Agents in Bioinformatics

The scope of the Technical Forum Group (TFG) on Agents in Bioinformatics (BIOAGENTS) was to inspire collaboration between the agent and bioinformatics communities with the aim of creating an opportunity to propose a different (agent-based) approach to the development of computational frameworks both for data analysis in bioinformatics and for system modelling in computational biology. During the day, the participants examined the future of research on agents in bioinformatics primarily through 12 invited talks selected to cover the most relevant topics. From the discussions, it became clear that there are many perspectives to the field, ranging from bio-conceptual languages for agent-based simulation, to the definition of bio-ontology-based declarative languages for use by information agents, and to the use of Grid agents, each of which requires further exploration. The interactions between participants encouraged the development of applications that describe a way of creating agent-based simulation models of biological systems, starting from an hypothesis and inferring new knowledge (or relations) by mining and analysing the huge amount of public biological data. In this report we summarise and reflect on the presentations and discussions

Identification of functionally related enzymes by learning-to-rank methods

Enzyme sequences and structures are routinely used in the biological sciences as queries to search for functionally related enzymes in online databases. To this end, one usually departs from some notion of similarity, comparing two enzymes by looking for correspondences in their sequences, structures or surfaces. For a given query, the search operation results in a ranking of the enzymes in the database, from very similar to dissimilar enzymes, while information about the biological function of annotated database enzymes is ignored. In this work we show that rankings of that kind can be substantially improved by applying kernel-based learning algorithms. This approach enables the detection of statistical dependencies between similarities of the active cleft and the biological function of annotated enzymes. This is in contrast to search-based approaches, which do not take annotated training data into account. Similarity measures based on the active cleft are known to outperform sequence-based or structure-based measures under certain conditions. We consider the Enzyme Commission (EC) classification hierarchy for obtaining annotated enzymes during the training phase. The results of a set of sizeable experiments indicate a consistent and significant improvement for a set of similarity measures that exploit information about small cavities in the surface of enzymes

Peptide vocabulary analysis reveals ultra-conservation and homonymity in protein sequences

A new algorithm is presented for vocabulary analysis (word detection) in texts of human origin. It performs at 60%–70% overall accuracy and greater than 80% accuracy for longer words, and approximately 85% sensitivity on Alice in Wonderland, a considerable improvement on previous methods. When applied to protein sequences, it detects short sequences analogous to words in human texts, i.e. intolerant to changes in spelling (mutation), and relatively contextindependent in their meaning (function). Some of these are homonyms of up to 7 amino acids, which can assume different structures in different proteins. Others are ultra-conserved stretches of up to 18 amino acids within proteins of less than 40% overall identity, reflecting extreme constraint or convergent evolution. Different species are found to have qualitatively different major peptide vocabularies, e.g. some are dominated by large gene families, while others are rich in simple repeats or dominated by internally repetitive proteins. This suggests the possibility of a peptide vocabulary signature, analogous to genome signatures in DNA. Homonyms may be useful in detecting convergent evolution and positive selection in protein evolution. Ultra-conserved words may be useful in identifying structures intolerant to substitution over long periods of evolutionary time

An empirical comparison of supervised machine learning techniques in bioinformatics

Research in bioinformatics is driven by the experimental data. Current biological databases are populated by vast amounts of experimental data. Machine learning has been widely applied to bioinformatics and has gained a lot of success in this research area. At present, with various learning algorithms available in the literature, researchers are facing difficulties in choosing the best method that can apply to their data. We performed an empirical study on 7 individual learning systems and 9 different combined methods on 4 different biological data sets, and provide some suggested issues to be considered when answering the following questions: (i) How does one choose which algorithm is best suitable for their data set? (ii) Are combined methods better than a single approach? (iii) How does one compare the effectiveness of a particular algorithm to the others

Bioinformatics: A challenge for statisticians

Bioinformatics is a subject that requires the skills of biologists, computer scientists, mathematicians and staisticians. This paper introduces the reader to one small aspect of the subject: the study of microarrays. It describes some of the complexities of the enormous amounts of data that are available and shows how simple statistical techniques can be used to highlight deficiencies in that data

DNALinux Virtual Desktop Edition

The new version of DNALinux (VDE) is presented. DNALinux VDE is a departure from traditional distributions since it uses a virtual machine to bundle together the operating system and bioinformatics applications. The main advantage of this approach is that a virtualized environment doesn't affect a installed system. With a virtual machine a Linux system can be run under a Windows system, provided that the virtual machine player is installed. The included programs are listed and specifications to add more programs are explained. We believe that DNALinux could be used as a standardized virtual machine for learning, using, developing and testing bioinformatics applications

XML in Motion from Genome to Drug

Information technology (IT) has emerged as a central to the solution of contemporary genomics and drug discovery problems. Researchers involved in genomics, proteomics, transcriptional profiling, high throughput structure determination, and in other sub-disciplines of bioinformatics have direct impact on this IT revolution. As the full genome sequences of many species, data from structural genomics, micro-arrays, and proteomics became available, integration of these data to a common platform require sophisticated bioinformatics tools. Organizing these data into knowledgeable databases and developing appropriate software tools for analyzing the same are going to be major challenges. XML (eXtensible Markup Language) forms the backbone of biological data representation and exchange over the internet, enabling researchers to aggregate data from various heterogeneous data resources. The present article covers a comprehensive idea of the integration of XML on particular type of biological databases mainly dealing with sequence-structure-function relationship and its application towards drug discovery. This e-medical science approach should be applied to other scientific domains and the latest trend in semantic web applications is also highlighted

Heterogeneous biomedical database integration using a hybrid strategy: a p53 cancer research database.

Complex problems in life science research give rise to multidisciplinary collaboration, and hence, to the need for heterogeneous database integration. The tumor suppressor p53 is mutated in close to 50% of human cancers, and a small drug-like molecule with the ability to restore native function to cancerous p53 mutants is a long-held medical goal of cancer treatment. The Cancer Research DataBase (CRDB) was designed in support of a project to find such small molecules. As a cancer informatics project, the CRDB involved small molecule data, computational docking results, functional assays, and protein structure data. As an example of the hybrid strategy for data integration, it combined the mediation and data warehousing approaches. This paper uses the CRDB to illustrate the hybrid strategy as a viable approach to heterogeneous data integration in biomedicine, and provides a design method for those considering similar systems. More efficient data sharing implies increased productivity, and, hopefully, improved chances of success in cancer research. (Code and database schemas are freely downloadable, http://www.igb.uci.edu/research/research.html.)

Alignment of Linear Biochemical Pathways Using Protein Structural Classification

Metabolic, signaling and regulatory pathways form the basis of biological processes and are important for the analysis of cellular behavior and evolution. This paper presents an approach of aligning biochemical pathways on the basis of the structure of involved proteins and their classification. The suitable information is retrieved from an integrated database system.
SIGNALIGN is available at: http://agbi.techfak.uni-bielefeld.de/signalign/index.jsp 

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