____             ____                 _     __  __ ____    _       _____ ____
|  _ \ _ __ ___  / ___|_ __ __ _ _ __ | |__ |  \/  / ___|  / \    _|_   _|  _ \
| |_) | '__/ _ \| |  _| '__/ _` | '_ \| '_ \| |\/| \___ \ / _ \ _| |_| | | |_) |
|  __/| | | (_) | |_| | | | (_| | |_) | | | | |  | |___) / ___ \_   _| | |  _ <
|_|   |_|  \___/ \____|_|  \__,_| .__/|_| |_|_|  |_|____/_/   \_\|_| |_| |_| \_\
                                |_|
       Fast and Robust Phylogeny-Aware Multiple Sequence Alignment
              + tandem repeat unit insertions and deletions


 ___                _
| _ \_  _ _ _  _ _ (_)_ _  __ _
|   / || | ' \| ' \| | ' \/ _` |
|_|_\\_,_|_||_|_||_|_|_||_\__, |
                          |___/
 ___          ___               _    __  __ ___   _
| _ \_ _ ___ / __|_ _ __ _ _ __| |_ |  \/  / __| /_\
|  _/ '_/ _ \ (_ | '_/ _` | '_ \ ' \| |\/| \__ \/ _ \
|_| |_| \___/\___|_| \__,_| .__/_||_|_|  |_|___/_/ \_\
                          |_|

The easiest way to run ProGraphMSA with the recommended command line parameters
is to use the wrapper script "ProGraphMSA+TR.sh" included in this package. Just run

./ProGraphMSA+TR.sh <file>

or

./ProGraphMSA+TR.sh -o <output_file> <file>


ProGraphMSA+TR will run using ML distances, the WAG model, and will output an
alignment in FASTA format. Further it will use T-REKS from the file T-Reks.jar
to detect tandem repeats. To use TRUST adjust the installation path in
trust2treks.py and run

./ProGraphMSA+TR.sh --custom_tr_cmd trust2treks.py <file>



  ___                              _   _ _
 / __|___ _ __  _ __  __ _ _ _  __| | | (_)_ _  ___
| (__/ _ \ '  \| '  \/ _` | ' \/ _` | | | | ' \/ -_)
 \___\___/_|_|_|_|_|_\__,_|_||_\__,_| |_|_|_||_\___|

                               _
 _ __  __ _ _ _ __ _ _ __  ___| |_ ___ _ _ ___
| '_ \/ _` | '_/ _` | '  \/ -_)  _/ -_) '_(_-<
| .__/\__,_|_| \__,_|_|_|_\___|\__\___|_| /__/
|_|


USAGE:

   ./ProGraphMSA   [--ancestral_seqs] [--all_trees] [-i <iterations>] [-T] [-I]
                   [-M] [-m] [-a] [-C <count>] [-F] [--custom_model <file>] [-w]
                   [-c <file>] [-r] [--custom_tr_cmd <command>] [--trd_output
                   <filename>] [--read_repeats <T-Reks format output>] [-R] ...
                   [--repalign] [--repeat_indel_ext <probability>]
                   [--repeat_indel_rate <rate>] [-A] [-P <distance>] [-p
                   <distance>] [-D <distance>] [-d <distance>] [-x <distance>]
                   [-s <probability>] [-l <distance>] [-E <probability>] [-e
                   <probability>] [-g <rate>] [-f] [--dna] [--codon] [--topology
                   <newick file>] [-t <newick file>] [-o <filename>] [--]
                   [--version] [-h] <fasta file>



Tandem-repeat related parameters:
=================================


   -R,  --repeats
     use T-REKS to identify tandem repeats

   --custom_tr_cmd <command>
     custom command for detecting tandem-repeats

   --trd_output <filename>
     write TR detector output to file

   --read_repeats <T-REKS format output>
     read TR detector output from file

   --repalign
     re-align detected tandem repeat units

   --repeat_indel_ext <probability>
     repeat indel extension probability

   --repeat_indel_rate <rate>
     insertion/deletion rate for repeat units (per site)


Guide tree, distances, and substitution model:
==============================================

   -i <iterations>,  --iterations <iterations>
     number of iterations re-estimating guide tree [default: 2]

   -m,  --mldist
     use distances estimated by a Maximum-Likelihood method

   -a,  --nwdist
     estimate initial distance tree from Needleman-Wunsch alignments

   -D <distance>,  --max_dist <distance>
     maximum distance for alignment

   -F,  --estimate_aafreqs
     estimate equilibrium amino acid frequencies from input data

   -w,  --darwin
     use model of evolution from Darwin (GONNET matrix and different indel model parameters, otherwise WAG will be used)

   --custom_model <file>
     custom substitution model in qmat format

   -c <file>,  --cs_profile <file>
     path to library of context-sensitive profiles (we distribute a copy in the 3rd_party folder)

   -A,  --no_force_align_m
     do not force alignment of initial Methionine


Parameters for adjusting the indel model:
=========================================

   -l <distance>,  --edge_halflife <distance>
     edge half-life (evolutionary distance at which the probability of re-using an unsused graph is halved)

   -E <probability>,  --end_indel_prob <probability>
     probability of mismatching sequence ends (set to -1 to disable this feature)

   -e <probability>,  --gap_ext <probability>
     gap extension probability

   -g <rate>,  --indel_rate <rate>
     insertion/deletion rate


Input/Output:
=============

   -f,  --fasta
     output fasta format (instead of stockholm)

   -t <newick file>,  --tree <newick file>
     initial guide tree

   -o <filename>,  --output <filename>
     Output file name

   -I,  --input_order
     output sequences in input order (default: tree order)

   --dna
     align DNA sequence

   --codon
     align DNA sequence based on a codon model

   --ancestral_seqs
     output all ancestral sequences

   <fasta file>
     (required) input sequences



 ___      _ _    _ _              __
| _ )_  _(_) |__| (_)_ _  __ _   / _|_ _ ___ _ __    ___ ___ _  _ _ _ __ ___
| _ \ || | | / _` | | ' \/ _` | |  _| '_/ _ \ '  \  (_-</ _ \ || | '_/ _/ -_)
|___/\_,_|_|_\__,_|_|_||_\__, | |_| |_| \___/_|_|_| /__/\___/\_,_|_| \__\___|
                         |___/

For building ProGraphMSA from source you need:

CMake   >=2.8           (http://www.cmake.org)
tclap   >=1.1.0         (http://tclap.sourceforge.net)
Eigen   2.0.x or 3.0.x  (http://eigen.tuxfamily.org)

on Debian/Ubuntu you can install these programs/libraries with:
sudo apt-get install build-essential cmake libtclap-dev libeigen3-dev

On a Mac, libraries can be installed with Homebrew:

    brew install gcc cmake eigen tclap

Note that homebrew installs these to non-default locations, so cmake should be
called with the following additional options:

    -D EIGEN_INCLUDE_DIR=/usr/local/include/eigen3 \
    -D CMAKE_C_COMPILER=/usr/local/bin/gcc-7 \
    -D CMAKE_CXX_COMPILER=/usr/local/bin/c++-7 \

ProGraphML is written with C++11. Using the default Apple compiler is not
recommended due to libc++ incompatibilities.

Then perform the following command to configure/build/install ProGraphMSA:

    cd BUILD
    cmake .. (press "c" to configure and "g" to generate the Makefile, see below
               for additional configuration options)
    make ProGraphMSA
    make install

An example build script is included (`build_ProGraphMSA.sh`) to illustrate this process.
It can be modified for your particular system.

Additional CMake configuration options (in "ccmake .."):

EIGEN2_INCLUDE_DIR: set this to the path, where Eigen is installed, if you use
                    Eigen 2.0.x or if Eigen has been installed at a non-default
                    location (default location: /usr/include/eigen3)

WITH_EIGEN3:        set this to ON, if you want to compile ProGraphMSA with
                    Eigen 3.0.x

CMAKE_CXX_FLAGS:    add options for the C++ compiler, like optimization flags,
                    or additional search paths for include files (-I <path>)

WITH_SSE:           disable this option, if you build ProGraphMSA for a machine
                    that does not support SSE2