Understanding the transmission of tuberculosis using Mycobacterium tuberculosis sequence data
Lead Research Organisation:
London School of Hygiene & Tropical Medicine
Department Name: Infectious and Tropical Diseases
Abstract
Tuberculosis is an infectious disease that causes a high public health burden. The World Health Organisation estimates that there are nine million new cases and nearly two million deaths each year. Establishing who transmits to whom and where is fundamental to disease control. By comparing the genetic profiles of tuberculosis-causing bacteria within large population-based studies we can identify likely transmissions based on the similarity of the strains. Our work will focus initially on a district of Malawi where tuberculosis disease prevalence has been high, and data and tuberculosis samples from nearly 2500 patients have been collected over twenty years. The inferred genetic profiles will use a higher proportion of the genome than used previously, allowing more accurate reconstructions of transmission chains. Factors influencing transmissibility will then be assessed directly by looking at the patterns of data within each transmission chain. These factors may be genetic variations within the bacteria themselves, or differences in the human hosts, including age, sex, HIV infection and treatment, and contact patterns. We will attempt to confirm any insights into these factors using data collected and generated from other populations. Ultimately, an improved understanding of the genetic and other processes underlying transmissibility could lead to the development of improved control measures. These could include novel drug or vaccine targets, or identification of geographical or socially determined hotspots of transmission.
Technical Summary
Tuberculosis, caused by Mycobacterium tuberculosis, is an important global public health issue. Understanding the factors underlying transmission is essential for disease control, but surprisingly little is known about the role of pathogen genomic variation, where most infections occur, the importance of host factors, or who transmits to whom. M. tuberculosis can be grouped into seven lineages or phylogenetic clades, and further into sub-lineages, which may vary in propensity to transmit and cause disease. By sequencing M. tuberculosis in a population-based setting it is possible to construct transmission chains using phylogenetic-based algorithms: strains with near identical genomes are most likely to be due to a transmission event, and will appear on the same branch of the phylogenetic tree. However, there are few large population-based studies in high tuberculosis prevalence areas that can apply long-term large-scale whole genome sequencing. Here we focus on the Karonga study in northern Malawi where substantial epidemiological data have been collected and ~2500 sequenced samples are available spanning a 20-year period. Sequencing studies to date have been limited to single nucleotide polymorphisms and have ignored insertions and deletions and highly variable regions such as the pe/ppe gene families. By including all these variations and considering all the tuberculosis cases in the Karongan population, it will be possible to build a probabilistic model of transmissions, and hence assess effects of pathogen variation and host factors (age, sex, HIV status, contact patterns, proximity) on transmissibility using regression-based methods. Further, it will be possible to adopt a genome-wide approach to identify loci in the bacteria that are associated with or under evolutionary selective pressure from a transmissibility phenotype. Loci identified as being associated with transmissibility will be validated using sequence data from other populations.
Planned Impact
The economy
Advances in sequencing technology now allow the genomic characterization of M.tuberculosis (the cause of tuberculosis (TB)) on an unprecedented scale, and have the potential to greatly accelerate research aimed at understanding the biology of the bacterium, its phylogeny and the epidemiology of the disease. The knowledge generated in the project and application of the research could ultimately benefit the pharmaceutical industry and those developing TB diagnostics and vaccines, as well as communities both in the UK and overseas exposed to the disease. Ultimately, through reduced occurrence of TB, the knowledge gained in this study could improve the health and wealth of the nation and globally. The methods used in this project could have application beyond TB, so help more widely in the control and prevention of infectious diseases in both humans and animals, with associated economic benefits.
The general public
M.tuberculosis is a major cause of disease, killing ~2 million people globally each year, and drug resistant forms of TB and HIV are making control difficult. Genomics insights into transmission could lead ultimately to improved control measures adopted globally. The project therefore specifically addresses the MRC strategic aim to impact positively on global health, and to assist with bringing the health impacts of fundamental research to people more quickly.
Academic and industrial organisations
New sequencing technologies have the ability to generate vast amounts of data, but there is a need to translate this information into knowledge useable by other research scientists and industry. Our work will provide tools useful for genomic data analysis and modeling, which can be utilized across infectious diseases and in different settings. An understanding of genomic variation underlying transmission could lead to laboratory experiments for M. tuberculosis pathogenesis and host interaction, improved tests for detecting transmissible M. tuberculosis, and insights for academics involved in policy formulation. Scientific developments arising would enhance the commercial private sector for the production of diagnostics, vaccines and other control measures. We have links with some of these companies (e.g. GSK) and where required will use licensing agreements through the LSHTM technology transfer office to ensure pipelines to vaccine or other translation tool production and exploitation are in place. Developing a basic understanding of the genomic pathways in this study will not only be important for understanding virulence and transmission mechanisms in M.tuberculosis, but has practical applications for other mycobacteria including M.bovis - the cause of TB in humans and cows.
Any technology developed may have enormous implications for policy makers for future disease outbreaks and impact on exports.
Training opportunities
The proposal will employ and train and develop a scientist with diverse experience with an 'omic mentality that can be applied in academia, the public sector and industry. The multidisciplinary project team will add to the UK science base in an important and economically vital research area. The researchers working on the project will develop team working and project management skills, which they can apply in all employment sectors. Importantly, the scope for multidisciplinary interactions in this proposal should not be underestimated. The researcher employed to carry out the planned activities will have unique opportunities for engagement with experts (e.g. in the LSHTM TB Centre) in TB biology, biotechnology, clinical care, genomic epidemiology, and public health. Thus, our proposal will impact on the creation of human resources that could subsequently be employed in challenging interdisciplinary projects in industry, academia and government.
Advances in sequencing technology now allow the genomic characterization of M.tuberculosis (the cause of tuberculosis (TB)) on an unprecedented scale, and have the potential to greatly accelerate research aimed at understanding the biology of the bacterium, its phylogeny and the epidemiology of the disease. The knowledge generated in the project and application of the research could ultimately benefit the pharmaceutical industry and those developing TB diagnostics and vaccines, as well as communities both in the UK and overseas exposed to the disease. Ultimately, through reduced occurrence of TB, the knowledge gained in this study could improve the health and wealth of the nation and globally. The methods used in this project could have application beyond TB, so help more widely in the control and prevention of infectious diseases in both humans and animals, with associated economic benefits.
The general public
M.tuberculosis is a major cause of disease, killing ~2 million people globally each year, and drug resistant forms of TB and HIV are making control difficult. Genomics insights into transmission could lead ultimately to improved control measures adopted globally. The project therefore specifically addresses the MRC strategic aim to impact positively on global health, and to assist with bringing the health impacts of fundamental research to people more quickly.
Academic and industrial organisations
New sequencing technologies have the ability to generate vast amounts of data, but there is a need to translate this information into knowledge useable by other research scientists and industry. Our work will provide tools useful for genomic data analysis and modeling, which can be utilized across infectious diseases and in different settings. An understanding of genomic variation underlying transmission could lead to laboratory experiments for M. tuberculosis pathogenesis and host interaction, improved tests for detecting transmissible M. tuberculosis, and insights for academics involved in policy formulation. Scientific developments arising would enhance the commercial private sector for the production of diagnostics, vaccines and other control measures. We have links with some of these companies (e.g. GSK) and where required will use licensing agreements through the LSHTM technology transfer office to ensure pipelines to vaccine or other translation tool production and exploitation are in place. Developing a basic understanding of the genomic pathways in this study will not only be important for understanding virulence and transmission mechanisms in M.tuberculosis, but has practical applications for other mycobacteria including M.bovis - the cause of TB in humans and cows.
Any technology developed may have enormous implications for policy makers for future disease outbreaks and impact on exports.
Training opportunities
The proposal will employ and train and develop a scientist with diverse experience with an 'omic mentality that can be applied in academia, the public sector and industry. The multidisciplinary project team will add to the UK science base in an important and economically vital research area. The researchers working on the project will develop team working and project management skills, which they can apply in all employment sectors. Importantly, the scope for multidisciplinary interactions in this proposal should not be underestimated. The researcher employed to carry out the planned activities will have unique opportunities for engagement with experts (e.g. in the LSHTM TB Centre) in TB biology, biotechnology, clinical care, genomic epidemiology, and public health. Thus, our proposal will impact on the creation of human resources that could subsequently be employed in challenging interdisciplinary projects in industry, academia and government.
People |
ORCID iD |
| Taane Clark (Principal Investigator) | |
| Judith Glynn (Co-Investigator) |
Publications
Acford-Palmer H
(2023)
Identification of two insecticide resistance markers in Ethiopian Anopheles stephensi mosquitoes using a multiplex amplicon sequencing assay.
in Scientific reports
Ajawatanawong P
(2019)
A novel Ancestral Beijing sublineage of Mycobacterium tuberculosis suggests the transition site to Modern Beijing sublineages.
in Scientific reports
Andreu N
(2017)
Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis.
in Scientific reports
Auburn S
(2018)
Genomic analysis of a pre-elimination Malaysian Plasmodium vivax population reveals selective pressures and changing transmission dynamics.
in Nature communications
Benavente ED
(2018)
Global genetic diversity of var2csa in Plasmodium falciparum with implications for malaria in pregnancy and vaccine development.
in Scientific reports
Benavente ED
(2018)
A reference genome and methylome for the Plasmodium knowlesi A1-H.1 line.
in International journal for parasitology
Benavente ED
(2021)
Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa.
in Nature communications
Billows N
(2023)
Feature weighted models to address lineage dependency in drug-resistance prediction from Mycobacterium tuberculosis genome sequences.
in Bioinformatics (Oxford, England)
Broad JB
(2019)
Diverticulosis and nine connective tissue disorders: epidemiological support for an association.
in Connective tissue research
Campino S
(2016)
Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines.
in Malaria journal
Campos MC
(2017)
Genome-wide mutagenesis and multi-drug resistance in American trypanosomes induced by the front-line drug benznidazole.
in Scientific reports
Coll F
(2022)
PowerBacGWAS: a computational pipeline to perform power calculations for bacterial genome-wide association studies.
in Communications biology
Coll F
(2018)
Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis.
in Nature genetics
Collins EL
(2022)
A next generation targeted amplicon sequencing method to screen for insecticide resistance mutations in Aedes aegypti populations reveals a rdl mutation in mosquitoes from Cabo Verde.
in PLoS neglected tropical diseases
Costa SS
(2018)
Genetic Diversity of norA, Coding for a Main Efflux Pump of Staphylococcus aureus.
in Frontiers in genetics
Da Veiga Leal S
(2021)
Drug resistance profile and clonality of Plasmodium falciparum parasites in Cape Verde: the 2017 malaria outbreak.
in Malaria journal
De Lourdes Do Carmo Guimarães Diniz J
(2021)
Whole-genome sequencing as a tool for studying the microevolution of drug-resistant serial Mycobacterium tuberculosis isolates
in Tuberculosis
Deelder W
(2022)
Geographical classification of malaria parasites through applying machine learning to whole genome sequence data.
in Scientific reports
Deelder W
(2021)
Using deep learning to identify recent positive selection in malaria parasite sequence data.
in Malaria journal
Dheda K
(2017)
The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.
in The Lancet. Respiratory medicine
Diez Benavente E
(2021)
Studying accelerated cardiovascular ageing in Russian adults through a novel deep-learning ECG biomarker
in Wellcome Open Research
Diez Benavente E
(2017)
Genomic variation in Plasmodium vivax malaria reveals regions under selective pressure.
in PloS one
Diez Benavente E
(2020)
A molecular barcode to inform the geographical origin and transmission dynamics of Plasmodium vivax malaria
in PLOS Genetics
Dombrowski J
(2023)
Genetic diversity of Plasmodium vivax isolates from pregnant women in the Western Brazilian Amazon: a prospective cohort study
in The Lancet Regional Health - Americas
Dombrowski JG
(2017)
G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon.
in Malaria journal
Dombrowski JG
(2019)
Association of Malaria Infection During Pregnancy With Head Circumference of Newborns in the Brazilian Amazon.
in JAMA network open
Dombrowski JG
(2021)
Adverse pregnancy outcomes are associated with Plasmodium vivax malaria in a prospective cohort of women from the Brazilian Amazon.
in PLoS neglected tropical diseases
Dong YM
(2021)
Reply to Collins et al.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Dong YM
(2021)
Development and Validation of a Nomogram for Assessing Survival in Patients With COVID-19 Pneumonia.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Elias R
(2022)
A phylogenomic approach for the analysis of colistin resistance-associated genes in Klebsiella pneumoniae, its mutational diversity and implications for phenotypic resistance.
in International journal of antimicrobial agents
Elias R
(2023)
Emergence of KPC-3- and OXA-181-producing ST13 and ST17 Klebsiella pneumoniae in Portugal: genomic insights on national and international dissemination.
in The Journal of antimicrobial chemotherapy
Gomes AR
(2017)
Genetic diversity of next generation antimalarial targets: A baseline for drug resistance surveillance programmes.
in International journal for parasitology. Drugs and drug resistance
Gomes LC
(2021)
Whole genome sequencing reveals large deletions and other loss of function mutations in Mycobacterium tuberculosis drug resistance genes.
in Microbial genomics
Gomez-Gonzalez PJ
(2019)
An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome.
in Scientific reports
Gómez-González PJ
(2022)
Portable sequencing of Mycobacterium tuberculosis for clinical and epidemiological applications.
in Briefings in bioinformatics
Gómez-González PJ
(2021)
Genetic diversity of candidate loci linked to Mycobacterium tuberculosis resistance to bedaquiline, delamanid and pretomanid.
in Scientific reports
Higgins M
(2019)
PrimedRPA: primer design for recombinase polymerase amplification assays.
in Bioinformatics (Oxford, England)
Higgins M
(2022)
Characterizing the Impact of Primer-Template Mismatches on Recombinase Polymerase Amplification.
in The Journal of molecular diagnostics : JMD
| Title | Additional file 1 of Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains |
| Description | Additional file 1: Figure S1. Analysis work flow, jpg image. |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2023 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_1_of_Large-scale_genomic_analysi... |
| Title | Additional file 1 of Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains |
| Description | Additional file 1: Figure S1. Analysis work flow, jpg image. |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2023 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_1_of_Large-scale_genomic_analysi... |
| Title | Additional file 10: Figure S9. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Non-neutral evolution for genes within Clusters of Orthologous Groups (COG*) categories. Boxplots are constructed using (-log10) p-values of non-neutral evolution for each gene. *ppe/Nâ =â pe/ppe genes annotated as COG category N, * COG categories: A RNA processing and modification, B Chromatin Structure and dynamics, C Energy production and conversion, D Cell cycle control and mitosis, E Amino Acid metabolism and transport, F Nucleotide metabolism and transport, G Carbohydrate metabolism and transport, H Coenzyme metabolism, I Lipid metabolism, J Translation, K Transcription, L Replication and repair, M Cell wall/membrane/envelope biogenesis, N Cell motility, O Post-translational modification, protein turnover, chaperone functions, P Inorganic ion transport and metabolism, Q Secondary Structure, T Signal Transduction, U Intracellular trafficking and secretion, Y Nuclear structure, Z Cytoskeleton, R General Functional Prediction only, S Function Unknown. (TIF 127Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_10_Figure_S9_of_Recombination_in... |
| Title | Additional file 10: Figure S9. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Non-neutral evolution for genes within Clusters of Orthologous Groups (COG*) categories. Boxplots are constructed using (-log10) p-values of non-neutral evolution for each gene. *ppe/Nâ =â pe/ppe genes annotated as COG category N, * COG categories: A RNA processing and modification, B Chromatin Structure and dynamics, C Energy production and conversion, D Cell cycle control and mitosis, E Amino Acid metabolism and transport, F Nucleotide metabolism and transport, G Carbohydrate metabolism and transport, H Coenzyme metabolism, I Lipid metabolism, J Translation, K Transcription, L Replication and repair, M Cell wall/membrane/envelope biogenesis, N Cell motility, O Post-translational modification, protein turnover, chaperone functions, P Inorganic ion transport and metabolism, Q Secondary Structure, T Signal Transduction, U Intracellular trafficking and secretion, Y Nuclear structure, Z Cytoskeleton, R General Functional Prediction only, S Function Unknown. (TIF 127Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_10_Figure_S9_of_Recombination_in... |
| Title | Additional file 2: Figure S1. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | The global distribution of geographic origin and lineage of the isolates. Lineages one to four are represented by blue, green, purple, and red, respectively. (PNG 265 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_2_Figure_S1_of___Mycobacterium_t... |
| Title | Additional file 2: Figure S1. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | The global distribution of geographic origin and lineage of the isolates. Lineages one to four are represented by blue, green, purple, and red, respectively. (PNG 265 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_2_Figure_S1_of___Mycobacterium_t... |
| Title | Additional file 2: Figure S1. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Allele frequency spectra for each lineage by synonymous (blue) and non-synonymous (red) mutations. The peaks at intermediate allele frequencies include sub-lineage defining SNPs (Lineage 1 Indo-Oceanic; Lineage 2 East-Asian (Beijing); Lineage 3 East-African-Indian; Lineage 4 Euro-American). (TIF 207Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_2_Figure_S1_of_Recombination_in_... |
| Title | Additional file 2: Figure S1. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Allele frequency spectra for each lineage by synonymous (blue) and non-synonymous (red) mutations. The peaks at intermediate allele frequencies include sub-lineage defining SNPs (Lineage 1 Indo-Oceanic; Lineage 2 East-Asian (Beijing); Lineage 3 East-African-Indian; Lineage 4 Euro-American). (TIF 207Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_2_Figure_S1_of_Recombination_in_... |
| Title | Additional file 3: Figure S2. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | SNP allele frequency spectrum. A large number of rare variants are observed. Peaks with higher allele frequency reflect the presence of lineage and sub-lineage specific SNPs. (PNG 33 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_3_Figure_S2_of___Mycobacterium_t... |
| Title | Additional file 3: Figure S2. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | SNP allele frequency spectrum. A large number of rare variants are observed. Peaks with higher allele frequency reflect the presence of lineage and sub-lineage specific SNPs. (PNG 33 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_3_Figure_S2_of___Mycobacterium_t... |
| Title | Additional file 3: Figure S2. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Gene-based nucleotide diversity (D ) for the 21 reference genomes. All genes with high nucleotide diversity (D â >â 0.0075) are labelled. (TIF 148Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_3_Figure_S2_of_Recombination_in_... |
| Title | Additional file 3: Figure S2. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Gene-based nucleotide diversity (D ) for the 21 reference genomes. All genes with high nucleotide diversity (D â >â 0.0075) are labelled. (TIF 148Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_3_Figure_S2_of_Recombination_in_... |
| Title | Additional file 4: Figure S3. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Phylogenetic tree constructed using 50,540 genome-wide SNPs. Clear clustering according to lineage can be seen (Lineage 1 (Indo-Oceanic, green), lineage 2 (East-Asian (Beijing), blue), lineage 3 (East-African-Indian, purple), lineage 4 (Euro-American, red)). Reference genomes are labelled. M. canetti is annotated in cyan. (TIF 69Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_4_Figure_S3_of_Recombination_in_... |
| Title | Additional file 4: Figure S3. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Phylogenetic tree constructed using 50,540 genome-wide SNPs. Clear clustering according to lineage can be seen (Lineage 1 (Indo-Oceanic, green), lineage 2 (East-Asian (Beijing), blue), lineage 3 (East-African-Indian, purple), lineage 4 (Euro-American, red)). Reference genomes are labelled. M. canetti is annotated in cyan. (TIF 69Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_4_Figure_S3_of_Recombination_in_... |
| Title | Additional file 5: Figure S4. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Identifying sites leading to differences in tree topologies based on all SNPs (Additional file 4: Figure S3a) and only those from pe/ppe genes (Additional file 4: Figure S3b). The Î Site wise log likelihood score (Î SSLS) is calculated for each SNP in the pe/ppe gene alignments. Negative differences indicate SNP positions favouring the pe/ppe tree. SNPs in pe_pgrs3, ppe57 and ppe60 produce strong phylogenetic signals supporting the pe/ppe tree. (TIF 113Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_5_Figure_S4_of_Recombination_in_... |
| Title | Additional file 5: Figure S4. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Identifying sites leading to differences in tree topologies based on all SNPs (Additional file 4: Figure S3a) and only those from pe/ppe genes (Additional file 4: Figure S3b). The Î Site wise log likelihood score (Î SSLS) is calculated for each SNP in the pe/ppe gene alignments. Negative differences indicate SNP positions favouring the pe/ppe tree. SNPs in pe_pgrs3, ppe57 and ppe60 produce strong phylogenetic signals supporting the pe/ppe tree. (TIF 113Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_5_Figure_S4_of_Recombination_in_... |
| Title | Additional file 6: Figure S5. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Phylogenetic tree created using only SNPs from pe_pgrs3. No clear clustering by lineage is observed. However there are two major clades, one consistent with H37Rv (bottom-left). (TIF 126Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_6_Figure_S5_of_Recombination_in_... |
| Title | Additional file 6: Figure S5. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Phylogenetic tree created using only SNPs from pe_pgrs3. No clear clustering by lineage is observed. However there are two major clades, one consistent with H37Rv (bottom-left). (TIF 126Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_6_Figure_S5_of_Recombination_in_... |
| Title | Additional file 7: Figure S6. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Molecular interactions established by wild-type residues in katG and rpoB residues. (A) The interactions established by Ser315 in katG. Given the proximity of the residue to the ligands INH and HEM, mutations to Asn and Thr, with slightly larger side chains, would potentially cause steric clashes. (B) The interactions of Asp435 in rpoB. It directly interacts with RMP via polar interactions that would be disrupted by mutations to Val. (C) Thr400 in rpoB is at the end of an alpha helix establishing intra molecular interactions. Giving its distance to RMP, it would be expected that its mutation to Ala would be a lower impact, which would arise from alosteric changes. (D) Ser450 establishes strong intra molecular interactions in the RMP binding site. Mutations to larger residues (Trp and Leu) could disrupt the packing of the region and therefore binding. (E). Ile491 performs hydrophobic interactions with RMP and its neighbouring residues. Mutations to Phe or Val would compromise packing, either inducing steric clashes or compromising packing. (F). His445 performs strong intra molecular interactions, including a donor-pi (blue dashes) and hydrogen bond (red dashes). Mutations to residues Asp, Tyr or Arg would imply in the loss of the pi interaction as well as potential introduction of steric clashes. (PNG 749 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_7_Figure_S6_of___Mycobacterium_t... |
| Title | Additional file 7: Figure S6. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Molecular interactions established by wild-type residues in katG and rpoB residues. (A) The interactions established by Ser315 in katG. Given the proximity of the residue to the ligands INH and HEM, mutations to Asn and Thr, with slightly larger side chains, would potentially cause steric clashes. (B) The interactions of Asp435 in rpoB. It directly interacts with RMP via polar interactions that would be disrupted by mutations to Val. (C) Thr400 in rpoB is at the end of an alpha helix establishing intra molecular interactions. Giving its distance to RMP, it would be expected that its mutation to Ala would be a lower impact, which would arise from alosteric changes. (D) Ser450 establishes strong intra molecular interactions in the RMP binding site. Mutations to larger residues (Trp and Leu) could disrupt the packing of the region and therefore binding. (E). Ile491 performs hydrophobic interactions with RMP and its neighbouring residues. Mutations to Phe or Val would compromise packing, either inducing steric clashes or compromising packing. (F). His445 performs strong intra molecular interactions, including a donor-pi (blue dashes) and hydrogen bond (red dashes). Mutations to residues Asp, Tyr or Arg would imply in the loss of the pi interaction as well as potential introduction of steric clashes. (PNG 749 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_7_Figure_S6_of___Mycobacterium_t... |
| Title | Additional file 7: Figure S6. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Lineage-specific recombination hotspots. Manhattan plots showing genes that are likely to be recombination hotspots in each lineage (Lineage 1 Indo-Oceanic; Lineage 2 East-Asian (Beijing); Lineage 3 East-African-Indian; Lineage 4 Euro-American). The (â log10) p-value for the phi statistic is plotted against genome position. All genes with p-valuesâ |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_7_Figure_S6_of_Recombination_in_... |
| Title | Additional file 7: Figure S6. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Lineage-specific recombination hotspots. Manhattan plots showing genes that are likely to be recombination hotspots in each lineage (Lineage 1 Indo-Oceanic; Lineage 2 East-Asian (Beijing); Lineage 3 East-African-Indian; Lineage 4 Euro-American). The (â log10) p-value for the phi statistic is plotted against genome position. All genes with p-valuesâ |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_7_Figure_S6_of_Recombination_in_... |
| Title | Additional file 8: Figure S7. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Evidence of recombination at a gene level in the 21 reference genomes. A Manhattan plot showing genes that are likely to be recombination hotspots. The (â log10) p-value for the phi statistic is plotted against genome position. Genes with p-values less than 0.05 are shown. (TIF 120Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_8_Figure_S7_of_Recombination_in_... |
| Title | Additional file 8: Figure S7. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Evidence of recombination at a gene level in the 21 reference genomes. A Manhattan plot showing genes that are likely to be recombination hotspots. The (â log10) p-value for the phi statistic is plotted against genome position. Genes with p-values less than 0.05 are shown. (TIF 120Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_8_Figure_S7_of_Recombination_in_... |
| Title | Additional file 9: Figure S8. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Selection dN/dS values for each gene within Clusters of Orthologous Groups (COG*) categories. *ppe/Nâ =â pe/ppe genes annotated as COG category N, * COG categories: A RNA processing and modification, B Chromatin Structure and dynamics, C Energy production and conversion, D Cell cycle control and mitosis, E Amino Acid metabolism and transport, F Nucleotide metabolism and transport, G Carbohydrate metabolism and transport, H Coenzyme metabolism, I Lipid metabolism, J Translation, K Transcription, L Replication and repair, M Cell wall/membrane/envelope biogenesis, N Cell motility, O Post-translational modification, protein turnover, chaperone functions, P Inorganic ion transport and metabolism, Q Secondary Structure, T Signal Transduction, U Intracellular trafficking and secretion, Y Nuclear structure, Z Cytoskeleton, R General Functional Prediction only, S Function Unknown. (TIF 124Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_9_Figure_S8_of_Recombination_in_... |
| Title | Additional file 9: Figure S8. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Selection dN/dS values for each gene within Clusters of Orthologous Groups (COG*) categories. *ppe/Nâ =â pe/ppe genes annotated as COG category N, * COG categories: A RNA processing and modification, B Chromatin Structure and dynamics, C Energy production and conversion, D Cell cycle control and mitosis, E Amino Acid metabolism and transport, F Nucleotide metabolism and transport, G Carbohydrate metabolism and transport, H Coenzyme metabolism, I Lipid metabolism, J Translation, K Transcription, L Replication and repair, M Cell wall/membrane/envelope biogenesis, N Cell motility, O Post-translational modification, protein turnover, chaperone functions, P Inorganic ion transport and metabolism, Q Secondary Structure, T Signal Transduction, U Intracellular trafficking and secretion, Y Nuclear structure, Z Cytoskeleton, R General Functional Prediction only, S Function Unknown. (TIF 124Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_9_Figure_S8_of_Recombination_in_... |
| Description | We have discovered potential (non-household) hotspots of TB transmission in Malawi, and follow-up work is investigating these. The methods developed and used in the Malawi study are now being applied in the context of the Philippines and Thailand. |
| Exploitation Route | We propose to apply for follow-up funding, including for studies involving the identification of those at greatest risk of TB and other co-morbidities (e.g. HIV), especially those living in other settings (e.g. Bangladesh and Pakistan). The development and updating of a shared genomics database, combined with rapid whole genome sequencing diagnostics, will lead to opportunities for personalised medicine grant funding opportunities. Follow-up laboratory work on Malawi samples has validated host-pathogen interactions revealed in the analysis of Malawi, Thailand and Philippines genomic data. Such insights could assist the development of vaccines and other anti-TB measures. |
| Sectors | Healthcare Government Democracy and Justice |
| Description | They are assisting policy makers, including in the application of genomics for identifying hotspots of disease transmission and drug resistance, and therefore informing disease control. Establishing that the majority of transmission is not between people that are closely related (e.g. families, neighbouring houses) has changed the focus of infection control to other settings (e.g. public transport, churches etc.). |
| Sector | Healthcare,Government, Democracy and Justice |
| Impact Types | Cultural Societal Policy & public services |
| Description | BBSRC UK-Philippines Swine & Poultry Research Initiative |
| Amount | £600,000 (GBP) |
| Funding ID | BB/R013063/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2018 |
| End | 03/2021 |
| Description | MRC - NSTDA - Newton: UK-Thailand Joint Initiative on Infectious Diseases |
| Amount | £600,000 (GBP) |
| Funding ID | MR/R020973/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2018 |
| End | 04/2021 |
| Description | MRC Newton UK-PCHRD Joint Research Health Call. Using host-responses and pathogen genomics to improve TB diagnostics |
| Amount | £750,000 (GBP) |
| Funding ID | N/A |
| Organisation | Newton Fund |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2018 |
| End | 09/2021 |
| Description | Newton Institutional Links Grant |
| Amount | £279,000 (GBP) |
| Funding ID | 261868591 |
| Organisation | British Council |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2017 |
| End | 04/2019 |
| Description | Newton Researcher Links Workshop Grants (Infectious Disease 'Omics (Philippines) ) |
| Amount | £60,000 (GBP) |
| Funding ID | 2017-RLWK8-10671 |
| Organisation | Newton Fund |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2018 |
| End | 12/2018 |
| Description | Newton Researcher Links Workshop Grants (Infectious Disease 'Omics (Philippines) ) |
| Amount | £60,000 (GBP) |
| Funding ID | Ref. 2017-RLWK9-110970 |
| Organisation | Newton Fund |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2018 |
| End | 12/2018 |
| Title | Algorithm for disentangling mixed infections using Mycobacterium tuberculosis whole genome sequencing data |
| Description | Using whole genome sequencing data we developed an algorithm for detecting mixed infections, estimating the multiplicity, and inferring parental sequences. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2017 |
| Provided To Others? | No |
| Impact | This will have impact as mixed infections are important. A manuscript is under review, and the software will be made available shortly. |
| Title | Methods to infer mixed infections |
| Description | This is an approach to characterising the extent of mixed infection in a sample. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | Others are citing our work and we are providing software tools for implementation on TB and other pathogens with genomic data. |
| Title | Tools for electronic data capture using tablets or mobile technologies |
| Description | We have developed electronic forms for the project, enabling the rapid and accurate capture of data from clinics and patients in the study. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | This is enabling the rapid analysis and tracking of study data. Therefore assisting with study project management and providing more timely insights into transmission patterns. The forms and technologies will be made available to other studies. |
| Title | Tools for inferring transmission chains |
| Description | This is a tool to infer transmission chains from whole genome sequence data, and identify mutations associated with transmissibility. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2018 |
| Provided To Others? | No |
| Impact | This will have impact as disease transmission is an important research area. A manuscript is in preparation, and software will be made available. |
| Title | Additional file 1: of Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data |
| Description | Strain information and full results table for clinically-derived Malawi samples, in silico replicate samples and Portuguese replicate samples. Lineage, total number of SNPs, number of heterozygous sites and the mixture analysis result for both Bayesian clustering and heterozygous sites approaches is included for each sample. (XLSX 162 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/Additional_file_1_of_Identifying_mixed_Mycobacterium_tu... |
| Title | Additional file 1: of Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data |
| Description | Strain information and full results table for clinically-derived Malawi samples, in silico replicate samples and Portuguese replicate samples. Lineage, total number of SNPs, number of heterozygous sites and the mixture analysis result for both Bayesian clustering and heterozygous sites approaches is included for each sample. (XLSX 162 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/Additional_file_1_of_Identifying_mixed_Mycobacterium_tu... |
| Title | Additional file 1: of Integrating informatics tools and portable sequencing technology for rapid detection of resistance to anti-tuberculous drugs |
| Description | Data S1. Mutations in the library (CSV 51 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/Additional_file_1_of_Integrating_informatics_tools_and_... |
| Title | Additional file 1: of Integrating informatics tools and portable sequencing technology for rapid detection of resistance to anti-tuberculous drugs |
| Description | Data S1. Mutations in the library (CSV 51 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/Additional_file_1_of_Integrating_informatics_tools_and_... |
| Title | Additional file 2 of Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains |
| Description | Additional file 2: Data S1. Samples AMR profile. Data S2. Plasmid sequences and their distribution. Data S3. Assignments of samples to clusters. Data S4. Contig IDs and Replicons. Data S5. Murray Collection Replicons |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Large-scale_genomic_analys... |
| Title | Additional file 2 of Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains |
| Description | Additional file 2: Data S1. Samples AMR profile. Data S2. Plasmid sequences and their distribution. Data S3. Assignments of samples to clusters. Data S4. Contig IDs and Replicons. Data S5. Murray Collection Replicons |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Large-scale_genomic_analys... |
| Title | Additional file 3 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 3. All BLASTN hits from AaegL5 assembly. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_3_of_Flavivirus_integrations_in... |
| Title | Additional file 3 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 3. All BLASTN hits from AaegL5 assembly. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_3_of_Flavivirus_integrations_in... |
| Title | Additional file 4 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 4. Accension IDs of all used flavivirus genomes. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_4_of_Flavivirus_integrations_in... |
| Title | Additional file 4 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 4. Accension IDs of all used flavivirus genomes. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_4_of_Flavivirus_integrations_in... |
| Title | Additional file 4: Figure S3. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Population structure analysis of the 144 isolates show clustering by lineage (Lineages one to four are represented by blue, green, purple, and red points, respectively). (a) A phylogenetic tree rooted with M. canetti. (b) First two principal components represent 33Â % and 30.5Â % of the variation explained between isolates, respectively. (ZIP 105 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_4_Figure_S3_of___Mycobacterium_... |
| Title | Additional file 4: Figure S3. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Population structure analysis of the 144 isolates show clustering by lineage (Lineages one to four are represented by blue, green, purple, and red points, respectively). (a) A phylogenetic tree rooted with M. canetti. (b) First two principal components represent 33Â % and 30.5Â % of the variation explained between isolates, respectively. (ZIP 105 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_4_Figure_S3_of___Mycobacterium_... |
| Title | Additional file 5 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 5. All BLASTN hits from AaloF2 assembly. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_5_of_Flavivirus_integrations_in... |
| Title | Additional file 5 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 5. All BLASTN hits from AaloF2 assembly. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_5_of_Flavivirus_integrations_in... |
| Title | Additional file 5: Figure S4. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | The relationship between the total number of non-synonymous SNPs in candidate loci and the MIC values. The size of the circle represents the number of isolates. a) Ethambutol (embB, embA, embA promoter, embC, embR and ubiA). b) Streptomycin (rpsL, rrs). The size of the circles is proportional to the frequency. The MIC values tend to increase with the number of non-synonymous mutations (ethambutol: rho = 0.24, slope = 0.29, p = 0.003; streptomycin: rho = 0.48, slope = 3.59, p = 1.65 × 10-8). The horizontal blue lines refer to the resistance cut-offs. (ZIP 92 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_5_Figure_S4_of___Mycobacterium_... |
| Title | Additional file 5: Figure S4. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | The relationship between the total number of non-synonymous SNPs in candidate loci and the MIC values. The size of the circle represents the number of isolates. a) Ethambutol (embB, embA, embA promoter, embC, embR and ubiA). b) Streptomycin (rpsL, rrs). The size of the circles is proportional to the frequency. The MIC values tend to increase with the number of non-synonymous mutations (ethambutol: rho = 0.24, slope = 0.29, p = 0.003; streptomycin: rho = 0.48, slope = 3.59, p = 1.65 × 10-8). The horizontal blue lines refer to the resistance cut-offs. (ZIP 92 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_5_Figure_S4_of___Mycobacterium_... |
| Title | Additional file 6 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 6. EVE coordinates and sequences identified in AaloF2. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_6_of_Flavivirus_integrations_in... |
| Title | Additional file 6 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 6. EVE coordinates and sequences identified in AaloF2. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_6_of_Flavivirus_integrations_in... |
| Title | Additional file 6: Figure S5. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Percentage of the variation in MIC values explained by each mutated codon in candidate genes. Bars in red represent significant independent associations with increased MIC (pâ |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_6_Figure_S5_of___Mycobacterium_... |
| Title | Additional file 6: Figure S5. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Percentage of the variation in MIC values explained by each mutated codon in candidate genes. Bars in red represent significant independent associations with increased MIC (pâ |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_6_Figure_S5_of___Mycobacterium_... |
| Title | Additional file 7 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 7. EVE bedfiles for AaegL5 and AaloF2 assemblies; phylogenetic trees and corresponding metadata for Ae. aegypti EVEs and cox1 gene. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_7_of_Flavivirus_integrations_in... |
| Title | Additional file 7 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 7. EVE bedfiles for AaegL5 and AaloF2 assemblies; phylogenetic trees and corresponding metadata for Ae. aegypti EVEs and cox1 gene. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_7_of_Flavivirus_integrations_in... |
| Title | Genomic evidence supporting the clonal expansion of extensively drug-resistant tuberculosis bacteria belonging to a rare proto-Beijing genotype |
| Description | Tuberculosis disease (TB), caused by Mycobacterium tuberculosis, is a major public health issue in Thailand. The high prevalence of modern Beijing (Lineage 2.2.1) strains has been associated with multi- and extensively drug-resistant infections (MDR-, XDR-TB), complicating disease control. The impact of rarer proto-Beijing (L2.1) strains is less clear. In our study of thirty-seven L2.1 clinical isolates spanning thirteen years, we found a high prevalence of XDR-TB cases (32.4%). With = 12 pairwise SNP distances, 43.2% of L2.1 patients belong to MDR-TB or XDR-TB transmission clusters suggesting a high level of clonal expansion across four Thai provinces. All XDR-TB (100%) were likely due to transmission rather than inadequate treatment. We found a 47 mutation signature and a partial deletion of the fadD14 gene in the circulating XDR-TB cluster, which can be used for surveillance of this rare and resilient M. tuberculosis strain-type that is causing increasing health burden. We also detected three novel deletion positions, a deletion of 1285 bp within desA3 (Rv3230c), large deletions in the plcB, plcA, and ppe38 gene which may play a role in the virulence, pathogenesis or evolution of the L2.1 strain-type. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| URL | https://tandf.figshare.com/articles/dataset/Genomic_evidence_supporting_the_clonal_expansion_of_exte... |
| Title | Genomic evidence supporting the clonal expansion of extensively drug-resistant tuberculosis bacteria belonging to a rare proto-Beijing genotype |
| Description | Tuberculosis disease (TB), caused by Mycobacterium tuberculosis, is a major public health issue in Thailand. The high prevalence of modern Beijing (Lineage 2.2.1) strains has been associated with multi- and extensively drug-resistant infections (MDR-, XDR-TB), complicating disease control. The impact of rarer proto-Beijing (L2.1) strains is less clear. In our study of thirty-seven L2.1 clinical isolates spanning thirteen years, we found a high prevalence of XDR-TB cases (32.4%). With = 12 pairwise SNP distances, 43.2% of L2.1 patients belong to MDR-TB or XDR-TB transmission clusters suggesting a high level of clonal expansion across four Thai provinces. All XDR-TB (100%) were likely due to transmission rather than inadequate treatment. We found a 47 mutation signature and a partial deletion of the fadD14 gene in the circulating XDR-TB cluster, which can be used for surveillance of this rare and resilient M. tuberculosis strain-type that is causing increasing health burden. We also detected three novel deletion positions, a deletion of 1285 bp within desA3 (Rv3230c), large deletions in the plcB, plcA, and ppe38 gene which may play a role in the virulence, pathogenesis or evolution of the L2.1 strain-type. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| URL | https://tandf.figshare.com/articles/dataset/Genomic_evidence_supporting_the_clonal_expansion_of_exte... |
| Title | High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates |
| Description | Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) make TB difficult to control. Global susceptibility data for six newly recommended anti-TB drugs against M/XDR-TB are still limited. Using publicly available whole-genome sequences, we determined the proportion of 513 phenotypically XDR-TB isolates that carried mutations associated with resistance against these drugs (bedaquiline, clofazimine, linezolid, delamanid, pretomanid and cycloserine). Mutations of Rv0678 and Rv1979c were detected in 69/513 isolates (13.5%) for bedaquiline resistance and 79/513 isolates (15.4%) for clofazimine resistance with additional mmpL5 mutations. Mutations conferring resistance to delamanid were detected in fbiB and ddn genes for 11/513 isolates (2.1%). For pretomanid, a mutation was detected in the ddn gene for 3/513 isolates (0.6%). Nineteen mutations of pykA, cycA, ald, and alr genes, conferring resistance to cycloserine, were found in 153/513 isolates (29.8%). No known mutations associated with linezolid resistance were detected. Cluster analysis showed that 408/513 isolates fell within 99 clusters and that 354 of these isolates were possible primary drug-resistant TB (292 XDR-TB, 57 pre-XDR-TB and 5 MDR-TB). Clonal transmission of primary XDR isolates might contribute significantly to the high prevalence of DR-TB globally. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| URL | https://tandf.figshare.com/articles/dataset/High_clustering_rate_and_genotypic_drug-susceptibility_s... |
| Title | High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates |
| Description | Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) make TB difficult to control. Global susceptibility data for six newly recommended anti-TB drugs against M/XDR-TB are still limited. Using publicly available whole-genome sequences, we determined the proportion of 513 phenotypically XDR-TB isolates that carried mutations associated with resistance against these drugs (bedaquiline, clofazimine, linezolid, delamanid, pretomanid and cycloserine). Mutations of Rv0678 and Rv1979c were detected in 69/513 isolates (13.5%) for bedaquiline resistance and 79/513 isolates (15.4%) for clofazimine resistance with additional mmpL5 mutations. Mutations conferring resistance to delamanid were detected in fbiB and ddn genes for 11/513 isolates (2.1%). For pretomanid, a mutation was detected in the ddn gene for 3/513 isolates (0.6%). Nineteen mutations of pykA, cycA, ald, and alr genes, conferring resistance to cycloserine, were found in 153/513 isolates (29.8%). No known mutations associated with linezolid resistance were detected. Cluster analysis showed that 408/513 isolates fell within 99 clusters and that 354 of these isolates were possible primary drug-resistant TB (292 XDR-TB, 57 pre-XDR-TB and 5 MDR-TB). Clonal transmission of primary XDR isolates might contribute significantly to the high prevalence of DR-TB globally. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| URL | https://tandf.figshare.com/articles/dataset/High_clustering_rate_and_genotypic_drug-susceptibility_s... |
| Title | Karonga sequencing database |
| Description | All raw and processed sequence data across ~3000 Mycobacterium tuberculosis. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| Impact | Scientific publications. |
| Title | MOESM1 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 1: Table S1. SNPs identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM1_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM1 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 1: Table S1. SNPs identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM1_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM2 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 2: Table S2. Insertions (INS) and deletions (DEL) identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM2_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM2 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 2: Table S2. Insertions (INS) and deletions (DEL) identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM2_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM3 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 3: Table S3. SNPs and Indels identified in the PF3D7_1222600 gene among P. falciparum field isolates from Africa and Asia. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM3_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM3 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 3: Table S3. SNPs and Indels identified in the PF3D7_1222600 gene among P. falciparum field isolates from Africa and Asia. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM3_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM4 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 4: Table S4. Structural variants identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM4_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM4 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 4: Table S4. Structural variants identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM4_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM7 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 7: Table S5. A scan for motifs in gene sequences (coding and UTR regions). |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM7_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM7 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 7: Table S5. A scan for motifs in gene sequences (coding and UTR regions). |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM7_of_Genomic_variation_in_two_gametocyte_n... |
| Description | Sequencing - GIS |
| Organisation | Agency for Science, Technology and Research (A*STAR) |
| Department | Genome Institute of Singapore |
| Country | Singapore |
| Sector | Academic/University |
| PI Contribution | Samples for pacino sequencing |
| Collaborator Contribution | Sequencing data. |
| Impact | Sequence data, and scientific publications. |
| Start Year | 2016 |
| Description | A genomics workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Other audiences |
| Results and Impact | It was a 3 day genomics capacity building workshop and two day symposium (July 2017) at the University of Philippines, which was attended by >150 people. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.up.edu.ph/index.php/ups-genome-center-holds-international-workshop-on-epidemiology-of-in... |
| Description | Asian TB Network meeting in Manilla |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | This was a meeting of Southeast Asian TB researchers and policy makers, with an interest in applying genomic tools for diagnosis, as well as the development of a joint genomic database across the region to assist with identifying important mutations for drug resistance and transmission. The meeting was hosted by the RITM in Manilla (March 2019). |
| Year(s) Of Engagement Activity | 2019 |
| Description | Capacity building workshop in genomics in LSHTM |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | 30 people attended a workshop covering TB genomics, which covered the analysis of transmission chains, phylogenies and association studies. A follow-up grant application was submitted that covered Malawi TB host and pathogen genomics. |
| Year(s) Of Engagement Activity | 2018 |