Charles B. Lawrence

Graph database systems

We have investigated using graphs as the foundation for database systems by developing a graph-based DBMS. We have demonstrated that: 1. Graph-based representations are useful for representing genome data. 2. A graph data model tailored to the requirements of genome data can be used as the basis of a database management system. 3. A graph database management system is a viable technology for storing genome data. We have found that graph-based technologies are useful in multiple aspects of database development, and we plan to expand on the capabilities of graphs for developing genome databases. >

Optimized homology searches of the gene and protein sequence data banks

Abstract A strategy is presented for searching the gene and protein sequence data banks which combines the use of two previously described algorithms. The implementation of this strategy is thoroughly evaluated with respect to sensitivity, specificity and speed. The establishment of standard benchmarks for comparing programs that search the sequence data banks for homology is proposed.

A graph-theoretic data model for genome mapping databases

Graphs are a natural foundation for genome map databases. Mapping and other genomic data can be clearly represented by graphs, and graphs can be stored in a database. Graphs are defined as a collection of nodes and arcs and can represent genomic objects and relationships between them. Mapping databases are needed to store the rapidly growing amount of mapping data. These databases must store the information contained in both published maps and laboratory notebooks. We describe a graph database which can store mapping data directly as graphs and formalize it as a graph-theoretic data model.<<ETX>>

An object model for genome information at all levels of resolution

An object model for genome data at all levels of resolution is described. The model was derived by considering the requirements for representing genome related objects in three application domains: genome maps, large-scale DNA sequencing, and exploring functional information in gene and protein sequences. The methodology used for the object-oriented analysis is also described.<<ETX>>

A graph conceptual model for developing human genome center databases

We have developed a representation of genome data which has proven itself useful for describing data at a Human Genome Center. Genomic data have a graph-like structure and representing the concepts and relationships of genetics as a graph simplifies the development of databases for genome laboratories. Graphs are a comfortable communication medium for biologists and computer scientists and graph diagrams assist in the development of databases by facilitating the exchange of expertise. We have tailored a graph language for modeling genomic data and describe our process of using graphs to develop genome databases.

Two new members of the OmpR superfamily detected by homology to a sensor-binding core domain.

SummaryThe OmpR superfamily includes proteins that act as transcriptional regulators of operons that respond to environmental stimuli. A homologous domain near the N-terminus, termed a sensor-binding core domain, is thought to play a role in recognition of a signal transduction protein. We have identified two previously unrecognized members of this regulator family of proteins: a 23.8-kd protein transcribed from theuvrC transcription unit and the PgtA gene product, which is a phosphoglycerate transport regulatory protein. The sensor-binding core domain is also present in four proteins that regulate bacterial sporulation and chemotaxis. The 23.8-kd protein also has sequence similarity to elongation factor Tu and two regulatory proteins: HtpR, the heat-shock regulatory protein, and TraJ, a regulator of expression of genes involved in conjugation. There is a 77-amino acid region near the C-terminus of the 23.8-kd protein that has 30% similarity with a 28.1-kd protein coded for by an open reading frame 5′ to the reading frame of the 23.8-kd protein in theuvrC transcription unit. Genetic distance analysis of amino acid sequences of proteins with a sensor-binding core domain suggests that the 23.8-kd protein and the chemotaxis regulatory proteins are distantly related to the other regulatory proteins in the OmpR superfamily.

Infection of bovine cells of embryonic origin by amphotropic retroviral vectors

Two amphotropic-based mouse retroviral vectors carrying the neomycin-resistance gene were used to infect four bovine cell lines. Two cell lines, bovine kidney and spleen cells, were refractory to the infection while two independent bovine cells of apparent embryonic origin were infected by the amphotropic retroviral vectors at a measurable liter. Southern blot analysis reveals the presence of neomycin-resistance gene in the G418- resistant bovine cells. The results demonstrate the successful transfer of a gene to bovine cells of embryonic origin using a murine retroviral vector system.

Data structures for DNA sequence manipulation

Two data structures designated Fragment and Construct are described. The Fragment data structure defines a continuous nucleic acid sequence from a unique genetic origin. The Construct defines a continuous sequence composed of sequences from multiple genetic origins. These data structures are manipulated by a set of software tools to simulate the construction of mosaic recombinant DNA molecules. They are also used as an interface between sequence data banks and analytical programs.

Application of fractal representation of genetic texts for recognition of genome functional and coding regions

By applying fractal representation of nucleotide sequences for plotting a set of functionally similar sequences, a new approach for classification of nucleic sequences was suggested and some measures of sequence similarity were introduced. Many examples of good separation of sequences belonging to different gene families were shown. The method does not require alignment procedure both for generating a recognition matrix of learning set and for searching homologous regions. The computer time does not depend on the length of the searching sequence and the fractal images of sequence sets can be compared easily by computer procedures as well as visually. The latter is especially convenient for representing the density of fractal mask as a third coordinate of the image. The method is successfully applied both for searching genes (globins, histories, etc.) and different kind of repetitive DNA sequences (Alu, LTR, etc.). The FRS approach is used also for revealing the gene structure in uncharacterized sequences. The fractal images for exons, introns, 5{prime}- and 3{prime}-region have significantly different patterns which permit one to find preliminary localizations of these gene regions.

Chemical modification as a tool for analysis of messenger RNA secondary structure in ribonucleoprotein particles

Chemical modification of unpaired bases is demonstrated in this study to be a reliable method for determining the conformation of nucleotides in mRNA. The modified nucleotides are identified by primer extension using reverse transcriptase. We have used this procedure to compare the structure of limited regions of SV40 T-antigen mRNA in solution, in nonpolysome-bound cytoplasmic messenger ribonucleoprotein particles, and in nuclear ribonucleoprotein complexes. The results indicate that SV40 T-antigen mRNA adopts a specific structure both in solution and when complexed with cellular proteins. The structures adopted by the mRNA in solution and in native cellular protein particles are very similar.