NAME¶
ncbi-seg - segment sequence(s) by local complexity
SYNOPSIS¶
ncbi-seg sequence [ W ] [ K(1) ] [ K(2) ] [ -x ] [ options ]
DESCRIPTION¶
ncbi-seg divides sequences into contrasting segments of low-complexity and
high-complexity. Low-complexity segments defined by the algorithm represent
"simple sequences" or "compositionally-biased regions".
Locally-optimized low-complexity segments are produced at defined levels of
stringency, based on formal definitions of local compositional complexity
(Wootton & Federhen, 1993). The segment lengths and the number of segments
per sequence are determined automatically by the algorithm.
The input is a FASTA-formatted sequence file, or a database file containing many
FASTA-formatted sequences. ncbi-seg is tuned for amino acid sequences. For
nucleotide sequences, see EXAMPLES OF PARAMETER SETS below.
The stringency of the search for low-complexity segments is determined by three
user-defined parameters, trigger window length [ W ], trigger complexity [
K(1) ] and extension complexity [ K(2)] (see below under PARAMETERS ). The
defaults provided are suitable for low-complexity masking of database search
query sequences [ -x option required, see below].
OUTPUTS AND APPLICATIONS¶
(1) Readable segmented sequence [Default]. Regions of contrasting complexity are
displayed in "tree format". See EXAMPLES.
(2) Low-complexity masking (see Altschul et al, 1994). Produce a masked
FASTA-formatted file, ready for input as a query sequence for database search
programs such as BLAST or FASTA. The amino acids in low-complexity regions are
replaced with "x" characters [-x option]. See EXAMPLES.
(3) Database construction. Produce FASTA-formatted files containing
low-complexity segments [-l option], or high-complexity segments [-h option],
or both [-a option]. Each segment is a separate sequence entry with an
informative header line.
ALGORITHM¶
The SEG algorithm has two stages. First, identification of approximate raw
segments of low- complexity; second local optimization.
At the first stage, the stringency and resolution of the search for
low-complexity segments is determined by the W, K(1) and K(2) parameters. All
trigger windows are defined, including overlapping windows, of length W and
complexity less than or equal to K(1). "Complexity" here is defined
by equation (3) of Wootton & Federhen (1993). Each trigger window is then
extended into a contig in both directions by merging with extension windows,
which are overlapping windows of length W and complexity less than or equal to
K(2). Each contig is a raw segment.
At the second stage, each raw segment is reduced to a single optimal
low-complexity segment, which may be the entire raw segment but is usually a
subsequence. The optimal subsequence has the lowest value of the probability
P(0) (equation (5) of Wootton & Federhen, 1993).
PARAMETERS¶
These three numeric parameters are in obligatory order after the sequence file
name.
Trigger window length [ W ]. An integer greater than zero [ Default 12 ].
Trigger complexity. [ K1 ]. The maximum complexity of a trigger window in units
of bits. K1 must be equal to or greater than zero. The maximum value is 4.322
(log[base 2]20) for amino acid sequences [ Default 2.2 ].
Extension complexity [ K2 ]. The maximum complexity of an extension window in
units of bits. Only values greater than K1 are effective in extending
triggered windows. Range of possible values is as for K1 [ Default 2.5 ].
OPTIONS¶
The following options may be placed in any order in the command line after the
W, K1 and K2 parameters:
- -a
- Output both low-complexity and high-complexity segments in a
FASTA-formatted file, as a set of separate entries with header lines.
- -c [characters-per-line]
- Number of sequence characters per line of output [Default 60]. Other
characters, such as residue numbers, are additional.
- -h
- Output only the high-complexity segments in a FASTA-formatted file, as a
set of separate entries with header lines.
- -l
- Output only the low-complexity segments in a FASTA-formatted file, as a
set of separate entries with header lines.
- -m [length]
- Minimum length in residues for a high-complexity segment [default 0].
Shorter segments are merged with adjacent low-complexity segments.
- -o
- Show all overlapping, independently-triggered low-complexity segments
[these are merged by default].
- -q
- Produce an output format with the sequence in a numbered block with
markings to assist residue counting. The low-complexity and
high-complexity segments are in lower- and upper-case characters
respectively.
- -t [length]
- "Maximum trim length" parameter [default 100]. This controls the
search space (and search time) during the optimization of raw segments
(see ALGORITHM above). By default, subsequences 100 or more residues
shorter than the raw segment are omitted from the search. This parameter
may be increased to give a more extensive search if raw segments are
longer than 100 residues.
- -x
- The masking option for amino acid sequences. Each input sequence is
represented by a single output sequence in FASTA-format with
low-complexity regions replaced by strings of "x"
characters.
EXAMPLES OF PARAMETER SETS¶
Default parameters are given by 'ncbi-seg sequence' (equivalent to 'ncbi-seg
sequence 12 2.2 2.5'). These parameters are appropriate for low- complexity
masking of many amino acid sequences [with -x option ].
Database-database comparisons:¶
More stringent (lower) complexity parameters are suitable when masked sequences
are compared with masked sequences. For example, for BLAST or FASTA searches
that compare two amino acid sequence databases, the following masking may be
applied to both databases:
ncbi-seg database 12 1.8 2.0 -x
Homopolymer analysis:¶
To examine all homopolymeric subsequences of length (for example) 7 or greater:
ncbi-seg sequence 7 0 0
Non-globular regions of protein sequences:¶
Many long non-globular domains may be diagnosed at longer window lengths,
typically:
ncbi-seg sequence 45 3.4 3.75
For some shorter non-globular domains, the following set is appropriate:
ncbi-seg sequence 25 3.0 3.3
Nucleotide sequences:¶
The maximum value of the complexity parameters is 2 (log[base 2]4). For masking,
the following is approximately equivalent in effect to the default parameters
for amino acid sequences:
ncbi-seg sequence.na 21 1.4 1.6
EXAMPLES¶
The following is a file named 'prion' in FASTA format:
>PRIO_HUMAN MAJOR PRION PROTEIN PRECURSOR
MANLGCWMLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQP
HGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHSQWNKPSKPKTNMKHMAGAAAAGA
VVGGLGGYMLGSAMSRPIIHFGSDYEDRYYRENMHRYPNQVYYRPMDEYSNQNNFVHDCV
NITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYERESQAYYQRGSSMVLFSSPPV
ILLISFLIFLIVG
The command line:
ncbi-seg /usr/share/doc/ncbi-seg/examples/prion.fa
gives the standard output below
>PRIO_HUMAN MAJOR PRION PROTEIN PRECURSOR
1-49 MANLGCWMLVLFVATWSDLGLCKKRPKPGG
WNTGGSRYPGQGSPGGNRY
ppqggggwgqphgggwgqphgggwgqphgg 50-94
gwgqphgggwgqggg
95-112 THSQWNKPSKPKTNMKHM
agaaaagavvgglggymlgsams 113-135
136-187 RPIIHFGSDYEDRYYRENMHRYPNQVYYRP
MDEYSNQNNFVHDCVNITIKQH
tvttttkgenftet 188-201
202-236 DVKMMERVVEQMCITQYERESQAYYQRGSS
MVLFS
sppvillisflifliv 237-252
253-253 G
The low-complexity sequences are on the left (lower case) and high-complexity
sequences are on the right (upper case). All sequence segments read from left
to right and their order in the sequence is from top to bottom, as shown by
the central column of residue numbers.
The command line:
ncbi-seg /usr/share/doc/ncbi-seg/examples/prion.fa -x
gives the following FASTA-formatted file:-
>PRIO_HUMAN MAJOR PRION PROTEIN PRECURSOR
MANLGCWMLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxTHSQWNKPSKPKTNMKHMxxxxxxxx
xxxxxxxxxxxxxxxRPIIHFGSDYEDRYYRENMHRYPNQVYYRPMDEYSNQNNFVHDCV
NITIKQHxxxxxxxxxxxxxxDVKMMERVVEQMCITQYERESQAYYQRGSSMVLFSxxxx
xxxxxxxxxxxxG
SEE ALSO¶
segn(1),
blast(1),
saps(1),
xnu(1)
AUTHORS¶
John Wootton: wootton@ncbi.nlm.nih.gov
Scott Federhen: federhen@ncbi.nlm.nih.gov
National Center for Biotechnology Information
Building 38A, Room 8N805
National Library of Medicine
National Institutes of Health
Bethesda, Maryland, MD 20894
U.S.A.
PRIMARY REFERENCE¶
Wootton, J.C., Federhen, S. (1993) Statistics of local complexity in amino acid
sequences and sequence databases. Computers & Chemistry 17: 149-163.
OTHER REFERENCES¶
Wootton, J.C. (1994) Non-globular domains in protein sequences: automated
segmentation using complexity measures. Computers & Chemistry 18: (in
press).
Altschul, S.F., Boguski, M., Gish, W., Wootton, J.C. (1994) Issues in searching
molecular sequence databases. Nature Genetics 6: 119-129.
Wootton, J.C. (1994) Simple sequences of protein and DNA. In: Nucleic Acid and
Protein Sequence Analysis: A Practical Approach. (Second Edition, Chapter 8,
Bishop, M.J. and Rawlings, C.R. Eds. IRL Press, Oxford) (In press).