picopili

Purpose

• Provide a pipeline for GWAS of family data with arbitrary pedigrees, from sib-pairs to extended pedigrees, to work in parallel to ricopili for case/control and trio data

Primary Functions

• qc_rel.py: runs QC for family GWAS data. Designed to be consistent with ricopili trio QC, with minor adjustments to mendelian error handling and streamlined output.
• pca_rel.py: main driver script to run PCA on family GWAS data. Includes strict QC (with LD pruning, etc), extraction of a set of unrelated individuals to compute PCs, and projection of PCA to full dataset. Jobs are submitted via UGER, and ricopili-like success/failure emails are sent on completion. See tasks strict_qc.py and imus_pca.py.
• admix_rel.py: estimates relatedness for admixed samples. Relatedness is estimated by starting with a subset of individuals who are unrelated, running an Admixture analysis, selecting "exemplar" individuals for each ancestry component, using those individuals to anchor a supervised Admixture analysis fo the full data, and using those Admixture results as the basis for ancestry-adjusted relatedness estimation using REAP.
• filter_ped.py: uses genetic relatedness information to flag (a) cryptic relatedness across FIDs, (b) unrelated individuals within FIDs, (c) possible parent/offspring pair not identified in .fam file, and (d) parent/offspring pairs indicated by pedigree that aren't supported by genetic relatedness. Provides a suggested sample exclusion list based on weighted preferences for phenotype, pedigree, and genotyping rate.
• ped_confirm.py: confirms that reported pedigrees in .fam file are consistent with genetic relatedness. Works as a wrapper to find_expected_pedigree.pl from PRIMUS.
• gwas_rel.py: Genome-wide association analysis (in parallelized chunks) with either plink --dfam or a GEE model.
• impute_rel.py: Imputation pipeline for related samples using SHAPEIT's --duohmm and IMPUTE2. Includes build check (with liftOver if needed), alignement to reference, phasing, imputation, and best-guess genotype calls with MAF/info score/mendelian error filtering.

Installation

1. The following assumes:

• You're working on the Broad UGER cluster (though can probably be adapted)
• You've already installed ricopili.
• You have git configured with a github account.

Note additional dependencies may exist for some modules (e.g. Admixture, REAP, PRIMUS).

2. Download picopili from github

mkdir ~/github
cd ~/github
git clone https://github.com/Nealelab/picopili.git

3. Add picopili to search path

In ~/.my.bashrc (or equivalent for your shell) add the line:

PATH=$HOME/github/picopili/rp_bin:$PATH

4. Logout and log back in.

Applies the changes in ~/.my.bashrc.