Maths helps understand disease

GARVAN INSTITUTE

The current challenge for systems biology, or the study of whole-body processes, is how to measure the changes that take place, moment by moment, among the roughly 12,000 proteins in a cell when that cell is exposed to a stimulus, such as the hormone insulin. Australian bioinformaticians have now created clever software that allows this kind of processing, enabling analysis of the vast quantity of data produced by an exquisitely sensitive new generation of mass spectrometers. The new software will even allow the re-processing of older data run in the lab, identifying at least 25% more proteins than previously identified. This is a giant leap forward in the not-so-exact science of systems biology, which sometimes struggles to ascertain whether or not a molecule is present in a sample. PhD student Pengyi Yang and Dr Jean Yee-Hwa Yang from Sydney’s Garvan Institute of Medical Research and the University of Sydney, respectively, have developed an algorithm that will allow scientists to identify specific proteins from hundreds of thousands of protein fragments in a sample. Details of the project are published in the Journal of Proteome Research. A tissue sample is ‘digested’ by an enzyme prior to being processed by a mass spectrometer, which breaks down the proteins into a peptide soup. Until now, it was only possible to ‘reassemble’ them (in a virtual sense) as members of protein groups. That is because over 2 million peptides are shared between two or more proteins within the 89,486 proteins recorded in the International Protein Index. The new software enhances protein identification and will enable scientists to investigate complex diseases (such as type 2 diabetes) as entire systems operate through time by monitoring the thousands of protein changes. “It’s now necessary to combine the disciplines of mathematics, computer science and biology to cope with the data being produced in systems biology,” said Pengyi Yang. “Previously, most labs focused on their favourite genes or proteins. Now, you need to look at all proteins and genes in a cell. When you try to do that, you need a computational methodology to analyse the information.” “For this project, we created a mathematical model and implemented it using a computational approach applied to biology.” Editor's Note: Original news release can be found here.