Canadian researchers develop software to store and analyze mass spectrometry data
(October 13, 2010—Toronto, ON) Researchers at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital and the University of Toronto have developed an innovative software platform—the first of its kind worldwide—designed to store and analyze protein-derived, mass spectrometry data. The software, called ProHits, will allow researchers globally to conduct genome-wide studies of protein interactions and communication pathways in cells faster and more efficiently, helping to further their studies of cancer and other illnesses.
The ProHits platform is described in the October issue of the international journal Nature Biotechnology.
Lunenfeld Principal Investigator Dr. Anne-Claude Gingras, the Lea Reichmann Research Chair in Cancer Proteomics, and Dr. Mike Tyers, now at the University of Edinburgh, developed ProHits to meet a key challenge in the field of protein mass spectrometry (a technology that helps researchers separate, identify, and quantify specific human proteins)—namely to systematically collect and organize data to enable analyses and comparisons with previously reported protein interactions. Previously, biomedical researchers have had little choice but to organize their mass spectrometry data manually, a laborious task that frequently led to inaccurate and inefficient data analysis.
“It has been very difficult for biologists to effectively organize and analyze their mass spectrometry data,” said Dr. Gingras. “We wanted to design a tool that would give users an efficient and intuitive way to interpret their results.”
ProHits was used to conduct research reported earlier this year by Drs. Gingras and Tyers, when their teams generated a comprehensive road map of the signaling proteins that control many aspects of cellular behaviour in yeast cells (www.yeastkinome.org)—a discovery reported in a May issue of Science. In the course of this research, Drs. Gingras and Tyers demonstrated the power of ProHits to manage large-scale interaction proteomics data.
“The sheer complexity of our data forced us to build better bioinformatics tools that we believe will become standard practice for future mass spectrometry-based studies,” said Dr. Gingras. “We believe that ProHits will accelerate discovery in our laboratories and for researchers using the tool in other centres.”
ProHits was first implemented in the Tyers lab and evolved over many years of internal development at the Lunenfeld through the collaborative efforts of the teams of Drs. Tyers and Gingras, as well as Drs. Tony Pawson and Jeff Wrana. After many design cycles, ProHits now provides an intuitive user interface from the biologist’s perspective, and can accommodate multiple instruments within a facility, multiple user groups, multiple laboratory locations and any number of parallel projects.
· ProHits can manage all project scales, and supports common experimental pipelines, including those utilizing gel-based separation, gel-free analysis and multi-dimensional protein or peptide separation.
· The Data Management module monitors the use of each instrument for reporting purposes. Raw MS files can be automatically converted to appropriate file formats using the open source ProteoWizard converters.
· The Analyst module organizes data by project, bait, experiment and/or sample, for gel-based or gel-free approaches. ProHits automatically retrieves the amino acid sequence and other annotation from its associated database.
· Once an experiment is created, multiple samples may be linked to it, for example technical replicates of the same sample, or chromatographic fractions derived from the same preparation.
· ProHits is an open source platform that is freely available to both the academic research community and industry (the software download is available at www.prohitsMS.com).
From ProHits, users can link to BioGRID (another freely available database listing all protein interactions noted in published literature, which was also created by Dr. Tyers), so that novel proteins can be distinguished from those previously reported.
In effect, the new tool allows researchers to pool their data for more collaborative science. The software is cost-effective to implement, easy to use and visually intuitive.
“These databases and analyses platforms for protein interactions help make the entire scientific literature accessible to all researchers, for the generation of new ideas and hypotheses about how cells function in health and disease,” said Dr. Tyers.
Dr. Matthias Gstaiger, group leader at the Swiss Federal Institute of Technology (ETH) Zurich, is developing experimental approaches to systematically analyze protein-protein interactions. “ProHits is the first intuitive solution to manage medium and large scale AP-MS projects for the next big challenge in proteomics: the human interactome,” said Dr. Gstaiger.
Dr. Gingras has encouraged many other Lunenfeld and University of Toronto scientists to use ProHits, and the platform is also being implemented at research institutes in Ottawa, Montreal, Michigan and Switzerland.
“I am working with a four-member protein complex, and the amount of data I have accumulated from performing mass spectrometry analysis on each subunit is massive,” said Leo Wan, a graduate student at the Lunenfeld. “The easy comparison option of ProHits, and the ability to screen out false positives made it simple for me to detect novel protein interactions to my protein complex.”
The development of ProHits was supported by the Canadian Institutes of Health Research, the National Institutes of Health, the Canada Foundation for Innovation, the Ontario Research Fund and Genome Canada, as well as the Mount Sinai Hospital Foundation.
About the Samuel Lunenfeld Research Institute of Mount Sinai Hospital
The Samuel Lunenfeld Research Institute of Mount Sinai Hospital, a University of Toronto affiliated research centre established in 1985, is one of the world’s premier centres in biomedical research. Thirty-four principal investigators lead research in diabetes, cancer biology, epidemiology, stem cell research, women’s and infants’ health, neurobiology and systems biology. For more information on the Samuel Lunenfeld Research Institute, please visit www.lunenfeld.ca.