PREAST - Founder Inference using PRANK and BEAST

To infer founder sequence(s) and time of infection:

bin/infer.sh <sequences.fa>

Example usage:

$ bin/infer.sh  sample_data/caprisa002/gp120/caprisa002_pda_gp120_1m6m_aln.fasta 
> caprisa002_pda_gp120_1m6m_aln_founder_1
GCTCCAGCTGGTTATGCGATTCTAAGGTGTAATAATAAGACATTCAATGGGACAGGACCATGCAACAATGTCAGCACAGTACAATGTACACATGGAATTAAGCCAGTGGTATCAACTCAACTACTGTTAAATGGTAGCCTAGCAGAAGAGGAGATAATAATTAGATCTGAAAATCTGACAAGCAATCACAAAACAATAATAGTACAGCTTAATAGATCCATAGAAATTGTGTGCATAAGACCCGGCAATAACACAAGAAAAAGTGTAAGGATAGGACCAGGACAAACATTCTATGCAACAGGTGACATAATAGGAGACATAAGAAAAGCATATTGTAACATTAGTGCAGAAAGATGGAATGAAACTTTAGAATGGGTAAAGGAAAAATTAGCAGAACACTTTCCTAATAAGACAATAAGATATAAGCCATCTTCAGGAGGGGACCCAGAAGTTACAATGCATAGCTTT
> caprisa002_pda_gp120_1m6m_aln_founder_2
GCTCCAGCTGGTTATGCGATTCTAAGGTGTAATAATAAGACATTCAATGGGACAGGACCATGCAACAATGTCAGCACAGTACAATGTACACATGGAATTAAGCCAGTGGTATCAACTCAACTACTGTTAAATGGTAGCCTAGCAGAAGAGGAGATAATAATTAGATCTGAAAATCTGACAAACAATCACAAAACAATAATAGTACAGCTTAATAGATCCATAGAAATTGTGTGCATAAGACCCGGCAATAACACAAGAAAAAGTGTAAGGATAGGACCAGGACAAACATTCTATGCAACAGGTGACATAATAGGAGACATAAGAAAAGCATATTGTAACATTAGTGCAGAAAGATGGAATGAAACTTTAGAATGGGTAAAGAAAAAATTGGCAGAACACTTTCCTAATAAGACAATAAGATATCAACCATCTTCAGGAGGGGACCCAGAAGTTACAATGCATAGCTTT
Estimated date of infection: 2005/06/19  (95% credible interval [2005/05/23 - 2005/07/15])

Runnning on Gizmo servers (rhino0*, stoat)

These scripts have dependencies on prank, beast, and a large number of python modules.

A Linux binary of prank is included in the bin/ directory. prank uses bppancestor which is also included in the bin/ directory. A requirements.txt file lists all necessary python packages. Beast and the Beagle optimization library are available in /apps. Access these applications may be established through module definitiions. A python virtual environment is included with all necessary python packages preinstalled.

For example, the following commands will run the inference on a simulated alignment (included in the repo as sample_aln.fa)

	 $ ssh rhino04
	 Last login: Mon Sep 28 22:39:27 2015 from juanite.fhcrc.org
	 $ git clone https://github.com/matsengrp/founder-inference-bakeoff.git
	 $ cd founder-inference-bakeoff
	 $ . <(./setup.sh)
	 $ bin/infer.sh sample_aln.fa 
	 > sample_aln_founder_1
    GCTCCAGCTGGTTATGCGATTCTAAGGTGTAATAATAAGACATTCAATGGGACAGGACCATGCAACAATGTTAGCACAGTACAATGTACACATGGAATTAAGCCAGTGGTATCAACTCAACTACTGTTAAATGGTAGCCTAGCAGAAGAGGAGATAATAATTAGATCTGAAAATCTGACAAGCAATCACAAAACAATAATAGTACAGCTTAATAGGTCCATAGAAATTGTGTGCATAAGACCCGGCAATAACACAAGACAAAGTGTAAGGATAGGAACAGGACAAACATTCTATGCAACAGGTGACATAATAGGAGACATAAGAAAAGCATATTGTAACATTAGTGCAGAAAGATGGAATGAAACTTTAGAATGGGTAAAGAAAAAATTGGCAGAACACTTTCCTAATAAGACAATAAGATATCAACCATCTTCAGGAGGGGACCCGGAAGTTACAACGCATAGCTTT
	 > sample_aln_founder_2
	 GCTCCAGCTGGTTATGCGATTCTAAGGTGTAATAATAAGACATTCAATGGGACAGGACCATGCAACAATGTCAGCACAGTACAATGTACACATGGAATTAAGCCTGTGGTATCAACTCAACTACTGTTAAATGGTAGCCTAGCAGAAGAGGAGATAATAATTAGATCTGAAAATCTGACAAGCAATCACAAAACAATAATAGTACAGCTTGATAGATCCATAGAAGTTGTGTGCATAAGACCCGGTAATAACACAAGAAAAAGTGTAAGGATAGGAATAGGACAAACATTCTATACAACAGGTAACATAATAGGAGACATAAGAAAAGCATATTGTAACATTAGTGCAGAAAGATGGAATGAAGCTTTAGAATGGGTAAAGAAAAAATTGGCAGAACACTTTCCTAATAAGACAATAAGATATCAACCATCTTCAGGAGGGGACCCATAAGTTACAATGCATAGCTTT
	 Estimated date of infection: 2011/05/20  (95% credible interval [2011/04/26 - 2011/06/12])

Methodology

Uses Prank¹ to create a multiple sequence alignment and to estimate founder sequence.

To infer multiple founders, the phylogenetic tree inferred by Prank is split at the root and the leaves on each half are used to infer separate founders.

Time of infection is inferred with Beast⁴. A strict clock and constant population size are used as priors. Tree height is constrained to be consistent with samples dates on the sequences.

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¹: Löytynoja, A., & Goldman, N. (2008). A model of evolution and structure for multiple sequence alignment. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 363(1512), 3913–3919. http://doi.org/10.1098/rstb.2008.0170
²: Giorgi EE, Funkhouser B, Athreya G, Perelson AS, Korber BT, Bhattacharya T. Estimating time since infection in early homogeneous HIV-1 samples using a Poisson model. BMC Bioinformatics 2010 Oct 25;11:532. PMID: 20973976
³: Giorgi EE and Bhattacharya T. A note on two-sample tests for comparing intra-individual genetic sequence diversity between populations. Biometrics December 2012; 68:4. PMID: 23004569
⁴: Drummond, Alexei J., and Andrew Rambaut. "BEAST: Bayesian evolutionary analysis by sampling trees." BMC evolutionary biology 7.1 (2007): 214.