GAIA - FRAMEWORK ANNOTATION OF GENOMIC SEQUENCE

As increasing amounts of genomic sequence from many organisms become a vailable, and as DNA sequences become a primary reagent in biologic in vestigations, the role of annotation as a prospective guide for labora tory experiments will expand rapidly. Here we describe a process of hi gh-throughput, reliable annotation, called Framework annotation, which is designed to provide a foundation for initial biologic characteriza tion of previously unexamined sequence. To examine this concept in pra ctice, we have constructed Genome Annotation and Information Analysis (GAIA), a prototype software architecture that implements several elem ents important for framework annotation. The center of GAIA consists o f an annotation database and the associated data management subsystem that forms the software bus along which other components communicate. The schema for this database defines three principal concepts: (I) Ent ries, consisting of sequence and associated historical data; (2) Featu res, comprising information of biologic interest; and (3) Experiments, describing the evidence that supports Features. The database permits tracking of annotation results over time, as well as assessment of the reliability of particular results. New framework annotation is produc ed by CARTA, a set of autonomous sensors that perform automatic analys es and assert results into the annotation database. These results are available via a Web-based query interface that uses graphical lava app lets as well as text-based HTML pages to display data at different lev els of resolution and permit interactive exploration of annotation. We present results for initial application of framework annotation to a set of test sequences, demonstrating its effectiveness in providing a starting point for biologic investigation, and discuss ways in which t he current prototype can be improved. The prototype is available for p ublic use and comment at http://www.cbil.upenn.edu/gaia.