FUNCTIONAL BIOINFORMATICS: THE CELLULAR RESPONSE DATABASE

James Sorace^1,2,3, Kip Canfield¹, Steven Russell¹

1 Department of Information Systems, University of Maryland Baltimore County, ²The Department of Pathology and Laboratory Service Baltimore VA Medical Center, ³ Department of Pathology, University of Maryland at Baltimore School of Medicine, Baltimore, Maryland

Received 4/3/97 Accepted 10/24/97

2. INTRODUCTION

Biological scientists function in an increasingly data rich environment. With the rapid advancements in molecular biology, particularly at the level of characterizing large sets of gene products, the roles of factors influencing cellular gene expression and regulation will become increasingly important. The teratogenic drug thalidomide is an excellent example of this level of complexity. Depending on the dose, carrier and cell lines tested, various changes in lipopolysaccharide (LPS) induced tumor necrosis factor-alpha (TNF-alpha) gene regulation have been reported. These include inhibition (1,2,3,4,), as well as upregulation (5). Another example can be found in the use of cellular cytotoxicity data and cellular activity data to search for candidate anticancer drugs as outlined in a recent publication (6). In this strategy the cytotoxicity profile of several thousand compounds in 60 cell lines was compared against a panel of 113 biochemical properties of the cell lines. This allowed previously unrecognized relationships between drug sensitivity and cellular biochemical activities to be established. An improved information infrastructure will be required to manage the experimental data that is beginning to be produced in these settings.

A necessary prerequisite for any type of enterprise-wide information system implementation, is the development of detailed specifications and data models that determine what information is to be stored and what types of queries the database will support. The importance of this early phase of planning cannot be overemphasized. If useful information is not entered, or if it is poorly stored, the ability of the system to support user needs, will be compromised. Difficulties in querying the current biological databases have already been noted as a concern of the biotechnology and pharmaceutical industries (7). In this paper, we describe the Cellular Response Database (CRD;http://130.85.105.176:8080/assaydb/). The purpose of this database and its associated web site is to develop the prototype database and collaborative research tools required to store and retrieve the functional data outlined above. The database is unique in that it treats the cell population, the target gene of interest, and the agents influencing gene expression equally, allowing querying on traits of any of these entities. This is important as genetic responses can vary widely depending on cell type, state of differentiation, and on the biological agent.