Affiliations: Friedrich-Schiller-Universität Jena, Institute of
Computer Science, Chair for Bioinformatics Ernst-Abbe-Platz 1-4, D-07743 Jena,
Germany. E-mail: {hiller, backofen, busch}@inf.uni-jena.de | Humboldt-Universität zu Berlin, Institute of
Computer Science Unter den Linden 6, D-10099 Berlin, Germany. E-mail:
{heymann, glaesser, freytag}@dbis.informatik.hu-berlin.de
Note: [] These authors contribute equally to this work
Note: [] These authors contribute equally to this work
Note: [] These authors contribute equally to this work
Abstract: Alternative splicing can yield manifold different mature mRNAs from
one precursor. New findings indicate that alternative splicing occurs much more
often than previously assumed. A major goal of functional genomics lies in
elucidating and characterizing the entire spectrum of alternative splice
forms. Existing approaches such as EST-alignments focus only on the mRNA
sequence to detect alternative splice forms. They do not consider function and
characteristics of the resulting proteins. One important example of such
functional characterization is homology to a known protein domain family. A
powerful description of protein domains are profile Hidden Markov models (HMM)
as stored in the Pfam database. In this paper we address the problem of identifying the splice form
with the highest similarity to a protein domain family. Therefore, we take into
consideration all possible splice forms. As demonstrated here for a number of
genes, this homology based approach can be used successfully for predicting
partial gene structures. Furthermore, we present some novel splice form
predictions with high-scoring protein domain homology and point out that the
detection of splice form specific protein domains helps to answer questions
concerning hereditary diseases. Simple approaches based on a BLASTP search cannot be applied here,
since the number of possible splice forms increases exponentially with the
number of exons. To this end, we have developed an efficient polynomial-time
algorithm, called ASFPred (Alternative Splice Form Prediction). This algorithm
needs only a set of exons as input.
Keywords: alternative splicing, novel splice forms, pfam, protein domain, viterbi algorithm, profile HMM, gene prediction
