• Alternative splicing
• Cancer stem cell
• Expression analysis
• Stem cell
• Transcriptome

• microtubule-associated proteins
• microtubules
• neuronal complexity
• stathmins
• tau
• tubulin

• Alternative Splicing/genetics
• Animals
• Brain/metabolism
• Gene Expression Profiling
• Mice, Inbred Strains
• Organ Specificity/genetics
• RNA, Messenger/genetics
• Receptors, Opioid, mu/genetics
• Species Specificity

• R56 DA002615 NIDA NIH HHS
• DA13997 NIDA NIH HHS
• T32 DA007242 NIDA NIH HHS
• R01 DA006241 NIDA NIH HHS
• P30 CA008748 NCI NIH HHS
• R21 DA029244 NIDA NIH HHS
• R37 DA007242 NIDA NIH HHS
• CA08748 NCI NIH HHS
• R01 DA007242 NIDA NIH HHS
• DA06241 NIDA NIH HHS
• R01 DA002615 NIDA NIH HHS
• DA029244 NIDA NIH HHS
• R01 DA013997 NIDA NIH HHS
• DA02615 NIDA NIH HHS
• DA07242 NIDA NIH HHS

• Kraepelinian dichotomy
• ZNF804A
• alternative splicing
• bioinformatics
• bipolar disorder
• genome-wide association scan
• schizophrenia
• zinc-finger protein

Standard 3′ Affymetrix gene expression arrays have contributed a significantly higher volume of existing gene expression data than other microarray platforms. These arrays were designed to identify differentially expressed genes, but not their alternatively spliced transcript forms. No resource can currently identify expression pattern of specific mRNA forms using these microarray data, even though it is possible to do this.

We report a web server for expression profiling of alternatively spliced transcripts using microarray data sets from 31 standard 3′ Affymetrix arrays for human, mouse and rat species. The tool has been experimentally validated for mRNAs transcribed or not-detected in a human disease condition (non-obstructive azoospermia, a male infertility condition). About 4000 gene expression datasets were downloaded from a public repository. ‘Good probes’ with complete coverage and identity to latest reference transcript sequences were first identified. Using them, ‘Transcript specific probe-clusters’ were derived for each platform and used to identify expression status of possible transcripts. The web server can lead the user to datasets corresponding to specific tissues, conditions via identifiers of the microarray studies or hybridizations, keywords, official gene symbols or reference transcript identifiers. It can identify, in the tissues and conditions of interest, about 40% of known transcripts as ‘transcribed’, ‘not-detected’ or ‘differentially regulated’. Corresponding additional information for probes, genes, transcripts and proteins can be viewed too. We identified the expression of transcripts in a specific clinical condition and validated a few of these transcripts by experiments (using reverse transcription followed by polymerase chain reaction). The experimental observations indicated higher agreements with the web server results, than contradictions. The tool is accessible at http://resource.ibab.ac.in/TIPMaP.

The newly developed online tool forms a reliable means for identification of alternatively spliced transcript-isoforms that may be differentially expressed in various tissues, cell types or physiological conditions. Thus, by making better use of existing data, TIPMaP avoids the dependence on precious tissue-samples, in experiments with a goal to establish expression profiles of alternative splice forms – at least in some cases.

Prior to the completion of the human genome project, the human genome was thought to have a greater number of genes as it seemed structurally and functionally more complex than other simpler organisms. This along with the belief of “one gene, one protein”, were demonstrated to be incorrect. The inequality in the ratio of gene to protein formation gave rise to the theory of alternative splicing (AS). AS is a mechanism by which one gene gives rise to multiple protein products. Numerous databases and online bioinformatic tools are available for the detection and analysis of AS. Bioinformatics provides an important approach to study mRNA and protein diversity by various tools such as expressed sequence tag (EST) sequences obtained from completely processed mRNA. Microarrays and deep sequencing approaches also aid in the detection of splicing events. Initially it was postulated that AS occurred only in about 5% of all genes but was later found to be more abundant. Using bioinformatic approaches, the level of AS in human genes was found to be fairly high with 35-59% of genes having at least one AS form. Our ability to determine and predict AS is important as disorders in splicing patterns may lead to abnormal splice variants resulting in genetic diseases. In addition, the diversity of proteins produced by AS poses a challenge for successful drug discovery and therefore a greater understanding of AS would be beneficial.

• Alternative splicing (AS)
• Bioinformatics
• Database
• Expressed sequence tags (ESTs)
• Microarray
• Protein
• Splice variants.
• mRNA

• Alternative splicing
• High-throughput sequencing
• RNA-seq
• Transcript isoform

During alternative splicing, the inclusion of an exon in the final mRNA molecule is determined by nuclear proteins that bind cis-regulatory sequences in a target pre-mRNA molecule. A recent study suggested that the regulatory codes of individual RNA-binding proteins may be nearly immutable between very diverse species such as mammals and insects. The model system Drosophila melanogaster therefore presents an excellent opportunity for the study of alternative splicing due to the availability of quality EST annotations in FlyBase.

In this paper, we describe an in silico analysis pipeline to extract putative exonic splicing regulatory sequences from a multiple alignment of 15 species of insects. Our method, ESTs-to-ESRs (E2E), uses graph analysis of EST splicing graphs to identify mutually exclusive (ME) exons and combines phylogenetic measures, a sliding window approach along the multiple alignment and the Welch's t statistic to extract conserved ESR motifs.

The most frequent 100% conserved word of length 5 bp in different insect exons was "ATGGA". We identified 799 statistically significant "spike" hexamers, 218 motifs with either a left or right FDR corrected spike magnitude p-value < 0.05 and 83 with both left and right uncorrected p < 0.01. 11 genes were identified with highly significant motifs in one ME exon but not in the other, suggesting regulation of ME exon splicing through these highly conserved hexamers. The majority of these genes have been shown to have regulated spatiotemporal expression. 10 elements were found to match three mammalian splicing regulator databases. A putative ESR motif, GATGCAG, was identified in the ME-13b but not in the ME-13a of Drosophila N-Cadherin, a gene that has been shown to have a distinct spatiotemporal expression pattern of spliced isoforms in a recent study.

Analysis of phylogenetic relationships and variability of sequence conservation as implemented in the E2E spikes method may lead to improved identification of ESRs. We found that approximately half of the putative ESRs in common between insects and mammals have a high statistical support (p < 0.01). Several Drosophila genes with spatiotemporal expression patterns were identified to contain putative ESRs located in one exon of the ME exon pairs but not in the other.

We herein describe an integrated system for the high-throughput analysis of splicing events and the identification of transcript variants. The system resolves individual splicing events and elucidates transcript variants via a pipeline that combines aspects such as bioinformatic analysis, high-throughput transcript variant amplification, and high-resolution capillary electrophoresis. For the 14 369 human genes known to have transcript variants, minimal primer sets were designed to amplify all transcript variants and examine all splicing events; these have been archived in the ASprimerDB database, which is newly described herein. A high-throughput thermocycler, dubbed GenTank, was developed to simultaneously perform thousands of PCR amplifications. Following the resolution of the various amplicons by capillary gel electrophoresis, two new computer programs, AmpliconViewer and VariantAssembler, may be used to analyze the splicing events, assemble the consecutive exons embodied by the PCR amplicons, and distinguish expressed versus putative transcript variants. This novel system not only facilitates the validation of putative transcript variants and the detection of novel transcript variants, it also semi-quantitatively measures the transcript variant expression levels of each gene. To demonstrate the system’s capability, we used it to resolve transcript variants yielded by single and multiple splicing events, and to decipher the exon connectivity of long transcripts.

Alternative transcript diversity manifests itself as a prime cause of complexity in higher eukaryotes. Recently, transcript diversity studies have suggested that 60–80% of human genes are alternatively spliced. We have used a splicing pattern approach for the bioinformatics analysis of Alternative Splicing (AS) in chicken, human and mouse. Exons involved in splicing are subdivided into distinct and variant exons, based on the prevalence of the exons across the transcripts. Four possible permutations of these two different groups of exons were categorised as class I (distinct-variant), class II (distinct-variant), class III (variant-distinct) and class IV (variant-variant). This classification quantifies the variation in transcript diversity in the three species.

In all, 3901 chicken AS genes have been compared with 16,715 human and 16,491 mouse AS genes, with 23% of chicken genes being alternatively spliced, compared to 68% in humans and 57% in mice. To minimize any gene structure bias in the input data, comparative genome analysis has been carried out on the orthologous subset of AS genes for the three species. Gene-level analysis suggested that chicken genes show fewer AS events compared to human and mouse. An event-level analysis showed that the percentage of AS events in chicken is similar to that of human, which implies that a smaller number of chicken genes show greater transcript diversity. Overall, chicken genes were found to have fewer transcripts per gene and shorter introns than human and mouse genes.

In chicken, the majority of genes generate only two or three isoforms, compared to almost eight in human and six in mouse. We observed that intron definition is expressed strongly when compared to exon definition for chicken genome, based on 3% intron retention in chicken, compared to 2% in human and mouse. Splicing patterns with variant exons account for 33% of AS chicken orthologous genes compared to 24% in human and 27% in mouse, providing a novel measure to describe the species-wise complexity due to alternative transcript diversity.

Alternative splicing generates an enormous amount of functional and proteomic diversity in metazoan organisms. This process is probably central to the macromolecular and cellular complexity of higher eukaryotes. While most studies have focused on the molecular mechanism triggering and controlling alternative splicing, as well as on its incidence in different species, its maintenance and evolution within populations has been little investigated. Here, we propose to address these questions by comparing the structural characteristics as well as the functional and transcriptional profiles of genes with monomorphic or polymorphic splicing, referred to as MS and PS genes, respectively. We find that MS and PS genes differ particularly in the number of tissues and cell types where they are expressed.We find a striking deficit of PS genes on the sex chromosomes, particularly on the Y chromosome where it is shown not to be due to the observed lower breadth of expression of genes on that chromosome. The development of a simple model of evolution of cis-regulated alternative splicing leads to predictions in agreement with these observations. It further predicts the conditions for the emergence and the maintenance of cis-regulated alternative splicing, which are both favored by the tissue specific expression of splicing variants. We finally propose that the width of the gene expression profile is an essential factor for the acquisition of new transcript isoforms that could later be maintained by a new form of balancing selection.

Carnitine acetyltransferase (CRAT) is an important enzyme for energy homeostasis and fat metabolism. We characterized the predicted full length cDNA sequence of the porcine CRAT gene. Its structure is very similar to that in humans with respect to the size and organization of the 14 exons. We demonstrated the existence of a porcine alternative transcript resulting from a partial intron-retention at the 5’ end of exon 2. To perform a comparison of the 5’ end variants of the mammalian CRAT gene, we analyzed the Genbank data, and here we propose a new 5’ variant for dog, rat and mouse. In contrast to other mammals where this variant encodes a shorter protein (−21 aa in human, mouse and rat, and −14 aa in dog), the pig variant encodes for a longer protein (+18 aa). In all mammalian species, variant 1 has a high probability of a preferential mitochondrial sub-cellular localization. Nevertheless, it is not evident, in particular in porcine and dog species, that the second variant is associated with a different sub-cellular specificity.

• Alternative Splicing
• Electronic Data Processing/methods
• Expressed Sequence Tags
• Genome, Human
• Humans
• RNA Precursors/genetics
• Sequence Analysis, DNA/methods

• U54 RR021813 NCRR NIH HHS

• Alternative Splicing/genetics
• Computational Biology
• Gene Expression Regulation/genetics
• Regulatory Sequences, Nucleic Acid/genetics

In the process of establishing more and more complete annotations of eukaryotic genomes, a constantly growing number of alternative splicing (AS) events has been reported over the last decade. Consequently, the increasing transcript coverage also revealed the real complexity of some variations in the exon–intron structure between transcript variants and the need for computational tools to address ‘complex’ AS events. ASTALAVISTA (alternative splicing transcriptional landscape visualization tool) employs an intuitive and complete notation system to univocally identify such events. The method extracts AS events dynamically from custom gene annotations, classifies them into groups of common types and visualizes a comprehensive picture of the resulting AS landscape. Thus, ASTALAVISTA can characterize AS for whole transcriptome data from reference annotations (GENCODE, REFSEQ, ENSEMBL) as well as for genes selected by the user according to common functional/structural attributes of interest: http://genome.imim.es/astalavista

• Alternative Splicing/genetics
• Chromosome Mapping/methods
• Computational Biology/methods
• DNA Probes/genetics
• Databases, Genetic
• Genome
• Humans
• Internet
• Oligonucleotide Array Sequence Analysis/instrumentation
• Oligonucleotide Array Sequence Analysis/methods
• RNA Splice Sites/genetics
• RNA, Messenger/metabolism
• Sequence Analysis, DNA/methods
• Software

• Algorithms
• Alternative Splicing
• Amino Acid Sequence
• Databases, Protein
• Exons
• Genetic Techniques
• Humans
• Introns
• Mass Spectrometry/methods
• Molecular Sequence Data
• Peptides/chemistry
• Peptides/genetics
• Polymorphism, Single Nucleotide
• Protein Array Analysis/methods
• Protein Array Analysis/statistics & numerical data
• Proteomics/methods
• Proteomics/statistics & numerical data
• Sequence Alignment

• R01 RR016522 NCRR NIH HHS
• C06 RR017588 NCRR NIH HHS
• P41 RR08605 NCRR NIH HHS
• RR016522-04A1 NCRR NIH HHS
• P41 RR008605 NCRR NIH HHS

• Algorithms
• Likelihood Functions
• Probability
• Sequence Analysis, Protein/methods
• Tandem Mass Spectrometry

• 1-R01-RR16522 NCRR NIH HHS

• tricarboxylic acid cycle (tcac)
• fumarate hydratase (fh)
• alternative exon
• hereditary leiomyomatosis and renal cell cancer (hlrcc)
• hypoxia
• heat shock
• stress

• Base Sequence
• Blotting, Western
• Cell Line
• DNA, Complementary
• Fluorescent Antibody Technique
• Fumarate Hydratase/genetics
• Gene Expression Regulation
• Humans
• Molecular Sequence Data
• Protein Biosynthesis
• Stress, Physiological/genetics
• Subcellular Fractions/enzymology

Recently, genomic sequencing efforts were finished for Oryza sativa (cultivated rice) and Arabidopsis thaliana (Arabidopsis). Additionally, these two plant species have extensive cDNA and expressed sequence tag (EST) libraries. We employed the Program to Assemble Spliced Alignments (PASA) to identify and analyze alternatively spliced isoforms in both species.

A comprehensive analysis of alternative splicing was performed in rice that started with >1.1 million publicly available spliced ESTs and over 30,000 full length cDNAs in conjunction with the newly enhanced PASA software. A parallel analysis was performed with Arabidopsis to compare and ascertain potential differences between monocots and dicots. Alternative splicing is a widespread phenomenon (observed in greater than 30% of the loci with transcript support) and we have described nine alternative splicing variations. While alternative splicing has the potential to create many RNA isoforms from a single locus, the majority of loci generate only two or three isoforms and transcript support indicates that these isoforms are generally not rare events. For the alternate donor (AD) and acceptor (AA) classes, the distance between the splice sites for the majority of events was found to be less than 50 basepairs (bp). In both species, the most frequent distance between AA is 3 bp, consistent with reports in mammalian systems. Conversely, the most frequent distance between AD is 4 bp in both plant species, as previously observed in mouse. Most alternative splicing variations are localized to the protein coding sequence and are predicted to significantly alter the coding sequence.

Alternative splicing is widespread in both rice and Arabidopsis and these species share many common features. Interestingly, alternative splicing may play a role beyond creating novel combinations of transcripts that expand the proteome. Many isoforms will presumably have negative consequences for protein structure and function, suggesting that their biological role involves post-transcriptional regulation of gene expression.

ECgene () was developed to provide functional annotation for alternatively spliced genes. The applications encompass the genome-based transcript modeling for alternative splicing (AS), domain analysis with Gene Ontology (GO) annotation and expression analysis based on the EST and SAGE data. We have expanded the ECgene's AS modeling and EST clustering to nine organisms for which sufficient EST data are available in the GenBank. As for the human genome, we have also introduced several new applications to analyze differential expression. ECprofiler is an ontology-based candidate gene search system that allows users to select an arbitrary combination of gene expression pattern and GO functional categories. DEGEST is a database of differentially expressed genes and isoforms based on the EST information. Importantly, gene expression is analyzed at three distinctive levels—gene, isoform and exon levels. The user interfaces for functional and expression analyses have been substantially improved. ASviewer is a dedicated java application that visualizes the transcript structure and functional features of alternatively spliced variants. The SAGE part of the expression module provides many additional features including SNP, differential expression and alternative tag positions.

• Alternative Splicing
• Animals
• Cluster Analysis
• Computer Graphics
• Databases, Genetic
• Dogs
• Drosophila melanogaster/genetics
• Exons
• Expressed Sequence Tags
• Gene Expression Profiling
• Genomics
• Humans
• Internet
• Mice
• Models, Genetic
• Protein Isoforms/genetics
• Protein Isoforms/metabolism
• RNA, Messenger/chemistry
• RNA, Messenger/metabolism
• Rats
• User-Computer Interface

• Bryopsida/genetics
• Bryopsida/metabolism
• Chromatography, Liquid
• Computational Biology/methods
• Cytokinins/metabolism
• Cytokinins/pharmacology
• Gene Expression Regulation, Plant/drug effects
• Phosphoproteins/genetics
• Phosphoproteins/isolation & purification
• Phosphoproteins/metabolism
• Phosphorylation
• Proteomics/methods
• Sequence Analysis, Protein
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

• Alternative Splicing
• Animals
• Expressed Sequence Tags
• Female
• Genomics/statistics & numerical data
• Humans
• Male
• Mice
• Pregnancy
• RNA, Messenger/genetics
• Software Design
• Species Specificity
• Tissue Distribution

• porphyromonas gingivalis
• gingival epithelial cells
• proteomics
• posttranslational modification
• protein expression
• invasion
• database search algorithm
• review
• mudpit

• Bacterial Proteins/chemistry
• Bacteroidaceae Infections/genetics
• Bacteroidaceae Infections/microbiology
• Chromatography, High Pressure Liquid
• Colony Count, Microbial
• Humans
• Mass Spectrometry/methods
• Porphyromonas gingivalis/genetics
• Porphyromonas gingivalis/pathogenicity
• Protein Processing, Post-Translational
• Proteomics/methods
• Reproducibility of Results

• R01 DE011111 NIDCR NIH HHS
• R37 DE011111 NIDCR NIH HHS
• R01 DE014372 NIDCR NIH HHS
• DE11111 NIDCR NIH HHS
• DE14372 NIDCR NIH HHS
• R01 DE014372-03 NIDCR NIH HHS
• R56 DE014372 NIDCR NIH HHS

• Active Transport, Cell Nucleus
• Adaptor Proteins, Signal Transducing/chemistry
• Adaptor Proteins, Signal Transducing/genetics
• Adaptor Proteins, Signal Transducing/metabolism
• Amino Acid Sequence
• CD4-Positive T-Lymphocytes/enzymology
• CD4-Positive T-Lymphocytes/immunology
• Cell Nucleus/metabolism
• Exons
• Gene Expression
• Humans
• Jurkat Cells
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism
• Molecular Sequence Data
• Phosphorylation
• Proline/analysis
• Protein Isoforms/chemistry
• Protein Isoforms/genetics
• Protein Isoforms/metabolism
• RNA, Messenger/metabolism
• Structure-Activity Relationship
• Tyrosine/metabolism
• src Homology Domains

• Alternative Splicing
• Computer Graphics
• Exons
• Humans
• Internet
• RNA Splice Sites
• Software
• User-Computer Interface

• Algorithms
• Alternative Splicing
• Chromosomes, Human, Pair 22
• Computer Simulation
• Expressed Sequence Tags
• HLA-D Antigens/genetics
• HLA-D Antigens/metabolism
• Humans
• Likelihood Functions
• Protein Isoforms/genetics
• Protein Isoforms/metabolism
• Tropomyosin/genetics
• Tropomyosin/metabolism

• U54 RR021813 NCRR NIH HHS
• U54-RR021813 NCRR NIH HHS

• Alternative Splicing
• Animals
• Humans
• Models, Molecular
• Protein Conformation
• Protein Isoforms/genetics
• Protein Isoforms/metabolism
• Proteins/chemistry
• Proteins/genetics
• Proteins/metabolism
• Transcription, Genetic/genetics

• R01 LM007688 NLM NIH HHS
• 5R01 LM 007688-02 NLM NIH HHS

• Amino Acid Sequence
• Base Sequence
• Brain/metabolism
• Cell Line
• DNA, Complementary/genetics
• DNA, Complementary/metabolism
• Exons/genetics
• Gene Expression Profiling
• Histidine/genetics
• Histidine/immunology
• Humans
• Jejunum/metabolism
• Membrane Potentials/genetics
• Membrane Potentials/physiology
• Microscopy, Confocal
• Molecular Sequence Data
• Myocardium/metabolism
• Nucleic Acid Conformation
• Potassium Channels, Voltage-Gated/genetics
• RNA/chemistry
• RNA/genetics
• Reverse Transcriptase Polymerase Chain Reaction
• Sequence Deletion
• Temperature
• Templates, Genetic
• Transcription, Genetic/genetics
• Transfection

• P01-DK-41315 NIDDK NIH HHS

• Alternative Splicing/genetics
• Chromosome Mapping/methods
• DNA Mutational Analysis/methods
• Genetic Variation/genetics
• Polyadenylation/genetics
• Software
• Transcription Factors/genetics

• Alternative Splicing
• Codon, Initiator/chemistry
• Computational Biology
• Databases, Nucleic Acid
• Exons
• Internet
• Regulatory Sequences, Ribonucleic Acid
• Sequence Analysis, RNA
• Systems Integration
• User-Computer Interface

Alternative splicing of the bcl-x gene generates two transcripts: the anti-apoptotic bcl-xL isoform and the pro-apoptotic bcl-xS isoform. The ratio between the two isoforms is a key factor in development and in cancer progression. Here, we show that a short antisense chimeric peptide nucleic acid (PNA) oligonucleotide conjugated to a polypeptide containing eight Ser-Arg repeats (SR)₈ can modulate splicing of bcl-x both in vitro and in vivo and induces apoptosis in HeLa cells. The PNA-SR oligo was targeted to a region of bcl-x that does not contain splicing regulatory sequences and was able to override the complex network of splicing enhancers and silencers that regulates the ratio between the two bcl-x isoforms. Thus, PNA-SR oligos are powerful tools that can potentially modulate splice site choice in endogenous genes independent of the presence of other splicing regulatory mechanisms on the target gene.

• Alternative Splicing
• Apoptosis
• HeLa Cells
• Humans
• Oligonucleotides, Antisense/chemistry
• Oligonucleotides, Antisense/pharmacology
• Peptide Nucleic Acids/chemistry
• Peptide Nucleic Acids/pharmacology
• RNA-Binding Proteins/metabolism
• Repetitive Sequences, Amino Acid
• bcl-X Protein/genetics
• bcl-X Protein/metabolism

• R01 AI052820 NIAID NIH HHS
• R01AI052820 NIAID NIH HHS
• R01AI052820-02S1 NIAID NIH HHS

• Alternative Splicing
• Amino Acid Sequence
• Animals
• Exons
• Humans
• Mice
• Molecular Sequence Data
• Phosphorylation
• Promoter Regions, Genetic
• RNA Precursors/genetics
• Rats
• Receptors, Opioid, mu/genetics
• Receptors, Opioid, mu/physiology

• R01 DA013997 NIDA NIH HHS
• DA00296 NIDA NIH HHS
• DA13997 NIDA NIH HHS

• Alternative Splicing
• Animals
• Drosophila/genetics
• Exons
• Genome, Human
• Humans
• Introns
• RNA Precursors/chemistry
• RNA Precursors/genetics

• R01 GM062287 NIGMS NIH HHS
• T32 GM007311 NIGMS NIH HHS
• GM 07311 NIGMS NIH HHS
• GM 62287 NIGMS NIH HHS

Currently available methods to predict splice sites are mainly based on the independent and progressive alignment of transcript data (mostly ESTs) to the genomic sequence. Apart from often being computationally expensive, this approach is vulnerable to several problems – hence the need to develop novel strategies.

We propose a method, based on a novel multiple genome-EST alignment algorithm, for the detection of splice sites. To avoid limitations of splice sites prediction (mainly, over-predictions) due to independent single EST alignments to the genomic sequence our approach performs a multiple alignment of transcript data to the genomic sequence based on the combined analysis of all available data. We recast the problem of predicting constitutive and alternative splicing as an optimization problem, where the optimal multiple transcript alignment minimizes the number of exons and hence of splice site observations.

We have implemented a splice site predictor based on this algorithm in the software tool ASPIC (Alternative Splicing PredICtion). It is distinguished from other methods based on BLAST-like tools by the incorporation of entirely new ad hoc procedures for accurate and computationally efficient transcript alignment and adopts dynamic programming for the refinement of intron boundaries. ASPIC also provides the minimal set of non-mergeable transcript isoforms compatible with the detected splicing events. The ASPIC web resource is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility.

Extensive bench marking shows that ASPIC outperforms other existing methods in the detection of novel splicing isoforms and in the minimization of over-predictions. ASPIC also requires a lower computation time for processing a single gene and an EST cluster. The ASPIC web resource is available at .

• Algorithms
• Animals
• Benchmarking
• Computers, Molecular
• Exons/genetics
• Gene Expression Profiling/methods
• Humans
• Introns/genetics
• Models, Molecular
• Sequence Alignment
• Software Design
• Software Validation

• GP0101Y01 Telethon

• Alternative Splicing
• Animals
• Base Sequence
• Conserved Sequence
• Databases, Nucleic Acid
• Dogs
• Exons
• Humans
• Mice
• Protein Structure, Tertiary
• Rats
• Reading Frames