.\" $Id$
.\" Christian Iseli, LICR ITO, Christian.Iseli@licr.org
.\"
.\" Copyright (c) 2004-2006 Swiss Institute of Bioinformatics.
.\"
.TH SIBsim4 1 "January 2006" Bioinformatics "User Manuals"
.SH NAME
SIBsim4 \- align RNA sequences with a DNA sequence, allowing for introns
.SH SYNOPSIS
.B SIBsim4 [
.I options
.B ]
.I dna rna_db
.SH DESCRIPTION
.B SIBsim4
is a similarity-based tool for aligning a collection of expressed
sequences (EST, mRNA) with a genomic DNA sequence. 

Launching
.B SIBsim4
without any arguments will print the options list, along with their
default values.

.B SIBsim4
employs a blast-based technique to first determine the basic
matching blocks representing the "exon cores".  In this first stage, it
detects all possible exact matches of W-mers (i.e., DNA words of size
W) between the two sequences and extends them to maximal scoring
gap-free segments.  In the second stage, the exon cores are extended
into the adjacent as-yet-unmatched fragments using greedy alignment
algorithms, and heuristics are used to favor configurations that
conform to the splice-site recognition signals (e.g., GT-AG). If
necessary, the process is repeated with less stringent parameters on
the unmatched fragments.

By default,
.B SIBsim4
searches both strands and reports the best matches,
measured by the number of matching nucleotides found in the alignment.
The
.B R
command line option can be used to restrict the search to one
orientation (strand) only.

Currently, four major alignment display options are supported,
controlled by the
.B A
option. By default, only the endpoints, overall similarity, and
orientation of the introns are reported. An arrow sign ('->' or '<-')
indicates the orientation of the intron.  The sign `==' marks the
absence from the alignment of a cDNA fragment starting at that
position.

In the description below, the term
.B MSP
denotes a maximal scoring pair, that is, a pair of highly similar
fragments in the two sequences, obtained during the blast-like
procedure by extending a W-mer hit by matches and perhaps a few
mismatches. 

.SH OPTIONS
.IP "-A <int>"
output format
  0: exon endpoints only
  1: alignment text
  3: both exon endpoints and alignment text
  4: both exon endpoints and alignment text with polyA info

Note that 2 is unimplemented.

Default value is 0.
.IP "-C <int>"
MSP score threshold for the second pass.

Default value is 12.
.IP "-c <int>"
minimum score cutoff value.  Alignments which have scores below this value
are not reported.

Default value is 50.
.IP "-E <int>"
cutoff value.

Default value is 3.
.IP "-f <int>"
score filter in percent.  When multiple hits are detected for the same RNA
element, only those having a score within this percentage of the maximal
score for that RNA element are reported.  Setting this value to 0 disables
filtering and all hits will be reported, provided their score is above the
cutoff value specified through the
.B c
option.

Default value is 75.
.IP "-g <int>"
join exons when gap on genomic and RNA have lengths which
differ at most by this percentage.

Default value is 10.
.IP "-I <int>"
window width in which to search for intron splicing.

Default value is 6.
.IP "-K <int>"
MSP score threshold for the first pass.

Default value is 16.
.IP "-L <str>"
a comma separated list of forward splice-types.

Default value is "GTAG,GCAG,GTAC,ATAC".
.IP "-M <int>"
scoring splice sites, evaluate match within M nucleotides.

Default value is 10.
.IP "-o <int>"
when printing results, offset nt positions in dna sequence by this amount.

Default value is 0.
.IP "-q <int>"
penalty for a nucleotide mismatch.

Default value is -5.
.IP "-R <int>"
direction of search
  0: search the '+' (direct) strand only
  1: search the '-' strand only
  2: search both strands

Default value is 2.
.IP "-r <int>"
reward for a nucleotide match.

Default value is 1.
.IP "-W <int>"
word size.

Default value is 12.
.IP "-X <int>"
value for terminating word extensions.

Default value is 12.