An FDA bioinformatics tool for microbial genomics research on molecular characterization of bacterial foodborne pathogens using microarrays

<p>Abstract</p> <p>Background</p> <p>Advances in microbial genomics and bioinformatics are offering greater insights into the emergence and spread of foodborne pathogens in outbreak scenarios. The Food and Drug Administration (FDA) has developed a genomics tool, ArrayTrack^TM, which provides extensive functionalities to manage, analyze, and interpret genomic data for mammalian species. ArrayTrack^TM has been widely adopted by the research community and used for pharmacogenomics data review in the FDA’s Voluntary Genomics Data Submission program. </p> <p>Results</p> <p>ArrayTrack^TM has been extended to manage and analyze genomics data from bacterial pathogens of human, animal, and food origin. It was populated with bioinformatics data from public databases such as NCBI, Swiss-Prot, KEGG Pathway, and Gene Ontology to facilitate pathogen detection and characterization. ArrayTrack^TM’s data processing and visualization tools were enhanced with analysis capabilities designed specifically for microbial genomics including flag-based hierarchical clustering analysis (HCA), flag concordance heat maps, and mixed scatter plots. These specific functionalities were evaluated on data generated from a custom Affymetrix array (FDA-ECSG) previously developed within the FDA. The FDA-ECSG array represents 32 complete genomes of <it>Escherichia coli</it> and<it> Shigella.</it> The new functions were also used to analyze microarray data focusing on antimicrobial resistance genes from <it>Salmonella</it> isolates in a poultry production environment using a universal antimicrobial resistance microarray developed by the United States Department of Agriculture (USDA).</p> <p>Conclusion</p> <p>The application of ArrayTrack^TM to different microarray platforms demonstrates its utility in microbial genomics research, and thus will improve the capabilities of the FDA to rapidly identify foodborne bacteria and their genetic traits (e.g., antimicrobial resistance, virulence, etc.) during outbreak investigations. ArrayTrack^TM is free to use and available to public, private, and academic researchers at <url>http://www.fda.gov/ArrayTrack</url>. </p

Studying the influence of PTPN22 gene in systemic scleroderma

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An EORTC-ECSG phase I study of LU 79553 administered every 21 or 42 days in patients with solid tumours.

A single-agent dose-escalating phase I and pharmacokinetic study on the naphthalamide agent, LU 79553, was performed to determine its safety profile, maximum tolerated dose (MTD) and recommended dose for phase II studies. LU 79553 was given intravenously (i.v.) every 3 weeks to patients with advanced solid cancers (an extended cohort of patients also received the drug every 6 weeks). 59 patients were enrolled into the study (50 patients in the 3-weekly schedule and 9 patients in the 6-weekly schedule). Dose levels studied ranged from 10 mg/m(2) to 160 mg/m(2). Neuro-muscular toxicity was identified as the dose-limiting toxicity (DLT). This muscular toxicity was observed after administrating total doses of 160-450 mg/m(2) (median 330 mg/m(2)). Non-DLTs consisted of diarrhoea, nausea and vomiting, fatigue and local venous phlebitis. The major haematological toxicities observed were anaemia and neutropenia (and were mainly observed at the two highest dose levels). The proposed dose for phase II studies using the 3-weekly regimen is 100 mg/m(2)/course (60 min infusion in 500 ml normal saline), but a close clinical follow-up of the patients for neuromuscular toxicity is mandatory. Prolongation of the treatment interval to 6 weeks, based upon the long half-life of the drug in the plasma and tissue, observed during this study, seemed not to be feasible in this heavily pretreated group of patients.Clinical TrialClinical Trial, Phase IJournal Articleinfo:eu-repo/semantics/publishe