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<HTML>

<HEAD>
  <TITLE>
  EMBOSS: water
  </TITLE>
</HEAD>
<BODY BGCOLOR="#FFFFFF" text="#000000">

<table align=center border=0 cellspacing=0 cellpadding=0>
<tr><td valign=top>
<A HREF="/" ONMOUSEOVER="self.status='Go to the EMBOSS home page';return true"><img border=0 src="emboss_icon.jpg" alt="" width=150 height=48></a>
</td>
<td align=left valign=middle>
<b><font size="+6">
water
</font></b>
</td></tr>
</table>
<br>&nbsp;
<p>


<H2>
    Function
</H2>
Smith-Waterman local alignment

<H2>
    Description
</H2>

<b>water</b> uses the Smith-Waterman algorithm (modified for speed
enhancments) to calculate the local alignment.

<P>

A local alignment searches for regions of local similarity between two
sequences and need not include the entire length of the sequences. 
Local alignment methods are very useful for scanning databases or other
circumsatnces when you wish to find matches between small regions of
sequences, for example between protein domains. 
<P>

<H3>
    Algorithm
</H3>

The Smith-Waterman algorithm is a member of the class of algorithms
that can calculate the best score and local alignment in the order of mn
steps, (where 'n' and 'm' are the lengths of the two sequences).  These
dynamic programming algorithms were first developed for protein sequence
comparison by Smith and Waterman, though similar methods were
independently devised during the late 1960's and early 1970's for use in
the fields of speech processing and computer science. 

<P>

Dynamic programming methods ensure
the optimal local alignment by exploring all possible alignments and
choosing the best.  It does this by reading in a scoring matrix that
contains values for every possible residue or nucleotide match.  <b>water</b>
finds an alignment with the maximum possible score where the score of an
alignment is equal to the sum of the matches taken from the scoring
matrix. 

<P>

An important problem is the treatment of gaps, i.e., spaces inserted to
optimise the alignment score.  A penalty is subtracted from the score
for each gap opened (the 'gap open' penalty) and a penalty is subtracted
from the score for the total number of gap spaces multiplied by a cost
(the 'gap extension' penalty). 

<P>

Typically, the cost of extending a gap is set to be 5-10 times lower
than the cost for opening a gap. 

<p>

There are two ways to compute a penalty for a gap of n positions :

<p>

<pre>
gap opening penalty + (n - 1) * gap extension penalty
gap penalty + n * gap length penalty
</pre>

<p>

The first way is used by EMBOSS and WU-BLAST
<br>
The second way is used by NCBI-BLAST, GCG, Staden and CLUSTAL.
Fasta used it for a long time the first way, but Prof. Pearson decided
recently to shift to the second.
 
<p>

The two methods are basically equivalent.

<p>      

The Smith-Waterman algorithm contains no negative scores in the path
matrix it creates. The algorithm starts the alignment at the highest
path matrix score and works backwards until a cell contains zero.

<p>

See the Reference <b>Smith et al.</b> for details.

<H2>
    Usage
</H2>
<b>Here is a sample session with water</b>
<p>

<p>
<table width="90%"><tr><td bgcolor="#CCFFFF"><pre>

% <b>water tsw:hba_human tsw:hbb_human </b>
Smith-Waterman local alignment.
Gap opening penalty [10.0]: <b></b>
Gap extension penalty [0.5]: <b></b>
Output alignment [hba_human.water]: <b></b>

</pre></td></tr></table><p>
<p>
<a href="#input.1">Go to the input files for this example</a><br><a href="#output.1">Go to the output files for this example</a><p><p>


<H2>
    Command line arguments
</H2>
<table CELLSPACING=0 CELLPADDING=3 BGCOLOR="#f5f5ff" ><tr><td>
<pre>
   Standard (Mandatory) qualifiers:
  [-asequence]         sequence   Sequence filename and optional format, or
                                  reference (input USA)
  [-bsequence]         seqall     Sequence(s) filename and optional format, or
                                  reference (input USA)
   -gapopen            float      [10.0 for any sequence] The gap open penalty
                                  is the score taken away when a gap is
                                  created. The best value depends on the
                                  choice of comparison matrix. The default
                                  value assumes you are using the EBLOSUM62
                                  matrix for protein sequences, and the
                                  EDNAFULL matrix for nucleotide sequences.
                                  (Number from 0.000 to 100.000)
   -gapextend          float      [0.5 for any sequence] The gap extension
                                  penalty is added to the standard gap penalty
                                  for each base or residue in the gap. This
                                  is how long gaps are penalized. Usually you
                                  will expect a few long gaps rather than many
                                  short gaps, so the gap extension penalty
                                  should be lower than the gap penalty. An
                                  exception is where one or both sequences are
                                  single reads with possible sequencing
                                  errors in which case you would expect many
                                  single base gaps. You can get this result by
                                  setting the gap open penalty to zero (or
                                  very low) and using the gap extension
                                  penalty to control gap scoring. (Number from
                                  0.000 to 10.000)
  [-outfile]           align      [*.water] Output alignment file name

   Additional (Optional) qualifiers:
   -datafile           matrixf    [EBLOSUM62 for protein, EDNAFULL for DNA]
                                  This is the scoring matrix file used when
                                  comparing sequences. By default it is the
                                  file 'EBLOSUM62' (for proteins) or the file
                                  'EDNAFULL' (for nucleic sequences). These
                                  files are found in the 'data' directory of
                                  the EMBOSS installation.

   Advanced (Unprompted) qualifiers:
   -[no]brief          boolean    [Y] Brief identity and similarity

   Associated qualifiers:

   "-asequence" associated qualifiers
   -sbegin1            integer    Start of the sequence to be used
   -send1              integer    End of the 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
   -sformat1           string     Input sequence format
   -sdbname1           string     Database name
   -sid1               string     Entryname
   -ufo1               string     UFO features
   -fformat1           string     Features format
   -fopenfile1         string     Features file name

   "-bsequence" associated qualifiers
   -sbegin2            integer    Start of each sequence to be used
   -send2              integer    End of each sequence to be used
   -sreverse2          boolean    Reverse (if DNA)
   -sask2              boolean    Ask for begin/end/reverse
   -snucleotide2       boolean    Sequence is nucleotide
   -sprotein2          boolean    Sequence is protein
   -slower2            boolean    Make lower case
   -supper2            boolean    Make upper case
   -sformat2           string     Input sequence format
   -sdbname2           string     Database name
   -sid2               string     Entryname
   -ufo2               string     UFO features
   -fformat2           string     Features format
   -fopenfile2         string     Features file name

   "-outfile" associated qualifiers
   -aformat3           string     Alignment format
   -aextension3        string     File name extension
   -adirectory3        string     Output directory
   -aname3             string     Base file name
   -awidth3            integer    Alignment width
   -aaccshow3          boolean    Show accession number in the header
   -adesshow3          boolean    Show description in the header
   -ausashow3          boolean    Show the full USA in the alignment
   -aglobal3           boolean    Show the full sequence in alignment

   General qualifiers:
   -auto               boolean    Turn off prompts
   -stdout             boolean    Write standard output
   -filter             boolean    Read standard input, write 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. 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

</pre>
</td></tr></table>
<P>
<table border cellspacing=0 cellpadding=3 bgcolor="#ccccff">
<tr bgcolor="#FFFFCC">
<th align="left" colspan=2>Standard (Mandatory) qualifiers</th>
<th align="left">Allowed values</th>
<th align="left">Default</th>
</tr>

<tr>
<td>[-asequence]<br>(Parameter 1)</td>
<td>Sequence filename and optional format, or reference (input USA)</td>
<td>Readable sequence</td>
<td><b>Required</b></td>
</tr>

<tr>
<td>[-bsequence]<br>(Parameter 2)</td>
<td>Sequence(s) filename and optional format, or reference (input USA)</td>
<td>Readable sequence(s)</td>
<td><b>Required</b></td>
</tr>

<tr>
<td>-gapopen</td>
<td>The gap open penalty is the score taken away when a gap is created. The best value depends on the choice of comparison matrix. The default value assumes you are using the EBLOSUM62 matrix for protein sequences, and the EDNAFULL matrix for nucleotide sequences.</td>
<td>Number from 0.000 to 100.000</td>
<td>10.0 for any sequence</td>
</tr>

<tr>
<td>-gapextend</td>
<td>The gap extension penalty is added to the standard gap penalty for each base or residue in the gap. This is how long gaps are penalized. Usually you will expect a few long gaps rather than many short gaps, so the gap extension penalty should be lower than the gap penalty. An exception is where one or both sequences are single reads with possible sequencing errors in which case you would expect many single base gaps. You can get this result by setting the gap open penalty to zero (or very low) and using the gap extension penalty to control gap scoring.</td>
<td>Number from 0.000 to 10.000</td>
<td>0.5 for any sequence</td>
</tr>

<tr>
<td>[-outfile]<br>(Parameter 3)</td>
<td>Output alignment file name</td>
<td>Alignment output file</td>
<td><i>&lt;*&gt;</i>.water</td>
</tr>

<tr bgcolor="#FFFFCC">
<th align="left" colspan=2>Additional (Optional) qualifiers</th>
<th align="left">Allowed values</th>
<th align="left">Default</th>
</tr>

<tr>
<td>-datafile</td>
<td>This is the scoring matrix file used when comparing sequences. By default it is the file 'EBLOSUM62' (for proteins) or the file 'EDNAFULL' (for nucleic sequences). These files are found in the 'data' directory of the EMBOSS installation.</td>
<td>Comparison matrix file in EMBOSS data path</td>
<td>EBLOSUM62 for protein<br>EDNAFULL for DNA</td>
</tr>

<tr bgcolor="#FFFFCC">
<th align="left" colspan=2>Advanced (Unprompted) qualifiers</th>
<th align="left">Allowed values</th>
<th align="left">Default</th>
</tr>

<tr>
<td>-[no]brief</td>
<td>Brief identity and similarity</td>
<td>Boolean value Yes/No</td>
<td>Yes</td>
</tr>

</table>


<H2>
    Input file format
</H2>


<b>water</b> reads any two sequence USAs of the same type (DNA or protein).

<p>


<a name="input.1"></a>
<h3>Input files for usage example </h3>

'tsw:hba_human' is a sequence entry in the example protein database 'tsw'
<p>
<p><h3>Database entry: tsw:hba_human</h3>
<table width="90%"><tr><td bgcolor="#FFCCFF">
<pre>
ID   HBA_HUMAN               Reviewed;         142 AA.
AC   P69905; P01922; Q96KF1; Q9NYR7;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   03-APR-2007, entry version 41.
DE   Hemoglobin subunit alpha (Hemoglobin alpha chain) (Alpha-globin).
GN   Name=HBA1;
GN   and
GN   Name=HBA2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HBA1).
RX   MEDLINE=81088339; PubMed=7448866; DOI=10.1016/0092-8674(80)90347-5;
RA   Michelson A.M., Orkin S.H.;
RT   "The 3' untranslated regions of the duplicated human alpha-globin
RT   genes are unexpectedly divergent.";
RL   Cell 22:371-377(1980).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (HBA2).
RX   MEDLINE=80137531; PubMed=6244294;
RA   Wilson J.T., Wilson L.B., Reddy V.B., Cavallesco C., Ghosh P.K.,
RA   Deriel J.K., Forget B.G., Weissman S.M.;
RT   "Nucleotide sequence of the coding portion of human alpha globin
RT   messenger RNA.";
RL   J. Biol. Chem. 255:2807-2815(1980).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HBA2).
RX   MEDLINE=81175088; PubMed=6452630;
RA   Liebhaber S.A., Goossens M.J., Kan Y.W.;
RT   "Cloning and complete nucleotide sequence of human 5'-alpha-globin
RT   gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 77:7054-7058(1980).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6946451;
RA   Orkin S.H., Goff S.C., Hechtman R.L.;
RT   "Mutation in an intervening sequence splice junction in man.";
RL   Proc. Natl. Acad. Sci. U.S.A. 78:5041-5045(1981).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-32.
RX   MEDLINE=21303311; PubMed=11410421;
RA   Zhao Y., Xu X.;
RT   "Alpha2(CD31 AGG--&gt;AAG, Arg--&gt;Lys) causing non-deletional alpha-
RT   thalassemia in a Chinese family with HbH disease.";
RL   Haematologica 86:541-542(2001).
RN   [6]


<font color=red>  [Part of this file has been deleted for brevity]</font>

FT                                /FTId=VAR_002840.
FT   VARIANT     131    131       A -&gt; D (in Yuda; O(2) affinity down).
FT                                /FTId=VAR_002842.
FT   VARIANT     131    131       A -&gt; P (in Sun Prairie; unstable).
FT                                /FTId=VAR_002841.
FT   VARIANT     132    132       S -&gt; P (in Questembert; highly unstable;
FT                                causes alpha-thalassemia).
FT                                /FTId=VAR_002843.
FT   VARIANT     134    134       S -&gt; R (in Val de Marne; O(2) affinity
FT                                up).
FT                                /FTId=VAR_002844.
FT   VARIANT     136    136       V -&gt; E (in Pavie).
FT                                /FTId=VAR_002845.
FT   VARIANT     137    137       L -&gt; M (in Chicago).
FT                                /FTId=VAR_002846.
FT   VARIANT     137    137       L -&gt; P (in Bibba; unstable; causes alpha-
FT                                thalassemia).
FT                                /FTId=VAR_002847.
FT   VARIANT     139    139       S -&gt; P (in Attleboro; O(2) affinity up).
FT                                /FTId=VAR_002848.
FT   VARIANT     140    140       K -&gt; E (in Hanamaki; O(2) affinity up).
FT                                /FTId=VAR_002849.
FT   VARIANT     140    140       K -&gt; T (in Tokoname; O(2) affinity up).
FT                                /FTId=VAR_002850.
FT   VARIANT     141    141       Y -&gt; H (in Rouen; O(2) affinity up).
FT                                /FTId=VAR_002851.
FT   VARIANT     142    142       R -&gt; C (in Nunobiki; O(2) affinity up).
FT                                /FTId=VAR_002852.
FT   VARIANT     142    142       R -&gt; H (in Suresnes; O(2) affinity up).
FT                                /FTId=VAR_002854.
FT   VARIANT     142    142       R -&gt; L (in Legnano; O(2) affinity up).
FT                                /FTId=VAR_002853.
FT   VARIANT     142    142       R -&gt; P (in Singapore).
FT                                /FTId=VAR_002855.
FT   HELIX         4     15
FT   HELIX        16     20
FT   HELIX        21     35
FT   HELIX        37     42
FT   HELIX        53     71
FT   HELIX        73     75
FT   HELIX        76     79
FT   HELIX        81     89
FT   HELIX        96    112
FT   TURN        114    116
FT   HELIX       119    136
FT   TURN        137    139
SQ   SEQUENCE   142 AA;  15258 MW;  15E13666573BBBAE CRC64;
     MVLSPADKTN VKAAWGKVGA HAGEYGAEAL ERMFLSFPTT KTYFPHFDLS HGSAQVKGHG
     KKVADALTNA VAHVDDMPNA LSALSDLHAH KLRVDPVNFK LLSHCLLVTL AAHLPAEFTP
     AVHASLDKFL ASVSTVLTSK YR
//
</pre>
</td></tr></table><p>
<p><h3>Database entry: tsw:hbb_human</h3>
<table width="90%"><tr><td bgcolor="#FFCCFF">
<pre>
ID   HBB_HUMAN               Reviewed;         147 AA.
AC   P68871; P02023; Q13852; Q14481; Q14510; Q45KT0; Q6FI08; Q8IZI1;
AC   Q9BX96; Q9UCP8; Q9UCP9;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   20-MAR-2007, entry version 43.
DE   Hemoglobin subunit beta (Hemoglobin beta chain) (Beta-globin).
GN   Name=HBB;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE.
RX   MEDLINE=81064667; PubMed=6254664; DOI=10.1016/0092-8674(80)90428-6;
RA   Lawn R.M., Efstratiadis A., O'Connell C., Maniatis T.;
RT   "The nucleotide sequence of the human beta-globin gene.";
RL   Cell 21:647-651(1980).
RN   [2]
RP   NUCLEOTIDE SEQUENCE.
RX   MEDLINE=77126403; PubMed=1019344;
RA   Marotta C., Forget B., Cohen-Solal M., Weissman S.M.;
RT   "Nucleotide sequence analysis of coding and noncoding regions of human
RT   beta-globin mRNA.";
RL   Prog. Nucleic Acid Res. Mol. Biol. 19:165-175(1976).
RN   [3]
RP   NUCLEOTIDE SEQUENCE.
RA   Lu L., Hu Z.H., Du C.S., Fu Y.S.;
RT   "DNA sequence of the human beta-globin gene isolated from a healthy
RT   Chinese.";
RL   Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE, AND VARIANT DURHAM-N.C. PRO-115.
RC   TISSUE=Blood;
RA   Kutlar F., Abboud M., Leithner C., Holley L., Brisco J., Kutlar A.;
RT   "Electrophoretically silent, very unstable, thalassemic mutation at
RT   codon 114 of beta globin (hemoglobin Durham-N.C.) detected by cDNA
RT   sequencing of mRNA, from a Russian women.";
RL   Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE, AND VARIANT LOUISVILLE LEU-43.
RC   TISSUE=Blood;
RA   Kutlar F., Harbin J., Brisco J., Kutlar A.;
RT   "Rapid detection of electrophoretically silent, unstable human
RT   hemoglobin 'Louisville', (Beta; Phe 42 Leu/TTT to CTT) by cDNA
RT   sequencing of mRNA.";
RL   Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE, AND VARIANT TY GARD GLN-125.


<font color=red>  [Part of this file has been deleted for brevity]</font>

FT   VARIANT     141    141       A -&gt; T (in St Jacques: O(2) affinity up).
FT                                /FTId=VAR_003081.
FT   VARIANT     141    141       A -&gt; V (in Puttelange; polycythemia; O(2)
FT                                affinity up).
FT                                /FTId=VAR_003082.
FT   VARIANT     142    142       L -&gt; R (in Olmsted; unstable).
FT                                /FTId=VAR_003083.
FT   VARIANT     143    143       A -&gt; D (in Ohio; O(2) affinity up).
FT                                /FTId=VAR_003084.
FT   VARIANT     144    144       H -&gt; D (in Rancho Mirage).
FT                                /FTId=VAR_003085.
FT   VARIANT     144    144       H -&gt; P (in Syracuse; O(2) affinity up).
FT                                /FTId=VAR_003087.
FT   VARIANT     144    144       H -&gt; Q (in Little Rock; O(2) affinity
FT                                up).
FT                                /FTId=VAR_003086.
FT   VARIANT     144    144       H -&gt; R (in Abruzzo; O(2) affinity up).
FT                                /FTId=VAR_003088.
FT   VARIANT     145    145       K -&gt; E (in Mito; O(2) affinity up).
FT                                /FTId=VAR_003089.
FT   VARIANT     146    146       Y -&gt; C (in Rainier; O(2) affinity up).
FT                                /FTId=VAR_003090.
FT   VARIANT     146    146       Y -&gt; H (in Bethesda; O(2) affinity up).
FT                                /FTId=VAR_003091.
FT   VARIANT     147    147       H -&gt; D (in Hiroshima; O(2) affinity up).
FT                                /FTId=VAR_003092.
FT   VARIANT     147    147       H -&gt; L (in Cowtown; O(2) affinity up).
FT                                /FTId=VAR_003093.
FT   VARIANT     147    147       H -&gt; P (in York; O(2) affinity up).
FT                                /FTId=VAR_003094.
FT   VARIANT     147    147       H -&gt; Q (in Kodaira; O(2) affinity up).
FT                                /FTId=VAR_003095.
FT   HELIX         5     15
FT   TURN         20     22
FT   HELIX        23     34
FT   HELIX        36     41
FT   HELIX        43     45
FT   HELIX        51     56
FT   HELIX        58     76
FT   TURN         77     79
FT   HELIX        81     93
FT   TURN         94     96
FT   HELIX       101    118
FT   HELIX       119    121
FT   HELIX       124    141
FT   HELIX       143    145
SQ   SEQUENCE   147 AA;  15998 MW;  A31F6D621C6556A1 CRC64;
     MVHLTPEEKS AVTALWGKVN VDEVGGEALG RLLVVYPWTQ RFFESFGDLS TPDAVMGNPK
     VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
     KEFTPPVQAA YQKVVAGVAN ALAHKYH
//
</pre>
</td></tr></table><p>

<H2>
    Output file format
</H2>

<p>

The output is a standard EMBOSS alignment file. 

<p>

The results can be output in one of several styles by using the
command-line qualifier <b>-aformat xxx</b>, where 'xxx' is replaced by
the name of the required format.  Some of the alignment formats can cope
with an unlimited number of sequences, while others are only for pairs
of sequences.  

<p>

The available multiple alignment format names are: unknown, multiple,
simple, fasta, msf, trace, srs

<p>

The available pairwise alignment format names are: pair, markx0, markx1,
markx2, markx3, markx10, srspair, score

<p>

See:
<A href="http://emboss.sf.net/docs/themes/AlignFormats.html">
http://emboss.sf.net/docs/themes/AlignFormats.html</A>
for further information on alignment formats.

<p>

<p>


<a name="output.1"></a>
<h3>Output files for usage example </h3>
<p><h3>File: hba_human.water </h3>
<table width="90%"><tr><td bgcolor="#CCFFCC">
<pre>
########################################
# Program: water
# Rundate: Sun 15 Jul 2007 12:00:00
# Commandline: water
#    [-asequence] tsw:hba_human
#    [-bsequence] tsw:hbb_human
# Align_format: srspair
# Report_file: hba_human.water
########################################

#=======================================
#
# Aligned_sequences: 2
# 1: HBA_HUMAN
# 2: HBB_HUMAN
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 145
# Identity:      63/145 (43.4%)
# Similarity:    88/145 (60.7%)
# Gaps:           8/145 ( 5.5%)
# Score: 293.5
# 
#
#=======================================

HBA_HUMAN          3 LSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHF-DLS-     50
                     |:|.:|:.|.|.||||  :..|.|.|||.|:.:.:|.|:.:|..| ||| 
HBB_HUMAN          4 LTPEEKSAVTALWGKV--NVDEVGGEALGRLLVVYPWTQRFFESFGDLST     51

HBA_HUMAN         51 ----HGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDP     96
                         .|:.:||.|||||..|.::.:||:|::....:.||:||..||.|||
HBB_HUMAN         52 PDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDP    101

HBA_HUMAN         97 VNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKY    141
                     .||:||.:.|:..||.|...||||.|.|:..|.:|.|:..|..||
HBB_HUMAN        102 ENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKY    146


#---------------------------------------
#---------------------------------------
</pre>
</td></tr></table><p>

<p>

The <b>Identity:</b> is the percentage of identical matches between the two
sequences over the reported aligned region (including any gaps in the length).

<p>

The <b>Similarity:</b> is the percentage of matches between the two
sequences over the reported aligned region (including any gaps in the length).


<H2>
    Data files
</H2>


For protein sequences EBLOSUM62 is used for the substitution
matrix. For nucleotide sequence, EDNAFULL is used. Others can be specified.

<p>
<p>
EMBOSS data files are distributed with the application and stored
in the standard EMBOSS data directory, which is defined
by the EMBOSS environment variable EMBOSS_DATA.

<p>

To see the available EMBOSS data files, run:
<p>
<pre>
% embossdata -showall
</pre>
<p>
To fetch one of the data files (for example 'Exxx.dat') into your
current directory for you to inspect or modify, run:

<pre>

% embossdata -fetch -file Exxx.dat

</pre>
<p>

Users can provide their own data files in their own directories.
Project specific files can be put in the current directory, or for
tidier directory listings in a subdirectory called
".embossdata". Files for all EMBOSS runs can be put in the user's home
directory, or again in a subdirectory called ".embossdata".

<p>
The directories are searched in the following order:

<ul>
   <li> . (your current directory)
   <li> .embossdata (under your current directory)
   <li> ~/ (your home directory)
   <li> ~/.embossdata
</ul>
<p>

<H2>
    Notes
</H2>

<b>water</b> is a true implementation of the Smith-Waterman algorithm
and so produces a full path matrix.  It therefore cannot be used with
genome sized sequences unless you have a <b>lot</b> of memory and a lot
of time. 

<H2>
    References
</H2>

<OL>

<LI>Smith TF, Waterman MS (1981) J. Mol. Biol 147(1);195-7

</OL>


<H2>
    Warnings
</H2>

Local alignment methods only report the best matching areas between two
sequences - there may be a large number of alternative local alignments
that do not score as highly.  If two proteins share more than one common
region, for example one has a single copy of a particular domain while
the other has two copies, it may be possible to "miss" the second and
subsequent alignments.  You will be able to see this situation if you
have done a dotplot and your local alignment does not show all the
features you expected to see. 
<P>

<b>water</b> is for aligning the best matching subsequences of two
sequences.  It does not necessarily align whole sequences against each
other; you should use <b>needle</b> if you wish to align closely related
sequences along their whole lengths. 
<P>

A true Smith Waterman implementation like <b>water</b> needs memory
proportional to the product of the sequence lengths.  For two sequences
of length 10,000,000 and 1,000 it therefore needs memory proportional to
10,000,000,000 characters.  Two arrays of this size are produced, one of
ints and one of floats so multiply that figure by 8 to get the memory
usage in bytes.  That doesn't include other overheads.  Therefore only
use water and needle for accurate alignment of reasonably short
sequences. 

<p>



If you run out of memory, try using <b>supermatcher</b> or
<b>matcher</b>.

<H2>
    Diagnostic Error Messages
</H2>

<PRE>
Uncaught exception
 Assertion failed
 raised at ajmem.c:xxx
</PRE>
<P>

Probably means you have run out of memory.  Try using
<b>supermatcher</b> or <b>matcher</b> if this happens. 

<H2>
    Exit status
</H2>

    0 if successful.

<H2>
    Known bugs
</H2>

None.


<h2><a name="See also">See also</a></h2>
<table border cellpadding=4 bgcolor="#FFFFF0">
<tr><th>Program name</th><th>Description</th></tr>
<tr>
<td><a href="matcher.html">matcher</a></td>
<td>Finds the best local alignments between two sequences</td>
</tr>

<tr>
<td><a href="seqmatchall.html">seqmatchall</a></td>
<td>All-against-all comparison of a set of sequences</td>
</tr>

<tr>
<td><a href="supermatcher.html">supermatcher</a></td>
<td>Match large sequences against one or more other sequences</td>
</tr>

<tr>
<td><a href="wordfinder.html">wordfinder</a></td>
<td>Match large sequences against one or more other sequences</td>
</tr>

<tr>
<td><a href="wordmatch.html">wordmatch</a></td>
<td>Finds all exact matches of a given size between 2 sequences</td>
</tr>

</table>
<p>

<b>matcher</b> is a local alignment program that gives as good an
alignment as <p>water</p> but it uses far less memory.  However,
<p>water</p> runs twice as fast as <b>matcher</b>. 

<p>

<b>supermatcher</b> is designed for local alignments of very large
sequences.  It gives good results as long as there is not significant
amounts of insertion or deletion in the alignment. 


<p>

<a href="supermatcher.html">supermatcher</a> Finds a match of a large
sequence against one or more sequences

<a href="matcher.html">matcher</a> Finds the best local alignments
between two sequences

<H2>
    Author(s)
</H2>


Alan Bleasby (ajb&nbsp;&copy;&nbsp;ebi.ac.uk)
<br>
European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK



<H2>
    History
</H2>

Completed 7th July 1999.
<p>
Modified 27th July 1999 - tweaking scoring.
<p>
Modified 22 Oct 2000 - added ID and Similarity scores.

<H2>
    Target users
</H2>
This program is intended to be used by everyone and everything, from naive users to embedded scripts.


<H2>
    Comments
</H2>
None

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