What is it?
Gretel is a Python package providing a command line tool for the recovery of haplotypes from metagenomic data sets. Gretel parses an alignment of reads into a Hansel matrix and uses the evidence of SNP pairs observed to appear on the same reads to probabilistically reconstruct the most likely haplotypes.
Gretel uses an L'th order Markov chain model to reconstruct likely sequences of variants that constitute haplotypes in the real metagenome. Our approach involves graph-like traversal of the data within the Hansel matrix. Edges are probabilitically weighted based on the evidence on the reads, as well as the haplotype as it has been reconstructed so far.
What can I use it for?
Gretel is designed to recover haplotypes from your data set, without the need for setting (or optimisation) of any parameters. Gretel does not require a priori knowledge of your input data (such as its contents, or the true number of haplotypes) and makes no assumptions regarding the distributions of alleles at variant sites and uses the available evidence from the aligned reads without altering or discarding the observed varations.
Why should I use it?
Gretel is the first tool capable of recovering haplotypes from metagenomes. Whilst tools exist for analogous haplotyping problems, such as the assembly of viral quasispecies, typically these tools rely on overlap approaches that create too many unranked haplotypes. Gretel is capable of ranking the haplotypes it outputs by their likelihood.
Gretel requires no parameters and our approach is robust to sequencing error and misalignment noise.
Requirements
$ pip install numpy hanselx pysam PyVCF
Install
$ pip install gretel
Alternatively, Gretel has been packaged for bioconda (Thanks @johnne!):
$ conda install -c bioconda gretel
Usage
You will require a sorted BAM containing your reads, aligned to some pseudo-reference. You can use any sequence as your reference, such as a consensus assembly of the metagenomic reads, or a known strain reference (such as HIV-1). You must bgzip and tabix your VCF.
$ gretel <bam> <vcf.gz> <contig> -s <1-start> -e <1-end> --master <master.fa> -o <outdir>
Citation
@article{10.1093/bioinformatics/btaa977,
author = {Nicholls, Samuel M and Aubrey, Wayne and De Grave, Kurt and Schietgat, Leander and Creevey, Christopher J and Clare, Amanda},
title = "{On the complexity of haplotyping a microbial community}",
journal = {Bioinformatics},
volume = {37},
number = {10},
pages = {1360-1366},
year = {2021},
month = {01},
issn = {1367-4803},
doi = {10.1093/bioinformatics/btaa977},
url = {https://doi.org/10.1093/bioinformatics/btaa977},
eprint = {https://academic.oup.com/bioinformatics/article-pdf/37/10/1360/38663805/btaa977.pdf},
}
License
Hansel and Gretel are distributed under the MIT license, see LICENSE.