Michael Hucka, Ph.D. - US grants

DESCRIPTION (provided by applicant): The Systems Biology Markup Language (SBML) is an XML-based format for the exchange of quantitative and qualitative models of biochemical reaction networks. An SBML Forum meeting, the ninth of a series of such meetings, will be held on the 14th and 15th October 2004 in Heidelberg, Germany, as an adjunct to the 5th International Conference on Systems Biology (ICSB 2004). We seek funding to help defray the costs of holding the SBML meeting and providing travel support for a subset of the attendees. The goals of this meeting include: (1) providing a forum where consensus decisions can be made about the development and adoption of future features of SBML; (2) ensuring that systems biology software interoperability is maximized through the correct use of SBML; and (3) providing a forum for software developers to exchange information about the systems biology software that is available or under development, thereby maximizing the use of that software both directly by users and within other software development projects. The agenda for the SBML Forum will be divided into presentation sessions and discussion sessions. The subject matter of the presentations will include the experiences of software developers using SBML in the field and proposals for mew features in future levels of SBML. Discussions will cover the development of suites of test models to ensure consistent interpretation of SBML and decisions concerning the adoption of feature proposals into the SBML standard. The meeting will attract an eclectic audience representing a variety of disciplines and stages of career development. The forum proceedings will be distributed to attendees and will be made available on the meeting's web site.

DESCRIPTION (provided by applicant): Molecular biologists are increasingly realizing that computational modeling of sub-cellular mechanisms is crucial for making sense of human biology and advancing medical research in the context of the vast quantities of complex experimental data that are now being collected. The biology community needs agreed-upon information standards if models are to be shared, evaluated and developed co-operatively. The Systems Biology Markup Language (SBML) is becoming a de facto standard exchange format for representing formal qualitative and quantitative models of systems of biochemical reactions. The long-term objectives of this proposal are to support and further develop SBML and related software infrastructure for the benefit of the computational biology community. The specific aims are the following: 1. Work with the community of software developers and users to (a) continue evolving SBML and extending the language into SBML Level 3 with features developers have been requesting, and (b) formalize the SBML language development process and transfer its control to the community. 2. Maintain and extend existing software libraries for working with SBML with facilities for (a) reading and writing SBML Level 3, (b) reading model definitions in other formats including CelIML, and (c) transforming model definitions into other formats such as CelIML, MATLAB, Mathematica, HTML, and others. 3. Produce documentation, including a "best practices" guide to working with SBML, and performing training functions to help educate software developers and modelers in the use of SBML and the software tools available for working with the language.

[unreadable] DESCRIPTION (provided by applicant): The Systems Biology Markup Language (SBML) is a popular, machine-readable, model representation format allowing computational models of biochemical networks to be exchanged between software tools such as editing programs, simulators, and databases. It is supported not only by open-source and commercial developers of systems biology software, but also by major journals such as Nature. Our group continues to lead and guide the evolution of SBML and related infrastructure, and as a result, we also keenly feel some of the limitations and challenges that have become apparent only as a result of SBML's exploding success. One such challenge is ensuring a high degree of conformance to the SBML specification by the steadily growing number of tools. We have come to realize that simply providing a definition of SBML, holding workshops and discussions, and so forth, are not enough to ensure consistent interpretation and behavior by different software systems. There need to be concrete and objective mechanisms for validating SBML implementations. In preliminary work over the past year, we developed a self-contained "SBML Semantic Test Suite" allowing software developers and users to test the behavior of simulation tools against SBML benchmark models ranging in complexity from basic to advanced, covering a majority of the features defined in the language. In this proposal, we aim to (1) extend and refine this preliminary effort into a comprehensive SBML Test Suite, and (2) develop a web-based system allowing anyone to upload test results, assess them independently, and optionally compare them to the results of other software tools. The overall goal is to provide objective facilities for validating different software tools' coverage and conformance to the definition of SBML, and thereby help ensure the highest level of consistency possible across SBML- aware software systems. This is something that is crucial for users to have confidence in SBML as a standard model representation format for simulation and analysis in biomedical research. [unreadable] [unreadable] [unreadable] [unreadable]

This grant provides partial travel support for ten participants attending the Eighth International Conference on Systems Biology (ICSB 2007) which will be held from October 1 to 6, 2007 in Long Beach, CA. ICSB is widely acknowledged as the premiere conference on systems biology. The purpose of the conference is to bring together scientists from a variety of disciplines to discuss creative and innovative approaches to systems biology, the quantitative study of biological processes as whole systems instead of isolated parts. In terms of intellectual merit, issues such as robustness, evolveability, design, and complexity will be featured prominently at ICSB 2007. How does one forward and reverse engineer complex biological systems? These are central challenges in the 21st century, and the meeting will stimulate progress through various aspects of the program.

The conference contains eight plenary sessions: (1) Morphogenesis, (2) Mathematical Frontiers, (3) Innovative Approaches, (4) Network Structure and Regulation, (5) Synthetic Biology, (6) Systems Bioinformatics, (7) Student Session, and (8) Systems Biomedicine. The organizers plan to select 25% of the speakers from the pool of submitted abstracts. There will be one day of tutorials and the opening keynote address and reception (October 1) followed by three days (October 2 - 4) of talks including a session consisting exclusively of student speakers, two poster sessions, and two minisymposia. The conference will conclude with two days (October 5 - 6) of workshops. Based on past experience, the meeting will attract an eclectic audience representing a variety of disciplines and stages of career development. A guiding principle of the meeting is encouraging information exchange in an informal atmosphere conducive to brainstorming. Special events include a minisymposium on systems biology education, a special issue of the journal Molecular Systems Biology devoted to the conference, and a tentatively planned inaugural meeting for the new International Society of Systems Biology, which will be a sponsoring organization for future conferences. The conference proceedings will be distributed to attendees in printed form and as a CD-ROM. More information on ICSB 2007 is available on the conference web site (www.icsb-2007.org).

An objective of ICSB is to demonstrate that systems biology is for the masses and not just the elite few. The key is to embrace the multidisciplinary nature of biology in the 21st century and the importance of collaborations. In terms of broader impact, the conference will bring together scientists from different intellectual backgrounds, perspectives, cultures, and countries in order to begin to formulate a fundamentally new way of thinking about biology and performing biology research that is accessible to the whole community and that will lead to revolutionary breakthroughs in biotechnology and medicine.

[unreadable] DESCRIPTION (provided by applicant): The Systems Biology Markup Language (SBML) is a machine-readable model representation language for software tools in computational systems biology. It provides a means of representing quantitative models of biochemical reaction networks in a tool-independent fashion. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. It is the most successful effort in this area to date, with over 100 software systems supporting SBML today and more SBML-compatible tools being announced monthly. The broad acceptance of a common, open format for exchanging models between software tools is a crucial step towards wider use of quantitative modeling in biology, because it allows researchers to publish and build upon each other's work with greater ease and accuracy. This proposal is a competing continuation application to the three-year grant (NIGMS GM070923) that has provided the major source of funding for SBML development since 2004. We propose to undertake a series of efforts aimed at supporting and enhancing SBML and critical SBML software infrastructure, developing an SBML testing framework, and supporting the SBML community. Our specific aims are: (1) continue development and evolution of the SBML language (including the completion of remaining SBML Level 3 work, organizing SBML workshops and other educational events, and applying SBML to modeling problems in synthetic biology); (2) develop interfaces between SBML and two recent complimentary efforts, BioPAX and SBGN; (3) continue developing and supporting libSBML, the most popular open-source application programming interface (API) library for reading, writing and manipulating SBML files and data streams; (4) develop a reference implementation of SBML Level 3 in an integrated software environment; and (5) develop a comprehensive test suite and associated facilities for testing the completeness and quality of SBML implementations in different software tools. [unreadable] [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): The Eighth International Conference on Systems Biology (ICSB 2007) PI: Michael Hucka (California Institute of Technology) Co-Chairs: Bruce E. Shapiro (California Institute of Technology) Arthur D. Lander (UC Irvine) Tau-Mu Yi (UC Irvine) [unreadable] [unreadable] The Eighth International Conference on Systems Biology (ICSB 2007) will be held from October 1 to 6, 2007 in Long Beach, CA at the Long Beach Convention Center. Caltech and the University of California, Irvine (UCI) are the sponsoring organizations. ICSB is widely acknowledged as the premiere conference on systems biology. The purpose of the conference is to bring together scientists from a variety of disciplines to discuss creative and innovative approaches to systems biology, the quantitative study of biological processes as whole systems instead of isolated parts. The confirmed keynote speakers are Drs. Eric Lander, Eric Wieschaus, and Claire Tomlin. There will be 9 plenary sessions: (1) Morphogenesis, (2) Mathematical Frontiers, (3) Technological Frontiers, (4) Networks, (5) Synthetic Biology, (6) Systems Bioinformatics, (7) Regulatory Systems, (8) Student Session, and (9) Systems Biomedicine. For the first time we will be selecting of the speakers from the pool of submitted abstracts. There will be one day of tutorials and the opening keynote address and reception (October 1) followed by three days (October 2-4) of talks including a session consisting exclusively of student speakers, two poster sessions, and three minisymposia. The conference will conclude with two days (October 5-6) of workshops. Based on past experience, the meeting will attract an eclectic audience representing a variety of disciplines and stages of career development. A guiding principle of the meeting is encouraging information exchange in an informal atmosphere conducive to brainstorming. Special events include a minisymposium on systems biology education, a special issue of the journal Molecular Systems Biology (Nature and EMBO Press) devoted to the conference and a tentatively planned inaugural meeting for the new International Society of Systems Biology, which will be a sponsoring organization for future conferences. The conference proceedings will be distributed to attendees in printed form and as a CD-ROM. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The Systems Biology Markup Language (SBML) is a machine-readable model representation language for software tools in computational systems biology. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. Previous work on GM070923 helped make SBML widely supported as a de facto standard; as of October, 2009, over 175 software systems (both open-source and commercial) are known to support it worldwide. Today, there are a number of international groups working on supporting the next generation of SBML and defining new modular packages to extend the features of SBML Level 3. It has become difficult to mandate or even predict the direction in which specific SBML features are de- veloped by the community. What the systems biology modeling community needs for the next few years is leeway to explore solutions at the timescales they deem appropriate. However, at the same time, it not yet possible to leave certain aspects of core software development and maintenance entirely to the rest of the community as self-sustaining open-source software projects. Consequently, this application is a renewal proposal for GM070923 with a narrow scope focused on SBML software only. We wish to perform additional software development and support of certain crucial software resources for the benefit of the SBML commu- nity for three more years. The software goals include maintaining and continuing to enhance libSBML, the SBML Test Suite, the SBML Demonstrator, SBMLeditor, and the online SBML validator; in addition, we will continue to develop plug-in extensions to libSBML to support SBML Level 3 language packages and develop an online database of SBML Test Suite results; and finally, we will undertake development of new software resources, specifically a Java version of libSBML, and formal schemas for SBML Level 3. 1 PUBLIC HEALTH RELEVANCE: Computation modeling is increasingly becoming a crucial aspect of biological research, and for modeling in biology to continue moving forward, researchers need to be able to create, exchange and publish models in an open format that is directly supported by most software tools. The de facto standard format for this purpose in systems biology is the Systems Biology Markup Language (SBML). Software developers and researchers who write software for modeling benefit by having certain open-source SBML software resources such as an API library (libSBML) available as starting points instead of having to program SBML support from scratch. The goals of this project are to develop, support and enhance a number of SBML software resources that have proven to be essential for the SBML-using community.

? DESCRIPTION (provided by applicant): The Systems Biology Markup Language (SBML) is a machine-readable model representation language for software tools in computational systems biology. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. SBML is supported by over 280 systems today, employed in model generation pipelines, accepted by hundreds of journals, used by large collaborative model construction efforts, described in textbooks, used in courses, and encouraged by NIH and other funding bodies. It is clear that SBML is central to a growing ecology of standards that collectively cover the whole life cycle of computational models. The modeling community at large is currently engaged in ?nalizing and applying recently-developed SBML extensions (known as SBML Level 3 packages) that provide additional constructs in SBML for the use of modeling formalisms such as ?ux balance analysis, qualitative models, rule-based models, spatial processes, and more. In this proposal for renewed funding, our focus is on resources that will enable the community to ful?ll the promise of SBML Level 3 as an exchange format for a wide range of biological research applications. We propose to (1) continue supporting, extending and generalizing crucial SBML software, including libraries such as libSBML and JSBML, and infrastructure such as SBML.org; (2) update and extend numerous software tools to support interoperability between SBML and other formats and systems that include MATLAB, Cytoscape, BioPAX and more; and (3) develop instructional materials for SBML, focusing especially on its use in different biological modeling scenarios as well as its relationships to other contemporary formats. This project will thus continue support for crucial SBML software and resources needed by developers and users alike; it will also derive new software libraries that other standardization efforts can reuse, develop tools that help bridge SBML with other formats and resources, and generate materials that will help everyone make more effective use of SBML for years to come.

When scientists need to find software for a task, they often use ad hoc methods such as asking their colleagues, searching the web, or using whatever others appear to be using. This unsystematic approach often results in unproductive effort and poorer scientific results because scientists cannot find the software that is best for their needs. If a comprehensive software index were available it would help enable more efficient use of existing software resources and tools and contribute to more efficient and effective investment in the scientific research itself.

Further, software is created and evolves too rapidly for humans to monitor; thus creation of the index should be automated. Also, while today's social-coding movement is putting more software into open-source repositories, thus offering greater opportunities to find and characterize software automatically, a significant obstacle remains: the lack of automated indexing methods that can produce results acceptable to humans. This proposed EAGER project seeks to investigate the use of innovative computing techniques for automating the creation of an index that can be used by scientists to find the software they need. Their test system (CASICS - Comprehensive and Automated Software Inventory Creation System) will be tested with an initial set of users and made available for public use.

In this project, the researchers will (1) extend an existing software ontology; (2) develop methods for source code analysis using the ontology; (3) adapt a repository crawler to apply the methods to projects in SourceForge and GitHub; (4) implement a browsing and search interface to the database of results; and (5) augment the search facility to use semantic similarity via the ontology. They will use the prototype system to explore variants of the code analysis methods, select the best, and assess the performance of inferring characteristics of software found in the repositories. For automated index creation to be feasible, software discovery and characterization algorithms need to improve, so that the index is complete and organized more meaningfully.

This project will explore the hypothesis that a deeper underlying knowledge structure, coupled with appropriate feature extraction and classification algorithms, can improve classification performance compared to past approaches. The use of ontologies to assist source code analysis has been explored in other work, but it has not been applied as proposed here. The project is expected to extend the state of the art in source code analysis and categorization.

The central question in this project is whether the ontology-based descriptions of software produced by the classification methods can compare with human labeling. To address this, and in addition to the intellectual merit of the classification approach described above, the researchers have also proposed unique methods for empirically evaluating the results of the classification, as follows: (a) assess the overlap between the output of their methods with the classifications already present in GitHub and SourceForge - the two software catalogs they propose to mine, (b) develop a test system to perform double-blind evaluation with human judges on the software that is classified and (c) compare the search in CASICS to Google using a set of benchmark search queries that users in astronomy and systems biology would issue for various scenarios, identified through a survey.