Computer Systems Laboratory (CSL) has integrated laboratory acquisition and data processing computer systems in the Receptor Biochemistry and Molecular Biology Branch (RBMB), NINDS. Seven automated DNA sequencers produce 168 sequence fragments or about 60,000 bases of sequence per day. We have specified, installed and administered the computer facilities used for analyzing and archiving this large volume of DNA sequence data. In FY92 CSL provided system management, programming and database support for the cDNA Project, funded in part by the Department of Energy Center for Disease Control, that seeks to identify and characterize the nearly 30,000 genes expressed in the human brain, producing expressed sequence tags (ESTs) from human brain cDNAs at the rate of approximately 100 templates/day. Over 6,000 EST sequences have been published and submitted to GenBank. Similarly, the goal of the smallpox project, a collaboration with the Department of Energy Centers for Disease Control (DECDC), is to sequence completely the 170 kilo-base smallpox genome prior to its destruction in December, 1993. Genome sequencing and assembly is nearly complete and analysis of the finished sequence is underway. System management assistance included daily operations support for this high-volume production system, specification and initiation of system backup procedures, and installation and testing of commercial and public domain software. A set of programs was created to batch process ESTs for database searching. A protein library motif comparison program was ported to the CSL parallel computer. CSL is purchasing a special purpose sequence assembly and analysis system based on a high speed text search computational engine to be made available to the NIH intramural community as a shared resource connected to the NIH network. During FY92, emphasis has continued to shift from sequence assembly to sequence analysis and data archival/retrieval. CSL will continue to concentrate on methods for processing and archiving extremely large volumes of sequence data, and help to make technologies developed through this project available to other investigators at NIH.