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Phy-Mer

Licensing:

Phy-Mer
Copyright (C) 2014  Daniel Navarro-Gomez (Daniel_navarro@meei.harvard.edu)

This program is free software: you can redistribute it and/or modify
it under the terms of the GNU Affero General Public License as
published by the Free Software Foundation, either version 3 of the
License, or (at your option) any later version.

This program is distributed in the hope that it will be useful,
but WITHOUT ANY WARRANTY; without even the implied warranty of
MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
GNU Affero General Public License for more details.

You should have received a copy of the GNU Affero General Public License
along with this program.  If not, see <http://www.gnu.org/licenses/>.

Citation:

Daniel Navarro-Gomez, Jeremy Leipzig, Lishuang Shen, Marie Lott, Alphons P.M. Stassen, Douglas C. Wallace, Janey L. Wiggs, Marni J. Falk, Mannis van Oven, and Xiaowu Gai Phy-Mer: a novel alignment-free and reference-independent mitochondrial haplogroup classifier.

Bioinformatics (2015) 31 (8): 1310-1312. doi: 10.1093/bioinformatics/btu825 -> http://bioinformatics.oxfordjournals.org/content/31/8/1310

1. Installation:

1.1. Installing dependences:

Download and install the dependencies. Installation instructions for each dependency are provided on its project website with the URL provided.

1.2. Download Phy-Mer package, uncompress it and uncompress the Library:

Download last version of Phy-Mer and utilities following this link (https://github.com/MEEIBioinformaticsCenter/phy-mer/archive/master.zip), uncompress it, open "phy-mer-master" folder and uncompress "PhyloTree_b16_k12.txt.gz".

wget https://github.com/MEEIBioinformaticsCenter/phy-mer/archive/master.zip 
unzip master.zip
cd phy-mer-master
gzip -d PhyloTree_b16_k12.txt.gz

2. Usage

SYNOPSIS
min_kmer_repeats=1
./Phy-Mer.py [--verbose] [--print-ranking] [--def-snps=haplogroup_def_motifs.csv] [--min-DoC=10] Library.txt INPUT_1 [INPUT_2 ... INPUT_X]
DESCRIPTION
Optinal arguments.
  --help                     Show this help.
  --verbose                  Print step by step process.
  --print-ranking            Print top 5 results instead of the best match.
  --def-snp=file.csv         Add Haplogroup defining snps to top matches
                             based in file.csv (Build_16_-_rCRS-based_haplogroup_motifs.csv
                             in resources folder).
  --min-DoC=10               Only apply to BAM inputs. Minimal number of occurences of a K-mer
                                 to be consider.


Mandatory arguments.
  Library.txt                Provided with the package: PhyloTree_b16_k12.txt
  INPUT_X                    One (required) or more input sequence files in FASTA, FASTQ, or BAM format.

3. Phy-Mer Output

3.1. Normal output
KF899911.fasta   I1a1a1  0.998459118106

KF899911.fasta: Name of the input file I1a1a1: Haplogroup prediction 0.998459118106: Score (See Score section for more info)

3.2. Verbose output (--verbose)
Opening Library and Checking k-mer size...
READING WHOLE FILE IN MEMORY
DONE
K-mer=12
Processing KF899911.fasta
Opening fasta file and loading it in memory...
Creating k-mer in memory (K=12)...
16531 K-mers as input
Comparing input with Library...
Creating score table...
KF899911.fasta   ['I1a1a1', 0.997856951513528, 0.9990612846989406, 0.9984591181062343]
3.3. Top 5 results output (--print-ranking)
KF899911.fasta
I1a1a1  0.998459118106
I1a1a   0.997688614168
I1a1a2  0.996884512927
I1a1    0.996884512927
I1a1e   0.996080411687

Top 5 scored results.

3.4. Haplogroup defining snps output (--def-snp=file.csv)
KF899911.fasta   I1a1a1  0.998459118106  [['73', '199', '203', '204', '250', '263', '455.1T', '573.XC', '750', '1438', '1719', '2706', '3447', '3990', '4529T', '4769', '6734', '7028', '8251', '8616T', '8860', '9053', '9947', '10034', '10238', '10398', '10915', '11719', '12501', '12705', '13780', '14766', '15043', '15326', '15547', '15924', '16129', '16172', '16223', '16311', '16391']]

4. Phy-Mer Scores

4.1. Standard score

Given a mitochondrial sequence as the input, Phy-Mer first decomposes its sequence into a set of all possible 12-mers, which are then compared against each of the 12-mer libraries of all haplogroups. As an example, an input sequence has x 12-mers that matches the 12-mers of haplogroup A, which has a total y 12-mers in its library. The sequence has on the other hand z 12-mers that match 12-mers of all haplogroup libraries.

Then a score is derived as (x/y + x/z)/2.

4.2. Verbose Scores

Following previous section, we define verbose scores as:

[ 'SAMPLE.fasta', x/y , x/z , (x/y + x/z)/2 ]

5. Utility Tools

5.1. Create a K-mer library:
SYNOPSIS
./build_Phy-Mer_Library.py MtDNA_Genome.fasta SNPS_HAPLOGROUPS.csv RESULT_Library.txt [min_k-mer_size]
DESCRIPTION

build_Phy-Mer_Library.py: Python program that creates the k-mer library of all haplogroups.

MtDNA_Genome.fasta: Mitochondrial reference genome sequence in FASTA format, e.g. the revised Cambridge Reference Sequence (rCRS).

SNPS_HAPLOGROUPS.csv: The list of haplogroup-defining SNPs based on the mitochondrial reference genome sequence. An example file for PhyloTree Build 16 based in rCRS is provided in the package, named Build_16_-_rCRS-based_haplogroup_motifs.csv.

RESULT_Library.txt: The output k-mer library of all haplogroups defined in the Build_16_-_rCRS-based_haplogroup_motifs.csv file.

min_k-mer_size: OPTIONAL, minimal k-mer size considered for the library

EXAMPLE
Ex: ./build_Phy-Mer_Library.py MtGenome_sequence.fasta Build_16_-_rCRS-based_haplogroup_motifs.csv Custom_PhyloTree_b16.txt
5.2. Create a FASTA file from snp data:
SYNOPSIS
./convert_MtSNP_to_MtFasta.py REFERENCE.fasta SNP.csv RESULT.fasta
DESCRIPTION

convert_MtSNP_to_MtFasta.py: Python script to create a FASTA formatted mtDNA sequence based on a list of SNPs

REFERENCE.fasta: mtDNA reference genome sequence upon which the SNPs are based

SNP.csv: SNP data in comm-delimited format.

RESULT.fasta: Output file to store the FASTA sequence

EXAMPLE
Ex: ./convert_MtSNP_to_MtFasta.py MtGenome_sequence.fasta example_snp.csv OUT.fasta

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