Systems Biology: An (simple) Introduction

Arthur Cheung

Systems Biology

P. Bork, Is there biological research beyond Systems Biology? A comparative analysis of terms, www.molecularsystemsbiology.com.

Systems Biology: An Overview, Arthur Cheung 2006

What is systems biology?

Systems biology is the study of an organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions which give rise to life. (Institute of Systems Biology) Instead of focusing on individual parts, the focus is on a complete system made up of different parts interacting with each other. Cf. Software systems made up of different modules interacting with each other. Based on the philosophy that the whole is greater than the sum of the parts. For example, the immune system isnt made up of one single component but instead a multitude of genes, proteins and external influences.
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What is systems biology?

The idea a systems approach to biology first suggested by Norbert Weiner. Such approaches not feasible to recently.

Systems Biology: An Overview, Arthur Cheung 2006

Why systems biology?

From the late 80s and throughout the 90s a large influx of biological data largely driven by the human genome project While significant, the human genome by itself does not tell us how the human body (or at least parts of it) behaves. The need to interpret the human genome spawned or reinvigorated various directly and indirectly related fields including: Bioinformatics (Computational Biology), data mining, biotechnology, molecular biology systems biology Brings understanding of biology to a higher level.

Systems Biology: An Overview, Arthur Cheung 2006

Why systems biology?

Allows insight as to what each part plays in the whole system Models from different species can be used to predict behaviour of similar systems in humans which in turn can be applied to develop new medical remedies.

Systems Biology: An Overview, Arthur Cheung 2006

The -omics
The lowest levels of a biological system: genome, transcriptome, proteome and metabolome. Genomics: study of a whole genome. Transcriptomics: study of the expression of genes at any given time. Proteomics: study of proteins. Metabolomics: study of metabolic interactions within a cell.

Systems Biology: An Overview, Arthur Cheung 2006

The -omics (cont.)

An explanation:
At the lowest level, genes can be compared to that of a particular function in a programming language. The genome can be considered a large library of code where a large amount wont be used and most likely be redundant, not unlike a library of code. At the transcriptomics level we try to explain the functions of the genes, like an API. There are special genes known as homeobox genes that code for proteins known as transcription factors. These controls what genes are coded into proteins, when and how. These are not unlike compilers The proteins can be seen as modular parts of a bigger program that is the cell.
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The -omics (cont.)

Metabolomics studies the interactions within the cells much like the message passing between functions in a program.

Systems Biology: An Overview, Arthur Cheung 2006

When things go wrong with homeobox genes

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Levels of abstraction
Currently, the level of abstraction in systems biology is not set in concrete and can range from the levels studied in the omics to the ends of the universe. Trends are leading towards molecular approach -> Molecular Systems Biology.

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Modelling and Simulation

Initiative directed towards modelling and simulation of biological processes. Modelling focussed on increasing the depth of understanding. Simulation focussed on predicting. Development of tools to aid modelling can aid in understanding of processes. Development of simulations can allow dry experiments to be used as a form of validation which can save time and resources.

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Modelling and Simulation

A unified method for modelling will encourage interoperability between different biological systems with a view to understand the whole picture

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Standards
No standards exist for developing models on biological systems. Current models are developed according to individual tastes and trends within certain fields. In general current existing models are specific with only their respective field in mind. Development of standards would need to be versatile enough to accommodate different fields. Standards are required to integrate established existing models in order to develop larger more comprehensive models.

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SBML and CellML

Systems Biology Markup Language and Cell Markup Language A step towards standardising modelling. Attempts to develop a method to share models between the multitude of modelling applications currently available. Both are XML based. Both are generally supported by most applications, but the purpose of a standardise language is defeated as most applications store important data in application specific annotations.

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SBML
Appears to be favoured in community over CellML Hierarchical structure as opposed to the modular structure of CellML. However, developments are underway to modularize the language in the next revision SBML.org claims that over 110 software systems support SBML. These include BioUML, JDesigner and CellDesigner

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Model Repositories
There are several repositories present that contain models of various formats including SBML and CellML. The most notable ones include:
BioModels.net KEGG (Kyoto Encyclopedia on Genes and Genomes) CellML.org repository

While these databases are growing, many more systems remain to be indentified and modelled.

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SBML

Components in an SBML model (Tools for Bioinformatics)

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Short-comings of SBML
Developers claim to have built SBML based on the principles of UML but it is really more a standard for data exchange rather than a modelling language. Hierarchical approach is a step away from the modular approach required in systems biology Too rigid, not flexible enough. Effectively exchanging data between incompatible applications.

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Short-comings of SBML

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Adapting Business Modelling Techniques

The similarities in biological systems to those found in business solutions are too big to ignore. Real modelling languages for biology might be able to be developed adapting the principles found existing business modelling languages such as UML and BPMN. The i* framework with its agent based properties may have potential in aiding the development of simulation models.

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Role of A.I.
A.I. can be applied especially in the development of simulations as we try to mimic how biological systems think. The same problems found in reasoning about actions (I.e. Frame problem, qualification problem and ramification problem) can be applicable to systems biology.

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Future
Still a maturing field, lots of potential. While there had been an influx of data, most of that has been at the genomic level. The field compliments the development of other fields in the lower levels such as the omics and molecular biology. As these fields grow so will this.

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Further Reading
N. Weiner, Cybernetics or Control and Communication in the Animal and the Machine (MIT Press, Cambridge, Ma, 1948). H. Kitano, Foundations of Systems Biology (MIT Press, Cambridge, MA, 2001). H. Kitano, Systems Biology: A Brief Overview, Systems Biology Volume 295 page 1663-1664. M.E. Csete and J.C. Doyle, Reverse Engineering of Biological Complexity, Systems Biology Volume 295 page 1664-1669. P. Bork, Is there biological research beyond Systems Biology? A comparative analysis of terms, www.molecularsystemsbiology.com. Klipp et al., Systems Biology in Practice (Wiley-VCH, Darmstadt, 2005).

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