A new collaboration between the University of Edinburgh and Japan’s Riken Genomic Research Center aims to add a new dimension or two to pharmacogenomics research.
The goal of the five-year project is to create mechanistic models for individual breast cancer patients that will help physicians prescribe specific therapies or combinations of therapies.
The effort is a step beyond most current pharmacogenomics efforts, which aim to guide treatment decisions based on specific alleles or gene-expression patterns, in that it intends to bring the latest advances in computational systems biology to bear on personalized medicine.
Gene expression-based methods reduce the complexity of biology to only a “single dimension” that is used to discriminate patients, Igor Goryanin, director of the Edinburgh Center for Bioinformatics and co-director of the Center for Systems Biology at Edinburgh, told BioInform. “We are talking about comparisons between models, and it’s not one parameter. It will be thousands of parameters that should be compared simultaneously.”
This approach is expected to identify novel biomarkers that will be based on “the state of the network” rather than one or two proteins or genes, Goryanin said.
The Edinburgh researchers are developing a number of new methods for the project, including a process algebra called PEPA (performance evaluation process algebra) for building the models as well as software for parameter estimation and bifurcation analysis — a method to determine which parameters are responsible for specific biological functions.
All the analysis will be performed on an IBM Blue Gene system at the Edinburgh Parallel Computing Center.
The project participants will use the Edinburgh Pathway Editor, a tool for visualizing and annotating biological networks, to map pathways involved in breast cancer. Riken will contribute phosphorylation and gene-expression data that will be used to flesh out the models. Then, the researchers will use clinical data and gene-expression data from several hundred breast cancer patients at the Edinburgh Cancer Research Center to create “a personalized model for every patient with breast cancer,” Goryanin said. “We will be able to distinguish the responders and non-responders and find out the combination of therapies or the most suitable therapy for particular patients from a number of currently available cancer drugs.”
“We will be able to distinguish the responders and non-responders and find out the combination of therapies or the most suitable therapy for particular patients from a number of currently available cancer drugs.”
The project is the second systems biology collaboration that the University of Edinburgh has signed with a major Japanese research institute this year. In February, the University entered a three-year agreement with Hiroaki Kitano’s team at the Systems Biology Institute in Tokyo to develop new computational methods for biological analysis.
The Center for Systems Biology at Edinburgh is one of six Centers for Integrative Systems Biology funded by the UK’s Biotechnology and Biological Sciences Research Council and Engineering and Physical Sciences Research Council. The CISB program awarded £20 million ($39 million) in 2005 to create centers at the University of Manchester, Imperial College London, and the University of Newcastle. This year, the BBSRC and EPSRC added Edinburgh, the University of Nottingham, and the University of Oxford to the list with an additional £27 million in funding.
Goryanin said that the six UK centers are currently in discussions regarding a shared computational infrastructure.
Also under discussion is a partnership with IUPHAR (the International Union of Basic and Clinical Pharmacology) regarding the IUPHAR Receptor Database, which is currently hosted at the University of Edinburgh. Goryanin said that the Edinburgh center may further develop the database to include an ontology and links to other systems biology resources.