               *** ALF - Alignment Free Sequence Comparison ***
                       https://www.seqan.de/apps/alf
                                January, 2012

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Table of Contents
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  1.   Overview
  2.   Installation
  3.   Usage
  4.   Output Format
  5.   Example
  6.   Contact and Reference

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1. Overview
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ALF can be used to calculate the pairwise similarity of sequences using
alignment-free methods. All methods which are implemented are based on
k-mer counts. More details can be found in the online documentation of the
alignment-free methods (www.seqan.de). By default, ALF uses the
N2 similarity measure.

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2. Installation
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ALF is distributed with SeqAn - The C++ Sequence Analysis Library (see
https://www.seqan.de). To build ALF from Git do the following:

  1) git clone https://github.com/seqan/seqan.git
  2) mkdir -p build/Release
  3) cd build/Release
  4) cmake ../../seqan -DCMAKE_BUILD_TYPE=Release
  5) make alf
  6) ./apps/alf/alf --help

On success, an executable file alf was build and a brief usage description
was dumped.

For more information about retrieving SeqAn and prerequisites please visit

  https://www.seqan.de/getting-started/

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3. Usage
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To get a short usage description of ALF, you can execute alf -h or
alf --help.

Usage: alf [OPTION]... -i <MULTI FASTA FILE>

ALF expects one DNA (multi-)Fasta file. For all pairs of sequences, the
pairwise scores will be computed. A matrix of pairwise scores will be
returned. The default behaviour can be modified by specifying the following
options at the command line:

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3.1. Main Options
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  [ -i ],   [ --input-file ]

  Name of the multi fasta input file. Mandatory.

  [ -o ],   [ --output-file ]

  Name of the file to which the tab delimited matrix with pairwise scores
  will be written. Default: stdout.

  [ -m ],   [ --method ]

  Method that will be udes for sequence comparison.
  Default:N2 [N2, D2, D2Star, D2z]

  [ -k ],   [ --k-mer-size ]

  Size of the k-mers that will be counted. Default:4 [integer]

  [ -mo ],  [ --bg-model-order ]

  Order of background markov model for N2, D2Star, D2z. Default:1 [integer]

  [ -rc ],  [ --reverse-complement ]

  N2 only. Specify how the k-mer counts from the reverse and foreward
  strand should be combined. By default, only the input sequence is used
  for the comparison. Select 'bothStrands' to calculate the pairwise score
  using both strands from the input sequences.  Default: input sequence
  only. ['bothStrands','mean','min','max']

  [ -mm ],  [ --mismatches ]

  N2 only. Select -mm 1 if you want to include all words with one mismatch
  to the k-mer neighbourhood. Default: Exact counts only [0,1]

  [ -mmw ], [ --mismatch-weight ]

  N2 only. Weight of counts for words with mismatches, only used in
  combination with -mm 1. Default:0.1 [Double]

  [ -kwf ], [ --k-mer-weights-file ]

  N2 only. Print k-mer weights for every sequence to this file.

  [ -v ],   [ --verbose ]

  Specify this option to print details on progress to the screen.

  [ -h ],  [ --help ]

  Displays help message

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4. Output Format
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The program returns a (tab delimited) matrix with pairwise scores for all
sequences from the input fasta file, for example:

  1         0.046   0.052
  0.046     1       0.992
  0.052     0.992   1

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5. Example
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These examples use the fasta file "small.fasta" which can be found in
seqan/apps/alf/example/. Copy this file to the directory where you
execute alf.

(1) Run ALF with default settings on two sequences:

  ./alf -i small.fasta

Output:

  1           0.0463497
  0.0463497   1

(2) Calculate scores using N2 (-m N2), counting words of length 5 (-k 5) on
both strands (-rc both_strands), including words with one mismatch into the
word neighbourhood (-mm 1) with a weight of 0.5 (-mmw 0.5) and a background
Markov model of order 1 (-mo 1), writing the output to a file
(-o results.txt), saving all k-mer weights to a file (-kwf kmerWeights.txt):

  ./alf -m N2 -k 5 -mo 1 -rc both_strands -mm 1 -mmw 0.5 -i small.fasta \
      -o results.txt -kwf kmerWeights.txt

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6. Contact and Reference
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For questions or comments, contact:
  Jonathan Goeke <goeke@molgen.mpg.de>

Please reference the following publication if you used ALF or the N2 method
for your analysis:

  Jonathan Goeke, Marcel H. Schulz, Julia Lasserre, and Martin Vingron.
  Estimation of Pairwise Sequence Similarity of Mammalian Enhancers with
  Word Neighbourhood Counts. Bioinformatics (2012).

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7. Version History
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* 2012-07-17: Version 1.1
  - Updated ALF to use the new ArgumentParser for command line parsing.
  - Changed long parameter names to use --parameter-name instead of
    --parameterName.

* 2012-01-05: Version 1.0
  - Initial Release of ALF.
