Sep 2, 2004
Thanks to bioinformatics researchers at Weill Cornell Medical College, cell biologists around the globe will soon have a powerful new tool to model complex biochemical processes within the cell, uploading and manipulating new data as they team up with research partners via the Internet.
What makes this possible is SigPath (www.sigpath.org), a new web-based information management system that goes beyond existing programs, aiming to provide researchers with a wealth of information on complex biochemical networks that govern cells.
These networks of interactions between molecules in the cell (proteins, signaling molecules) determine the functions of every cell in an organism, and are often at the very heart of diseases that continue to challenge researchers.
Our chief goal is to enable quantitative computational descriptions of the complex processes in the cell, and to allow researchers in different locations to enter the information they produce in their labs into SigPath via the Internet, so that they can participate in extensive collaborations across the Internet, explained SigPath co-creator Dr. Fabien Campagne, Assistant Professor of Physiology and Biophysics at the Institute of Computational Biomedicine (ICB), Weill Cornell Medical College.
The team at the newly created ICB at Weill Cornell Medical College partnered with the laboratory of Dr. Ravi Iyengar, Chair of the Department of Pharmacology and Biological Chemistry at the Mount Sinai School of Medicine, to develop the SigPath system, as described in the current issue of Science's Signal Transduction Knowledge Environment.
Only with the completion of the historic milestone of sequencing the human genome did it become clear how much more needs to be achieved in order to understand and interact with the workings of individual cells, said Dr. Harel Weinstein,Chair of the Department of Physiology and Biophysics, and Director of the ICBat Weill Cornell Medical College. The pursuit of this understanding is one of the central goals of the ICB, and SigPath is a shining example of the progress we are making.
In the cell you have molecules of different types, Dr. Campagne explained. There are proteins, small molecules, mRNA, and so on. And they are not arranged at random their interactions form networks.
These networks occur in great numbers and involve a huge variety of components and interactions, he said, so the creation of computer information systems focusing on cellular networks still represents 'a grand challenge' in science.
Existing programs tend to represent molecules as names that cannot describe the wealth of information accumulated in bioinformatics databases about each of these entities.
SigPath is different. By clicking on any one element in a given biochemical interaction, users can immediately access detailed descriptions of the molecule, from its basic structure to the gene that encodes it, going step by step right up to the genome, according to Dr. Campagne.
SigPath also goes beyond a listing of molecules involved in a particular network a kind of information researchers call qualitative to quantitative information about the dynamics of these interactions.
This allows scientists to go beyond the 'parts list,' into a deeper understanding of the molecular processes within the cell, Dr. Campagne said.
And because SigPath is interactive, scientists can upload emerging data as it appears in their laboratories or in the literature, sharing new insights with a global community of experts, and speeding research.
No special computer equipment is needed to access SigPath, and it's been designed to work seamlessly with mathematical procedures in currently available computer packages such as Virtual Cell, Kinetikit/Genesis, and JSim that carry out “mathematical modeling” of the cell.
More work needs to be done, of course, including the ongoing collection of new data, and the development of capabilities to include in the simulations the geometrical features of cell systems obtained with advanced methods of structural biology and imaging.
Such advanced methods have been introduced with great success in the laboratories of researchers at Weill Cornell Medical College, and are the basis for extensive collaborations among researchers here, which will also impact on the further development of SigPath, said Dr. Weinstein.
The SigPath source code is distributed under the Gnu General Public License, to allow the largest community of researchers to participate in such developments.
In essence, Dr. Campagne envisions SigPath as an electronic bridge between bioinformatics databases and tools that allow researchers to simulate biochemical processes on the computer, before trying them out in the lab.
The creators of this bioinformatics tool are particularly keen on the many ways in which SigPath can facilitate research breakthroughs in biomedicine. As a hypothesis-generating tool, the modeling enabled by SigPath makes it possible to imagine the nature and outcome of a particular cellular interaction, and then follow the consequences on the computer screen to evaluate the impact of this interaction.
If something turns up, then you go and design an experiment. If you're lucky, you find something interesting, said Dr. Campagne. From the results,one can both recognize the relation between a specific gene mutation and a resulting cell malfunction that leads to disease, and learn new ways to prevent or eliminate such malfunctions.
Research into SigPath was supported by a P20 Pre-Center of Excellence grant to Dr. Weinstein from the National Institutes of Health.