Ron Caspi | SRI International (original) (raw)

Papers by Ron Caspi

Additional file 4 Set of 69 similar KEGG and EcoCyc pathways, used to generate Supplement Figure S2.

Pathway Tools is a bioinformatics software environment with a broad set of capabilities. The soft... more Pathway Tools is a bioinformatics software environment with a broad set of capabilities. The software provides genome-informatics tools such as a genome browser, sequence alignments, a genome-variant analyzer, and comparative-genomics operations. It offers metabolic-informatics tools, such as metabolic reconstruction, quantitative metabolic modeling, prediction of reaction atom mappings, and metabolic route search. Pathway Tools also provides regulatory-informatics tools, such as the ability to represent and visualize a wide range of regulatory interactions. The software creates and manages a type of organism-specific database called a Pathway/Genome Database (PGDB), which the software enables database curators to interactively edit. It supports web publishing of PGDBs and provides a large number of query, visualization, and omics-data analysis tools. Scientists around the world have created more than 9,800 PGDBs by using Pathway Tools, many of which are curated databases for import...

The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible resource for metaboli... more The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible resource for metabolic pathways and enzymes from all domains of life. The pathways in MetaCyc are experimentally determined, small-molecule metabolic pathways and are curated from the primary scientific literature. With more than 1400 pathways, MetaCyc is the largest collection of metabolic pathways currently available. Pathways reactions are linked to one or more well-characterized enzymes, and both pathways and enzymes are annotated with reviews, evidence codes, and literature citations. BioCyc (BioCyc.org) is a collection of more than 500 organism-specific Pathway/Genome Databases (PGDBs). Each BioCyc PGDB contains the full genome and predicted metabolic network of one organism. The network, which is predicted by the Pathway Tools software using MetaCyc as a reference, consists of metabolites, enzymes, reactions and metabolic pathways. BioCyc PGDBs also contain additional features, such as predicted operons, transport systems, and pathway holefillers. The BioCyc Web site offers several tools for the analysis of the PGDBs, including Omics Viewers that enable visualization of omics datasets on two different genome-scale diagrams and tools for comparative analysis. The BioCyc PGDBs generated by SRI are offered for adoption by any party interested in curation of metabolic, regulatory, and genomerelated information about an organism.

MetaCyc (MetaCyc.org) is a universal database of metabolic pathways and enzymes from all domains ... more MetaCyc (MetaCyc.org) is a universal database of metabolic pathways and enzymes from all domains of life. The pathways in MetaCyc are curated from the primary scientific literature, and are experimentally determined small-molecule metabolic pathways. Each reaction in a MetaCyc pathway is annotated with one or more well-characterized enzymes. Because MetaCyc contains only experimentally elucidated knowledge, it provides a uniquely high-quality resource for metabolic pathways and enzymes. BioCyc (BioCyc.org) is a collection of more than 350 organism-specific Pathway/ Genome Databases (PGDBs). Each BioCyc PGDB contains the predicted metabolic network of one organism, including metabolic pathways, enzymes, metabolites and reactions predicted by the Pathway Tools software using MetaCyc as a reference database. BioCyc PGDBs also contain predicted operons and predicted pathway hole fillers-predictions of which enzymes may catalyze pathway reactions that have not been assigned to an enzyme. The BioCyc website offers many tools for computational analysis of PGDBs, including comparative analysis and analysis of omics data in a pathway context. The BioCyc PGDBs generated by SRI are offered for adoption by any interested party for the ongoing integration of metabolic and genome-related information about an organism.

A systematic comparison of the MetaCyc and KEGG pathway databases

Microbe Magazine, 2011

Genome sequencing capabilities and capacity are so advanced that the genomes of virtually all mic... more Genome sequencing capabilities and capacity are so advanced that the genomes of virtually all microbial species of interest are likely to be deciphered during the next decade. Improved means for interpreting and applying this sequence information enhance its value. The BioCyc database collection and website include data for more than 1,000 microbial genomes as well as tools for analyzing that information. These resources help users to address key questions such as: What are the functions of the upstream and downstream neighbors of a gene? How far apart are the genes, and are they likely to form an operon? What is the sequence of the gene and DNA segments near it? What metabolic pathway does a gene play a role in?

The FASEB Journal, 2016

BioCyc.org is a genomic resource that contains more than 7600 Pathway/Genome Databases (PGDBs) fo... more BioCyc.org is a genomic resource that contains more than 7600 Pathway/Genome Databases (PGDBs) for organisms whose genomes have been completely sequenced. Although most PGDBs are bacterial, PGDBs e...

Frontiers in Microbiology, 2021

The EcoCyc model-organism database collects and summarizes experimental data for Escherichia coli... more The EcoCyc model-organism database collects and summarizes experimental data for Escherichia coli K-12. EcoCyc is regularly updated by the manual curation of individual database entries, such as genes, proteins, and metabolic pathways, and by the programmatic addition of results from select high-throughput analyses. Updates to the Pathway Tools software that supports EcoCyc and to the web interface that enables user access have continuously improved its usability and expanded its functionality. This article highlights recent improvements to the curated data in the areas of metabolism, transport, DNA repair, and regulation of gene expression. New and revised data analysis and visualization tools include an interactive metabolic network explorer, a circular genome viewer, and various improvements to the speed and usability of existing tools.

BMC Genomics, 2021

Background Enrichment or over-representation analysis is a common method used in bioinformatics s... more Background Enrichment or over-representation analysis is a common method used in bioinformatics studies of transcriptomics, metabolomics, and microbiome datasets. The key idea behind enrichment analysis is: given a set of significantly expressed genes (or metabolites), use that set to infer a smaller set of perturbed biological pathways or processes, in which those genes (or metabolites) play a role. Enrichment computations rely on collections of defined biological pathways and/or processes, which are usually drawn from pathway databases. Although practitioners of enrichment analysis take great care to employ statistical corrections (e.g., for multiple testing), they appear unaware that enrichment results are quite sensitive to the pathway definitions that the calculation uses. Results We show that alternative pathway definitions can alter enrichment p-values by up to nine orders of magnitude, whereas statistical corrections typically alter enrichment p-values by only two orders of ...

Pathogens, 2021

Porphyromonas gingivalis is an oral human pathogen. The bacterium destroys dental tissue and is a... more Porphyromonas gingivalis is an oral human pathogen. The bacterium destroys dental tissue and is a serious health problem worldwide. Experimental data and bioinformatic analysis revealed that the pathogen produces three types of lipopolysaccharides (LPS): normal (O-type), anionic (A-type), and capsular (K-type). The enzymes involved in the production of all three types of lipopolysaccharide have been largely identified for the first two and partially for the third type. In the current work, we use bioinformatics tools to predict biosynthetic pathways for the production of the normal (O-type) lipopolysaccharide in the W50 strain Porphyromonas gingivalis and compare the pathway with other putative pathways in fully sequenced and completed genomes of other pathogenic strains. Selected enzymes from the pathway have been modeled and putative structures are presented. The pathway for the A-type antigen could not be predicted at this time due to two mutually exclusive structures proposed in...

EcoSal Plus, 2014

EcoCyc is a bioinformatics database available at EcoCyc.org that describes the genome and the bio... more EcoCyc is a bioinformatics database available at EcoCyc.org that describes the genome and the biochemical machinery of Escherichia coli K-12 MG1655. The long-term goal of the project is to describe the complete molecular catalog of the E. coli cell, as well as the functions of each of its molecular parts, to facilitate a system-level understanding of E. coli . EcoCyc is an electronic reference source for E. coli biologists and for biologists who work with related microorganisms. The database includes information pages on each E. coli gene, metabolite, reaction, operon, and metabolic pathway. The database also includes information on E. coli gene essentiality and on nutrient conditions that do or do not support the growth of E. coli . The website and downloadable software contain tools for analysis of high-throughput data sets. In addition, a steady-state metabolic flux model is generated from each new version of EcoCyc. The model can predict metabolic flux rates, nutrient uptake rat...

Analytical Biochemistry, 1999

lipid-based reagent and electroporation, we conclude that two cell lines, J-774 and THP-1, are th... more lipid-based reagent and electroporation, we conclude that two cell lines, J-774 and THP-1, are the easiest to transfect. Transfection efficiency is very low for HL-60 and U-937 cell lines. This difference in cell reactivity probably results from their respective physiological state. The physiological cellular state influences cellular response since once differentiated, THP-1, HL-60, and U-937 can no longer be transfected. This fact appears to be characteristic of differentiated myelomonocytic cells, as also observed by other authors (4). Therefore, if required, the introduction of exogeneous genes must be carried out prior to the differentiation process if their effects are studied in the differentiated state. This can be achieved by transfection for either transient or stable expression. We did not find that in the myelomonocytic cell lines tested the overall transfer efficiency of electroporation was much higher than that obtained by the tested lipid-based reagent. ␤-Gal-expressing cells did not exceed 3% of the viable cells which represented 20-30% of the initial cell number. On the other hand, with the amount of chemical reagent we used, no cytotoxicity was observed. If viable cell number is taken into account, the overall number of transfected cells is roughly equivalent in the two transfer techniques. High cell mortality caused by electroporation is also detrimental for the cell culture so that dead cells must be disgarded for further cell culture. A smaller number of cells are required for transfection with the chemical reagent that we tested (10 6 instead of 10 7 cells). This is particularly interesting when cells are difficult to grow. The amount of plasmid is also lower in gene transfer using lipid-based reagent (4 instead of 40 g). Finally, in actuality it is wise to use electroporation only for a stable expression of genes introduced in sensible myelomonocytic cells since this gene transfer technique may induce adverse responses and impair cellular functions. In summary, this communication reports a differential cellular response to transfection among the four myelomonocytic cell lines, J-774, THP-1, HL-60, and U-937, tested. We also conclude that transfection with a lipid-based reagent is more advantageous than electroporation because in addition to the absence of cytotoxicity, fewer cells and less plasmid are required with nevertheless equivalent transfer efficiency.

The entries below are proposed additions and amendments to the Enzyme Nomenclature list. They wer... more The entries below are proposed additions and amendments to the Enzyme Nomenclature list. They were prepared for the NCIUBMB by Keith Tipton, Sinéad Boyce, Gerry Moss and Hal Dixon, with occasional help from other Committee members, and were put on the web by Gerry Moss. Comments and suggestions on these draft entries should be sent to Professor K.F. Tipton and Dr S. Boyce (Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland) by 20 May 2006, after which, the entries will be made official and will be incorporated into the main enzyme list. To prevent confusion please do not quote new EC numbers until they are incorporated into the main list.

Briefings in Bioinformatics

BioCyc.org is a microbial genome Web portal that combines thousands of genomes with additional in... more BioCyc.org is a microbial genome Web portal that combines thousands of genomes with additional information inferred by computer programs, imported from other databases and curated from the biomedical literature by biologist curators. BioCyc also provides an extensive range of query tools, visualization services and analysis software. Recent advances in BioCyc include an expansion in the content of BioCyc in terms of both the number of genomes and the types of information available for each genome; an expansion in the amount of curated content within BioCyc; and new developments in the BioCyc software tools including redesigned gene/protein pages and metabolite pages; new search tools; a new sequence-alignment tool; a new tool for visualizing groups of related metabolic pathways; and a facility called SmartTables, which enables biologists to perform analyses that previously would have required a programmer’s assistance.

Nucleic acids research, Jan 4, 2017

EcoCyc (EcoCyc.org) is a freely accessible, comprehensive database that collects and summarizes e... more EcoCyc (EcoCyc.org) is a freely accessible, comprehensive database that collects and summarizes experimental data for Escherichia coli K-12, the best-studied bacterial model organism. New experimental discoveries about gene products, their function and regulation, new metabolic pathways, enzymes and cofactors are regularly added to EcoCyc. New SmartTable tools allow users to browse collections of related EcoCyc content. SmartTables can also serve as repositories for user- or curator-generated lists. EcoCyc now supports running and modifying E. coli metabolic models directly on the EcoCyc website.