| frestml

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## Function

Restriction site maximum likelihood method

## Description

Estimation of phylogenies by maximum likelihood using restriction sites data (not restriction fragments but presence/absence of individual sites). It employs the Jukes-Cantor symmetrical model of nucleotide change, which does not allow for differences of rate between transitions and transversions. This program is very slow.

## Algorithm

This program implements a maximum likelihood method for restriction sites data (not restriction fragment data). This program is one of the slowest programs in this package, and can be very tedious to run. It is possible to have the program search for the maximum likelihood tree. It will be more practical for some users (those that do not have fast machines) to use the U (User Tree) option, which takes less run time, optimizing branch lengths and computing likelihoods for particular tree topologies suggested by the user. The model used here is essentially identical to that used by Smouse and Li (1987) who give explicit expressions for computing the likelihood for three-species trees. It does not place prior probabilities on trees as they do. The present program extends their approach to multiple species by a technique which, while it does not give explicit expressions for likelihoods, does enable their computation and the iterative improvement of branch lengths. It also allows for multiple restriction enzymes. The algorithm has been described in a paper (Felsenstein, 1992). Another relevant paper is that of DeBry and Slade (1985).

The assumptions of the present model are:

1. Each restriction site evolves independently.
2. Different lineages evolve independently.
3. Each site undergoes substitution at an expected rate which we specify.
4. Substitutions consist of replacement of a nucleotide by one of the other three nucleotides, chosen at random.

Note that if the existing base is, say, an A, the chance of it being replaced by a G is 1/3, and so is the chance that it is replaced by a T. This means that there can be no difference in the (expected) rate of transitions and transversions. Users who are upset at this might ponder the fact that a version allowing different rates of transitions and transversions would run an estimated 16 times slower. If it also allowed for unequal frequencies of the four bases, it would run about 300,000 times slower! For the moment, until a better method is available, I guess I'll stick with this one!

Subject to these assumptions, the program is an approximately correct maximum likelihood method.

## Usage

Here is a sample session with frestml

    % frestml
    Restriction site maximum likelihood method
    Input file: restml.dat
    Phylip tree file (optional):
    Phylip restml program output file [restml.frestml]:

    numseqs: 1

    Adding species:
       1. Alpha
       2. Beta
       3. Gamma
       4. Delta
       5. Epsilon

    Output written to file "restml.frestml"

    Tree also written onto file "restml.treefile"

    Done.

Go to the input files for this example
Go to the output files for this example

## Command line arguments

    Restriction site maximum likelihood method
    Version: EMBOSS:6.5.0.0

       Standard (Mandatory) qualifiers:
      [-data]              discretestates File containing one or more sets of
                                      restriction data
      [-intreefile]        tree       Phylip tree file (optional)
      [-outfile]           outfile    [*.frestml] Phylip restml program output
                                      file

       Additional (Optional) qualifiers (* if not always prompted):
       -weights            properties Weights file
       -njumble            integer    [0] Number of times to randomise (Integer 0
                                      or more)
    *  -seed               integer    [1] Random number seed between 1 and 32767
                                      (must be odd) (Integer from 1 to 32767)
       -outgrno            integer    [0] Species number to use as outgroup
                                      (Integer 0 or more)
       -[no]allsites       boolean    [Y] All sites detected
    *  -lengths            boolean    [N] Use lengths from user trees
       -sitelength         integer    [6] Site length (Integer from 1 to 8)
    *  -global             boolean    [N] Global rearrangements
    *  -[no]rough          boolean    [Y] Speedier but rougher analysis
       -[no]trout          toggle     [Y] Write out trees to tree file
    *  -outtreefile        outfile    [*.frestml] Phylip tree output file
       -printdata          boolean    [N] Print data at start of run
       -[no]progress       boolean    [Y] Print indications of progress of run
       -[no]treeprint      boolean    [Y] Print out tree

       Advanced (Unprompted) qualifiers: (none)
       Associated qualifiers:

       "-outfile" associated qualifiers
       -odirectory3        string     Output directory

       "-outtreefile" associated qualifiers
       -odirectory         string     Output directory

       General qualifiers:
       -auto               boolean    Turn off prompts
       -stdout             boolean    Write first file to standard output
       -filter             boolean    Read first file from standard input, write
                                      first file to standard output
       -options            boolean    Prompt for standard and additional values
       -debug              boolean    Write debug output to program.dbg
       -verbose            boolean    Report some/full command line options
       -help               boolean    Report command line options and exit. More
                                      information on associated and general
                                      qualifiers can be found with -help -verbose
       -warning            boolean    Report warnings
       -error              boolean    Report errors
       -fatal              boolean    Report fatal errors
       -die                boolean    Report dying program messages
       -version            boolean    Report version number and exit

Qualifier | Type | Description | Allowed values | Default
--- | --- | --- | --- | ---
Standard (Mandatory) qualifiers
[-data] (Parameter 1) | discretestates | File containing one or more sets of restriction data | Discrete states file |
[-intreefile] (Parameter 2) | tree | Phylip tree file (optional) | Phylogenetic tree |
[-outfile] (Parameter 3) | outfile | Phylip restml program output file | Output file | <*>.frestml
Additional (Optional) qualifiers
-weights | properties | Weights file | Property value(s) |
-njumble | integer | Number of times to randomise | Integer 0 or more | 0
-seed | integer | Random number seed between 1 and 32767 (must be odd) | Integer from 1 to 32767 | 1
-outgrno | integer | Species number to use as outgroup | Integer 0 or more | 0
-[no]allsites | boolean | All sites detected | Boolean value Yes/No | Yes
-lengths | boolean | Use lengths from user trees | Boolean value Yes/No | No
-sitelength | integer | Site length | Integer from 1 to 8 | 6
-global | boolean | Global rearrangements | Boolean value Yes/No | No
-[no]rough | boolean | Speedier but rougher analysis | Boolean value Yes/No | Yes
-[no]trout | toggle | Write out trees to tree file | Toggle value Yes/No | Yes
-outtreefile | outfile | Phylip tree output file | Output file | <*>.frestml
-printdata | boolean | Print data at start of run | Boolean value Yes/No | No
-[no]progress | boolean | Print indications of progress of run | Boolean value Yes/No | Yes
-[no]treeprint | boolean | Print out tree | Boolean value Yes/No | Yes
Advanced (Unprompted) qualifiers
(none)
Associated qualifiers
"-outfile" associated outfile qualifiers
-odirectory3 -odirectory_outfile | string | Output directory | Any string |
"-outtreefile" associated outfile qualifiers
-odirectory | string | Output directory | Any string |
General qualifiers
-auto | boolean | Turn off prompts | Boolean value Yes/No | N
-stdout | boolean | Write first file to standard output | Boolean value Yes/No | N
-filter | boolean | Read first file from standard input, write first file to standard output | Boolean value Yes/No | N
-options | boolean | Prompt for standard and additional values | Boolean value Yes/No | N
-debug | boolean | Write debug output to program.dbg | Boolean value Yes/No | N
-verbose | boolean | Report some/full command line options | Boolean value Yes/No | Y
-help | boolean | Report command line options and exit. More information on associated and general qualifiers can be found with -help -verbose | Boolean value Yes/No | N
-warning | boolean | Report warnings | Boolean value Yes/No | Y
-error | boolean | Report errors | Boolean value Yes/No | Y
-fatal | boolean | Report fatal errors | Boolean value Yes/No | Y
-die | boolean | Report dying program messages | Boolean value Yes/No | Y
-version | boolean | Report version number and exit | Boolean value Yes/No | N

## Input file format

frestml input is fairly standard, with one addition. As usual the first line of the file gives the number of species and the number of sites, but there is also a third number, which is the number of different restriction enzymes that were used to detect the restriction sites. Thus a data set with 10 species and 35 different sites, representing digestion with 4 different enzymes, would have the first line of the data file look like this:

       10   35    4

The first line of the data file will also contain a letter W following these numbers (and separated from them by a space) if the Weights option is being used. As with all programs using the weights option, a line or lines must then follow, before the data, with the weights for each site.

The site data are in standard form. Each species starts with a species name whose maximum length is given by the constant "nmlngth" (whose value in the program as distributed is 10 characters). The name should, as usual, be padded out to that length with blanks if necessary. The sites data then follows, one character per site (any blanks will be skipped and ignored). Like the DNA and protein sequence data, the restriction sites data may be either in the "interleaved" form or the "sequential" form. Note that if you are analyzing restriction sites data with the programs DOLLOP or MIX or other discrete character programs, at the moment those programs do not use the "aligned" or "interleaved" data format. Therefore you may want to avoid that format when you have restriction sites data that you will want to feed into those programs.

The presence of a site is indicated by a "+" and the absence by a "-". I have also allowed the use of "1" and "0" as synonyms for "+" and "-", for compatibility with MIX and DOLLOP which do not allow "+" and "-". If the presence of the site is unknown (for example, if the DNA containing it has been deleted so that one does not know whether it would have contained the site) then the state "?" can be used to indicate that the state of this site is unknown.

User-defined trees may follow the data in the usual way. The trees must be unrooted, which means that at their base they must have a trifurcation.

### Input files for usage example

### File: restml.dat

       5   13   2
    Alpha     ++-+-++--+++-
    Beta      ++++--+--+++-
    Gamma     -+--+-++-+-++
    Delta     ++-+----++---
    Epsilon   ++++----++---

## Output file format

frestml outputs a graph to the specified graphics device. outputs a report format file. The default format is ...

### Output files for usage example

### File: restml.frestml

    Restriction site Maximum Likelihood method, version 3.69.650

      Recognition sequences all 6 bases long

    Sites absent from all species are assumed to have been omitted

      +----Gamma
      |
      |  +Beta
      1--2
      |  |  +Epsilon
      |  +--3
      |     +Delta
      |
      +Alpha

    remember: this is an unrooted tree!

    Ln Likelihood =   -40.47082

     Between        And            Length      Approx. Confidence Limits
     -------        ---            ------      ------- ---------- ------
       1          Gamma           0.10794     (  0.01144,     0.21872) **
       1             2            0.01244     (     zero,     0.04712)
       2          Beta            0.00100     (     zero,    infinity)
       2             3            0.05878     (     zero,     0.12675) **
       3          Epsilon         0.00022     (     zero,    infinity)
       3          Delta           0.01451     (     zero,     0.04459) **
       1          Alpha           0.01244     (     zero,     0.04717)

         *  = significantly positive, P < 0.05
         ** = significantly positive, P < 0.01

### File: restml.treefile

    (Gamma:0.10794,(Beta:0.00100,(Epsilon:0.00022,
    Delta:0.01451):0.05878):0.01244,Alpha:0.01244);

## Data files

None

## Notes

None.

## References

None.

## Warnings

None.

## Diagnostic Error Messages

None.

## Exit status

It always exits with status 0.

## Known bugs

None.

## See also

Program name | Description
--- | ---
distmat | Create a distance matrix from a multiple sequence alignment
ednacomp | DNA compatibility algorithm
ednadist | Nucleic acid sequence distance matrix program
ednainvar | Nucleic acid sequence invariants method
ednaml | Phylogenies from nucleic acid maximum likelihood
ednamlk | Phylogenies from nucleic acid maximum likelihood with clock
ednapars | DNA parsimony algorithm
ednapenny | Penny algorithm for DNA
eprotdist | Protein distance algorithm
eprotpars | Protein parsimony algorithm
erestml | Restriction site maximum likelihood method
eseqboot | Bootstrapped sequences algorithm
fdiscboot | Bootstrapped discrete sites algorithm
fdnacomp | DNA compatibility algorithm
fdnadist | Nucleic acid sequence distance matrix program
fdnainvar | Nucleic acid sequence invariants method
fdnaml | Estimate nucleotide phylogeny by maximum likelihood
fdnamlk | Estimates nucleotide phylogeny by maximum likelihood
fdnamove | Interactive DNA parsimony
fdnapars | DNA parsimony algorithm
fdnapenny | Penny algorithm for DNA
fdolmove | Interactive Dollo or polymorphism parsimony
ffreqboot | Bootstrapped genetic frequencies algorithm
fproml | Protein phylogeny by maximum likelihood
fpromlk | Protein phylogeny by maximum likelihood
fprotdist | Protein distance algorithm
fprotpars | Protein parsimony algorithm
frestboot | Bootstrapped restriction sites algorithm
frestdist | Calculate distance matrix from restriction sites or fragments
fseqboot | Bootstrapped sequences algorithm
fseqbootall | Bootstrapped sequences algorithm

## Author(s)

This program is an EMBOSS conversion of a program written by Joe Felsenstein as part of his PHYLIP package.

Please report all bugs to the EMBOSS bug team (emboss-bug © emboss.open-bio.org) not to the original author.

## History

Written (2004) - Joe Felsenstein, University of Washington.

Converted (August 2004) to an EMBASSY program by the EMBOSS team.

## Target users

This program is intended to be used by everyone and everything, from naive users to embedded scripts.

## Comments

    None