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Solutions: MSKCC Comp Bio Team Builds Community Around Pathway Tools, Standards

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Manhattan’s tony Upper East Side isn’t generally considered a bioinformatics hotbed, but researchers at Memorial Sloan Kettering Cancer Center’s Computational Biology Center are hoping that several projects supporting cancer research there will find broader acceptance in the bioinformatics community.

The most well-known of these projects is likely the BioPax standards initiative. Chris Sander, director of the MSKCC Computational Biology Center, first suggested the concept behind BioPax — an XML-based standard for exchanging various types of pathway data — during a discussion panel at ISMB in 2001. Since then, Sander has rallied the bioinformatics community around the emerging effort, winning support from some pathway database projects that had initially resisted the initiative.

In late January, MSKCC hosted a meeting for BioPax participants to discuss the second phase of the project, dubbed “Level 2” (see participant list below). BioPax Level 1, released in July, provided an exchange language for sharing metabolic pathway data. Now, according to Gary Bader, a postdoc in Sander’s lab, members of the consortium have agreed on the structure of Level 2, which will support molecular interaction databases such as BIND and DIP. A beta release of BioPax Level 2 is expected sometime in March, Bader said.

Bader said that the BioPax consortium is cooperating with members of the European Bioinformatics Institute’s Protein Standards Initiative to ensure that BioPax Level 2 is compatible with PSI-MI — PSI’s own standard for molecular interaction data. The groups are currently developing a converter for the two standards, Bader said.

The recent meeting also addressed initial plans for BioPax Level 3, Bader said, which will cover signal transduction and regulatory networks.

Joanne Luciano of consulting firm Predictive Medicine told BioInform that progress on Level 2 has not been as rapid as originally expected, but the recent meeting is evidence that the effort is “back on track now and going strong.”

BioPax is envisioned as complementary to the Systems Biology Markup Language, Bader said. BioPax, he noted, will cover only pathway data — not the computational models that can use pathway data as input. SBML, on the other hand, aims to provide a means of sharing and exchanging the computational models themselves.

Sander noted that as pathway databases continue to proliferate — the MSKCC team has identified more than 170 so far — it’s unlikely that all that data will ever be gathered in a central repository. Therefore, he said, the community will require some means of accessing distributed information. This multi-center, distributed model should work, Sander said, provided everyone agrees on a means of exchanging the data. In addition, he said, a distributed model should scale better than a centralized resource, “if it’s set up in the right way.”

But the MSKCC Computational Biology Center’s community-based projects don’t stop at BioPax. Researchers within the 20-person team are also contributing to Cytoscape (http://www.cytoscape.org/), an open-source software package for visualizing biological network data. In addition, the team has developed cPath (http://www.cbio.mskcc.org/cpath/index.jsp), a software package for aggregating pathway data from multiple resources into a single database. This project is still in “early beta,” Bader said, but he added that researchers are welcome to download the software and provide feedback.

Bader noted that the center’s focus on pathway informatics is closely tied with the research needs of cancer biologists at MSKCC. Certain pathways, he said, such as the TGF-ß pathway, are known to be involved in cancer, but the biological mechanisms responsible for slowing or promoting cellular growth remain unknown. In collaboration with experimental biologists at MSKCC, the bioinformatics group is refining its knowledge of specific cancer-related pathways, with the ultimate goal of being able to quantitatively model pathways and networks to predict response to therapeutics.

That goal may be a long way off, but Bader said it drives the bioinformatics team. “Ideally, what we’re doing can help clinicians understand specific cancers,” he said.

Plans call for the MSKCC Computational Biology Center to eventually grow to 70 people, and Sander is still seeking five faculty members to lead research efforts within the group. So far, two faculty members — Jose Vilar and Alex Lash — lead a two-person integrative biological modeling research team and a six-member bioinformatics core facility, respectively.

The center is currently housed in temporary quarters on East 63rd street, while MSKCC wraps up construction on a new 22-floor research building four blocks north. The computational biology center is expected to move into its new facility some time in 2006.

— BT

Participants at January BioPax Meeting*
Organization
Project
Argonne National Lab WIT/PUMA2
AstraZeneca OntoSieve
Bilkent University PATIKA
BIOBASE BIOBASE
Biopathways Consortium BioPAX
Caltech SBML
CBRC INOH
Cold Spring Harbor Lab Reactome
Columbia University GeneWays
Dana Farber BioPAX
Harvard University BioGraphNet
Millennium PARIS
MSKCC BioPAX
NCI eMIM
NYU Reactome
SRI BioCyc
Università di Milano Bicocca GCA
Université Libre de Bruxelles aMAZE
Vassar College GenMapp
*This list is not representative of the entire BioPax Consortium, only those members present at the most
recent meeting.

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