TinkerCell: Modular CAD Tool for Synthetic Biology

Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD) is necessary in order to bridge the gap between computational modeling and biological data. An application named TinkerCell has been created in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various C and Python programs that are hosted by TinkerCell via an extensive C and Python API. TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. Because TinkerCell associates parameters and equations in a model with their respective part, parts can be loaded from databases along with their parameters and rate equations. The modular network design can be used to exchange modules as well as test the concept of modularity in biological systems. The flexible modeling framework along with the C and Python API allows TinkerCell to serve as a host to numerous third-party algorithms. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at www.tinkercell.com.Comment: 23 pages, 20 figure

The Hopfield model and its role in the development of synthetic biology

Neural network models make extensive use of concepts coming from physics and engineering. How do scientists justify the use of these concepts in the representation of biological systems? How is evidence for or against the use of these concepts produced in the application and manipulation of the models? It will be shown in this article that neural network models are evaluated differently depending on the scientific context and its modeling practice. In the case of the Hopfield model, the different modeling practices related to theoretical physics and neurobiology played a central role for how the model was received and used in the different scientific communities. In theoretical physics, where the Hopfield model has its roots, mathematical modeling is much more common and established than in neurobiology which is strongly experiment driven. These differences in modeling practice contributed to the development of the new field of synthetic biology which introduced a third type of model which combines mathematical modeling and experimenting on biological systems and by doing so mediates between the different modeling practices

Causality, Information and Biological Computation: An algorithmic software approach to life, disease and the immune system

Biology has taken strong steps towards becoming a computer science aiming at reprogramming nature after the realisation that nature herself has reprogrammed organisms by harnessing the power of natural selection and the digital prescriptive nature of replicating DNA. Here we further unpack ideas related to computability, algorithmic information theory and software engineering, in the context of the extent to which biology can be (re)programmed, and with how we may go about doing so in a more systematic way with all the tools and concepts offered by theoretical computer science in a translation exercise from computing to molecular biology and back. These concepts provide a means to a hierarchical organization thereby blurring previously clear-cut lines between concepts like matter and life, or between tumour types that are otherwise taken as different and may not have however a different cause. This does not diminish the properties of life or make its components and functions less interesting. On the contrary, this approach makes for a more encompassing and integrated view of nature, one that subsumes observer and observed within the same system, and can generate new perspectives and tools with which to view complex diseases like cancer, approaching them afresh from a software-engineering viewpoint that casts evolution in the role of programmer, cells as computing machines, DNA and genes as instructions and computer programs, viruses as hacking devices, the immune system as a software debugging tool, and diseases as an information-theoretic battlefield where all these forces deploy. We show how information theory and algorithmic programming may explain fundamental mechanisms of life and death.Comment: 30 pages, 8 figures. Invited chapter contribution to Information and Causality: From Matter to Life. Sara I. Walker, Paul C.W. Davies and George Ellis (eds.), Cambridge University Pres

A Process Algebraical Approach to Modelling Compartmentalized Biological Systems

This paper introduces Protein Calculus, a special modeling language designed for encoding and calculating the behaviors of compartmentilized biological systems. The formalism combines, in a unified framework, two successful computational paradigms - process algebras and membrane systems. The goal of Protein Calculus is to provide a formal tool for transforming collected information from in vivo experiments into coded definition of the different types of proteins, complexes of proteins, and membrane-organized systems of such entities. Using this encoded information as input, our calculus computes, in silico, the possible behaviors of a living system. This is the preliminary version of a paper that was published in Proceedings of International Conference of Computational Methods in Sciences and Engineering (ICCMSE), American Institute of Physics, AIP Proceedings, N 2: 642-646, 2007 (http://scitation.aip.org/dbt/dbt.jsp?KEY=APCPCS&Volume=963&Issue=2)