Carl F. Schaefer

The Pathway Interaction Database (PID, http://pid.nci.nih.gov) is a freely available collection of curated and peer-reviewed pathways composed of human molecular signaling and regulatory events and key cellular processes. Created in a collaboration between the US National Cancer Institute and Nature Publishing Group, the database serves as a research tool for the cancer research community and others interested in cellular pathways, such as neuroscientists, developmental biologists and immunologists. PID offers a range of search features to facilitate pathway exploration. Users can browse the predefined set of pathways or create interaction network maps centered on a single molecule or cellular process of interest. In addition, the batch query tool allows users to upload long list(s) of molecules, such as those derived from microarray experiments, and either overlay these molecules onto predefined pathways or visualize the complete molecular connectivity map. Users can also download molecule lists, citation lists and complete database content in extensible markup language (XML) and Biological Pathways Exchange (BioPAX) Level 2 format. The database is updated with new pathway content every month and supplemented by specially commissioned articles on the practical uses of other relevant online tools.

The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

A gene's expression pattern provides clues to its role in normal physiology and disease. To provide quantitative expression levels on a genome-wide scale, the Cancer Genome Anatomy Project (CGAP) uses serial analysis of gene expression (SAGE). Over 5 million transcript tags from more than 100 human cell types have been assembled. To enhance the utility of this data, the CGAP SAGE project created SAGE Genie, a web site for the analysis and presentation of SAGE data (http://cgap.nci.nih.gov/SAGE). SAGE Genie provides an automatic link between gene names and SAGE transcript levels, accounting for alternative transcription and many potential errors. These informatics advances provide a rapid and intuitive view of transcript expression in the human body or brain, displayed on the SAGE Anatomic Viewer. We report here an easily accessible view of nearly any gene's expression in a wide variety of malignant and normal tissues.

VHDL is a comprehensive language that allows a user to deal with design complexity. Design, and the data representing a design, are complex by the very nature of a modern digital system constructed fr