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iSplice is
a web-based tool utilizing GO algorithm to assess the likelihood for a cryptic 5' splice site to become activated in competing
with a 5' splice site selection. In iSplice, three major functions are described in the followings.
Search
iSplice contains carefully curated and
integrated annotations of human mutations and associated splicing information
in hyperlinks. Initially included are 215
paired data of human authentic and cryptic 5' splice sites, consisting of 215
activated cases, for the purpose of jumpstarting this
system. While we will be striving to add more useful records, we also provide a
function (see "Submit" below) to allow users submitting their own
splicing information (for human or related organisms), which will be
incorporated into our system subject to internal validation.
As
its current form, iSplice requires users to choose one gene from a listed gene names
and designate one mutant type. The system then outputs related mutant splicing information, including the sequences at the authentic and
cryptic 5' splice
sites.
Based on these (see "Analyze/Mutation" below), the users can then interactively investigate various splicing events by choosing
a mixture of point mutations in their mutagenesis experiments.
Analyze
1.Pair_data
(a) Input data
A paired sequences containing an authentic 5' splice site and a cryptic 5' splice site of interest.
(b) Output data
A delta GO
score suggesting whether the queried
cryptic 5' splice site is activated or not.
2.Mutation
(a) Input data
A paired sequences containing an authentic 5' splice site and a cryptic 5' splice site of interest.
The users have the option
of introducing point mutations on either the authentic or cryptic splice site
and assess the likelihood of whether the cryptic splice site is activated for
all permutations of authentic/cryptic 5' splice
site pairs based on the specified mixing of point mutations.
(b) Output data
A list of top-ranked
permutated pairs on how each of their cryptic splice sites will be activated
according to their scores subject to GO algorithm.
A graph showing scores and
ranking for all permuted pairs under investigation is also presented.
3. Sequence
(a) Input data
A
DNA (or RNA) sequence containing only one
authentic 5' splice site in FASTA format. A
list of cryptic splice site(s) associated with this authentic splice site is predicted
using GO algorithm, associated with the
function of introducing point mutations on either the authentic or
cryptic splice site and assess the likelihood of whether the cryptic splice site
is activated for all the permutated authentic/cryptic pairs.
(b) Output data
A list of scores of all permutated pairs suggesting whether the
individual cryptic 5' splice site is
activated or not.
Submit
To extend the
usage and accuracy of iSplice, users are encouraged to submit their own
activated cryptic 5' splice site information, which will be incorporated into our system subject to internal validation.
Datasets
Two sets of human mutation splicing sequence data were used for the development and evaluation of iSplice.