SVM-based prediction of caspase substrate cleavage sites

BACKGROUND: Caspases belong to a class of cysteine proteases which function as critical effectors in apoptosis and inflammation by cleaving substrates immediately after unique sites. Prediction of such cleavage sites will complement structural and functional studies on substrates cleavage as well as discovery of new substrates. Recently, different computational methods have been developed to predict the cleavage sites of caspase substrates with varying degrees of success. As the support vector machines (SVM) algorithm has been shown to be useful in several biological classification problems, we have implemented an SVM-based method to investigate its applicability to this domain. RESULTS: A set of unique caspase substrates cleavage sites were obtained from literature and used for evaluating the SVM method. Datasets containing (i) the tetrapeptide cleavage sites, (ii) the tetrapeptide cleavage sites, augmented by two adjacent residues, P(1)' and P(2)' amino acids and (iii) the tetrapeptide cleavage sites with ten additional upstream and downstream flanking sequences (where available) were tested. The SVM method achieved an accuracy ranging from 81.25% to 97.92% on independent test sets. The SVM method successfully predicted the cleavage of a novel caspase substrate and its mutants. CONCLUSION: This study presents an SVM approach for predicting caspase substrate cleavage sites based on the cleavage sites and the downstream and upstream flanking sequences. The method shows an improvement over existing methods and may be useful for predicting hitherto undiscovered cleavage sites

A multi-factor model for caspase degradome prediction

<p>Abstract</p> <p>Background</p> <p>Caspases belong to a class of cysteine proteases which function as critical effectors in cellular processes such as apoptosis and inflammation by cleaving substrates immediately after unique tetrapeptide sites. With hundreds of reported substrates and many more expected to be discovered, the elucidation of the caspase degradome will be an important milestone in the study of these proteases in human health and disease. Several computational methods for predicting caspase cleavage sites have been developed recently for identifying potential substrates. However, as most of these methods are based primarily on the detection of the tetrapeptide cleavage sites - a factor necessary but not sufficient for predicting <it>in vivo </it>substrate cleavage - prediction outcomes will inevitably include many false positives.</p> <p>Results</p> <p>In this paper, we show that structural factors such as the presence of disorder and solvent exposure in the vicinity of the cleavage site are important and can be used to enhance results from cleavage site prediction. We constructed a two-step model incorporating cleavage site prediction and these factors to predict caspase substrates. Sequences are first predicted for cleavage sites using CASVM or GraBCas. Predicted cleavage sites are then scored, ranked and filtered against a cut-off based on their propensities for locating in disordered and solvent exposed regions. Using an independent dataset of caspase substrates, the model was shown to achieve greater positive predictive values compared to CASVM or GraBCas alone, and was able to reduce the false positives pool by up to 13% and 53% respectively while retaining all true positives. We applied our prediction model on the family of receptor tyrosine kinases (RTKs) and highlighted several members as potential caspase targets. The results suggest that RTKs may be generally regulated by caspase cleavage and in some cases, promote the induction of apoptotic cell death - a function distinct from their role as transducers of survival and growth signals.</p> <p>Conclusion</p> <p>As a step towards the prediction of <it>in vivo </it>caspase substrates, we have developed an accurate method incorporating cleavage site prediction and structural factors. The multi-factor model augments existing methods and complements experimental efforts to define the caspase degradome on the systems-wide basis.</p

Metacuration Standards and Minimum Information about a Bioinformatics Investigation

Many bioinformatics databases published in journals are here this year and gone the next. There is generally (i) no requirement, mandatory or otherwise, by reviewers, editors or publishers for full disclosure of how databases are built and how they are maintained; (ii) no standardized requirement for data in public access databases to be kept as backup for release and access when a project ends, when funds expire and website terminates; (iii) the case of proprietary resources, there is no requirement for data to be kept in escrow for release under stated conditions such as when a published database disappears due to company closure. Consequently, much of the biological databases published in the past twenty years are easily lost, even though the publications describing or referencing these databases and webservices remain. Given the volume of publications today, even though it is practically possible for reviewers to re-create databases as described in a manuscript, there is usually insufficient disclosure and raw data for this to be done, even if there is sufficient time and resources available to perform this. Consequently, verification and validation is assumed, and claims of the paper accepted as true and correct at face value. A solution to this growing problem is to experiment with some kind of minimum standards of reporting such as the Minimum Information About a Bioinformatics Investigation (MIABi) and standardized requirements of data deposition and escrow for enabling persistence and reproducibility. With easy availability of cloud computing, such a level of reproducibility can become a reality in the near term. Through standards in meta-curation and minimum standards of reporting that uphold the tenets of scientific reproducibility, verifiability, sustainability and continuity of data resources, the knowledge preserved will underpin tomorrow&#x27;s scientific research. Other issues include disambiguation of authors or database names, and unique identifiers to support non-repudiability, possibly in multiple languages. The International Conference on Bioinformatics and its publications are now in the process of making attempts at addressing these issues and this presentation will highlight some of the current efforts

SPdb – a signal peptide database

BACKGROUND: The signal peptide plays an important role in protein targeting and protein translocation in both prokaryotic and eukaryotic cells. This transient, short peptide sequence functions like a postal address on an envelope by targeting proteins for secretion or for transfer to specific organelles for further processing. Understanding how signal peptides function is crucial in predicting where proteins are translocated. To support this understanding, we present SPdb signal peptide database , a repository of experimentally determined and computationally predicted signal peptides. RESULTS: SPdb integrates information from two sources (a) Swiss-Prot protein sequence database which is now part of UniProt and (b) EMBL nucleotide sequence database. The database update is semi-automated with human checking and verification of the data to ensure the correctness of the data stored. The latest release SPdb release 3.2 contains 18,146 entries of which 2,584 entries are experimentally verified signal sequences; the remaining 15,562 entries are either signal sequences that fail to meet our filtering criteria or entries that contain unverified signal sequences. CONCLUSION: SPdb is a manually curated database constructed to support the understanding and analysis of signal peptides. SPdb tracks the major updates of the two underlying primary databases thereby ensuring that its information remains up-to-date

Challenges of the next decade for the Asia Pacific region: 2010 International Conference in Bioinformatics (InCoB 2010)

The 2010 annual conference of the Asia Pacific Bioinformatics Network (APBioNet), Asia’s oldest bioinformatics organisation formed in 1998, was organized as the 9th International Conference on Bioinformatics (InCoB), Sept. 26-28, 2010 in Tokyo, Japan. Initially, APBioNet created InCoB as forum to foster bioinformatics in the Asia Pacific region. Given the growing importance of interdisciplinary research, InCoB2010 included topics targeting scientists in the fields of genomic medicine, immunology and chemoinformatics, supporting translational research. Peer-reviewed manuscripts that were accepted for publication in this supplement, represent key areas of research interests that have emerged in our region. We also highlight some of the current challenges bioinformatics is facing in the Asia Pacific region and conclude our report with the announcement of APBioNet’s 100 BioDatabases (BioDB100) initiative. BioDB100 will comply with the database criteria set out earlier in our proposal for Minimum Information about a Bioinformatics and Investigation (MIABi), setting the standards for biocuration and bioinformatics research, on which we will report at the next InCoB, Nov. 27 – Dec. 2, 2011 at Kuala Lumpur, Malaysia

Exploring the transcriptome of non-model oleaginous microalga Dunaliella tertiolecta through high-throughput sequencing and high performance computing

GO analysis list. (DOCX 92 kb

Extending Asia Pacific bioinformatics into new realms in the "-omics" era

The 2009 annual conference of the Asia Pacific Bioinformatics Network (APBioNet), Asia's oldest bioinformatics organisation dating back to 1998, was organized as the 8th International Conference on Bioinformatics (InCoB), Sept. 7-11, 2009 at Biopolis, Singapore. Besides bringing together scientists from the field of bioinformatics in this region, InCoB has actively engaged clinicians and researchers from the area of systems biology, to facilitate greater synergy between these two groups. InCoB2009 followed on from a series of successful annual events in Bangkok (Thailand), Penang (Malaysia), Auckland (New Zealand), Busan (South Korea), New Delhi (India), Hong Kong and Taipei (Taiwan), with InCoB2010 scheduled to be held in Tokyo, Japan, Sept. 26-28, 2010. The Workshop on Education in Bioinformatics and Computational Biology (WEBCB) and symposia on Clinical Bioinformatics (CBAS), the Singapore Symposium on Computational Biology (SYMBIO) and training tutorials were scheduled prior to the scientific meeting, and provided ample opportunity for in-depth learning and special interest meetings for educators, clinicians and students. We provide a brief overview of the peer-reviewed bioinformatics manuscripts accepted for publication in this supplement, grouped into thematic areas. In order to facilitate scientific reproducibility and accountability, we have, for the first time, introduced minimum information criteria for our pubilcations, including compliance to a Minimum Information about a Bioinformatics Investigation (MIABi). As the regional research expertise in bioinformatics matures, we have delineated a minimum set of bioinformatics skills required for addressing the computational challenges of the "-omics" era

ASGS: an alternative splicing graph web service

Alternative transcript diversity manifests itself a prime cause of complexity in higher eukaryotes. The Alternative Splicing Graph Server (ASGS) is a web service facilitating the systematic study of alternatively spliced genes of higher eukaryotes by generating splicing graphs for the compact visual representation of transcript diversity from a single gene. Taking a set of transcripts in General Feature Format as input, ASGS identifies distinct reference and variable exons, generates a transcript splicing graph, an exon summary, splicing events classification and a single line graph to facilitate experimental analysis. This freely available web service can be accessed at