Article
Biochemistry & Molecular Biology
Pooja Singh, Salma Jamal, Faraz Ahmed, Najumu Saqib, Seema Mehra, Waseem Ali, Deodutta Roy, Nasreen Z. Ehtesham, Seyed E. Hasnain
Summary: This study aims to develop an updated database including almost all reported substitutions within Mycobacterium tuberculosis drug target genes and use bioinformatics tools to evaluate the impact of these mutations. They have created a comprehensive online resource named MycoTRAP-DB that connects gene mutations with structural, functional, and pathogenic implications. This integrated platform allows for comprehensive analysis and prioritization of SNPs for the development of improved antimycobacterial medications.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Infectious Diseases
Connie Lam, Elena Martinez, Taryn Crighton, Catriona Furlong, Ellen Donnan, Ben J. Marais, Vitali Sintchenko
Summary: Routine whole genome sequencing (WGS) provides better guidance for drug resistance management of Mycobacterium tuberculosis compared to commercial genotypic assays. WGS identified additional drug resistance mutations not detected by conventional phenotypic DST, leading to a significant increase in drug resistance detection.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Microbiology
Benjamin I. Baarda, Ryszard A. Zielke, Alaina K. Holm, Aleksandra E. Sikora
Summary: Extensive bioinformatic analyses identified promising, conserved gonorrhea vaccine candidates with highly conserved and well-distributed antigenic properties. The research is significant for the development of a gonorrhea vaccine and provides strong support for structural vaccinology.
Article
Infectious Diseases
Alice Kizny Gordon, Ben Marais, Timothy M. Walker, Vitali Sintchenko
Summary: Tuberculosis remains a significant public health issue globally, particularly in low-income countries. The COVID-19 pandemic has had a negative impact on TB control, while whole genome sequencing technology holds important value in the diagnosis and management of tuberculosis.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Amina Al-Jardan, Fatma Al Yaquobi, Chamila Adikaram, Adil Al Wahaibi, Laila Al-Balushi, Samiya Al-Zadjali, Bader Al Abri, Khalsa Al-Thuhli, Seif Al-Abri
Summary: This study used whole genome sequencing to analyze the epidemiology and geospatial distribution of tuberculosis in Oman, identifying multiple genotype clusters and predominant lineages. The considerable genetic variation in TB strains in Oman may be attributed to the high percentage of non-national population and frequent travel to high TB burden countries.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Biotechnology & Applied Microbiology
Yustinus Maladan, Hana Krismawati, Tri Wahyuni, Ratna Tanjung, Kamla Awaludin, Kholis Abdurachim Audah, Arli Aditya Parikesit
Summary: The study utilized whole-genome sequencing of TB clinical samples from Papua, Indonesia to detect mutations associated with TB-drug resistance, revealing multiple mutations in genes linked to resistance against various TB drugs. The results contribute to the surveillance of TB-drug resistance, identifying MDR samples but no XDR samples, with resistance mainly observed against the second-line drug Amikacin.
Article
Genetics & Heredity
Tim H. Heupink, Lennert Verboven, Robin M. Warren, Annelies Van Rie
Summary: Improving the understanding and detection of genomic variants in Mycobacterium tuberculosis is crucial for controlling tuberculosis. The XBS bioinformatics pipeline has shown superior accuracy in identifying variants in complex genomic regions and samples with low coverage and high contamination levels, making it a valuable tool for future clinical applications and genetic studies related to drug resistance and transmission analysis.
MICROBIAL GENOMICS
(2021)
Article
Infectious Diseases
Fathiah Zakham, Tarja Sironen, Olli Vapalahti, Ravi Kant
Summary: This study aimed to conduct a comparative genome analysis of human adapted Mycobacterium tuberculosis complex species, including BCG vaccine strains, to identify and pinpoint conserved genes related to virulence across all species. The core genome consists of 1166 conserved genes among these species, representing a small portion of the 7036 genes in the pan-genome, suggesting potential for vaccine candidate development.
Article
Microbiology
Nabila Ismail, Anzaan Dippenaar, George Morgan, Melanie Grobbelaar, Felicia Wells, Jessica Caffry, Cristiana Morais, Krzysztof Gizynski, David McGurk, Eduardo Boada, Heather Murton, Robin M. Warren, Annelies Van Rie
Summary: Diagnosis of tuberculosis often requires culturing and phenotypic drug susceptibility testing or culturing followed by whole-genome sequencing (WGS). The WGS route is attractive, but culturing is a bottleneck. In this proof-of-principle study, microfluidics-based cell capture was used to enrich Mycobacterium tuberculosis from clinical sputum samples for culture-free WGS. The results suggest that this method could be promising for M. tuberculosis enrichment in clinical samples, facilitating culture-free WGS.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Lucas Boeck, Sophie Burbaud, Marcin Skwark, Will H. Pearson, Jasper Sangen, Andreas W. Wuest, Eleanor K. P. Marshall, Aaron Weimann, Isobel Everall, Josephine M. Bryant, Sony Malhotra, Bridget P. Bannerman, Katrin Kierdorf, Tom L. Blundell, Marc S. Dionne, Julian Parkhill, R. Andres Floto
Summary: This study demonstrates the use of phenogenomic analysis, combining high-dimensional phenotyping with whole-genome sequencing, to rapidly reveal insights into bacterial pathobiology. By phenotyping 331 clinical isolates of Mycobacterium abscessus, three distinct clusters of isolates were discovered, each associated with different virulence traits and clinical outcomes. Genome-wide association studies, proteome-wide structural modeling, and direct coupling analysis were employed to identify causal variants and gene networks, leading to the discovery of clinically relevant virulence factors. This highlights the potential of phenogenomics in uncovering critical pathways in emerging pathogenic bacteria.
NATURE MICROBIOLOGY
(2022)
Article
Microbiology
Mahadev Rao, Kurt Wollenberg, Michael Harris, Shrivathsa Kulavalli, Levin Thomas, Kiran Chawla, Vishnu Prasad Shenoy, Muralidhar Varma, Kavitha Saravu, H. Manjunatha Hande, Chidananda Sanju Shanthigrama Vasudeva, Brendan Jeffrey, Andrei Gabrielian, Alex Rosenthal
Summary: Whole-genome sequencing has provided a comprehensive picture of genetic polymorphisms in tuberculosis, but studies in high tuberculosis burden countries are lacking. This study performed whole-genome sequencing on 242 clinical isolates from a hospital in Southern India and identified several mutations associated with drug resistance. The study highlights the value of whole-genome sequencing as a supplemental tool and suggests further research directions.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Mahadev Rao, Kurt Wollenberg, Michael Harris, Shrivathsa Kulavalli, Levin Thomas, Kiran Chawla, Vishnu Prasad Shenoy, Muralidhar Varma, Kavitha Saravu, H. Manjunatha Hande, Chidananda Sanju Shanthigrama Vasudeva, Brendan Jeffrey, Andrei Gabrielian, Alex Rosenthal
Summary: This study used whole-genome sequencing to study 242 clinical isolates of Mycobacterium tuberculosis from tuberculosis patients in Southern India, and identified several genetic variations in M. tuberculosis that confer resistance to antitubercular drugs. The findings highlight the utility of whole-genome sequencing as a potential supplemental tool for monitoring drug resistance and characterizing the lineage of M. tuberculosis.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemical Research Methods
Emmanuel Riviere, Tim H. Heupink, Nabila Ismail, Anzaan Dippenaar, Charlene Clarke, Gemeda Abebe, Peter Heusden, Rob Warren, Conor J. Meehan, Annelies Van Rie
Summary: Asia and Africa are underrepresented in Mtb WGS research compared to their TB burden, leading to adaptations in training, mentoring, and infrastructure building. Utilizing case studies created a safe space for students to voice and defend their opinions. Ensuring quality DNA extraction, biosafety level 3 and general laboratory skill training, commercial DNA extraction kits, and a combination of training in a highly equipped laboratory and local setting were added to the program.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biotechnology & Applied Microbiology
Kelvin W. C. S. Leong, Sanjay S. Gautam, Manoj Pradhan, Y. Ibotomba K. Singh, K. C. R. Rajendra, Sagar Rajbhandari, Gokarna R. Ghimire, Krishna Adhikari, Uma Shrestha, Raina Chaudhary, Gyanendra Ghimire, Sundar Khadka, Ronan F. O'Toole
Summary: Nepal has a comparable tuberculosis incidence rate to its neighboring high incidence countries, and it also sees a significant number of multi-drug resistant tuberculosis cases each year. This study analyzed the whole-genome of multi-drug resistant tuberculosis isolates from Nepal and identified specific mutations related to their resistance. The study also found a high proportion of fluoroquinolone resistance among the Nepal isolates. These findings have important implications for the management of tuberculosis in Nepal.
Article
Biochemical Research Methods
Sander N. Goossens, Tim H. Heupink, Elise De Vos, Anzaan Dippenaar, Margaretha De Vos, Rob Warren, Annelies Van Rie
Summary: The study evaluated the performance of the variant calling tool LoFreq in detecting minor variants in Mycobacterium tuberculosis next generation sequencing data. LoFreq showed high precision and sensitivity in detecting various types and frequencies of minor variants. It can successfully detect minor variant populations and reduce false positive variants due to sequencing errors. The findings can guide future studies in determining the depth of sequencing and the limit of detection in whole genome sequencing data of M. tuberculosis.
BRIEFINGS IN BIOINFORMATICS
(2022)