Extraction of Transcript Diversity from Scientific Literature

Transcript diversity generated by alternative splicing and associated mechanisms contributes heavily to the functional complexity of biological systems. The numerous examples of the mechanisms and functional implications of these events are scattered throughout the scientific literature. Thus, it is crucial to have a tool that can automatically extract the relevant facts and collect them in a knowledge base that can aid the interpretation of data from high-throughput methods. We have developed and applied a composite text-mining method for extracting information on transcript diversity from the entire MEDLINE database in order to create a database of genes with alternative transcripts. It contains information on tissue specificity, number of isoforms, causative mechanisms, functional implications, and experimental methods used for detection. We have mined this resource to identify 959 instances of tissue-specific splicing. Our results in combination with those from EST-based methods suggest that alternative splicing is the preferred mechanism for generating transcript diversity in the nervous system. We provide new annotations for 1,860 genes with the potential for generating transcript diversity. We assign the MeSH term “alternative splicing” to 1,536 additional abstracts in the MEDLINE database and suggest new MeSH terms for other events. We have successfully extracted information about transcript diversity and semiautomatically generated a database, LSAT, that can provide a quantitative understanding of the mechanisms behind tissue-specific gene expression. LSAT (Literature Support for Alternative Transcripts) is publicly available at http://www.bork.embl.de/LSAT/

Modeling Life as Cognitive Info-Computation

This article presents a naturalist approach to cognition understood as a network of info-computational, autopoietic processes in living systems. It provides a conceptual framework for the unified view of cognition as evolved from the simplest to the most complex organisms, based on new empirical and theoretical results. It addresses three fundamental questions: what cognition is, how cognition works and what cognition does at different levels of complexity of living organisms. By explicating the info-computational character of cognition, its evolution, agent-dependency and generative mechanisms we can better understand its life-sustaining and life-propagating role. The info-computational approach contributes to rethinking cognition as a process of natural computation in living beings that can be applied for cognitive computation in artificial systems.Comment: Manuscript submitted to Computability in Europe CiE 201

Modelling epistasis in genetic disease using Petri nets, evolutionary computation and frequent itemset mining

Petri nets are useful for mathematically modelling disease-causing genetic epistasis. A Petri net model of an interaction has the potential to lead to biological insight into the cause of a genetic disease. However, defining a Petri net by hand for a particular interaction is extremely difficult because of the sheer complexity of the problem and degrees of freedom inherent in a Petri net’s architecture. We propose therefore a novel method, based on evolutionary computation and data mining, for automatically constructing Petri net models of non-linear gene interactions. The method comprises two main steps. Firstly, an initial partial Petri net is set up with several repeated sub-nets that model individual genes and a set of constraints, comprising relevant common sense and biological knowledge, is also defined. These constraints characterise the class of Petri nets that are desired. Secondly, this initial Petri net structure and the constraints are used as the input to a genetic algorithm. The genetic algorithm searches for a Petri net architecture that is both a superset of the initial net, and also conforms to all of the given constraints. The genetic algorithm evaluation function that we employ gives equal weighting to both the accuracy of the net and also its parsimony. We demonstrate our method using an epistatic model related to the presence of digital ulcers in systemic sclerosis patients that was recently reported in the literature. Our results show that although individual “perfect” Petri nets can frequently be discovered for this interaction, the true value of this approach lies in generating many different perfect nets, and applying data mining techniques to them in order to elucidate common and statistically significant patterns of interaction

"Going back to our roots": second generation biocomputing

Researchers in the field of biocomputing have, for many years, successfully "harvested and exploited" the natural world for inspiration in developing systems that are robust, adaptable and capable of generating novel and even "creative" solutions to human-defined problems. However, in this position paper we argue that the time has now come for a reassessment of how we exploit biology to generate new computational systems. Previous solutions (the "first generation" of biocomputing techniques), whilst reasonably effective, are crude analogues of actual biological systems. We believe that a new, inherently inter-disciplinary approach is needed for the development of the emerging "second generation" of bio-inspired methods. This new modus operandi will require much closer interaction between the engineering and life sciences communities, as well as a bidirectional flow of concepts, applications and expertise. We support our argument by examining, in this new light, three existing areas of biocomputing (genetic programming, artificial immune systems and evolvable hardware), as well as an emerging area (natural genetic engineering) which may provide useful pointers as to the way forward.Comment: Submitted to the International Journal of Unconventional Computin