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Biomedical subjects

S Paley

Publications and source records attributed to S Paley.

5 recordsLinked to original sources

An evidence ontology for use in pathway/genome databases.

An important emerging need in Model Organism Databases (MODs) and other bioinformatics databases (DBs) is that of capturing the scientific evidence that supports the information within a DB. This need has become particularly acute as more DB content consists of computationally predicted information, such as predicted gene functions, operons, metabolic pathways, and protein properties. This paper presents an ontology for encoding the type of support and the degree of support for DB assertions, and for encoding the literature source in which that support is reported. The ontology includes a hierarchy of 35 evidence codes for modeling different types of wet-lab and computational evidence for the existence of operons and metabolic pathways, and for gene functions. We also describe an implementation of the ontology within the Pathway Tools software environment, which is used to query and update Pathway/Genome DBs such as EcoCyc, MetaCyc, and HumanCyc.

Computational Biology↗

Database verification studies of SWISS-PROT and GenBank.

PROBLEM STATEMENT: We have studied the relationships among SWISS-PROT, TrEMBL, and GenBank with two goals. First is to determine whether users can reliably identify those proteins in SWISS-PROT whose functions were determined experimentally, as opposed to proteins whose functions were predicted computationally. If this information was present in reasonable quantities, it would allow researchers to decrease the propagation of incorrect function predictions during sequence annotation, and to assemble training sets for developing the next generation of sequence-analysis algorithms. Second is to assess the consistency between translated GenBank sequences and sequences in SWISS-PROT and TrEMBL. RESULTS: (1) Contrary to claims by the SWISS-PROT authors, we conclude that SWISS-PROT does not identify a significant number of experimentally characterized proteins. (2) SWISS-PROT is more incomplete than we expected in that version 38.0 from July 1999 lacks many proteins from the full genomes of important organisms that were sequenced years earlier. (3) Even if we combine SWISS-PROT and TrEMBL, some sequences from the full genomes are missing from the combined dataset. (4) In many cases, translated GenBank genes do not exactly match the corresponding SWISS-PROT sequences, for reasons that include missing or removed methionines, differing translation start positions, individual amino-acid differences, and inclusion of sequence data from multiple sequencing projects. For example, results show that for Escherichia coli, 80.6% of the proteins in the GenBank entry for the complete genome have identical sequence matches with SWISS-PROT/TrEMBL sequences, 13.4% have exact substring matches, and matches for 4.1% can be found using BLAST search; the remaining 2.0% of E.coli protein sequences (most of which are ORFs) have no clear matches to SWISS-PROT/TrEMBL. Although many of these differences can be explained by the complexity of the DB, and by the curation processes used to create it, the scale of the differences is notable.

Algorithms↗

Integrated pathway-genome databases and their role in drug discovery.

Integrated pathway-genome databases describe the genes and genome of an organism, as well as its predicted pathways, reactions, enzymes and metabolites. In conjunction with visualization and analysis software, these databases provide a framework for improved understanding of microbial physiology and for antimicrobial drug discovery. We describe pathway-based analyses of the genomes of a number of medically relevant microorganisms and a novel software tool that visualizes gene-expression data on a diagram showing the whole metabolic network of the microorganism.

Anti-Bacterial Agents↗

Integrated access to metabolic and genomic data.

The EcoCyc system consists of a knowledge base (KB) that describes the genes and intermediary metabolism of Escherichia coli, and a graphical user interface (GUI) for accessing that knowledge. This paper addresses two problems: How can we create a GUI that provides integrated access to metabolic and genomic data? We describe the design and implementation of visual presentations that closely mimic those found in the biology literature, and that offer hypertext navigation among related entities, and multiple views of the same entity. We employ a frame knowledge representation system (FRS) called HyperTHEO to manage the EcoCyc knowledge base. Among the advantages of FRSs are an expressive data model for capturing the complexities of biological information, and schema-evolution capabilities that facilitate the constant schema changes that biological databases tend to undergo. HyperTHEO also includes rule-based inference facilities that are the foundation of expert systems, a constraint language for maintaining data integrity, and a declarative query language. A graphic KB editor and browser allow the EcoCyc developers to interactively inspect and modify this evolving KB.

Artificial Intelligence↗

HinCyc: a knowledge base of the complete genome and metabolic pathways of H. influenzae.

We present a methodology for predicting the metabolic pathways of an organism from its genomic sequence by reference to a knowledge base of known metabolic pathways. We applied these techniques to the genome of H. influenzae by reference to the EcoCyc knowledge base to predict which of 81 metabolic pathways of E. coli are found in H. influenzae. The resulting prediction is a complex hypothesis that is presented in computer form as HinCyc: an electronic encyclopedia of the genes and metabolic pathways of H. influenzae. HinCyc connects the predicted genes, enzymes, enzyme-catalyzed reactions, and biochemical pathways in a WWW-accessible knowledge base to allow scientists to explore this complex hypothesis.

Computer Communication Networks↗