                                  fdnadist



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Function

   Nucleic acid sequence distance matrix program

Description

   Computes four different distances between species from nucleic acid
   sequences. The distances can then be used in the distance matrix
   programs. The distances are the Jukes-Cantor formula, one based on
   Kimura's 2- parameter method, the F84 model used in DNAML, and the
   LogDet distance. The distances can also be corrected for
   gamma-distributed and gamma-plus-invariant-sites-distributed rates of
   change in different sites. Rates of evolution can vary among sites in a
   prespecified way, and also according to a Hidden Markov model. The
   program can also make a table of percentage similarity among sequences.

Algorithm

   This program uses nucleotide sequences to compute a distance matrix,
   under four different models of nucleotide substitution. It can also
   compute a table of similarity between the nucleotide sequences. The
   distance for each pair of species estimates the total branch length
   between the two species, and can be used in the distance matrix
   programs FITCH, KITSCH or NEIGHBOR. This is an alternative to use of
   the sequence data itself in the maximum likelihood program DNAML or the
   parsimony program DNAPARS.

   The program reads in nucleotide sequences and writes an output file
   containing the distance matrix, or else a table of similarity between
   sequences. The four models of nucleotide substitution are those of
   Jukes and Cantor (1969), Kimura (1980), the F84 model (Kishino and
   Hasegawa, 1989; Felsenstein and Churchill, 1996), and the model
   underlying the LogDet distance (Barry and Hartigan, 1987; Lake, 1994;
   Steel, 1994; Lockhart et. al., 1994). All except the LogDet distance
   can be made to allow for for unequal rates of substitution at different
   sites, as Jin and Nei (1990) did for the Jukes-Cantor model. The
   program correctly takes into account a variety of sequence ambiguities,
   although in cases where they exist it can be slow.

   Jukes and Cantor's (1969) model assumes that there is independent
   change at all sites, with equal probability. Whether a base changes is
   independent of its identity, and when it changes there is an equal
   probability of ending up with each of the other three bases. Thus the
   transition probability matrix (this is a technical term from
   probability theory and has nothing to do with transitions as opposed to
   transversions) for a short period of time dt is:

              To:    A        G        C        T
                   ---------------------------------
               A  | 1-3a      a         a       a
       From:   G  |  a       1-3a       a       a
               C  |  a        a        1-3a     a
               T  |  a        a         a      1-3a


   where a is u dt, the product of the rate of substitution per unit time
   (u) and the length dt of the time interval. For longer periods of time
   this implies that the probability that two sequences will differ at a
   given site is:

      p = 3/4 ( 1 - e- 4/3 u t)

   and hence that if we observe p, we can compute an estimate of the
   branch length ut by inverting this to get

     ut = - 3/4 loge ( 1 - 4/3 p )

   The Kimura "2-parameter" model is almost as symmetric as this, but
   allows for a difference between transition and transversion rates. Its
   transition probability matrix for a short interval of time is:


              To:     A        G        C        T
                   ---------------------------------
               A  | 1-a-2b     a         b       b
       From:   G  |   a      1-a-2b      b       b
               C  |   b        b       1-a-2b    a
               T  |   b        b         a     1-a-2b


   where a is u dt, the product of the rate of transitions per unit time
   and dt is the length dt of the time interval, and b is v dt, the
   product of half the rate of transversions (i.e., the rate of a specific
   transversion) and the length dt of the time interval.

   The F84 model incorporates different rates of transition and
   transversion, but also allowing for different frequencies of the four
   nucleotides. It is the model which is used in DNAML, the maximum
   likelihood nucelotide sequence phylogenies program in this package. You
   will find the model described in the document for that program. The
   transition probabilities for this model are given by Kishino and
   Hasegawa (1989), and further explained in a paper by me and Gary
   Churchill (1996).

   The LogDet distance allows a fairly general model of substitution. It
   computes the distance from the determinant of the empirically observed
   matrix of joint probabilities of nucleotides in the two species. An
   explanation of it is available in the chapter by Swofford et, al.
   (1996).

   The first three models are closely related. The DNAML model reduces to
   Kimura's two-parameter model if we assume that the equilibrium
   frequencies of the four bases are equal. The Jukes-Cantor model in turn
   is a special case of the Kimura 2-parameter model where a = b. Thus
   each model is a special case of the ones that follow it, Jukes-Cantor
   being a special case of both of the others.

   The Jin and Nei (1990) correction for variation in rate of evolution
   from site to site can be adapted to all of the first three models. It
   assumes that the rate of substitution varies from site to site
   according to a gamma distribution, with a coefficient of variation that
   is specified by the user. The user is asked for it when choosing this
   option in the menu.

   Each distance that is calculated is an estimate, from that particular
   pair of species, of the divergence time between those two species. For
   the Jukes- Cantor model, the estimate is computed using the formula for
   ut given above, as long as the nucleotide symbols in the two sequences
   are all either A, C, G, T, U, N, X, ?, or - (the latter four indicate a
   deletion or an unknown nucleotide. This estimate is a maximum
   likelihood estimate for that model. For the Kimura 2-parameter model,
   with only these nucleotide symbols, formulas special to that estimate
   are also computed. These are also, in effect, computing the maximum
   likelihood estimate for that model. In the Kimura case it depends on
   the observed sequences only through the sequence length and the
   observed number of transition and transversion differences between
   those two sequences. The calculation in that case is a maximum
   likelihood estimate and will differ somewhat from the estimate obtained
   from the formulas in Kimura's original paper. That formula was also a
   maximum likelihood estimate, but with the transition/transversion ratio
   estimated empirically, separately for each pair of sequences. In the
   present case, one overall preset transition/transversion ratio is used
   which makes the computations harder but achieves greater consistency
   between different comparisons.

   For the F84 model, or for any of the models where one or both sequences
   contain at least one of the other ambiguity codons such as Y, R, etc.,
   a maximum likelihood calculation is also done using code which was
   originally written for DNAML. Its disadvantage is that it is slow. The
   resulting distance is in effect a maximum likelihood estimate of the
   divergence time (total branch length between) the two sequences.
   However the present program will be much faster than versions earlier
   than 3.5, because I have speeded up the iterations.

   The LogDet model computes the distance from the determinant of the
   matrix of co-occurrence of nucleotides in the two species, according to
   the formula

   D  = - 1/4(loge(|F|) - 1/2loge(fA1fC1fG1fT1fA2fC2fG2fT2))


   Where F is a matrix whose (i,j) element is the fraction of sites at
   which base i occurs in one species and base j occurs in the other. fji
   is the fraction of sites at which species i has base j. The LogDet
   distance cannot cope with ambiguity codes. It must have completely
   defined sequences. One limitation of the LogDet distance is that it may
   be infinite sometimes, if there are too many changes between certain
   pairs of nucleotides. This can be particularly noticeable with
   distances computed from bootstrapped sequences. Note that there is an
   assumption that we are looking at all sites, including those that have
   not changed at all. It is important not to restrict attention to some
   sites based on whether or not they have changed; doing that would bias
   the distances by making them too large, and that in turn would cause
   the distances to misinterpret the meaning of those sites that had
   changed.

   For all of these distance methods, the program allows us to specify
   that "third position" bases have a different rate of substitution than
   first and second positions, that introns have a different rate than
   exons, and so on. The Categories option which does this allows us to
   make up to 9 categories of sites and specify different rates of change
   for them.

   In addition to the four distance calculations, the program can also
   compute a table of similarities between nucleotide sequences. These
   values are the fractions of sites identical between the sequences. The
   diagonal values are 1.0000. No attempt is made to count similarity of
   nonidentical nucleotides, so that no credit is given for having (for
   example) different purines at corresponding sites in the two sequences.
   This option has been requested by many users, who need it for
   descriptive purposes. It is not intended that the table be used for
   inferring the tree.

Usage

   Here is a sample session with fdnadist


% fdnadist
Nucleic acid sequence distance matrix program
Input (aligned) nucleotide sequence set(s): dnadist.dat
Distance methods
         f : F84 distance model
         k : Kimura 2-parameter distance
         j : Jukes-Cantor distance
         l : LogDet distance
         s : Similarity table
Choose the method to use [F84 distance model]:
Phylip distance matrix output file [dnadist.fdnadist]:

Distances calculated for species
    Alpha        ....
    Beta         ...
    Gamma        ..
    Delta        .
    Epsilon

Distances written to file "dnadist.fdnadist"

Done.



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

Command line arguments

Nucleic acid sequence distance matrix program
Version: EMBOSS:6.5.0.0

   Standard (Mandatory) qualifiers:
  [-sequence]          seqsetall  File containing one or more sequence
                                  alignments
   -method             menu       [F84 distance model] Choose the method to
                                  use (Values: f (F84 distance model); k
                                  (Kimura 2-parameter distance); j
                                  (Jukes-Cantor distance); l (LogDet
                                  distance); s (Similarity table))
  [-outfile]           outfile    [*.fdnadist] Phylip distance matrix output
                                  file

   Additional (Optional) qualifiers (* if not always prompted):
*  -gammatype          menu       [No distribution parameters used] Gamma
                                  distribution (Values: g (Gamma distributed
                                  rates); i (Gamma+invariant sites); n (No
                                  distribution parameters used))
*  -ncategories        integer    [1] Number of substitution rate categories
                                  (Integer from 1 to 9)
*  -rate               array      [1.0] Category rates
*  -categories         properties File of substitution rate categories
   -weights            properties Weights file
*  -gammacoefficient   float      [1] Coefficient of variation of substitution
                                  rate among sites (Number 0.001 or more)
*  -invarfrac          float      [0.0] Fraction of invariant sites (Number
                                  from 0.000 to 1.000)
*  -ttratio            float      [2.0] Transition/transversion ratio (Number
                                  0.001 or more)
*  -[no]freqsfrom      toggle     [Y] Use empirical base frequencies from
                                  seqeunce input
*  -basefreq           array      [0.25 0.25 0.25 0.25] Base frequencies for A
                                  C G T/U (use blanks to separate)
   -lower              boolean    [N] Output as a lower triangular distance
                                  matrix
   -humanreadable      boolean    [@($(method)==s?Y:N)] Output as a
                                  human-readable distance matrix
   -printdata          boolean    [N] Print data at start of run
   -[no]progress       boolean    [Y] Print indications of progress of run

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

   "-sequence" associated qualifiers
   -sbegin1            integer    Start of each sequence to be used
   -send1              integer    End of each sequence to be used
   -sreverse1          boolean    Reverse (if DNA)
   -sask1              boolean    Ask for begin/end/reverse
   -snucleotide1       boolean    Sequence is nucleotide
   -sprotein1          boolean    Sequence is protein
   -slower1            boolean    Make lower case
   -supper1            boolean    Make upper case
   -scircular1         boolean    Sequence is circular
   -sformat1           string     Input sequence format
   -iquery1            string     Input query fields or ID list
   -ioffset1           integer    Input start position offset
   -sdbname1           string     Database name
   -sid1               string     Entryname
   -ufo1               string     UFO features
   -fformat1           string     Features format
   -fopenfile1         string     Features file name

   "-outfile" associated qualifiers
   -odirectory2        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


Input file format

   fdnadist reads any normal sequence USAs.

  Input files for usage example

  File: dnadist.dat

   5   13
Alpha     AACGTGGCCACAT
Beta      AAGGTCGCCACAC
Gamma     CAGTTCGCCACAA
Delta     GAGATTTCCGCCT
Epsilon   GAGATCTCCGCCC

Output file format

   fdnadist output contains on its first line the number of species. The
   distance matrix is then printed in standard form, with each species
   starting on a new line with the species name, followed by the distances
   to the species in order. These continue onto a new line after every
   nine distances. If the L option is used, the matrix or distances is in
   lower triangular form, so that only the distances to the other species
   that precede each species are printed. Otherwise the distance matrix is
   square with zero distances on the diagonal. In general the format of
   the distance matrix is such that it can serve as input to any of the
   distance matrix programs.

   If the option to print out the data is selected, the output file will
   precede the data by more complete information on the input and the menu
   selections. The output file begins by giving the number of species and
   the number of characters, and the identity of the distance measure that
   is being used.

   If the C (Categories) option is used a table of the relative rates of
   expected substitution at each category of sites is printed, and a
   listing of the categories each site is in.

   There will then follow the equilibrium frequencies of the four bases.
   If the Jukes-Cantor or Kimura distances are used, these will
   necessarily be 0.25 : 0.25 : 0.25 : 0.25. The output then shows the
   transition/transversion ratio that was specified or used by default. In
   the case of the Jukes-Cantor distance this will always be 0.5. The
   transition-transversion parameter (as opposed to the ratio) is also
   printed out: this is used within the program and can be ignored. There
   then follow the data sequences, with the base sequences printed in
   groups of ten bases along the lines of the Genbank and EMBL formats.

   The distances printed out are scaled in terms of expected numbers of
   substitutions, counting both transitions and transversions but not
   replacements of a base by itself, and scaled so that the average rate
   of change, averaged over all sites analyzed, is set to 1.0 if there are
   multiple categories of sites. This means that whether or not there are
   multiple categories of sites, the expected fraction of change for very
   small branches is equal to the branch length. Of course, when a branch
   is twice as long this does not mean that there will be twice as much
   net change expected along it, since some of the changes may occur in
   the same site and overlie or even reverse each other. The branch
   lengths estimates here are in terms of the expected underlying numbers
   of changes. That means that a branch of length 0.26 is 26 times as long
   as one which would show a 1% difference between the nucleotide
   sequences at the beginning and end of the branch. But we would not
   expect the sequences at the beginning and end of the branch to be 26%
   different, as there would be some overlaying of changes.

   One problem that can arise is that two or more of the species can be so
   dissimilar that the distance between them would have to be infinite, as
   the likelihood rises indefinitely as the estimated divergence time
   increases. For example, with the Jukes-Cantor model, if the two
   sequences differ in 75% or more of their positions then the estimate of
   dovergence time would be infinite. Since there is no way to represent
   an infinite distance in the output file, the program regards this as an
   error, issues an error message indicating which pair of species are
   causing the problem, and stops. It might be that, had it continued
   running, it would have also run into the same problem with other pairs
   of species. If the Kimura distance is being used there may be no error
   message; the program may simply give a large distance value (it is
   iterating towards infinity and the value is just where the iteration
   stopped). Likewise some maximum likelihood estimates may also become
   large for the same reason (the sequences showing more divergence than
   is expected even with infinite branch length). I hope in the future to
   add more warning messages that would alert the user the this.

   If the similarity table is selected, the table that is produced is not
   in a format that can be used as input to the distance matrix programs.
   it has a heading, and the species names are also put at the tops of the
   columns of the table (or rather, the first 8 characters of each species
   name is there, the other two characters omitted to save space). There
   is not an option to put the table into a format that can be read by the
   distance matrix programs, nor is there one to make it into a table of
   fractions of difference by subtracting the similarity values from 1.
   This is done deliberately to make it more difficult for the use to use
   these values to construct trees. The similarity values are not
   corrected for multiple changes, and their use to construct trees (even
   after converting them to fractions of difference) would be wrong, as it
   would lead to severe conflict between the distant pairs of sequences
   and the close pairs of sequences.

  Output files for usage example

  File: dnadist.fdnadist

    5
Alpha      0.000000 0.303900 0.857544 1.158927 1.542899
Beta       0.303900 0.000000 0.339727 0.913522 0.619671
Gamma      0.857544 0.339727 0.000000 1.631729 1.293713
Delta      1.158927 0.913522 1.631729 0.000000 0.165882
Epsilon    1.542899 0.619671 1.293713 0.165882 0.000000

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
                    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
                    frestml      Restriction site maximum likelihood method
                    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 (c) 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
