What is CovCheck?

The CovCheck analysis computes a personal genome report indicating 'risk of severe symptoms' (CFR) from COVID-19 infection.

The risk analysis is based on published, peer-reviewed studies: https://www.covid19hg.org/publications/

Personal genome data and age (if provided) is read from a simple 'genome file' in JSON format.

Note that this analyis is work in progress!!!

CI/CD

Installation and Usage

To install, pull from git:

git@github.com:Geromics/covcheck.git

change to the appropriate directory:

cd covcheck

and run the code:

python3 covid_genetic_check.py -h

usage: check.py [-h] [--version] [--verbose] infile [outfile]

Score an individual.

positional arguments:
  infile         JSON format file containing individual data
  outfile        JSON format results file (default: <stdout>)

optional arguments:
  -h, --help     show this help message and exit
  --version      show program's version number and exit
  --verbose, -v

The only formal requirements (requirements.txt) are for testing:

pip install -r requirements.txt

which is done by:

python3 -m pytest -v .

Note, project dependncies are not managed by a high level tool such as flit, poetry or Pipenv.

Analysis details

The analysis of risk with age is based on data from here:

• https://ourworldindata.org/mortality-risk-covid#case-fatality-rate-of-covid-19-by-age

and has been done with help from:

• https://realrisk.wintoncentre.uk/

The genome report is currently based on the analysis in this preprint: https://www.researchsquare.com/article/rs-37798/v1

Notes from the preprint...

##reference=GRCh38.p12
chr21 41480570 rs12329760 C T . . .
chr21 41507982 rs75603675 C A . . .

rs12329760, TMPRSS2(-), V197M, C->T (G->A, V[GTG] -> M[ATG])
C is the risk allele, T is 'protective'

rs75603675, TMPRSS2(-), G008V, C->A (G->T, G[GGT] -> V[GTT])
A is the risk allele, C is 'protective'

Spearman’s correlation with COVID-19 CFR:
ρ = -0.464, P = 0.0157 for V197M C->T (G->A)
ρ = +0.713, P = 0.0018 for G008V C->A (G->T)

The higher the score, the greater your genetic risk of severe
COVID-19 infection.

Additional references

COVID:

• QCovid® risk calculator
  • https://qcovid.org/
• The Association of Local Authority Medical Advisors (ALAMA), COVID-AGE
  • https://alama.org.uk/covid-19-medical-risk-assessment/
• Charlson Comorbidity Index
  • https://www.mdcalc.com/charlson-comorbidity-index-cci
• GenOMICC COVID-19 Study
  • https://genomicc.org/
  • https://www.genomicsengland.co.uk/covid-19/

Polygenic Risk Scores:

• From Basic Science to Clinical Application of Polygenic Risk Scores: A Primer.
  • https://europepmc.org/article/MED/32997097
• Towards clinical utility of polygenic risk scores.
  • http://europepmc.org/article/MED/31363735

Papers studying the genetics of COVID

• Genetic susceptibility of COVID-19: a systematic review of current evidence
  • https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-021-00516-8
• Mapping the human genetic architecture of COVID-19
  • https://www.nature.com/articles/s41586-021-03767-x
• Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus
  • https://www.nature.com/articles/s41588-021-00955-3
• The major genetic risk factor for severe COVID-19 is inherited from Neanderthals
  • https://www.nature.com/articles/s41586-020-2818-3
• Genetic mechanisms of critical illness in COVID-19
  • https://www.nature.com/articles/s41586-020-03065-y
• The quest to find genes that drive severe COVID
  • https://www.nature.com/articles/d41586-021-01827-w
• A catalog of associations between rare coding variants and COVID-19 outcomes
  • https://www.medrxiv.org/content/10.1101/2020.10.28.20221804v2

Random notes

A common pattern to mark an unfinished code is to raise a NotImplementedError that is noticed at runtime:

@classmethod
def from_api(cls, url):
    raise NotImplementedError  # TODO

TODO: Use a few tools to automatically take care of code formatting (black), flag style-related problems (flake8), as well as warn about potential bugs (pylint).