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Integrating informatics tools and portable sequencing technology for rapid dete...
Phelan, Jody E.; O'Sullivan, Denise M.; Machado, Diana; Ramos, Jorge; Oppong, Yaa E.A.; Campino, Susana; O'Grady, Justin; McNerney, RuthBackground: Mycobacterium tuberculosis resistance to anti-tuberculosis drugs is a major threat to global public health. Whole genome sequencing (WGS) is rapidly gaining traction as a diagnostic tool for clinical tuberculosis settings. To support this informatically, previous work led to the development of the widely used TBProfiler webtool, which predicts resistance to 14 drugs from WGS data. However, for accur...
CPLP-TB:
Perdigão, João; Silva, Carla; Diniz, Jaciara; Pereira, Catarina; Machado, Diana; Ramos, Jorge; Silva, Hugo; Abilleira , Fernanda; Brum, ClariceA Tuberculose (TB) permanece um grave problema de saúde pública na Comunidade dos Países de Língua Portuguesa (CPLP). Apesar da ampla variância da incidência da TB nos seus estados-membro e de um fluxo migratório contínuo entre os países que integram este grupo, existe uma enorme lacuna no que diz respeito ao conhecimento da estrutura populacional conjunta do Mycobacterium tuberculosis e circulação de estirpes ...
Methylation in Mycobacterium tuberculosis is lineage specific with associated m...
Phelan, Jody; De Sessions, Paola Florez; Tientcheu, Leopold; Perdigao, Joao; Machado, Diana; Hasan, Rumina; Hasan, Zahra; Bergval, Indra L.DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances in PacBio sequencing technologies can be used to robustly reveal methylation sites. The methylome of the Mycobacterium tuberculosis complex is poorly understood but may be involved in virulence, hypoxic survival and the emergence of drug resist...
Identifying mixed Mycobacterium tuberculosis infections from whole genome seque...
Sobkowiak, Benjamin; Glynn, Judith R.; Houben, Rein M.G.J.; Mallard, Kim; Phelan, Jody E.; Guerra-Assunção, José Afonso; Banda, Louis; Mzembe, ThembaBackground: Mixed, polyclonal Mycobacterium tuberculosis infection occurs in natural populations. Developing an effective method for detecting such cases is important in measuring the success of treatment and reconstruction of transmission between patients. Using whole genome sequence (WGS) data, we assess two methods for detecting mixed infection: (i) a combination of the number of heterozygous sites and the p...
The variability and reproducibility of whole genome sequencing technology for d...
Phelan, Jody; O'Sullivan, Denise M.; Machado, Diana; Ramos, Jorge; Whale, Alexandra S.; O'Grady, Justin; Dheda, Keertan; Campino, Susana; McNerney, RuthBackground: The emergence of resistance to anti-tuberculosis drugs is a serious and growing threat to public health. Next-generation sequencing is rapidly gaining traction as a diagnostic tool for investigating drug resistance in Mycobacterium tuberculosis to aid treatment decisions. However, there are few little data regarding the precision of such sequencing for assigning resistance profiles. Methods: We inve...
Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium...
Phelan, Jody E.; Coll, Francesc; Bergval, Indra; Anthony, Richard M.; Warren, Rob; Sampson, Samantha L.; Gey van Pittius, Nicolaas C.; Glynn, Judith R.Background: Approximately 10 % of the Mycobacterium tuberculosis genome is made up of two families of genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE and PPE families are typified by their highly conserved N-terminal domains that incorporate proline-glutamate (PE) and proline-proline-glutamate (PPE) signature motifs. They are hypothesised to be important vir...
Multidrug-resistant mycobacterium tuberculosis of the Latin American mediterran...
Dalla Costa, Elis R.; Vasconcelos, Sidra E G; Esteves, Leonardo S.; Gomes, Harrison M.; Gomes, Lia L.; Da Silva, Pedro Almeida; Perdigão, JoãoPMID: 26400784 WOS:000367532800016; We recently detected the spoligotype patterns of strains of Mycobacterium pinnipedii, a species of the Mycobacterium tuberculosis complex, in sputum samples from nine cases with pulmonary tuberculosis residing in Porto Alegre, South Brazil. Because this species is rarely encountered in humans, we further characterized these nine isolates by additional genotyping techniques, i...
Rapid determination of anti-tuberculosis drug resistance from whole-genome sequ...
Coll, Francesc; McNerney, Ruth; Preston, Mark D.; Guerra-Assunção, José Afonso; Warry, Andrew; Hill-Cawthorne, Grant; Mallard, Kim; Nair, MridulPMID: 26019726 WOS:000355073700001; Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was c...
Rapid determination of antituberculosis drug resistance from wholegenome sequen...
Coll, Francesc; McNerney, Ruth; Preston, Mark D.; Guerra-Assunção, José Afonso; Warry, Andrew; Hill-Cawthorne, Grant; Mallard, Kim; Nair, MridulMycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them...
A robust SNP barcode for typing Mycobacterium tuberculosis complex strains
Coll, Francesc; McNerney, Ruth; Guerra-Assunção, José Afonso; Glynn, Judith R.; Perdigão, João; Viveiros, Miguel; Portugal, Isabel; Pain, ArnabPMID:25176035 WOS:000342929000002; Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robu...