title: Integration of published information into a resistance-associated mutation database for Mycobacterium tuberculosis.
abstract: Tuberculosis remains a major global public health challenge. Although incidence is decreasing, the proportion of drug-resistant cases is increasing. Technical and operational complexities prevent Mycobacterium tuberculosis drug susceptibility phenotyping in the vast majority of new and retreatment cases. The advent of molecular technologies provides an opportunity to obtain results rapidly as compared to phenotypic culture. However, correlations between genetic mutations and resistance to multiple drugs have not been systematically evaluated. Molecular testing of M. tuberculosis sampled from a typical patient continues to provide a partial picture of drug resistance. A database of phenotypic and genotypic testing results, especially where prospectively collected, could document statistically significant associations and may reveal new, predictive molecular patterns. We examine the feasibility of integrating existing molecular and phenotypic drug susceptibility data to identify associations observed across multiple studies and demonstrate potential for well-integrated M. tuberculosis mutation data to reveal actionable findings.
authors.affiliation: Knowledge Synthesis Inc., Berkeley, California.
authors.forename: Hugh
authors.initials: H
authors.lastname: Salamon
authors.affiliation: Knowledge Synthesis Inc., Berkeley, California.
authors.forename: Ken D
authors.initials: KD
authors.lastname: Yamaguchi
authors.affiliation: IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Cirillo
authors.affiliation: IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Miotto
authors.affiliation: HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of, Military Medicine, Inc., NIH, DHHS, Bethesda, Maryland.
authors.forename: Marco
authors.initials: M
authors.lastname: Schito
authors.affiliation: Center for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: James
authors.initials: J
authors.lastname: Posey
authors.affiliation: Center for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Starks
authors.affiliation: Forschungszentrum Borstel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Niemann
authors.affiliation: Rutgers University, New Jersey.
authors.forename: David
authors.initials: D
authors.lastname: Alland
authors.affiliation: Critical Path Institute, Tucson, Arizona.
authors.forename: Debra
authors.initials: D
authors.lastname: Hanna
authors.affiliation: Critical Path Institute, Tucson, Arizona.
authors.forename: Enrique
authors.initials: E
authors.lastname: Aviles
authors.affiliation: FIND, Geneva, Switzerland.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Perkins
authors.affiliation: FIND, Geneva, Switzerland.
authors.forename: David L
authors.initials: DL
authors.lastname: Dolinger
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D030541:Databases, Genetic; D024881:Drug Resistance, Bacterial; D005838:Genotype; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents
keywords: database; drug resistance; drug susceptibility testing; genomic sequencing; resistance-associated mutations; tuberculosis