNL and CADD-SNVs)
wget http://molgenis.org/downloads/gavin/demo/GAVIN-Plus_Demo_1000G_Spiked.vcf
wget http://molgenis.org/downloads/gavin/demo/GAVIN-Plus_Demo_1000G_Spiked.fromCadd.tsv

## Q1. How many DNA variants are present in GAVIN-Plus_Demo_1000G_Spiked.vcf?
## Q2. On which chromosome are these variants located?

## Show all options of GAVIN+, this includes options to keep all variants and/or sample data
java -jar gavin-tools/GAVIN-Plus-1.3beta.jar -h

## Run analysis on GAVIN-Plus_Demo_1000G_Spiked.vcf
java -jar gavin-tools/GAVIN-Plus-1.3beta.jar -i GAVIN-Plus_Demo_1000G_Spiked.vcf -o GAVIN-Plus_Demo_1000G_Spiked.RVCF.firstpass.vcf -m CREATEFILEFORCADD -c GAVIN-Plus_Demo_1000G_Spiked.toCadd.tsv -p gavin-tools/clinvar.vkgl.patho.26june2018.vcf.gz -d gavin-tools/CGD_26jun2018.txt.gz -f gavin-tools/FDR_allGenes_r1.2.tsv -g gavin-tools/GAVIN_calibrations_r0.5.tsv

## Q3. Inspect the results, how many interesting variants did we find?

## Note that not all variants could be immediately assessed due to missing CADD scores.
## The variants that have missing scores are written to a file (GAVIN-Plus_Demo_1000G_Spiked.toCadd.tsv).
## Normally, CADD scores are calculated for these variants, but don't do this.
## Q4. What type of variants are included in this file?

## For your convenience, the CADD output is already included in the demo files.
## Use GAVIN-Plus_Demo_1000G_Spiked.fromCadd.tsv to finish the analysis.
java -jar gavin-tools/GAVIN-Plus-1.3beta.jar -i GAVIN-Plus_Demo_1000G_Spiked.vcf -o GAVIN-Plus_Demo_1000G_Spiked.RVCF.vcf -m ANALYSIS -c GAVIN-Plus_Demo_1000G_Spiked.fromCadd.tsv -p gavin-tools/clinvar.vkgl.patho.26june2018.vcf.gz -d gavin-tools/CGD_26jun2018.txt.gz -f gavin-tools/FDR_allGenes_r1.2.tsv -g gavin-tools/GAVIN_calibrations_r0.5.tsv

## Q5. Inspect the results, how many variants are there now?
## Q6. What is/are the RS identifier(s) of the additional variant(s)?

## Create a human-readable genome report in HTML format from the output data.
java -jar gavin-tools/genomereport-1.0.0-SNAPSHOT-jar-with-dependencies.jar -i GAVIN-Plus_Demo_1000G_Spiked.RVCF.vcf -o GAVIN-Plus_Demo_1000G_Report.html

## Open the report, the default web browser will be used. If not, open manually. Use Chrome or similar modern browser.
open GAVIN-Plus_Demo_1000G_Report.html

## Suppose that the patient has been clinically diagnosed with a form of colorectal cancer. 
## Q7. Use virtual gene panel filter within the genome report to pinpoint the most likely causal variant. Click on variants to see details. What is its RS identifier?
## Q8. Suppose the patient has a wish for progeny with a 'healthy' partner. What is the chance that his or her offspring would inherit this particular disease?
## Q9. In which other virtual gene panel do we find a candidate variant?
## Q10. What is the European allele frequency of this variant?
## Q11. Based on this frequency, is this variant likely to be pathogenic?
## Q12. If this were a preconception carrier screening test, which variant would undergo further interpretation?