Open Competition 5 - Information Technology

Technologies for Target Assessment

Sponsor: Icoria, Inc. (formerly Paradigm Genetics, Inc.)

• Project Performance Period: 8/1/2002 - 10/18/2007
• Total project (est.): $23,584,513.00
• Requested ATP funds: $11,768,672.00

Determining gene function or mechanism of action as a basis for developing new pharmaceutical and chemical products is a key challenge in biotechnology. A variety of techniques, such as DNA sequencing and gene expression profiling, are used. Each has strengths and weaknesses, each organizes data in different ways and answers different questions, and none is sufficient to identify the function of all genes. Many potentially valuable relationships may remain obscure because there is no widely used means of combining and analyzing the large volumes of data generated by the different research methods. Paradigm Genetics and partner LION bioscience, Inc. (Cleveland, Ohio, facility) plan a five-year project to develop robust technologies that will improve data integration, transform data from different platforms into one coherent data set, and analyze these data sets to identify gene function or mechanism of action -- and potential product research targets -- rapidly, reliably, and efficiently. The new technologies will include algorithms, standards and protocols, decision trees, and analytical tools. Software and database components will be developed for integrating data both physically and logically as it is produced, through modification of a laboratory information management system. The key advance will be establishing statistical methods for combining data from a variety of sources into a coherent data set, an innovative concept that will be defined both conceptually and statistically. The development and validation of these data sets will require expertise in data management, statistics, biology, genetics and software engineering. Existing analytical tools will be selected and new tools developed as needed to effectively analyze the coherent data sets. The team will begin by establishing coherence for a relatively simple data set from a well-defined mechanism of action study and then extend this work to larger and more complicated data sets representative of high throughput genomics research. The analytical tools will be used to generate hypotheses of gene function and mechanism of action, and these hypotheses will be subjected to laboratory validation studies. Laboratory results will then feedback to tool development in an iterative process. The combination of experimental laboratory science and software engineering is a key innovation of the proposal. ATP support is needed to bring together this synergistic research team of a biotechnology company and a software development company because of the technical barriers in successfully integrating data across a wide variety of possible research technologies and biological systems. Available research capital is focused on safer projects to incrementally improve existing systems. If successful, the project will lead to a Target Assessment Technologies Suite (TATS) of software and database products applicable to any organism or cell culture system. TATS goes beyond data integration to allow researchers to create, validate and analyze coherent data sets to identify high quality targets. The ability to compare data across multiple research platforms in a way that is biologically relevant and statistically sound will greatly improve the ability to identify gene function and increase the number of product leads that succeed in clinical trials in the pharmaceutical and agrochemical industries. At present, more than 80 percent of new drug candidates fail during clinical trials; averting even a small percentage of these failures could save the pharmaceutical industry tens of millions of dollars annually. The proposed project will potentially revolutionize target and lead assessment, one of the biggest bottlenecks in drug discovery today.

For project information:

Melissa Matson, (919) 425-3725
mmatson@paragen.com

Active Project Participants

• Agilent Technologies, Inc. (Santa Clara, CA)
  [New Member since original JV was formed]
  
• IO Informatics (Emeryville, CA)
  [Original, Active Member]
  

ATP Project Manager

Francis Barros, (301) 975-2617
francis.barros@nist.gov