Toxicogenomics through the Eyes of Informatics: conference overview and recommendations.Virginia Bioinformatics Institute The Virginia Bioinformatics Institute (VBI) is a premier bioinformatics, computational biology, and systems biology research facility that opened on the Blacksburg campus of Virginia Tech in 2000. , in conjunction with National Institutes of Environmental Health Sciences, hosted a conference, "Toxicogenomics through the Eyes of Informatics Same as information technology and information systems. The term is more widely used in Europe. ," in Bethesda, Maryland Bethesda is an urbanized, but unincorporated, area in southern Montgomery County, Maryland, just Northwest of Washington, D.C. It takes its name from a church located there, the Bethesda Presbyterian Church, built in 1820 and rebuilt in 1850, which in turn took its name from , USA, on 12-13 May 2003. Researchers around the world met to discuss how the application of bioinformatics tools, methodologies, and technologies will enhance our understanding of how cells and organisms respond to toxins. Conference topics included statistical methods, quantitative molecular data sets, computational algorithms for data analysis, computational modeling
Computational biology is an interdisciplinary field that applies the techniques of computer science, applied mathematics, and statistics to address problems inspired by biology. , and information technology infrastructure for data and tool management. This meeting report is a summary of conference presentations, survey results, current toxicogenomics concerns, and future directions of the toxicogenomics community. In conclusion this report discusses toxicogenomics as related to environmental agents, cell-chemical reactions, and gene-environment interactions Gene-environment interaction is a term used to describe any phenotypic effects that are due to interactions between the environment and genes. Naive nature versus nurture debates assume that variation in a given trait is primarily due to either genes, or the individual's . Key words: bioinformatics, cell-chemical reactions, environmental agents, toxicogenomics, toxins, Virginia Bioinformatics Institute.
The availability of genome-scale DNA sequence DNA sequence Genetics The precise order of bases–A,T,G,C–in a segment of DNA, gene, chromosome, or an entire genome. See Base pair, Base sequence analysis, Chromosome, Gene, Genome. information has radically altered life science research. Moreover, the human genome The human genome is the genome of Homo sapiens, which is composed of 24 distinct pairs of chromosomes (22 autosomal + X + Y) with a total of approximately 3 billion DNA base pairs containing an estimated 20,000–25,000 genes. project has revolutionized the practice of biology and the potential of medicine. The field of toxicology toxicology, study of poisons, or toxins, from the standpoint of detection, isolation, identification, and determination of their effects on the human body. Toxicology may be considered the branch of pharmacology devoted to the study of the poisonous effects of drugs. will be greatly augmented by the application of the knowledge of genetics and its sister sciences. Consequently, researchers have entered a new area of specialty--toxicogenomics--the marriage of toxicology and genomics. Data generated by such research will impact many areas including health and environmental sciences. In addition, the science and health care communities will also be better able to identify a wide range of human health risks. However, to realize the potential of toxicogenomics, a global view of gene function and temporal and spatial regulations for all genes at different physiological or pathological states Noun 1. pathological state - a physical condition that is caused by disease
physical condition, physiological condition, physiological state - the condition or state of the body or bodily functions or developmental stages is paramount. The expanding field of bioinformatics offers the convergence of biological, mathematical, and computational platforms to better understand the effects of toxins on biological systems.
Scientists using data developed by the modern advent of biotechnology need novel and efficient bioinformatics tools to monitor gene-environment interactions on a large scale. These bioinformatics platforms (hardware, software, portals, and models, for example) will allow the conversion of data into useful knowledge to prevent disease resulting from environmental exposures.
The conference "Toxicogenomics through the Eyes of Informatics" was held 12-13 May 2003 in Bethesda, Maryland, USA. The purpose of the conference was to bring together researchers around the world to discuss the application of bioinformatics tools, methodologies, and technologies in order to increase our understanding of how cells and organisms respond to toxins. By understanding the mechanisms from a genomic and a systems view, investigators can more rationally assess and evaluate the risk that toxins pose to humans. The format of this meeting aimed to facilitate input from the range of disciplines that can now provide insight into the field. Table 1 illustrates the conference program with speakers and events. By integrating experimental studies at the structural, molecular, and cellular levels with mathematical and biochemical modeling and informatics, the conference surveyed the integration and merger of advancing technologies. This conference provided a forum to explore the potential applications and implications of the new technologies, centering on toxicogenomics research platforms.
Recommendations and Survey Report
Researchers completed a survey about the future and importance of toxicogenomics (Table 2). The presentations and survey responses are summarized in the following observations:
* The complex characteristics of biological data generated by bioinformatics approaches (genomics, transcriptomics, metabolomics, proteomics) offer an opportunity to explore data analysis and standardization standardization
In industry, the development and application of standards that make it possible to manufacture a large volume of interchangeable parts. Standardization may focus on engineering standards, such as properties of materials, fits and tolerances, and drafting . Furthermore, data analysis via mathematical and biochemical modeling is paramount in predicting the effects of toxins on biological systems.
* Novel visualization tools will be required for researchers to realize the usefulness of bioinformatics data in toxicogenomics research, For investigators to catalyze cat·a·lyze
To modify, especially to increase, the rate of a chemical reaction by catalysis.
to cause or produce catalysis. forward movement in these new directions, however, baseline (or normal) data for systems, including normal ranges of variation, must be generated and centrally stored in publicly available databases.
* To study the effects of toxins on biological organisms holistically, we must develop more sophisticated and robust computational methods and bioinformatics infrastructures for biological knowledge discovery, including novel [information technology (IT)] and database applications. In addition, predictive modeling will allow for greater understanding and, in turn, knowledge extraction from metabolic and proteomic profiles currently being generated.
* To develop and establish coordinated database and informatics platforms (e.g., portals) for data exchange and analysis, we need to define primary end-user needs and major issues facing relevant subdisciplines. The computational and networking needs for toxicogenomics research should be defined. Moreover, the system must integrate with similar efforts in other health-related disciplines to merge all areas of the life sciences in a scalable, flexible system. This effort will depend on exploring data standards and system interoperability The capability of two or more hardware devices or two or more software routines to work harmoniously together. For example, in an Ethernet network, display adapters, hubs, switches and routers from different vendors must conform to the Ethernet standard and interoperate with each other. concurrently. The development of toxicogenomics data generation center(s) of excellence linked via bioinformatics center(s) of excellence would allow the compilation, analysis, and sharing of relevant data and tools.
* Toxicogenomics research programs should be developed to facilitate interoperability among the varying activities under way. Each individual research project will be more successful, ultimately, if it is part of a larger coordinated and synergistic synergistic /syn·er·gis·tic/ (sin?er-jis´tik)
1. acting together.
2. enhancing the effect of another force or agent.
* Mathematical modeling
* Several reports concur CONCUR - ["CONCUR, A Language for Continuous Concurrent Processes", R.M. Salter et al, Comp Langs 5(3):163-189 (1981)]. that the demand for qualified bioinformaticians far outstrips the current number of qualified graduates. The development of multidisciplinary educational and training programs in bioinformatics, and training for toxicogenomics research in particular, must be in step with scientific discovery.
* Programs to support additional toxicogenomics conferences and workshops would allow communities to foster communication and coordinate efforts.
Bioinformatics tools for disease research will catalyze our quest to understand how individuals differ in their susceptibility to environmental agents and how these susceptibilities change over time. As the inherent goal of systems biology Systems biology, a field of study in the biosciences, focuses on the systematic study of complex interactions in biological systems. Particularly from 2000 onwards, the term is used widely in the biosciences, and in a variety of contexts. continues to intertwine experimentation, mathematical modeling, and computation, enhancing the investment in each of these efforts will hasten has·ten
v. has·tened, has·ten·ing, has·tens
To move or act swiftly.
1. To cause to hurry.
2. our understanding of cell-chemical interactions. At this level, functional, structural, and comparative analysis help provide insights into the environmental influence predisposing plants, animals, and humans to disease. Recent contributions of bioinformatics research have yielded molecular data on expressed genes (RNA RNA: see nucleic acid.
in full ribonucleic acid
One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic ), proteins, and metabolites Metabolites
Substances produced by metabolism or by a metabolic process.
Mentioned in: Interactions . Unlike genomic sequencing genomic sequencing
The sequencing of the entire genome of an organism.
A Closer Look The technique that allows researchers to read and decipher the genetic information found in the DNA of anything from bacteria to plants to animals is (DNA DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. ), proteomic, metabolomic, and transcriptomic data provide "state" information that helps form a dynamic description of how the organism interacts with its environment. Age, developmental stage, general health, and nutritional status nutritional status,
n the assessment of the state of nourishment of a patient or subject. have significant influence on disease outbreaks, whether caused by environmental pollution, toxic agents, or pathogens. An integrated approach to exposure assessment, epidemiology, and data collection, for example, would allow quicker identification of susceptibility genes and characterization of their functions. If bioinformatics data relating to relating to relate prep → concernant
relating to relate prep → bezüglich +gen, mit Bezug auf +acc human disease, regardless of cause, could be integrated and manipulated via bioinformatics platforms available to all research stakeholders Stakeholders
All parties that have an interest, financial or otherwise, in a firm-stockholders, creditors, bondholders, employees, customers, management, the community, and the government. , the scientific community could achieve an integrated view of gene-environment interaction at the level of whole organisms.
This resulting comprehensive catalog of human gene variation and response would increase our understanding of chronic disease. Subsequently, our capability to control environmental toxin toxin, poison produced by living organisms. Toxins are classified as either exotoxins or endotoxins. Exotoxins are a diverse group of soluble proteins released into the surrounding tissue by living bacterial cells. levels and pathogens that cause disease to plants, animals, and humans would increase. However, many of the clinical, scientific, and pathogen Pathogen
Any agent capable of causing disease. The term pathogen is usually restricted to living agents, which include viruses, rickettsia, bacteria, fungi, yeasts, protozoa, helminths, and certain insect larval stages. data generated today are not put into a meaningful and integrated context that would enable problem solving problem solving
Process involved in finding a solution to a problem. Many animals routinely solve problems of locomotion, food finding, and shelter through trial and error. via bioinformatics applications. Limited bioinformatics platforms allow biological annotations to be easily integrated with related host-baseline or broader environment or ecosystem data when available. A centrally funded program in bioinformatics research dedicated to the synthesis and informatics to support toxicogenomics research would provide for the realization of unprecedented opportunities to elucidate e·lu·ci·date
v. e·lu·ci·dat·ed, e·lu·ci·dat·ing, e·lu·ci·dates
To make clear or plain, especially by explanation; clarify.
To give an explanation that serves to clarify. biological responses to environmental toxicants and stressors at the genomic level.
Table 1. Toxicogenomics through the Eyes of Informatics: conference program and presentations. Session/speaker Affiliation Title of presentation IT infrastructure Barbara Eckman IBM Life Sciences Data integration and management for molecular and cell biology Rolf Apweiler European Integration and Bioinformatics standardization: Institute driving forces in the development of database resources Shankar Subramaniam University of Bioinformatics California San Diego challenges in the post-genomic era Computational modeling and simulation Zoltan Oltvai Northwestern Organization of University cellular networks Pedro Mendes Virginia Inferring biochemical Bioinformatics networks from Institute functional genomic data Hiroaki Kitano Luncheon address Reinhard Laubenbacher Virginia Reverse-engineering in Bioinformatics computational Institute immunology Herbert Sauro Keck Graduate Data exchange and Institute programmatic resource sharing: the Systems Biology Workbench (SBW), bioSPICE, and the Systems Biology Markup language John Tyson Virginia Polytechnic From molecular Institute and State regulatory networks to University cell physiology Charles deLisi Boston University Inferring the function of genes and networks Statistical methods and quantitative molecular data sets Bruce Weir North Carolina State Association patterns in University the human genome Lloyd Sumner Noble Foundation Proteomics and metabolomics: temporal snapshots of the biochemistry of Medicago truncatula Carolyn Mattingly Mount Desert Island The Comparative Biological Laboratory Toxicogenomics Database (CTD): new perspectives through data integration and curation John Quackenbush The Institute for Interpreting expression Genomic Research through biology Ute Roessner-Tunali Max-Planck-Institute Contrasting and for Molecular Plant combining information Physiology derived from the systems biology approaches of metabolite and transcript profiling Computational algorithms for data analysis and visualization Heike Hofmann Iowa State University Graphical opportunities in exploring microarray data Lior Pachter University of Comparative genomics California Berkeley by phylogenetic shadowing Tarif Awad Affymetrix, Inc. Gene ontology graphs as mining and display tools for gene expression data Keith Allen Paradigm Genetics Integrating metabolomic and gene expression data Computational biology: looking forward Stefan Unger Sun Microsystems Computational biology: challenges and opportunities Congressman Virgil H. Fifth District of Passing the hat Goode Jr. Virginia Table 2. Conference participant questionnaire. In your view, what are critical areas of research--that if enhanced via additional funding--would enable the integration and use of mathematics, modeling, simulation, and IT infrastructure to enhance our understanding of cell-chemical interactions? How do you think experimental approaches will be altered or enhanced via advances in mathematics, modeling, simulation, and IT infrastructure? For example, can experimental designs be altered to maximize data set utility? How might mathematics, modeling, simulation, and IT infrastructure alter laboratory, macrostructures, and "omics" data generation and vice versa? What do experimentalists require most of mathematics, modeling, simulation, and IT infrastructure to remove key bottlenecks?
Kenneth Olden old·en
Of, relating to, or belonging to time long past; old or ancient: olden days.
[Middle English : old, old; see old + -en, adj. , (1) Neysa Call, (2) Bruno Sobral, (2) and Robin Oakes Robin Oake QPM is the former Chief Constable of the Isle of Man Constabulary and prior to that Assistant Chief Constable in the Greater Manchester Police.
He was Chief Constable of the Isle of Man from 1986 to 1999, when he was succeeded by Mike Culverhouse. (2)
(1) National Institute of Environmental Health Sciences The National Institute of Environmental Health Sciences (NIEHS) is one of 27 Institutes and Centers of the National Institutes of Health (NIH),which is a component of the Department of Health and Human Services (DHHS). The Director of the NIEHS is Dr. David A. Schwartz. , National Institutes of Health, Department of Health and Human Services Noun 1. Department of Health and Human Services - the United States federal department that administers all federal programs dealing with health and welfare; created in 1979
Health and Human Services, HHS , Research Triangle Park Research Triangle Park, research, business, medical, and educational complex situated in central North Carolina. It has an area of 6,900 acres (2,795 hectares) and is 8 × 2 mi (13 × 3 km) in size. Named for the triangle formed by Duke Univ. , North Carolina North Carolina, state in the SE United States. It is bordered by the Atlantic Ocean (E), South Carolina and Georgia (S), Tennessee (W), and Virginia (N). Facts and Figures
Area, 52,586 sq mi (136,198 sq km). Pop. , USA; (2) Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University Virginia Polytechnic Institute and State University, at Blacksburg; land-grant and state supported; coeducational; chartered and opened 1872 as an agricultural and mechanical college. , Blacksburg, Virginia Blacksburg is an incorporated town located in Montgomery County, Virginia. As of the 2000 census, the town had a total population of 39,573, making it one of Virginia's larger towns. , USA
Address correspondence to B, Sobral, Virginia Bioinformatics Institute, Virginia Tech, Bioinformatics Facility 1 (0477), Blacksburg, VA 24061 USA. Telephone: (540) 231-1259, Fax: (540) 231-2606. E-mail: email@example.com
We thank J. Selkirk from the National Institutes of Environmental Health Sciences for his scientific guidance. We also thank C. Phillips from Virginia Bioinformatics Institute for her assistance with conference arrangements and logistics.
The authors declare they have no competing financial interests.
Received 14 October 2003; accepted 31 March 2004.