George S. Michaels

Accumulation and decay of DG42 gene products follow a gradient pattern during Xenopus embryogenesis

The DG42 gene is expressed during a short window during embryogenesis of Xenopus laevis. The mRNA for this gene can be first detected just after midblastula, peaks at late gastrula, and decays by the end of neurulation. The sequence of the DG42 cDNA and genomic DNA predicts a 70,000-Da protein that is not related to any other known protein. Antibodies prepared against portions of the DG42 open reading frame that had been expressed in bacteria detected a 70,000-Da protein in the embryo with a temporal course of appearance and decay that follows that of the RNA by several hours. Localization of the mRNA in dissected embryos and immunohistochemical detection of the protein showed that DG42 expression moves as a wave or gradient through the embryo. The RNA is first detected in the animal region of the blastula, and by early gastrula is found everywhere except in the outer layer of the dorsal blastopore lip. By midgastrula DG42 protein is present in the inner ectodermal layer and the endoderm; it disappears from dorsal ectoderm as the neural plate is induced and later decays in a dorsoventral direction. The last remnants of DG42 protein are seen in ventral regions of the gut at the tailbud stage.

An Integrated Database to Support Research on Escherichia Coli

We have used logic programming to design and implement a prototype database of genomic information for the model bacterial organism Escherichia coli. This report presents the fundamental database primitives that can be used to access and manipulate data relating to the E. coli genome. The present system, combined with a tutorial manual, provides immediate access to the integrated knowledge base for E. coli chromosome data. It also serves as the foundation for development of more user-friendly interfaces that have the same retrieval power and high-level tools to analyze complex chromosome organization.

Searching for genomic organizational motifs: Explorations of the Escherichia coli chromosome☆

Understanding the coordinated control of gene expression is a central goal for much of the work in molecular biology. In order to understand how the mechanics of these control systems operate at the genome level, the data for the genetic organization of the model organism in question needs to be accessible. In previous work, we developed an integrated database to support analysis of the Escherichia coli genome. That system provided a pidgin English query facility, rudimentary pattern matching capabilities, and the ability to rapidly extract answers to a wide variety of questions about the organization of the E. coli genome. We have used a parser/grammar approach to identify the chromosomal positions of all of the mapped tRNA genes to be found in the aligned sequence fragments. Also, we have used this integrated data set to explore the global organization of the E. coli chromosome. We have begun to develop regulation classifications based on the arrangements of control features in relation to specific genetic control components. For example, using the individual DNA sequences for 111 known transcriptional promoters as a the starting position for analysis, we have identified the relative positions of potential control sites for 47 different procaryotic transcription factors, sigma factor 70 binding sites, and potential ribosome binding sites that occur within the region −500 to +500 bases upstream or downstream of the anchor position (the first base of the sequence feature). We have defined local descriptions for regulation based on the cross-correlated control features revealed through these analyses.

Metabolic pathway interface to molecular biology databases

We present results of providing database support to biomedicine via federation of SDB Cooperation/Integration based upon the KEGG GUI for molecular biology. The federation provides a common link to three molecular biology databases. The added value of the federation is freedom from consulting multiple references to ascertain the full set of enzymatic reactions in a metabolic pathway, and the option of selecting multiple queries to submit to the federated SDBs. Each of the SDBs is extensive, but incomplete. The union of the SDBs, implemented transparently by the federation, is more complete. Each SDB provides a different approach to the options available for data presentation and a different set of Web server tools for data analysis. Thus, an important part of the added value of the federation is the cross-fertilization available in the union of the molecular biological content, the presentation of data, and the tools available for analysis.

Comparative analysis of genomic data: A global look at structural and regulatory features

One of the goals of any large scale DNA sequencing project is to understand the molecular details about the metabolic control sites that will be found in the sequence of the chromosome region being studied. In addition, once an interesting observation has been made, questions will quickly arise concerning the distribution of such sites within the genome and how well the same observations hold between related species. This paper will discuss the authors` approach toward building a flexible analysis environment that facilitates the analysis of genomic sequence data. The Integrated Genomic Database (IGD), developed by Ray Hagstrom, Ross Overbeek, Morgan Price and Dave Zawada at the Argonne National Laboratory, organizes genome mapping and sequencing data to provide a global chromosome view for multiple genomes. The authors describe here their use of the IGD system and how they employ it for relational analysis of sequence features that are found distributed throughout the genome under study. The primary goal of this work is to provide a system to support research on the global organization of genomic regulation patterns.

GenoGraphics for OpenWindows{trademark}

GenoGraphics is a generic utility for constructing and querying one-dimensional linear plots. The outgrowth of a request from Dr. Cassandra Smith for a tool to facilitate her genome mapping research. GenoGraphics development has benefited from a continued collaboration with her. Written in Sun Microsystem`s OpenWindows environment and the BTOL toolkit developed at Argonne National Laboratory. GenoGraphics provides an interactive, intuitive, graphical interface. Its features include: viewing multiple maps simultaneously, zooming, and querying by mouse clicking. By expediting plot generation, GenoGraphics gives the scientist more time to analyze data and a novel means for deducing conclusions.