FOCUS (Fine-mapping Of CaUsal gene Sets) is software to fine-map transcriptome-wide association study statistics at genomic risk regions. The software takes as input summary GWAS data along with eQTL weights and outputs a credible set of genes to explain observed genomic risk.
This approach is described in,
Probabilistic fine-mapping of transcriptome-wide association studies. Nicholas Mancuso, Malika K. Freund, Ruth Johnson, Huwenbo Shi, Gleb Kichaev, Alexander Gusev, and Bogdan Pasaniuc. Nature Genetics 51, 675-682 (2019).
The easiest way to install is with pip:
pip install pyfocus --user
Check that FOCUS was installed by typing
focus --help
If that did not work, and pip install pyfocus --user was specified, please check that your local user path is included in
$PATH environment variable. --user location and can be appended to $PATH
by executing
export PATH=`python -m site --user-base`/bin/:$PATH
which can be saved in ~/.bashrc or ~/.bash_profile. To reload the environment type source ~/.bashrc or ~/source .bash_profile depending where you entered it.
Alternatively you can download the latest repo and then use setuptools:
git clone https://github.com/bogdanlab/focus.git
cd focus
python setup.py install
We currently only support Python3.6+.
A conda-forge recipe that should simplify installation is currently underway.
Here is an example of how to perform LDL fine-mapping while prioritizing predictive models from adipose tissues:
focus finemap LDL_2010.clean.sumstats.gz 1000G.EUR.QC.1 gtex_v7.db --chr 1 --tissue adipose --out LDL_2010.chr1
This command will scan LDL_2010.clean.sumstats.gz for risk regions and then perform TWAS+fine-mapping using LD estimated from plink-formatted 1000G.EUR.QC.1 and eQTL weights from gtex_v7.db.
Please see the wiki for more details on how to use focus and links to database files.
Version 0.6.10: Fixed bug where weight database allele mismatch with GWAS broke infererence.
Version 0.6.5: Fixed bug in newer versions of matplotlib not accepting string for colormaps. Fixed legend bug in plot. Fixed bug that mismatched string and category when supplying custom locations.
Version 0.6: Fixed bug where only one of the two alleles was reversed complemented breaking alignment. For now these instances are dropped. Added option --use-ens-id for FUSION import to indicate the main model label is an Ensembl ID rather than HGNC symbol.
Version 0.5: Plotting sorts genes based on tx start. Various bugfixes that limited the number of queried SNPs and plotting when using newer matplotlib.
Version 0.4: Added FUSION import support.
Version 0.3: Initial release. More to come soon.
If you have any questions or comments please contact nicholas.mancuso@med.usc.edu
For performing various inferences using summary data from large-scale GWASs please find the following useful software: