naa a22 4500 530060043 20181025071937.0 cr unu---uuuuu 181025s2018 xx s 000 0 eng 0169-5487 10.1038/s41598-018-33731-1 doi (EDOC)oai:edoc.unibas.ch:66263 30337678 pmid Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase [Elektronische Daten] [Matthew Ezewudo, Amanda Borens, Álvaro Chiner-Oms, Paolo Miotto, Leonid Chindelevitch, Angela M. Starks, Debra Hanna, Richard Liwski, Matteo Zignol, Christopher Gilpin, Stefan Niemann, Thomas Andreas Kohl, Robin M. Warren, Derrick Crook, Sebastien Gagneux, Sven Hoffner, Camilla Rodrigues, Iñaki Comas, David M. Engelthaler, David Alland, Leen Rigouts, Christoph Lange, Keertan Dheda, Rumina Hasan, Ruth McNerney, Daniela M. Cirillo, Marco Schito, Timothy C. Rodwell, James Posey] Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited 98.9% agreement with the variants identified using Sanger sequencing and was 100% concordant with conventional methods of assigning lineage. We analyzed 4636 publicly available MTBC isolates in the ReSeqTB platform representing all seven major MTBC lineages. The variants detected have an above 94% accuracy of predicting drug based on the accompanying DST results in the platform. The aggregation of variants over time in the platform will establish confidence-graded mutations statistically associated with phenotypic drug resistance. These tools serve as critical reference standards for future molecular diagnostic assay developers, researchers, public health agencies and clinicians working towards the control of drug-resistant tuberculosis. Ezewudo Matthew joint author Borens Amanda joint author Chiner-Oms Álvaro joint author Miotto Paolo joint author Chindelevitch Leonid joint author Starks Angela M. joint author Hanna Debra joint author Liwski Richard joint author Zignol Matteo joint author Gilpin Christopher joint author Niemann Stefan joint author Kohl Thomas Andreas joint author Warren Robin M. joint author Crook Derrick joint author Gagneux Sebastien joint author Hoffner Sven joint author Rodrigues Camilla joint author Comas Iñaki joint author Engelthaler David M. joint author Alland David joint author Rigouts Leen joint author Lange Christoph joint author Dheda Keertan joint author Hasan Rumina joint author McNerney Ruth joint author Cirillo Daniela M. joint author Schito Marco joint author Rodwell Timothy C. joint author Posey James joint author Scientific Reports 8 (1), p. 15382 0169-5487 https://edoc.unibas.ch/66263/1/20181023093115_5bcece4363adc.pdf text/html WWW-Backlink auf das Repository 1 Article edoc PeerReviewed edoc peerstatus EDOC 856 40 https://edoc.unibas.ch/66263/1/20181023093115_5bcece4363adc.pdf text/html WWW-Backlink auf das Repository EDOC 700 1- Ezewudo Matthew joint author EDOC 700 1- Borens Amanda joint author EDOC 700 1- Chiner-Oms Álvaro joint author EDOC 700 1- Miotto Paolo joint author EDOC 700 1- Chindelevitch Leonid joint author EDOC 700 1- Starks Angela M. joint author EDOC 700 1- Hanna Debra joint author EDOC 700 1- Liwski Richard joint author EDOC 700 1- Zignol Matteo joint author EDOC 700 1- Gilpin Christopher joint author EDOC 700 1- Niemann Stefan joint author EDOC 700 1- Kohl Thomas Andreas joint author EDOC 700 1- Warren Robin M. joint author EDOC 700 1- Crook Derrick joint author EDOC 700 1- Gagneux Sebastien joint author EDOC 700 1- Hoffner Sven joint author EDOC 700 1- Rodrigues Camilla joint author EDOC 700 1- Comas Iñaki joint author EDOC 700 1- Engelthaler David M. joint author EDOC 700 1- Alland David joint author EDOC 700 1- Rigouts Leen joint author EDOC 700 1- Lange Christoph joint author EDOC 700 1- Dheda Keertan joint author EDOC 700 1- Hasan Rumina joint author EDOC 700 1- McNerney Ruth joint author EDOC 700 1- Cirillo Daniela M. joint author EDOC 700 1- Schito Marco joint author EDOC 700 1- Rodwell Timothy C. joint author EDOC 700 1- Posey James joint author EDOC 773 0- Scientific Reports 8 (1), p. 15382 0169-5487 BK010053 XK010053 XK010000 EDOC EDOC EDOC Article