Developed at North Carolina State University, the processes include those responsible for gene expression, cell signalling, stress response, and metabolism.
‘Our goal was to identify modules, or functional units, which are critical to the performance of the biochemical pathways that govern a host of biological processes,’ said Dr. Cranos Williams, an assistant professor of electrical and computer engineering at NC State and senior author of a paper describing the work.
’For example, a car has lots of modules – the parts that make it go, the parts that make it stop, the parts that let you steer, etc. If you understand those modules, you understand how the car works. But if you just have a list of parts, that’s not very helpful.
’And what we have right now for many biochemical pathways is essentially just a list of parts – metabolites, biochemical reactions and enzymes that facilitate those reactions – and, in some cases, how those parts change over time. What we need is a clear understanding of which parts work together. That’s where our new algorithm comes in.’
The researchers developed an algorithm that allows them to identify which parts – the metabolites, reactions and enzymes – are related to each other and can be grouped into functional modules. The algorithm is also said to identify whether an individual component plays a role in multiple modules; an enzyme may play a primary role in critical stress response pathways and a secondary role in processes associated with programmed cell maintenance or death.
According to NCSU, the algorithm also characterises how the relationships between different modules and individual components may change over time and under different internal and external conditions.
The input for the algorithm comes from using well-established dynamic models to observe changes in concentrations of metabolites, reactions and enzymes under various conditions. The algorithm then processes that data to establish primary and secondary relationships between all of the constituent parts.
‘When modifying biological processes, there are thousands of possible combinations of metabolites, reactions and enzymes for any given biochemical pathway,’ Williams said in a statement. ‘Our work should help life scientists narrow down the list of key players in order to target their research efforts on functional groups that are most likely to improve our ability to understand and control important biological processes. This has applications in everything from biomedical research to agriculture to biofuels.’
The paper, Hierarchical Modularization Of Biochemical Pathways Using Fuzzy-C Means Clustering, appears in IEEE Transactions on Cybernetics. Lead author of the paper is Dr. Maria de Luis Balaguer, a former Ph.D. student at NC State.
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