Bayesian Gene Heritability Analysis

The Bayesian Gene Heritability Analysis software (BAGHERA) estimates the contribution to the heritability of a trait/disease of all the SNPs in the genome (genome-wide heritability) and those nearby protein-coding genes (gene-level heritability).

BAGHERA requires only summary statistics from a Genome-wide Association Study (GWAS), LD scores calculated from a population matching the ethnicity of the GWAS study and a gene annotation file in GTF format.

Installation

The easiest and fastest way to install BAGHERA using conda

$ conda install -c stracquadaniolab -c bioconda -c conda-forge baghera

Tutorial

A typical BAGHERA analysis consists of 3 steps:

1. Build a SNP annotation file, where SNPs are annotated to genes and are assigned an LD score. We used precomputed LD scores (https://github.com/bulik/ldsc), from the set of variants for the European population in 1000 Genomes, and protein coding genes as annotated in Gencode v31 (https://www.gencodegenes.org/releases/current.html). Overlapping genes within 50Kb were considered together, obtaining a dataset of 15,000 non-overlapping genes. To build your own annotation files, you should run the following command:

    $ baghera-tool create-files -l <ldscore_folder> -a <annotation.gtf> -s <ld_annotated_snps> -g <genes_table>

2. Annotate summary statistics with the SNP annotation built in step 2. We used summary statistics available at http://www.nealelab.is/uk-biobank, followed by the command below:

    $ baghera-tool generate-snp-file -s <stats file> -i <input_type> -o <snps_file> -a <ld_annotated_snps>

3. Run the regression.

    $ baghera-tool gene-heritability <snps_file> <results_table> <summary_table> <log_file> --sweeps <samples> --burnin <tuning> --n-chains <chains> --n-cores <cores> -m <models>

Example

Running BAGHERA on the UK Biobank summary statistics for breast cancer, using EUR LD scores and the Gencode annotation.

  $ baghera-tool create-files -l data/eur_w_ld_chr/ -a data/gencode.v31lift37.basic.annotation.gtf -s data/ld_annotated_gencode_v31.csv -g data/genes_gencode_v31.csv
  $ baghera-tool generate-snp-file -s data/C50.gwas.imputed_v3.both_sexes.tsv -i position_ukbb -o data/c50.snps.csv -a data/ld_annotated_gencode_v31.csv
  $ baghera-tool gene-heritability data/c50.snps.csv data/results_normal_c50.csv data/summary_normal_c50.csv data/log_normal_c50.txt --sweeps 10000 --burnin 2500 --n-chains 4 --n-cores 4 -m normal

Workflow

Alongside BAGHERA, we are providing a Snakemake workflow https://github.com/stracquadaniolab/workflow-baghera, including sample data to test our method.

Authors

• Viola Fanfani (v.fanfani@sms.ed.ac.uk): mantainer.
• Giovanni Stracquadanio (giovanni.stracquadanio@ed.ac.uk)

Citation

The landscape of the heritable cancer genome Viola Fanfani, Luca Citi, Adrian L Harris, Francesco Pezzella and Giovanni Stracquadanio Cancer Res March 17 2021 DOI: 10.1158/0008-5472.CAN-20-3348

@article {Fanfani2021,
	author = {Fanfani, Viola and Citi, Luca and Harris, Adrian L and Pezzella, Francesco and Stracquadanio, Giovanni},
	title = {The landscape of the heritable cancer genome},
	elocation-id = {canres.3348.2020},
	year = {2021},
	doi = {10.1158/0008-5472.CAN-20-3348},
	publisher = {American Association for Cancer Research},
	issn = {0008-5472},
	journal = {Cancer Research}
}

Issues

We just released a major upgrade of the code, please report any issue.