<s>
Clustal	B-Application
is	O
a	O
series	O
of	O
widely	O
used	O
computer	B-Application
programs	I-Application
used	O
in	O
bioinformatics	O
for	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
.	O
</s>
<s>
There	O
have	O
been	O
many	O
versions	O
of	O
Clustal	B-Application
over	O
the	O
development	O
of	O
the	O
algorithm	O
that	O
are	O
listed	O
below	O
.	O
</s>
<s>
Available	O
operating	O
systems	O
listed	O
in	O
the	O
sidebar	O
are	O
a	O
combination	O
of	O
the	O
software	O
availability	O
and	O
may	O
not	O
be	O
supported	O
for	O
every	O
current	O
version	O
of	O
the	O
Clustal	B-Application
tools	O
.	O
</s>
<s>
Clustal	B-Application
Omega	I-Application
has	O
the	O
widest	O
variety	O
of	O
operating	O
systems	O
out	O
of	O
all	O
the	O
Clustal	B-Application
tools	O
.	O
</s>
<s>
There	O
have	O
been	O
many	O
variations	O
of	O
the	O
Clustal	B-Application
software	O
,	O
all	O
of	O
which	O
are	O
listed	O
below	O
:	O
</s>
<s>
Clustal	B-Application
:	O
The	O
original	O
software	O
for	O
multiple	O
sequence	B-Algorithm
alignments	I-Algorithm
,	O
created	O
by	O
Des	O
Higgins	O
in	O
1988	O
,	O
was	O
based	O
on	O
deriving	O
phylogenetic	O
trees	O
from	O
pairwise	O
sequences	O
of	O
amino	O
acids	O
or	O
nucleotides	O
.	O
</s>
<s>
ClustalV	O
:	O
The	O
second	O
generation	O
of	O
the	O
Clustal	B-Application
software	O
was	O
released	O
in	O
1992	O
and	O
was	O
a	O
rewrite	O
of	O
the	O
original	O
Clustal	B-Application
package	O
.	O
</s>
<s>
It	O
introduced	O
phylogenetic	O
tree	O
reconstruction	O
on	O
the	O
final	O
alignment	O
,	O
the	O
ability	O
to	O
create	O
alignments	O
from	O
existing	O
alignments	O
,	O
and	O
the	O
option	O
to	O
create	O
trees	O
from	O
alignments	O
using	O
a	O
method	O
called	O
Neighbor	B-Algorithm
joining	I-Algorithm
.	O
</s>
<s>
ClustalW	B-Application
:	O
The	O
third	O
generation	O
,	O
released	O
in	O
1994	O
,	O
greatly	O
improved	O
upon	O
the	O
previous	O
versions	O
.	O
</s>
<s>
ClustalX	B-Application
:	O
This	O
version	O
,	O
released	O
in	O
1997	O
,	O
was	O
the	O
first	O
to	O
have	O
a	O
graphical	O
user	O
interface	O
.	O
</s>
<s>
ClustalΩ	B-Application
(	O
Omega	O
)	O
:	O
The	O
current	O
standard	O
version	O
.	O
</s>
<s>
Clustal2	O
:	O
The	O
updated	O
versions	O
of	O
both	O
ClustalW	B-Application
and	O
ClustalX	B-Application
with	O
higher	O
accuracy	O
and	O
efficiency	O
.	O
</s>
<s>
The	O
papers	O
describing	O
the	O
clustal	B-Application
software	O
have	O
been	O
very	O
highly	O
cited	O
,	O
with	O
two	O
of	O
them	O
amongst	O
the	O
most	O
cited	O
papers	O
of	O
all	O
time	O
.	O
</s>
<s>
The	O
most	O
recent	O
version	O
of	O
the	O
software	O
is	O
available	O
for	O
Windows	O
,	O
Mac	B-Device
OS	O
,	O
and	O
Unix/Linux	O
.	O
</s>
<s>
The	O
guide	O
tree	O
in	O
the	O
initial	O
programs	O
was	O
constructed	O
via	O
a	O
UPGMA	B-Algorithm
cluster	O
analysis	O
of	O
the	O
pairwise	O
alignments	O
,	O
hence	O
the	O
name	O
CLUSTAL.cf	O
.	O
</s>
<s>
In	O
1994	O
and	O
in	O
1997	O
,	O
for	O
the	O
next	O
two	O
versions	O
,	O
the	O
letters	O
after	O
the	O
letter	O
V	O
were	O
used	O
and	O
made	O
to	O
correspond	O
to	O
W	O
for	O
Weighted	O
and	O
X	B-Operating_System
for	O
X	B-Operating_System
Window.cf	O
.	O
</s>
<s>
All	O
variations	O
of	O
the	O
Clustal	B-Application
software	O
align	O
sequences	O
using	O
a	O
heuristic	B-Algorithm
that	O
progressively	O
builds	O
a	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
from	O
a	O
series	O
of	O
pairwise	O
alignments	O
.	O
</s>
<s>
This	O
method	O
works	O
by	O
analyzing	O
the	O
sequences	O
as	O
a	O
whole	O
,	O
then	O
utilizing	O
the	O
UPGMA/Neighbor	O
-joining	O
method	O
to	O
generate	O
a	O
distance	O
matrix	O
.	O
</s>
<s>
A	O
guide	O
tree	O
is	O
then	O
calculated	O
from	O
the	O
scores	O
of	O
the	O
sequences	O
in	O
the	O
matrix	O
,	O
then	O
subsequently	O
used	O
to	O
build	O
the	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
by	O
progressively	O
aligning	O
the	O
sequences	O
in	O
order	O
of	O
similarity	O
.	O
</s>
<s>
Essentially	O
,	O
Clustal	B-Application
creates	O
multiple	O
sequence	B-Algorithm
alignments	I-Algorithm
through	O
three	O
main	O
steps	O
:	O
</s>
<s>
This	O
program	O
accepts	O
a	O
wide	O
range	O
of	O
input	O
formats	O
,	O
including	O
NBRF/PIR	O
,	O
FASTA	O
,	O
EMBL/Swiss	O
-Prot	O
,	O
Clustal	B-Application
,	O
GCC/MSF	O
,	O
GCG9	O
RSF	O
,	O
and	O
GDE	O
.	O
</s>
<s>
The	O
output	O
format	O
can	O
be	O
one	O
or	O
many	O
of	O
the	O
following	O
:	O
Clustal	B-Application
,	O
NBRF/PIR	O
,	O
GCG/MSF	O
,	O
PHYLIP	B-Application
,	O
GDE	O
,	O
or	O
NEXUS	O
.	O
</s>
<s>
The	O
original	O
program	O
in	O
the	O
Clustal	B-Application
series	O
of	O
software	O
was	O
developed	O
in	O
1988	O
as	O
a	O
way	O
to	O
generate	O
multiple	O
sequence	B-Algorithm
alignments	I-Algorithm
on	O
personal	O
computers	O
.	O
</s>
<s>
Once	O
the	O
sequences	O
are	O
scored	O
,	O
a	O
dendrogram	B-Application
is	O
generated	O
through	O
the	O
UPGMA	B-Algorithm
to	O
represent	O
the	O
ordering	O
of	O
the	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
.	O
</s>
<s>
This	O
gives	O
the	O
user	O
the	O
option	O
to	O
gradually	O
and	O
methodically	O
create	O
multiple	O
sequence	B-Algorithm
alignments	I-Algorithm
with	O
more	O
control	O
than	O
the	O
basic	O
option	O
.	O
</s>
<s>
The	O
option	O
to	O
run	O
from	O
the	O
command	O
line	O
greatly	O
expedites	O
the	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
process	O
.	O
</s>
<s>
When	O
the	O
program	O
is	O
completed	O
,	O
the	O
output	O
of	O
the	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
as	O
well	O
as	O
the	O
dendrogram	B-Application
go	O
to	O
files	O
with	O
.aln	O
and	O
.dnd	O
extensions	O
respectively	O
.	O
</s>
<s>
ClustalW	B-Application
like	O
the	O
other	O
Clustal	B-Application
tools	O
is	O
used	O
for	O
aligning	O
multiple	O
nucleotide	O
or	O
protein	O
sequences	O
in	O
an	O
efficient	O
manner	O
.	O
</s>
<s>
ClustalW	B-Application
is	O
a	O
matrix-based	O
algorithm	O
,	O
whereas	O
tools	O
like	O
T-Coffee	B-Application
and	O
Dialign	B-Application
are	O
consistency-based	O
.	O
</s>
<s>
ClustalW	B-Application
has	O
a	O
fairly	O
efficient	O
algorithm	O
that	O
competes	O
well	O
against	O
other	O
software	O
.	O
</s>
<s>
This	O
program	O
requires	O
three	O
or	O
more	O
sequences	O
in	O
order	O
to	O
calculate	O
a	O
global	O
alignment	O
,	O
for	O
pairwise	O
sequence	B-Algorithm
alignment	I-Algorithm
(	O
only	O
two	O
sequences	O
)	O
other	O
tools	O
such	O
as	O
EMBOSS	B-Application
or	O
should	O
be	O
used	O
.	O
</s>
<s>
ClustalW	B-Application
uses	O
progressive	O
alignment	O
methods	O
as	O
stated	O
above	O
.	O
</s>
<s>
This	O
heuristic	B-Algorithm
approach	O
is	O
necessary	O
due	O
to	O
the	O
time	O
and	O
memory	O
demand	O
of	O
finding	O
the	O
global	O
optimal	O
solution	O
.	O
</s>
<s>
The	O
first	O
step	O
to	O
the	O
algorithm	O
is	O
computing	O
a	O
rough	O
distance	O
matrix	O
between	O
each	O
pair	O
of	O
sequences	O
,	O
also	O
known	O
as	O
pairwise	O
sequence	B-Algorithm
alignment	I-Algorithm
.	O
</s>
<s>
The	O
next	O
step	O
is	O
a	O
neighbor-joining	B-Algorithm
method	I-Algorithm
that	O
uses	O
midpoint	O
rooting	O
to	O
create	O
an	O
overall	O
guide	O
tree	O
.	O
</s>
<s>
ClustalW	B-Application
has	O
a	O
time	O
complexity	O
of	O
because	O
of	O
its	O
use	O
of	O
the	O
neighbor-joining	B-Algorithm
method	I-Algorithm
.	O
</s>
<s>
In	O
the	O
updated	O
version	O
(	O
ClustalW2	O
)	O
there	O
is	O
an	O
option	O
built	O
into	O
the	O
software	O
to	O
use	O
UPGMA	B-Algorithm
which	O
is	O
faster	O
with	O
large	O
input	O
sizes	O
.	O
</s>
<s>
The	O
command	O
line	O
flag	O
in	O
order	O
to	O
use	O
it	O
instead	O
of	O
neighbor-joining	B-Algorithm
is:For	O
example	O
,	O
on	O
a	O
standard	O
desktop	O
,	O
running	O
UPGMA	B-Algorithm
on	O
10,000	O
sequences	O
would	O
produce	O
results	O
in	O
less	O
than	O
a	O
minute	O
while	O
neighbor-joining	B-Algorithm
would	O
take	O
over	O
an	O
hour	O
.	O
</s>
<s>
By	O
running	O
the	O
ClustalW	B-Application
algorithm	O
with	O
this	O
adjustment	O
,	O
it	O
saves	O
significant	O
amounts	O
of	O
time	O
.	O
</s>
<s>
The	O
algorithm	O
ClustalW	B-Application
uses	O
provides	O
a	O
nearly	O
optimal	O
result	O
.	O
</s>
<s>
ClustalW	B-Application
was	O
one	O
of	O
the	O
first	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
algorithms	O
to	O
combine	O
pairwise	B-Algorithm
alignment	I-Algorithm
and	O
global	O
alignment	O
to	O
increase	O
speed	O
,	O
but	O
this	O
trade-off	O
results	O
in	O
decreased	O
accuracy	O
.	O
</s>
<s>
ClustalW	B-Application
,	O
when	O
compared	O
to	O
other	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
algorithms	O
in	O
2014	O
,	O
performed	O
as	O
one	O
of	O
the	O
quickest	O
while	O
still	O
maintaining	O
an	O
acceptable	O
level	O
of	O
accuracy	O
,	O
but	O
there	O
was	O
room	O
for	O
improvement	O
compared	O
to	O
consistency-based	O
competitors	O
such	O
as	O
T-Coffee	B-Application
.	O
</s>
<s>
The	O
accuracy	O
of	O
ClustalW	B-Application
when	O
tested	O
against	O
MAFFT	B-Application
,	O
T-Coffee	B-Application
,	O
Clustal	B-Application
Omega	I-Application
,	O
and	O
other	O
algorithms	O
was	O
the	O
lowest	O
for	O
full-length	O
sequences	O
,	O
but	O
still	O
considered	O
acceptable	O
.	O
</s>
<s>
It	O
had	O
the	O
most	O
memory	O
(	O
RAM	B-Architecture
)	O
efficient	O
algorithm	O
out	O
of	O
all	O
those	O
tested	O
in	O
the	O
study	O
.	O
</s>
<s>
ClustalΩ	B-Application
(	O
alternatively	O
written	O
as	O
Clustal	B-Application
O	O
and	O
Clustal	B-Application
Omega	I-Application
)	O
is	O
a	O
fast	O
and	O
scalable	O
program	O
written	O
in	O
C	O
and	O
C++	O
used	O
for	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
.	O
</s>
<s>
The	O
program	O
requires	O
three	O
or	O
more	O
sequences	O
in	O
order	O
to	O
calculate	O
the	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
,	O
for	O
two	O
sequences	O
use	O
pairwise	O
sequence	B-Algorithm
alignment	I-Algorithm
tools	O
(	O
EMBOSS	B-Application
,	O
)	O
.	O
</s>
<s>
Clustal	B-Application
Omega	I-Application
is	O
consistency-based	O
and	O
is	O
widely	O
viewed	O
as	O
one	O
of	O
the	O
fastest	O
online	O
implementations	O
of	O
all	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
tools	O
and	O
still	O
ranks	O
high	O
in	O
accuracy	O
,	O
among	O
both	O
consistency-based	O
and	O
matrix-based	O
algorithms	O
.	O
</s>
<s>
Clustal	B-Application
Omega	I-Application
has	O
five	O
main	O
steps	O
in	O
order	O
to	O
generate	O
the	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
.	O
</s>
<s>
The	O
first	O
is	O
producing	O
a	O
pairwise	B-Algorithm
alignment	I-Algorithm
using	O
the	O
k-tuple	O
method	O
,	O
also	O
known	O
as	O
the	O
word	O
method	O
.	O
</s>
<s>
This	O
,	O
in	O
summary	O
,	O
is	O
a	O
heuristic	B-Algorithm
method	O
that	O
is	O
n't	O
guaranteed	O
to	O
find	O
an	O
optimal	O
alignment	O
solution	O
,	O
but	O
is	O
significantly	O
more	O
efficient	O
than	O
the	O
dynamic	O
programming	O
method	O
of	O
alignment	O
.	O
</s>
<s>
This	O
step	O
is	O
followed	O
by	O
the	O
k-means	B-Algorithm
clustering	I-Algorithm
method	I-Algorithm
.	O
</s>
<s>
Next	O
,	O
the	O
guide	O
tree	O
is	O
constructed	O
using	O
the	O
UPGMA	B-Algorithm
method	I-Algorithm
.	O
</s>
<s>
This	O
is	O
shown	O
as	O
multiple	O
guide	O
tree	O
steps	O
leading	O
into	O
one	O
final	O
guide	O
tree	O
construction	O
because	O
of	O
the	O
way	O
the	O
UPGMA	B-Algorithm
algorithm	O
works	O
.	O
</s>
<s>
In	O
the	O
final	O
step	O
,	O
the	O
multiple	O
sequence	B-Algorithm
alignment	I-Algorithm
is	O
produced	O
using	O
HHAlign	O
package	O
from	O
the	O
HH-Suite	B-Application
,	O
which	O
uses	O
two	O
profile	O
HMM	O
's	O
.	O
</s>
<s>
Clustal	B-Application
Omega	I-Application
uses	O
a	O
modified	O
version	O
of	O
mBed	O
which	O
has	O
a	O
complexity	O
of	O
,	O
and	O
produces	O
guide	O
trees	O
that	O
are	O
just	O
as	O
accurate	O
as	O
those	O
from	O
conventional	O
methods	O
.	O
</s>
<s>
The	O
speed	O
and	O
accuracy	O
of	O
the	O
guide	O
trees	O
in	O
Clustal	B-Application
Omega	I-Application
is	O
attributed	O
to	O
the	O
implementation	O
of	O
a	O
modified	O
mBed	O
algorithm	O
.	O
</s>
<s>
The	O
accuracy	O
of	O
Clustal	B-Application
Omega	I-Application
on	O
a	O
small	O
number	O
of	O
sequences	O
is	O
,	O
on	O
average	O
,	O
very	O
similar	O
to	O
what	O
are	O
considered	O
high	O
quality	O
sequence	O
aligners	O
.	O
</s>
<s>
In	O
these	O
cases	O
,	O
Clustal	B-Application
Omega	I-Application
outperforms	O
other	O
algorithms	O
across	O
the	O
board	O
.	O
</s>
<s>
Clustal	B-Application
Omega	I-Application
uses	O
the	O
HHAlign	O
package	O
of	O
the	O
HH-Suite	B-Application
,	O
which	O
aligns	O
two	O
profile	O
Hidden	O
Markov	O
Models	O
instead	O
of	O
a	O
profile-profile	O
comparison	O
.	O
</s>
<s>
This	O
,	O
combined	O
with	O
the	O
mBed	O
method	O
,	O
gives	O
Clustal	B-Application
Omega	I-Application
its	O
advantage	O
over	O
other	O
sequence	O
aligners	O
.	O
</s>
<s>
On	O
data	O
sets	O
with	O
nonconserved	O
terminal	O
bases	O
,	O
Clustal	B-Application
Omega	I-Application
may	O
be	O
more	O
accurate	O
than	O
Probcons	O
and	O
T-Coffee	B-Application
despite	O
the	O
fact	O
that	O
both	O
of	O
these	O
are	O
consistency-based	O
algorithms	O
,	O
in	O
contrast	O
to	O
Clustal	B-Application
Omega	I-Application
.	O
</s>
<s>
On	O
an	O
efficiency	O
test	O
with	O
programs	O
that	O
produce	O
high	O
accuracy	O
scores	O
,	O
MAFFT	B-Application
was	O
the	O
fastest	O
,	O
closely	O
followed	O
by	O
Clustal	B-Application
Omega	I-Application
.	O
</s>
<s>
Both	O
were	O
faster	O
than	O
T-Coffee	B-Application
,	O
however	O
,	O
MAFFT	B-Application
and	O
Clustal	B-Application
Omega	I-Application
required	O
more	O
memory	O
to	O
run	O
.	O
</s>
<s>
is	O
the	O
packaged	O
release	O
of	O
both	O
the	O
command-line	O
ClustalW	B-Application
and	O
graphical	O
Clustal	B-Application
X	B-Operating_System
.	O
</s>
<s>
Both	O
downloads	O
come	O
precompiled	O
for	O
many	O
operating	O
systems	O
like	O
Linux	B-Application
,	O
Mac	B-Device
OS	O
X	B-Operating_System
and	O
Windows	O
(	O
both	O
XP	O
and	O
Vista	O
)	O
.	O
</s>
<s>
Clustal2	O
is	O
version	O
2	O
of	O
both	O
ClustalW	B-Application
and	O
ClustalX	B-Application
,	O
which	O
is	O
where	O
it	O
gets	O
its	O
name	O
.	O
</s>
