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PubMed2003

Applications of pharmacogenomics in general dental practice.

The human oral cavity represents a complex ecology of approximately 500 microbial species existing as commensals, and interacting with human/host factors. Perturbation of this ecosystem can lead to diseases of the oral cavity. The oral cavity also acts as a mirror of complex systemic diseases. Unique challenges and opportunities in oral healthcare exist in the diagnosis and treatment of primary disorders of the oral cavity or manifestations of systemic diseases. The completion of human and microbial genome projects has provided a wealth of information that will permit the application of pharmacogenomics - how genetic variations within the commensal and the host will impact the efficacy of drugs, and the diagnosis and treatment of oral disease. This review highlights opportunities focusing on oral health where pharmacogenomics can be applied.

Diagnosis, Oral↗
PubMed2005

Proteomics for biodefense applications: progress and opportunities.

The increasing threat of bioterrorism and continued emergence of new infectious diseases has driven a major resurgence in biomedical research efforts to develop improved treatments, diagnostics and vaccines, as well as increase the fundamental understanding of the host immune response to infectious agents. The availability of multiple mass spectrometry platforms combined with multidimensional separation technologies and microbial genomic databases provides an unprecedented opportunity to develop these much needed resources. An overview of current proteomic strategies applied to microbes and viruses considered potential bioterrorism agents is presented. The emerging area of immunoproteomics as applied to the development of new vaccine targets is also summarized. These powerful research approaches can generate a multitude of potential new protein targets; however, translating these proteomic discoveries to useful counter-bioterrorism products will require large collaborative research efforts across multiple basic science and clinical disciplines. A translational proteomic research paradigm illustrating this approach using influenza virus as an example is discussed.

Adult↗
PubMed2002

Protein interaction domain mapping for the selection of validated targets and lead compounds in the anti-infectious area.

Despite considerable progress in the analysis of microbial genomes, the number of validated targets suitable for the development of drugs acting on agents causing infectious diseases remains modest. The diversity of new chemical entities specific for such targets has almost not increased over the last years, while resistance to anti-infectious drugs has, in contrast, become a real threat in certain surroundings. New strategies are thus needed for selecting novel validated targets. We discuss here a combined approach which uses protein interaction mapping as the basic strategy to identify interacting domains which then serve to validate newly identified targets. The interactome of Helicobacter pylori is used as model to successively describe high-throughput protein interaction mapping, use of the H. pylori data to predict the interactome from other bacteria, analysis of interacting domains, and evaluation of the capacity of one such domain to block synthesis of flagella. The general applicability of this approach to target identification and validation, and to development of novel compounds is also discussed.

Bacterial Proteins↗
PubMed2026

Trustworthy Agentic AI in Bioinformatics: From Workflow Automation to Traceable and Validated Biological Inference.

Agentic artificial intelligence is extending bioinformatics beyond conversational assistance by enabling systems to select tools, execute code, revise analytical plans, and interpret biological data. These capabilities may accelerate research, but they also redistribute decisions that determine whether biological conclusions are valid. We conducted a targeted, structured PubMed search in July 2026 and identified 11 peer-reviewed agentic bioinformatics systems for descriptive review based on predefined eligibility criteria for analytical decision-making, tool or code execution, iterative evaluation, or coordinated agent activity. The evidence base covered single-cell transcriptomics, microbial genomics, cancer genomics, and omics applications, together with methodological literature on reproducibility and biological validation. We examined how current systems report delegated authority, provenance, validation, evidence, abstention, and human oversight. Existing platforms implement safeguards such as sandboxed execution, restricted commands, interaction logs, evidence identifiers, automated checks, critic agents, quality scores, and expert assessment. However, published reports rarely provide a connected account linking the original biological question to samples, reference resources, analytical decisions, computational actions, statistical results, supporting evidence, validation outcomes, and final claims. We distinguish inherited bioinformatics errors, errors amplified through autonomous action, and emergent failures arising from memory, retrieval, tool interaction, or agent coordination. We further propose a multidimensional decision-rights profile, consequence-sensitive validation gates, and a claim-to-evidence provenance architecture organized through the Traceable History of Research Evidence, Agent Actions, and Decisions in Bioinformatics (THREAD-Bio) framework. Illustrative cases show that technically successful execution may still support misleading inference. Trustworthy agentic bioinformatics therefore requires claims to remain reconstructible, challengeable, validated, and proportionate to the evidence.

accountable autonomy↗
PubMed1999

Optical mapping of Plasmodium falciparum chromosome 2.

Detailed restriction maps of microbial genomes are a valuable resource in genome sequencing studies but are toilsome to construct by contig construction of maps derived from cloned DNA. Analysis of genomic DNA enables large stretches of the genome to be mapped and circumvents library construction and associated cloning artifacts. We used pulsed-field gel electrophoresis purified Plasmodium falciparum chromosome 2 DNA as the starting material for optical mapping, a system for making ordered restriction maps from ensembles of individual DNA molecules. DNA molecules were bound to derivatized glass surfaces, cleaved with NheI or BamHI, and imaged by digital fluorescence microscopy. Large pieces of the chromosome containing ordered DNA restriction fragments were mapped. Maps were assembled from 50 molecules producing an average contig depth of 15 molecules and high-resolution restriction maps covering the entire chromosome. Chromosome 2 was found to be 976 kb by optical mapping with NheI, and 946 kb with BamHI, which compares closely to the published size of 947 kb from large-scale sequencing. The maps were used to further verify assemblies from the plasmid library used for sequencing. Maps generated in silico from the sequence data were compared to the optical mapping data, and good correspondence was found. Such high-resolution restriction maps may become an indispensable resource for large-scale genome sequencing projects.

Animals↗
PubMed2000

The ATCG of drug discovery.

The publication of human and microbial genomic sequences has resulted in the availability of large amounts of data that are directly relevant to the discovery of novel and useful drug targets. The elucidation of the function of new genes is not a simple matter and human genetic studies have been among the most useful in identifying genes implicated in disease, although homologs, or orthologs, of human genes in mouse, worm, fly and yeast genomes have also been useful in deciphering gene function. The advent of genomics has led into the study of protein structure and function under the rubric of proteomics. Proteins function in a cell mostly by interacting with other proteins, and protein interaction maps of cellular circuits are now available. Screening strategies to address protein-protein interactions are being developed, and many drug targets in the future are expected to be directed towards these interactions. In addition to using genetic and analytical approaches for finding new drug targets, chemical libraries can be used to inhibit the activity of new proteins, and thus reveal function. The combination of high-throughput screening with testing compounds for ADME (absorption, distribution, metabolism and excretion) and toxicity will help in the early clarification of clinical utility of both new drug targets, as well as drug candidates.

Animals↗
PubMed2003

Using flow cytometry to quantify microbial heterogeneity.

Flow cytometry is a powerful technique for the study of single cells, and thus it is of particular utility in the study of heterogeneity in microbial populations. This review seeks to highlight the role of flow cytometric analyses in studies of microbial heterogeneity, drawing wherever possible on recently published research articles. Whilst microbial heterogeneity is well documented in both natural and laboratory environments, the underlying causes are less well understood. Possible sources for the heterogeneity that is observed in microbial systems are discussed, together with the flow cytometric tools that aid its study. The role of flow cytometry in molecular biology is discussed with reference to gene reporter systems, which enable heterogeneity of gene expression to be monitored. With the recent sequencing of a variety of microbial genomes, it is anticipated that flow cytometry will have an increasing role to play in studying the effects of gene expression and mutation on heterogeneity, and in resolving the interactions of genetics and physiology.

Bacteria↗
PubMed2004

SCE jumping: genetic tool for allelic exchange in bacteria.

As more microbial genome sequence information becomes available, the field of bacterial pathogenesis would benefit from the development of new genetic tools designed to facilitate gene function studies on a genomic scale. The complete DNA sequence of the bacterium Pseudomonas aeruginosa provides an opportunity to apply functional genomics to a major opportunistic human pathogen. Here, I describe the development of a new gene replacement scheme termed "SCE jumping" in P. aeruginosa. The system uses the yeast I-SceI homing endonuclease in conjunction with in vitro mariner-transposon mutagenesis to generate mutations within targeted regions of the chromosome for genetic footprinting. Use of SCE jumping for generating transposon insertion mutants is anticipated to be widely applicable to other bacterial organisms. This allelic exchange strategy is discussed in context with other methods of gene replacement strategies available in P. aeruginosa. Development of SCE jumping provides an excellent example of the power of importing systems from unrelated organisms to circumvent practical challenges in molecular genetics.

Alleles↗
PubMed1989

Analysis of Mycobacterium tuberculosis genoma and production of a recombinant protein containing specific B and T cell antigenic determinants--new approaches to second generation antituberculosis vaccines.

Tuberculosis is still a major health problem in almost all over the world. Thus, new directions in basic and applied research of tuberculosis are under investigation in several laboratories. In this paper, we provide recent data obtained in our laboratory with the recombinant DNA technology which allow a systematic survey of the microbial genome. Screening of the M. tuberculosis genomic DNA library in the phage lambda gt11 expression vector, using E. coli as surrogate host, has evidenced the possibility of producing recombinant M. tuberculosis proteins recognized by sera from tuberculosis patients and by specific monoclonal antibodies. Using this technology, we have isolated a recombinant protein (molecular weight 130 kilodaltons) which is identified by a murine monoclonal antibody recognizing a mycobacterial cell wall antigenic determinant present on a mycobacterial protein. This protein is only present on the mycobacterial species related to the tuberculosis complex (M. tuberculosis, M. bovis, M. africanum) and does not crossreact with nonpathogenic Mycobacteria. Since the immune response to mycobacterial infections is cell-mediated, the question arises about the use of M. tuberculosis-specific T lymphocytes to screen this gene bank. Thus, the recombinant mycobacterial protein isolated by antibodies has been then used to stimulate the proliferation of T lymphocytes from patients with tubercular pleuritis. This experiment indicates that the recombinant protein contains antigenic determinants recognized by T cells. Moreover, such protein is able to elicit delayed type hypersensitivity skin reaction in mice immunized or infected with M. tuberculosis and M. bovis. Finally, gene mapping and hybridization studies with native M. tuberculosis DNA confirme the mycobacterial nature of the recombinant DNA insert. Thus a good candidate for the prophylaxis and the immunodiagnosis of tuberculosis has been identified. The identification and selection of genes encoding antigenic determinants recognized by mycobacteria-specific T cells with protective functions will allow in the near future the construction by genetic engineering of recombinant vaccines effective in the control of this disease. This paper will briefly discuss the present strategy used in our laboratory to reach this goal.

Animals↗
PubMed2006

Genomic dissection of microbial pathogenesis in cultured Drosophila cells.

Recent RNA interference screens that were performed at a genome-wide level have identified host factors that are important for the growth of Listeria monocytogenes in cultured cells from the fruit fly Drosophila melanogaster. The screens identified genes that are involved in phagocytosis but did not detect genes known to be involved in immune signaling pathways. These studies provide a foundation for the identification of host factors and virulence mechanisms.

Animals↗
PubMed2004

[Application of M-RAPD technique to obtain the genomic fingerprints of various pathogenic microbials].

OBJECTIVE: To obtain genomic fingerprints of different pathogenic microbials and make certain whether their patterns can be used in the identification of microbials by means of multiplex random amplified polymorphic DNA analysis (M-RAPD). METHODS: Arbitrary primers of 10 oligonucleotides were randomly grouped, and various microbials chromosomal DNA were amplified with three combinatorial primers at a special higher annealing temperature. The products were detected by 15 g/L agarose electrophoresis and the patterns were analyzed by the software of Gelworks 1d Intermediate. RESULTS: Specific and resistant DNA fingerprints for different pathogenic microbials with combinatorial primers were gained. The profiles were clear, well-distributed and the number was great. The products of the three primers included most products of every two primers and would appear with no relation to their length, but small products had more opportunity; three primers could provide information contents half as many again as that two primers could provide for the same pathogenic microbials. There were obvious differences among different drug-resistant strains and between the drug-resistant strains and the corresponding reference strains, but different strains of the same microorganism had more similarity than discrepancy. The analytic data of the software of Gelworks 1d Intermediate also support our results. CONCLUSION: M-RAPD is a simple and rapid technique for the identification of different kinds of pathogenic microbials, and it can provide rich genetic information.

DNA Fingerprinting↗
PubMed2005

Bioinformatics for whole-genome shotgun sequencing of microbial communities.

The application of whole-genome shotgun sequencing to microbial communities represents a major development in metagenomics, the study of uncultured microbes via the tools of modern genomic analysis. In the past year, whole-genome shotgun sequencing projects of prokaryotic communities from an acid mine biofilm, the Sargasso Sea, Minnesota farm soil, three deep-sea whale falls, and deep-sea sediments have been reported, adding to previously published work on viral communities from marine and fecal samples. The interpretation of this new kind of data poses a wide variety of exciting and difficult bioinformatics problems. The aim of this review is to introduce the bioinformatics community to this emerging field by surveying existing techniques and promising new approaches for several of the most interesting of these computational problems.

Journal Article↗
PubMed2004

DNA microarrays--techniques and applications in microbial systems.

Genome projects produce a huge amount of sequence information. As a result, the focus of genomics research is turning toward deduction of functional information about newly discovered genes. Thus structural genomics paves the way for a new discipline called functional genomics by providing the information required for microarray manufacture. Microarray technology is the result of automation and miniaturization in the detection of differential gene expression. By using this technology one can make a parallel analysis of RNA abundance and DNA homology for thousands of genes in a single experiment. Over the past several years, this unique technology has been used to explore hundreds transcriptional patterns and genome differences for a variety of microbial species. Applications of microarrays extend beyond the boundaries of basic biology into diagnostics, environmental monitoring, pharmacology, toxicology and biotechnology. We describe comprehensive nature of DNA microarray technology with emphasis on fabrication of DNA microarrays and application of this technology in biological environment with primary accent on microbial systems.

Bacteria↗
PubMed2004

Metagenomics: genomic analysis of microbial communities.

Uncultured microorganisms comprise the majority of the planet's biological diversity. Microorganisms represent two of the three domains of life and contain vast diversity that is the product of an estimated 3.8 billion years of evolution. In many environments, as many as 99% of the microorganisms cannot be cultured by standard techniques, and the uncultured fraction includes diverse organisms that are only distantly related to the cultured ones. Therefore, culture-independent methods are essential to understand the genetic diversity, population structure, and ecological roles of the majority of microorganisms. Metagenomics, or the culture-independent genomic analysis of an assemblage of microorganisms, has potential to answer fundamental questions in microbial ecology. This review describes progress toward understanding the biology of uncultured Bacteria, Archaea, and viruses through metagenomic analyses.

Archaea↗