NAME

       rate4site - detector of conserved amino-acid sites

SYNOPSIS

       rate4site [OPTIONS] -s <MSA FILE>

DESCRIPTION

       The rate of evolution is not constant among amino acid sites: some positions evolve slowly
       and are commonly referred to as "conserved", while others evolve rapidly and are referred
       to as "variable". The rate variations correspond to different levels of purifying
       selection acting on these sites. The purifying selection can be the result of geometrical
       constraints on the folding of the protein into its 3D structure, constraints at amino acid
       sites involved in enzymatic activity or in ligand binding or, alternatively, at amino acid
       sites that take part in protein-protein interactions. Rate4Site calculates the relative
       evolutionary rate at each site using a probabilistic-based evolutionary model. This allows
       taking into account the stochastic process underlying sequence evolution within protein
       families and the phylogenetic tree of the proteins in the family. The conservation score
       at a site corresponds to the site's evolutionary rate.

METHODOLOGY

       The sole obligatory input to Rate4Site is an MSA file. The program then computes a
       phylogenetic tree that is consistent with the available MSA (the user can also input a
       pre-calculated tree). It then calculates the relative conservation score for each site in
       the MSA. This is carried out using either an empirical Bayesian method or a maximum
       likelihood method (Pupko et al., 2002). The differences between the two methods are
       explained in details in Mayrose et al (2004).

REFERENCES

       Mayrose, I., Graur, D., Ben-Tal, N., and Pupko, T. 2004. Comparison of site-specific rate-
       inference methods: Bayesian methods are superior. Mol Biol Evol 21: 1781-1791.

OPTIONS

       -s MSA_FILE
           The input sequence file name. The following formats are supported: Mase, Molphy,
           Phylip, Clustal, Fasta

       -t  The input tree file name (in Newick format)

       -o OUTPUT_FILE
           The results output file

       -a  Reference sequence name in the MSA. The conservation scores are printed based on the
           amino-acids in this sequence.

       -k  The number of discrete Gamma categories

       -m  Evolutionary model. The following amino-acids models are supported:

                   DAY (-md), JTT (-mj), REV (-mr), aaJC (-ma), LG (-Ml), WAG (-Mw) .

                   For nucleotides, the following models are supported: JC (-mn), HKY (-Mh), Tamura92 (-Mt), GTR (-Mg).

       -b  Branch lengths optimization flag:

                   -bn = no Branch lengths optimization

                   -bh = optimization using a homogenous model (no among-site-rate-variation)

                   -bg = optimization using a Gamma model

       -i  Rate inference method flag:

                   -Im = rates are inferred using the maximum likelihood method

                   -Ib = rates are inferred using the empirical Bayes method

       -z  Tree constructing method

                   zj = Neighbor-joining tree with Jukes-Cantor distances

                   zn = Neighbor-joining tree with maximum likelihood distances

       -h  Short help message

AUTHOR

       Nir Ben-Tal <NirB@tauex.tau.ac.il>

SEE ALSO

       Main website
           <http://www.tau.ac.il/~itaymay/cp/rate4site.html>