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MorbidUpdateR

The goal of MorbidUpdateR is to conveniently update our Morbid Genes Panel. The user can simply run the functions without editing the variables, as the default values already point to the correct and relevant files and paths.

For more flexibility and for testing purposes, the user can also specify new paths, versions and files (which is, however, not recommended, as the alternative input values have not been extensively tested yet).

So in summary, just run the functions every month for an efficient update of the Morbid Genes Panel.

Installation

You can install the development version from GitHub with:

# install.packages("devtools")
devtools::install_github("HUGLeipzig/MorbidUpdateR")

Config file

Some functions require values specified in a config.yml file. The required values are:

• omim_id: your personal OMIM identifier, needed for downloading the OMIM files
• varvis_target: your Varvis target, needed for the URL generation, e.g. "your-university"
• varvis_user: the username for your Varvis API
• varvis_password: the password for your Varvis API (can be Unicode)
• hgmd_csv_path: the path and filename to your stored HGMD csv file
• panelapp_tsv_path: the path and filename where the PanelApp downloads should be stored
• sysndd_tsv_path: the path and filename where the SysNDD downloads should be stored

Getting started

The package contains several function, most of them can be run "as is" without specifying variables and paths:

library(MorbidUpdateR)

# generate directory and download all the relevant files 
StartNewVersion()

# add/edit the downloaded files automatically
Add_all()

# build and save the panel
Build_MorbidGenesPanel()

That's basically it. For a more comprehensive list of variables and how to manipulate your input/output files, just run ?function in the command line

Default CutOffs

The functions in this package have precomputed cutoffs to determine if a gene is a morbidgene or not. If ONE of the following points is true, then a genes is considered to be a morbidgene:

• >=4 pathogenic variants in ClinVar
  • column clinvar_pathogenic_cutoff
• >=4 pathogenic variants in HGMD (= "DM" Variant)
  • column hgmd_pathogenic_cutoff
• TRUE has an OMIM phenotype
  • column omim_phenotype
• TRUE is green gene in PanelApp England OR PanelApp Australia
  • column panelapp
• TRUE has status 'definitive' in GenCC
  • column gencc
• TRUE has status 'definite' in SysNDD
  • column sysndd
• TRUE was added manually
  • column manually_added