GenoWAP

Post-GWAS Prioritization through Integrated Analysis of Tissue-specific Functional Annotation

Dependencies

• requests
• progressbar2 >= 2.7.3
• scipy
• numpy
• intervaltree - used in extractScores.py

Description

GenoWAP uses GWAS results as input, calculating the probability of a locus being related to the disease given its p-value in GWAS and GS score. The GS score is a measure of functionality of a locus within a user-defined tissue type. User must upload a customized functional score constructed from a collection of tissue-specific annotation data.

Data Format

The following format is for GWAS_DATA, ANNOTATION, and TISSUE_ANNOTATION files:

A tab-delimited text file with three fields: An integer chromosome label (X and Y are 23 and 24, respectively), a genomic coordinate, and a GWAS p-value (for GWAS_DATA) or posterior functionality prediction score (for ANNOTATION or TISSUE_ANNOTATION). The file should NOT include a header. See sampleDataFormat.txt for an example.

NOTE: Duplicate coordinates are automatically filtered out of the output script

###Using GenoWAP

GenoWAP can be used either as a traditional python script, or built into a stand-alone executable with cx_Freeze.

Build into executable

freeze.py is used for building executables. Please use cx_Freeze for the build:

1. Make sure all dependencies are installed for the preferred python version with which you wish to run GenoWAP.

2. Run (where python points to the preferred version of python):

python freeze.py build

The executable will be named GenoWAP under the build directory and can be executed by calling the file directly.

./GenoWAP -h

Execute as a python script

Alternatively, GenoWAP can be run as a stand alone script. To use GenoWAP in this way, run:

python GenoWAP.py -h

Extract GS Scores from Annotation bed file

To generate the TISSUE_ANNOTATION file for tissue-specific mode, download and unzip the desired tissue type from the GenoSkyline web portal (http://genocanyon.med.yale.edu/GenoSkyline) and use the extractScores.py script. For example:

wget http://genocanyon.med.yale.edu/GenoSkylineFiles/Blood_GenoSkyline.bed.zip
unzip Blood_GenoSkyline.bed.zip
python extractScores.py sampleDataFormat.txt Blood_GenoSkyline.bed

Calling GenoWAP

GenoWAP [-h] [-o DESTINATION_PATH] [-b NBINS] [-t THRESHOLD] [-a ANNOTATION_PATH] [-ts TISSUE_ANNOTATION_PATH] GWAS_DATA_PATH

positional arguments:

GWAS_DATA_PATH: Path to GWAS Data

optional arguments:

-h, --help: show help message and exit

-o DESTINATION_PATH: Path to output file, default to result.out

-b NBINS: Number of bins of the histogram, which is used for estimating the distribution of p-values of non-functional loci (defined by THRESHOLD and functional score). A positive integer. If not provided, use cross-validation to choose the best number of bins.

-t THRESHOLD: Threshold for defining functional loci according to the functional score provided, range in (0,1). If functional annotation score of a locus is greater than the threshold, define the locus as functional. If not provided, the default is 0.1.

-a ANNOTATION_PATH: Path to functional annotation file, when not specified, GenoWAP tries to download data from GenoCanyon, and save to file "GenoCanyon_Prediction.data" in the current directory.

-ts TISSUE_ANNOTATION_PATH: Path to tissue-specific annotation.

###Genocanyon Server For functional annotation, if using the Genocanyon online database (if -a is not supplied), please note the following:

1. A GenoCanyon_Prediction.data file containing the GenoCanyon data used in analysis will be generated in current directory and can be reused with -a flag for the same data set.

2. The default timeout for HTTP request is set to 3 minutes and maximum retry is 3. After 3 tries, user can decide to continue or cancel downloading.

3. When many users query GenoCanyon database at the same time, all queries will wait in a queue. Therefore downloading may take a relatively long time or even time out before its turn in the queue.

###Frequently Asked Questions Q1. What do I do if the EM convergence is out-of-bound?

A1. If theta[0]>0.5 or theta[1] is not in (0,1), then the input data has a very weak signal and it is advised to use -b1 flag.

Q2. What do I do if EM algorithm does not converge to within 1e-10 after 20000 iterations?

A2. If theta values do not converge, you can choose to compute prioritization regardless, or modify the parameters in the source code in the CONSTANT section.