36 results on '"Brynildsrud O"'
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2. S85 Bedaquiline resistance in Mycobacterium tuberculosis predates its clinical use
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Nimmo, C, primary, van Dorp, L, additional, Torres Ortiz, A, additional, Pang, J, additional, Acman, M, additional, Millard, J, additional, Padayatchi, N, additional, Grant, A, additional, O’Donnell, M, additional, Brynildsrud, O, additional, Eldholm, V, additional, Grandjean, L, additional, Didelot, X, additional, and Balloux, F, additional
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- 2021
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3. Meningococcal carriage in Norwegian teenagers: strain characterisation and assessment of risk factors
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Watle, S. V., primary, Caugant, D. A., additional, Tunheim, G., additional, Bekkevold, T., additional, Laake, I., additional, Brynildsrud, O. B., additional, and Næss, L. M., additional
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- 2020
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4. Giardia duodenalisin primates: Classification and host specificity based on phylogenetic analysis of sequence data
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Brynildsrud, O., primary, Tysnes, K. R., additional, Robertson, L. J., additional, and Debenham, J. J., additional
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- 2018
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5. Giardia duodenalis in primates: Classification and host specificity based on phylogenetic analysis of sequence data.
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Brynildsrud, O., Tysnes, K. R., Robertson, L. J., and Debenham, J. J.
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GIARDIA , *HOST specificity (Biology) , *ZOONOSES , *GENOTYPES , *PRIMATES - Abstract
Summary: Giardia duodenalis colonizes the gastrointestinal tract of a wide range of hosts, including humans and other primates. It is grouped into eight different Assemblages and, beyond that, into a number of sub‐Assemblages, defined ad hoc on the basis of genetic differences; these various groups are often considered to be associated with a specific restricted host range. The aim of this study was to use publicly available genotyping data to investigate the relatedness of human and non‐human primate (NHP) Giardia isolates in order to evaluate the usefulness of current taxonomic classification and to assess whether there is potential for zoonotic transmission between humans and NHP. Our final data set consisted of sequence data from 165 isolates, 111 from NHP and 54 from humans. Assemblages were well defined, but sub‐Assemblages across Assemblage B were not resolved. Although sub‐Assemblages AI and AII were resolved, the terms were not found to capture any useful molecular or host/deme properties. In the phylogenetic tree, NHP isolates were scattered among human isolates across Assemblages A and B, and were even found in Assemblage E. We conclude that there does not appear to be significant molecular distinction between human and NHP Giardia isolates across these four molecular markers. Thus, on the basis of these markers, we cannot exclude a risk for zoonotic and anthropozoonotic transmission of Assemblages A and B isolates, irrespective of sub‐Assemblage classification. We further evaluated the relative merit of the four genes used in genotyping studies. The tpi, gdh and bg genes gave relatively congruent tree topologies, but the SSU gene did not resolve Assemblages according to the current classification. Future genotyping efforts should aim for multilocus or whole‐genome approaches and, in particular, use of the SSU gene as the sole marker should be avoided when possible. [ABSTRACT FROM AUTHOR]
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- 2018
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6. Scoary2: rapid association of phenotypic multi-omics data with microbial pan-genomes.
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Roder T, Pimentel G, Fuchsmann P, Stern MT, von Ah U, Vergères G, Peischl S, Brynildsrud O, Bruggmann R, and Bär C
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- Phenotype, Genes, Bacterial, Genomics, Genome-Wide Association Study, Multiomics
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Unraveling bacterial gene function drives progress in various areas, such as food production, pharmacology, and ecology. While omics technologies capture high-dimensional phenotypic data, linking them to genomic data is challenging, leaving 40-60% of bacterial genes undescribed. To address this bottleneck, we introduce Scoary2, an ultra-fast microbial genome-wide association studies (mGWAS) software. With its data exploration app and improved performance, Scoary2 is the first tool to enable the study of large phenotypic datasets using mGWAS. As proof of concept, we explore the metabolome of yogurts, each produced with a different Propionibacterium reichii strain and discover two genes affecting carnitine metabolism., (© 2024. The Author(s).)
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- 2024
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7. Tracing the adaptive evolution of SARS-CoV-2 during vaccine roll-out in Norway.
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Garcia I, Lee Y, Brynildsrud O, Eldholm V, Magnus P, Blomfeldt A, Leegaard TM, Müller F, Dudman S, and Caugant DA
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Vaccination against SARS-CoV-2 has greatly mitigated the impact of the COVID-19 pandemic. However, concerns have been raised about the degree to which vaccination might drive the emergence and selection of immune escape mutations that will hamper the efficacy of the vaccines. In this study, we investigate whether vaccination impacted the micro-scale adaptive evolution of SARS-CoV-2 in the Oslo region of Norway, during the first nine months of 2021, a period in which the population went from near-zero to almost 90 per cent vaccine coverage in the population over 50 years old. Weekly aggregated data stratified by age on vaccine uptake and number of SARS-CoV-2 cases in the area were obtained from the National Immunization Registry and the Norwegian Surveillance System for Communicable Diseases, respectively. A total of 6,438 virus sequences (7.5 per cent of the registered cases) along with metadata were available. We used a causal-driven approach to investigate the relationship between vaccination progress and changes in the frequency of 362 mutations present in at least ten samples, conditioned on the emergence of new lineages, time, and population vaccination coverage. After validating our approach, we identified 21 positive and 12 negative connections between vaccination progress and mutation prevalence, and most of them were outside the Spike protein. We observed a tendency for the mutations that we identified as positively connected with vaccination to decrease as the vaccinated population increased. After modelling the fitness of different competing mutations in a population, we found that our observations could be explained by a clonal interference phenomenon in which high fitness mutations would be outcompeted by the emergence or introduction of other high-fitness mutations., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2023
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8. Naturally occurring Neisseria gonorrhoeae can have large deletions in housekeeping gene abcZ , making them untypable with multilocus sequence typing.
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Vollan HS, Caugant DA, Eldholm V, Alfsnes K, Debech N, and Brynildsrud O
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- Adenosine Triphosphate, Amino Acids, Humans, Multilocus Sequence Typing, Genes, Essential genetics, Neisseria gonorrhoeae
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The abcZ gene is an essential housekeeping gene in all the Neisseria species. It is one of the seven genes used for multilocus sequence typing (MLST) this genus. It encodes the cytosolic component of an ATP-binding cassette (ABC) transporter complex of unknown function. We report here the finding of a strain of Neisseria gonorrhoeae with a 485 base pair deletion in the 5' region of the abcZ gene that truncates the protein product from 636 amino acids to 89 amino acids. A second open reading frame (ORF), encoding the latter 388 amino acids of the abcZ gene, was predicted downstream. The deletion will affect MLST profiling; interrogation of genomic sequences from PubMLST revealed that this isolate is not an anomaly. Deletions in abcZ were identified in 256 Neisseria genomes, roughly 0.6% of isolates. Furthermore, these deletions could leave the abcZ gene in a pseudogenized state. Our strain, isolated from a patient with symptoms of gonorrheal infection, nevertheless behaved normal in terms of growth and in vitro phenotypic properties.
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- 2022
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9. International links between Streptococcus pneumoniae vaccine serotype 4 sequence type (ST) 801 in Northern European shipyard outbreaks of invasive pneumococcal disease.
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Gladstone RA, Siira L, Brynildsrud OB, Vestrheim DF, Turner P, Clarke SC, Srifuengfung S, Ford R, Lehmann D, Egorova E, Voropaeva E, Haraldsson G, Kristinsson KG, McGee L, Breiman RF, Bentley SD, Sheppard CL, Fry NK, Corander J, Toropainen M, and Steens A
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- Disease Outbreaks, Finland, Genome, Bacterial, Humans, Northern Ireland, Norway, Occupational Exposure, Phylogeny, Polymorphism, Single Nucleotide, Serogroup, Serotyping, Ships, Pneumococcal Infections epidemiology, Pneumococcal Infections prevention & control, Streptococcus pneumoniae
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Background: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them., Methods: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating., Results: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017., Conclusion: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [R.A.G received a PhD stipend from Pfizer 2009–2011. L.S is a co-investigator in an unrelated study, for which THL has received research funding from GlaxoSmithKline Vaccines. S.C.C: acts as principal investigator on studies conducted on behalf of University Hospital Southampton NHS Foundation Trust/University of Southampton that are sponsored by vaccine manufacturers but receives no personal payments from them. S.C.C. has participated in advisory boards for vaccine manufacturers but receives no personal payments for this work. S.C.C. has received financial assistance from vaccine manufacturers to attend conferences. All grants and honoraria are paid into accounts within the respective NHS Trusts or Universities, or to independent charities. N.K.F, C.L.S The Immunisation and Countermeasures Division, Public Health England - National Infection Service, London, UK provides vaccine manufacturers with post-marketing surveillance reports, which the Marketing Authorization Holders are required to submit to the UK Licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. N.K.F and C.S. conduct contract research funded by vaccine manufacturers (including GlaxoSmithKline and Pfizer) on behalf of Public Health England. No personal remuneration is received. M.T reports grants from GlaxoSmithKline and Pfizer to the Finnish Institute for Health and Welfare for unrelated research projects in which she is a co-investigator. All remaining authors report no conflicts of interest.]., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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10. Whole Genome Sequencing of Drug Resistant and Drug Susceptible Mycobacterium tuberculosis Isolates From Tigray Region, Ethiopia.
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Welekidan LN, Yimer SA, Skjerve E, Dejene TA, Homberset H, Tønjum T, and Brynildsrud O
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Background: Tuberculosis, mainly caused by Mycobacterium tuberculosis (Mtb), is an ancient human disease that gravely affects millions of people annually. We wanted to explore the genetic diversity and lineage-specific association of Mtb with drug resistance among pulmonary tuberculosis patients. Methods: Sputum samples were collected from pulmonary tuberculosis patients at six different healthcare institutions in Tigray, Ethiopia, between July 2018 and August 2019. DNA was extracted from 74 Mtb complex isolates for whole-genome sequencing (WGS). All genomes were typed and screened for mutations with known associations with antimicrobial resistance using in silico methods, and results were cross-verified with wet lab methods. Results: Lineage (L) 4 (55.8%) was predominant, followed by L3 (41.2%); L1 (1.5%) and L2 (1.5%) occurred rarely. The most frequently detected sublineage was CAS (38.2%), followed by Ural (29.4%), and Haarlem (11.8%). The recent transmission index (RTI) was relatively low. L4 and Ural strains were more resistant than the other strains to any anti-TB drug ( P < 0.05). The most frequent mutations to RIF, INH, EMB, SM, PZA, ETH, FLQs, and 2nd-line injectable drugs occurred at rpoB S450L, katG S315T, embB M306I/V, rps L K43R, pncA V139A, ethA M1R, gyr A D94G, and rrs A1401G, respectively. Disputed rpoB mutations were also shown in four (16%) of RIF-resistant isolates. Conclusion: Our WGS analysis revealed the presence of diverse Mtb genotypes. The presence of a significant proportion of disputed rpoB mutations highlighted the need to establish a WGS facility at the regional level to monitor drug-resistant mutations. This will help control the transmission of DR-TB and ultimately contribute to the attainment of 100% DST coverage for TB patients as per the End TB strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Welekidan, Yimer, Skjerve, Dejene, Homberset, Tønjum and Brynildsrud.)
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- 2021
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11. Correction: Characteristics of pulmonary multidrug-resistant tuberculosis patients in Tigray Region, Ethiopia: A cross-sectional study.
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Welekidan LN, Skjerve E, Dejene TA, Gebremichael MW, Brynildsrud O, Agdestein A, Tessema GT, Tønjum T, and Yimer SA
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[This corrects the article DOI: 10.1371/journal.pone.0236362.].
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- 2021
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12. The impact of global lineage dynamics, border restrictions, and emergence of the B.1.1.7 lineage on the SARS-CoV-2 epidemic in Norway.
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Osnes MN, Alfsnes K, Bråte J, Garcia I, Riis RK, Instefjord KH, Elshaug H, Vollan HS, Moen LV, Pedersen BN, Caugant DA, Stene-Johansen K, Hungnes O, Bragstad K, Brynildsrud O, and Eldholm V
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As the COVID-19 pandemic swept through an immunologically naïve human population, academics and public health professionals scrambled to establish methods and platforms for genomic surveillance and data sharing. This offered a rare opportunity to study the ecology and evolution of SARS-CoV-2 over the course of the ongoing pandemic. Here, we use population genetic and phylogenetic methodology to characterize the population dynamics of SARS-CoV-2 and reconstruct patterns of virus introductions and local transmission in Norway against this backdrop. The analyses demonstrated that the epidemic in Norway was largely import driven and characterized by the repeated introduction, establishment, and suppression of new transmission lineages. This pattern changed with the arrival of the B.1.1.7 lineage, which was able to establish a stable presence concomitant with the imposition of severe border restrictions., (© The Author(s) 2021. Published by Oxford University Press.)
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- 2021
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13. Endospore Appendages: a novel pilus superfamily from the endospores of pathogenic Bacilli.
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Pradhan B, Liedtke J, Sleutel M, Lindbäck T, Zegeye ED, O Sullivan K, Llarena AK, Brynildsrud O, Aspholm M, and Remaut H
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- Bacillus cereus genetics, Bacterial Proteins genetics, Cryoelectron Microscopy, Fimbriae, Bacterial chemistry, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Stability, Bacillus cereus ultrastructure, Bacterial Proteins chemistry, Fimbriae, Bacterial ultrastructure
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Bacillus cereus sensu lato is a group of Gram-positive endospore-forming bacteria with high ecological diversity. Their endospores are decorated with micrometer-long appendages of unknown identity and function. Here, we isolate endospore appendages (Enas) from the food poisoning outbreak strain B. cereus NVH 0075-95 and find proteinaceous fibers of two main morphologies: S- and L-Ena. By using cryoEM and 3D helical reconstruction of S-Enas, we show these to represent a novel class of Gram-positive pili. S-Enas consist of single domain subunits with jellyroll topology that are laterally stacked by β-sheet augmentation. S-Enas are longitudinally stabilized by disulfide bonding through N-terminal connector peptides that bridge the helical turns. Together, this results in flexible pili that are highly resistant to heat, drought, and chemical damage. Phylogenomic analysis reveals a ubiquitous presence of the ena-gene cluster in the B. cereus group, which include species of clinical, environmental, and food importance. We propose Enas to represent a new class of pili specifically adapted to the harsh conditions encountered by bacterial spores., (© 2021 The Authors.)
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- 2021
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14. Evolution and emergence of multidrug-resistant Mycobacterium tuberculosis in Chisinau, Moldova.
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Brown TS, Eldholm V, Brynildsrud O, Osnes M, Levy N, Stimson J, Colijn C, Alexandru S, Noroc E, Ciobanu N, Crudu V, Cohen T, and Mathema B
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- Bayes Theorem, Drug Resistance, Multiple, Bacterial genetics, Female, Genomics, Humans, Male, Moldova epidemiology, Molecular Epidemiology, Mutation, Mycobacterium tuberculosis classification, Phylogeny, Prevalence, Tuberculosis, Multidrug-Resistant epidemiology, Whole Genome Sequencing, Evolution, Molecular, Mycobacterium tuberculosis genetics, Tuberculosis, Multidrug-Resistant classification, Tuberculosis, Multidrug-Resistant genetics
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The evolution and emergence of drug-resistant tuberculosis (TB) has been studied extensively in some contexts, but the ecological drivers of these two processes remain poorly understood. This study sought to describe the joint evolutionary and epidemiological histories of a novel multidrug-resistant Mycobacterium tuberculosis strain recently identified in the capital city of the Republic of Moldova (MDR Ural/4.2), where genomic surveillance of drug-resistant M. tuberculosis has been limited thus far. Using whole genome sequence data and Bayesian phylogenomic methods, we reconstruct the stepwise acquisition of drug resistance mutations in the MDR Ural/4.2 strain, estimate its historical bacterial population size over time, and infer the migration history of this strain between Eastern European countries. We infer that MDR Ural/4.2 likely evolved (via acquisition of rpoB S450L, which confers resistance to rifampin) in the early 1990s, during a period of social turmoil following Moldovan independence from the Soviet Union. This strain subsequently underwent substantial population size expansion in the early 2000s, at a time when national guidelines encouraged inpatient treatment of TB patients. We infer exportation of this strain and its isoniazid-resistant ancestral precursor from Moldova to neighbouring countries starting as early as 1985. Our findings suggest temporal and ecological associations between specific public health practices, including inpatient hospitalization of drug-resistant TB cases from the early 2000s until 2013, and the evolution of drug-resistant M. tuberculosis in Moldova. These findings underscore the need for regional coordination in TB control and expanded genomic surveillance efforts across Eastern Europe.
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- 2021
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15. The effect of recombination on the evolution of a population of Neisseria meningitidis .
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MacAlasdair N, Pesonen M, Brynildsrud O, Eldholm V, Kristiansen PA, Corander J, Caugant DA, and Bentley SD
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Neisseria meningitidis (the meningococcus) is a major human pathogen with a history of high invasive disease burden, particularly in sub-Saharan Africa. Our current understanding of the evolution of meningococcal genomes is limited by the rarity of large-scale genomic population studies and lack of in-depth investigation of the genomic events associated with routine pathogen transmission. Here, we fill this knowledge gap by a detailed analysis of 2839 meningococcal genomes obtained through a carriage study of over 50,000 samples collected systematically in Burkina Faso, West Africa, before, during, and after the serogroup A vaccine rollout, 2009-2012. Our findings indicate that the meningococcal genome is highly dynamic, with highly recombinant loci and frequent gene sharing across deeply separated lineages in a structured population. Furthermore, our findings illustrate how population structure can correlate with genome flexibility, as some lineages in Burkina Faso are orders of magnitude more recombinant than others. We also examine the effect of selection on the population, in particular how it is correlated with recombination. We find that recombination principally acts to prevent the accumulation of deleterious mutations, although we do also find an example of recombination acting to speed the adaptation of a gene. In general, we show the importance of recombination in the evolution of a geographically expansive population with deep population structure in a short timescale. This has important consequences for our ability to both foresee the outcomes of vaccination programs and, using surveillance data, predict when lineages of the meningococcus are likely to become a public health concern., (© 2021 MacAlasdair et al.; Published by Cold Spring Harbor Laboratory Press.)
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- 2021
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16. Frequency and patterns of first- and second-line drug resistance-conferring mutations in Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in a cross-sectional study in Tigray Region, Ethiopia.
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Welekidan LN, Skjerve E, Dejene TA, Gebremichael MW, Brynildsrud O, Tønjum T, and Yimer SA
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- Antitubercular Agents pharmacology, Cross-Sectional Studies, Ethiopia epidemiology, Humans, Microbial Sensitivity Tests, Mutation, Drug Resistance, Bacterial genetics, Mycobacterium tuberculosis genetics, Tuberculosis, Pulmonary epidemiology, Tuberculosis, Pulmonary microbiology
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Objectives: Tuberculosis (TB) is a preventable and treatable infectious disease, but the continuing emergence and spread of multidrug-resistant TB is threatening global TB control efforts. This study aimed to describe the frequency and patterns of drug resistance-conferring mutations of Mycobacterium tuberculosis (MTB) isolates detected from pulmonary TB patients in Tigray Region, Ethiopia., Methods: A cross-sectional study design was employed to collect sputum samples from pulmonary TB patients between July 2018 to August 2019. Culture and identification tests were done at Tigray Health Research Institute (THRI). Mutations conferring rifampicin (RIF), isoniazid (INH) and fluoroquinolone (FQ) resistance were determined in 227 MTB isolates using GenoType MTBDRplus and GenoType MTBDRsl., Results: Mutations conferring resistance to RIF, INH and FQs were detected in 40/227 (17.6%), 41/227 (18.1%) and 2/38 (5.3%) MTB isolates, respectively. The majority of mutations for RIF, INH and FQs occurred at codons rpoB S531L (70%), katG S315T (78%) and gyrA D94Y/N (100%), respectively. This study revealed a significant number of unknown mutations in the rpoB, katG and inhA genes., Conclusion: High rates of mutations conferring resistance to RIF, INH and FQs were observed in this study. A large number of isolates showed unknown mutations, which require further DNA sequencing analysis. Periodic drug resistance surveillance and scaling-up of drug resistance testing facilities are imperative to prevent the transmission of drug-resistant TB in the community., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2021
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17. A simple stochastic model describing genomic evolution over time of GC content in microbial symbionts.
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Bohlin J, Rose B, Brynildsrud O, and Birgitte Freiesleben De Blasio
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- Base Composition, Genomics, Phylogeny, Evolution, Molecular, Genome
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An organism's genomic base composition is usually summarized by its AT or GC content due to Chargaff's parity laws. Variation in prokaryotic GC content can be substantial between taxa but is generally small within microbial genomes. This variation has been found to correlate with both phylogeny and environmental factors. Since novel single-nucleotide polymorphisms (SNPs) within genomes are at least partially linked to the environment through natural selection, SNP GC content can be considered a compound measure of an organism's environmental influences, lifestyle, phylogeny as well as other more or less random processes. While there are several models describing genomic GC content few, if any, consider AT/GC mutation rates subjected to random perturbations. We present a mathematical model that describes how GC content in microbial genomes evolves over time as a function of the AT → GC and GC → AT mutation rates with Gaussian white noise disturbances. The model, which is suited specifically to non-recombining vertically transmitted prokaryotic symbionts, suggests that small differences in the AT/GC mutation rates can lead to profound differences in outcome due to the ensuing stochastic process. In other words, the model indicates that time to extinction could be a consequence of the mutation rate trajectory on which the symbiont embarked early on in its evolutionary history., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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18. Characteristics of pulmonary multidrug-resistant tuberculosis patients in Tigray Region, Ethiopia: A cross-sectional study.
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Welekidan LN, Skjerve E, Dejene TA, Gebremichael MW, Brynildsrud O, Agdestein A, Tessema GT, Tønjum T, and Yimer SA
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- Adolescent, Adult, Aged, Aged, 80 and over, Antitubercular Agents therapeutic use, Cross-Sectional Studies, Ethiopia epidemiology, Female, HIV Infections epidemiology, HIV Infections microbiology, HIV Infections pathology, Humans, Isoniazid therapeutic use, Male, Microbial Sensitivity Tests, Middle Aged, Mycobacterium tuberculosis pathogenicity, Rifampin therapeutic use, Risk Factors, Sputum drug effects, Sputum microbiology, Tuberculosis, Multidrug-Resistant epidemiology, Tuberculosis, Multidrug-Resistant microbiology, Tuberculosis, Multidrug-Resistant pathology, Tuberculosis, Pulmonary epidemiology, Tuberculosis, Pulmonary microbiology, Tuberculosis, Pulmonary pathology, Young Adult, HIV Infections drug therapy, Mycobacterium tuberculosis drug effects, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Pulmonary drug therapy
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Background: Tuberculosis (TB) is among the top 10 causes of mortality and the first killer among infectious diseases worldwide. One of the factors fuelling the TB epidemic is the global rise of multidrug resistant TB (MDR-TB). The aim of this study was to determine the magnitude and factors associated with MDR-TB in the Tigray Region, Ethiopia., Method: This study employed a facility-based cross-sectional study design, which was conducted between July 2018 and August 2019. The inclusion criteria for the study participants were GeneXpert-positive who were not under treatment for TB, PTB patients' ≥15 years of age and who provided written informed consent. A total of 300 participants were enrolled in the study, with a structured questionnaire used to collect data on clinical, sociodemographic and behavioral factors. Sputum samples were collected and processed for acid-fast bacilli staining, culture and drug susceptibility testing. Drug susceptibility testing was performed using a line probe assay. Logistic regression was used to analyze associations between outcome and predictor variables., Results: The overall proportion of MDR-TB was 16.7% (11.6% and 32.7% for new and previously treated patients, respectively). Of the total MDR-TB isolates, 5.3% were pre-XDR-TB. The proportion of MDR-TB/HIV co-infection was 21.1%. A previous history of TB treatment AOR 3.75; 95% CI (0.7-2.24), cigarette smoking AOR 6.09; CI (1.65-2.50) and patients who had an intermittent fever (AOR = 2.54, 95% CI = 1.21-5.4) were strongly associated with MDR-TB development., Conclusions: The magnitude of MDR-TB observed among new and previously treated patients is very alarming, which calls for an urgent need for intervention. The high proportion of MDR-TB among newly diagnosed cases indicates ongoing transmission, which suggests the need for enhanced TB control program performance to interrupt transmission. The increased proportion of MDR-TB among previously treated cases indicates a need for better patient management to prevent the evolution of drug resistance. Assessing the TB control program performance gaps and an optimal implementation of the WHO recommended priority actions for the management of drug-resistant TB, is imperative to help reduce the current high MDR-TB burden in the study region., Competing Interests: The authors have declared that no competing interests exist
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- 2020
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19. COVID-19 prevalence estimation by random sampling in population - optimal sample pooling under varying assumptions about true prevalence.
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Brynildsrud O
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- Algorithms, Betacoronavirus genetics, COVID-19, Coronavirus Infections epidemiology, Coronavirus Infections virology, Humans, Pandemics, Pneumonia, Viral epidemiology, Pneumonia, Viral virology, Prevalence, Reproducibility of Results, Reverse Transcriptase Polymerase Chain Reaction methods, SARS-CoV-2, Sample Size, Sensitivity and Specificity, Betacoronavirus isolation & purification, Coronavirus Infections diagnosis, Diagnostic Tests, Routine methods, Pneumonia, Viral diagnosis, Population Surveillance methods, Specimen Handling methods
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Background: The number of confirmed COVID-19 cases divided by population size is used as a coarse measurement for the burden of disease in a population. However, this fraction depends heavily on the sampling intensity and the various test criteria used in different jurisdictions, and many sources indicate that a large fraction of cases tend to go undetected., Methods: Estimates of the true prevalence of COVID-19 in a population can be made by random sampling and pooling of RT-PCR tests. Here I use simulations to explore how experiment sample size and degrees of sample pooling impact precision of prevalence estimates and potential for minimizing the total number of tests required to get individual-level diagnostic results., Results: Sample pooling can greatly reduce the total number of tests required for prevalence estimation. In low-prevalence populations, it is theoretically possible to pool hundreds of samples with only marginal loss of precision. Even when the true prevalence is as high as 10% it can be appropriate to pool up to 15 samples. Sample pooling can be particularly beneficial when the test has imperfect specificity by providing more accurate estimates of the prevalence than an equal number of individual-level tests., Conclusion: Sample pooling should be considered in COVID-19 prevalence estimation efforts.
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- 2020
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20. Haematological and serum biochemical values in Norwegian sled dogs before and after competing in a 600 km race.
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Jahr TH, Fergestad ME, Brynildsrud O, Brun-Hansen H, and Skancke E
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- Animals, Blood Chemical Analysis veterinary, Cohort Studies, Dogs physiology, Female, Hematologic Tests veterinary, Male, Norway, Physical Conditioning, Animal physiology, Prospective Studies, Reference Values, Dogs blood, Physical Endurance physiology, Running, Sports
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Background: Long-distance racing is known to cause alterations in haematological and serum biochemical parameters in sled dogs. Given that finishing status reflects the physical condition in dogs completing a race, such variations will mainly be the result of physiological adaption achieved during endurance exercise. However, changes observed in withdrawn dogs may indicate pathological conditions. The aim of this study was to reveal changes in haematological and serum biochemical values in sled dogs participating in a long-distance race, with emphasis on the withdrawn dogs. Sixty-five sled dogs participated in a clinical prospective cohort study: 46 dogs competed in the 600 km race (25 finishing and 21 withdrawn dogs), and 19 dogs served as controls. Blood sampling was performed early in the training season and after the race., Results: When compared to control dogs, both withdrawn and finishing dogs showed significant increases in neutrophil count, C-reactive protein, blood urea nitrogen and sodium/potassium ratio. Significant decreases were found in erythrocytes and eosinophil cell count, and in haematocrit, haemoglobin, total protein, albumin, globulin, creatinine, potassium and calcium levels. Finishing dogs presented significant increases in white blood cells, large unstained cells, monocyte count and cortisol level compared to control dogs. In contrast, withdrawn dogs had significant elevations in alanine aminotransferase and alkaline phosphatase activity, as well as parameters associated with muscle metabolism, such as aspartate aminotransferase, creatine kinase and phosphorus concentration., Conclusions: Competing sled dogs experienced minor changes in blood parameters in general, mainly revealing the same pattern among withdrawals and finishers. This might indicate that numerous changes simply reflect physiological adaption due to endurance exercise. However, the serum concentration of muscle enzymes was significantly increased only in the withdrawals, and were well above reference ranges. This reflects muscle degradation, which could be the main cause of performance failure in some of the withdrawals.
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- 2019
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21. Prenatal exposure to persistent organic pollutants in Northern Tanzania and their distribution between breast milk, maternal blood, placenta and cord blood.
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Müller MHB, Polder A, Brynildsrud OB, Grønnestad R, Karimi M, Lie E, Manyilizu WB, Mdegela RH, Mokiti F, Murtadha M, Nonga HE, Skaare JU, Solhaug A, and Lyche JL
- Subjects
- Environmental Monitoring, Family, Female, Fetal Blood, Humans, Infant, Kenya, Maternal Exposure statistics & numerical data, Placenta, Polychlorinated Biphenyls metabolism, Pregnancy, Tanzania epidemiology, Environmental Pollutants metabolism, Milk, Human metabolism, Prenatal Exposure Delayed Effects epidemiology
- Abstract
Human exposure to persistent organic pollutants (POPs) begins during pregnancy and may cause adverse health effects in the fetus or later in life. The present study aimed to assess prenatal POPs exposure to Tanzanian infants and evaluate the distribution of POPs between breast milk, maternal blood, placenta and cord blood. For assessment of prenatal exposure, 48 maternal blood samples from Mount Meru Regional Referral Hospital (MMRRH), Arusha Tanzania, were analyzed for organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), dioxin-like (DL) activity and perfluorinated alkyl substances (PFASs). For evaluation of POPs distribution between maternal/infant compartments, breast milk, placenta and cord blood corresponding to the maternal blood were analyzed for OCPs, PCBs and BFRs. In maternal blood, p,p´- DDE was detected in 100% of the samples ranging between 29 and 1890 ng/g lipid weight (lw). PCB-153 was the only PCB detected in maternal blood, with detection rate of 29% and concentrations up to 116 ng/g lw. BDE-47 was detected in 65% of the maternal blood samples, ranging between
- Published
- 2019
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22. From Theory to Practice: Translating Whole-Genome Sequencing (WGS) into the Clinic.
- Author
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Balloux F, Brønstad Brynildsrud O, van Dorp L, Shaw LP, Chen H, Harris KA, Wang H, and Eldholm V
- Subjects
- Bacteria pathogenicity, Base Sequence, Cross Infection diagnosis, Cross Infection epidemiology, Cross Infection microbiology, Diagnostic Tests, Routine economics, Drug Resistance, Bacterial, Genes, Bacterial, Humans, Multilocus Sequence Typing, Phenotype, Sequence Analysis, DNA, Virulence genetics, Virulence Factors genetics, Whole Genome Sequencing economics, Bacteria genetics, Bacteria isolation & purification, Diagnostic Tests, Routine methods, Genome, Bacterial, Whole Genome Sequencing methods
- Abstract
Hospitals worldwide are facing an increasing incidence of hard-to-treat infections. Limiting infections and providing patients with optimal drug regimens require timely strain identification as well as virulence and drug-resistance profiling. Additionally, prophylactic interventions based on the identification of environmental sources of recurrent infections (e.g., contaminated sinks) and reconstruction of transmission chains (i.e., who infected whom) could help to reduce the incidence of nosocomial infections. WGS could hold the key to solving these issues. However, uptake in the clinic has been slow. Some major scientific and logistical challenges need to be solved before WGS fulfils its potential in clinical microbial diagnostics. In this review we identify major bottlenecks that need to be resolved for WGS to routinely inform clinical intervention and discuss possible solutions., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2018
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23. Modeling of the GC content of the substituted bases in bacterial core genomes.
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Bohlin J, Eldholm V, Brynildsrud O, Petterson JH, and Alfsnes K
- Subjects
- Evolution, Molecular, Genome, Bacterial, Models, Genetic, Models, Theoretical, Bacteria genetics, Base Composition, Mutation
- Abstract
Background: The purpose of the present study was to examine the GC content of substituted bases (sbGC) in the core genomes of 35 bacterial species. Each species, or core genome, constituted genomes from at least 10 strains. We also wanted to explore whether sbGC for each strain was associated with the corresponding species' core genome GC content (cgGC). We present a simple mathematical model that estimates sbGC from cgGC. The model assumes only that the estimated sbGC is a function of cgGC proportional to fixed AT→GC (α) and GC → AT (β) mutation rates. Non-linear regression was used to estimate parameters α and β from the empirical data described above., Results: We found that sbGC for each strain showed a non-linear association with the corresponding cgGC with a bias towards higher GC content for most core genomes (66.3% of the strains), assuming as a null-hypothesis that sbGC should be approximately equal to cgGC. The most GC rich core genomes (i.e. approximately %GC > 60), on the other hand, exhibited slightly less GC-biased sbGC than expected. The best fitted regression model indicates that GC → AT mutation rates β = (1.91 ± 0.13) p < 0.001 are approximately (1.91/0.79) = 2.42 times as high, on average, as AT→GC α = (- 0.79 ± 0.25) p < 0.001 mutation rates. Whether the observed sbGC GC-bias for all but the most GC-rich prokaryotic species is due to selection, compensating for the GC → AT mutation bias, and/or selective neutral processes is currently debated. Residual standard error was found to be σ = 0.076 indicating estimated errors of sbGC to be approximately within ±15.2% GC (95% confidence interval) for the strains of all species in the study., Conclusion: Not only did our mathematical model give reasonable estimates of sbGC it also provides further support to previous observations that mutation rates in prokaryotes exhibit a universal GC → AT bias that appears to be remarkably consistent between taxa.
- Published
- 2018
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- View/download PDF
24. Read Depth Analysis to Identify CNV in Bacteria Using CNOGpro.
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Brynildsrud O
- Subjects
- Bacteria genetics, DNA Copy Number Variations, Genome, Bacterial, Sequence Analysis, DNA methods
- Abstract
Whole-genome sequencing with short-read technologies is well suited for calling single nucleotide polymorphisms, but has major problems with the detection of structural variants larger than the read length. One such type of variation is copy number variation (CNV), which entails deletion or duplication of genomic regions, and the expansion or contraction of repeated elements. Duplicated and deleted regions will typically be collapsed during de novo assembly of sequence data, or ignored when mapping reads toward a reference. However, signatures of the copy number variation can be detected in the resultant read depth at each position in the genome. We here provide instructions on how to analyze this read depth signal with the R package CNOGpro, allowing for estimation of copy numbers with uncertainty for each feature in a genome.
- Published
- 2018
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- View/download PDF
25. Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human breast milk and associated health risks to nursing infants in Northern Tanzania.
- Author
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Müller MHB, Polder A, Brynildsrud OB, Karimi M, Lie E, Manyilizu WB, Mdegela RH, Mokiti F, Murtadha M, Nonga HE, Skaare JU, and Lyche JL
- Subjects
- Adult, Breast Feeding, Environmental Monitoring, Environmental Pollutants analysis, Female, Humans, Infant, Infant Health, Kenya, Polychlorinated Biphenyls analysis, Pregnancy, Risk Assessment, Tanzania, Young Adult, DDT analysis, Dichlorodiphenyl Dichloroethylene analysis, Environmental Exposure analysis, Hydrocarbons, Chlorinated analysis, Maternal Exposure, Milk, Human chemistry, Pesticides analysis
- Abstract
This is the first study to report organochlorines (OCs), including chlorinated pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human milk from Tanzania. The main aims of this study were to assess the level of contamination and the possible health risks related to OC exposure in nursing infants from the Northern parts of Tanzania. Ninety-five healthy mother-infant couples attending Mount Meru Regional Referral Hospital (MMRRH), Arusha, Tanzania, were assessed for associations between maternal/infant characteristics, i.e. mother's age, BMI, gestational weight gain, occupation, residence and fetal growth parameters and breast milk levels of OCPs, such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, dieldrin and PCBs. p,p'-DDE and p,p'-DDT were detected in 100% and 75% of the breast milk samples, respectively, and ranged between 24 and 2400ng/g lipid weight (lw) and
- Published
- 2017
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- View/download PDF
26. The nucleotide composition of microbial genomes indicates differential patterns of selection on core and accessory genomes.
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Bohlin J, Eldholm V, Pettersson JH, Brynildsrud O, and Snipen L
- Subjects
- Base Composition, GC Rich Sequence, Nucleotides genetics, Evolution, Molecular, Genome, Microbial genetics, Nucleotides chemistry, Selection, Genetic
- Abstract
Background: The core genome consists of genes shared by the vast majority of a species and is therefore assumed to have been subjected to substantially stronger purifying selection than the more mobile elements of the genome, also known as the accessory genome. Here we examine intragenic base composition differences in core genomes and corresponding accessory genomes in 36 species, represented by the genomes of 731 bacterial strains, to assess the impact of selective forces on base composition in microbes. We also explore, in turn, how these results compare with findings for whole genome intragenic regions., Results: We found that GC content in coding regions is significantly higher in core genomes than accessory genomes and whole genomes. Likewise, GC content variation within coding regions was significantly lower in core genomes than in accessory genomes and whole genomes. Relative entropy in coding regions, measured as the difference between observed and expected trinucleotide frequencies estimated from mononucleotide frequencies, was significantly higher in the core genomes than in accessory and whole genomes. Relative entropy was positively associated with coding region GC content within the accessory genomes, but not within the corresponding coding regions of core or whole genomes., Conclusion: The higher intragenic GC content and relative entropy, as well as the lower GC content variation, observed in the core genomes is most likely associated with selective constraints. It is unclear whether the positive association between GC content and relative entropy in the more mobile accessory genomes constitutes signatures of selection or selective neutral processes.
- Published
- 2017
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27. Erratum to: Rapid scoring of genes in microbial pan-genome-wide association studies with Scoary.
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Brynildsrud O, Bohlin J, Scheffer L, and Eldholm V
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- 2016
- Full Text
- View/download PDF
28. Rapid scoring of genes in microbial pan-genome-wide association studies with Scoary.
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Brynildsrud O, Bohlin J, Scheffer L, and Eldholm V
- Abstract
Genome-wide association studies (GWAS) have become indispensable in human medicine and genomics, but very few have been carried out on bacteria. Here we introduce Scoary, an ultra-fast, easy-to-use, and widely applicable software tool that scores the components of the pan-genome for associations to observed phenotypic traits while accounting for population stratification, with minimal assumptions about evolutionary processes. We call our approach pan-GWAS to distinguish it from traditional, single nucleotide polymorphism (SNP)-based GWAS. Scoary is implemented in Python and is available under an open source GPLv3 license at https://github.com/AdmiralenOla/Scoary .
- Published
- 2016
- Full Text
- View/download PDF
29. The epidemiological and economic effects from systematic depopulation of Norwegian marine salmon farms infected with pancreas disease virus.
- Author
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Pettersen JM, Brynildsrud OB, Huseby RB, Rich KM, Aunsmo A, Bang BJ, and Aldrin M
- Subjects
- Animals, Computer Simulation, Cost-Benefit Analysis, Fish Diseases economics, Fish Diseases prevention & control, Fish Diseases virology, Models, Biological, Norway, Pancreatic Diseases economics, Pancreatic Diseases prevention & control, Pancreatic Diseases virology, Population Dynamics, Risk Factors, Fish Diseases epidemiology, Fisheries economics, Pancreatic Diseases veterinary, Salmon virology
- Abstract
Pancreas disease (PD) is a viral disease associated with significant economic losses in Scottish, Irish, and Norwegian marine salmon aquaculture. In this paper, we investigate how disease-triggered harvest strategies (systematic depopulation of infected marine salmon farms) towards PD can affect disease dynamics and salmon producer profits in an endemic area in the southwestern part of Norway. Four different types of disease-triggered harvest strategies were evaluated over a four-year period (2011-2014), each scenario with different disease-screening procedures, timing for initiating the harvest interventions on infected cohorts, and levels of farmer compliance to the strategy. Our approach applies a spatio-temporal stochastic model for simulating the spread of PD in the separate scenarios. Results from these simulations were then used in cost-benefit analyses to estimate the net benefits of different harvest strategies over time. We find that the most aggressive strategy, in which infected farms are harvested without delay, was most efficient in terms of reducing infection pressure in the area and providing economic benefits for the studied group of salmon producers. On the other hand, lower farm compliance leads to higher infection pressure and less economic benefits. Model results further highlight trade-offs in strategies between those that primarily benefit individual producers and those that have collective benefits, suggesting a need for institutional mechanisms that address these potential tensions., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
30. Dioxins, PCBs, chlorinated pesticides and brominated flame retardants in free-range chicken eggs from peri-urban areas in Arusha, Tanzania: Levels and implications for human health.
- Author
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Polder A, Müller MB, Brynildsrud OB, de Boer J, Hamers T, Kamstra JH, Lie E, Mdegela RH, Moberg H, Nonga HE, Sandvik M, Skaare JU, and Lyche JL
- Subjects
- Animals, Chickens, Environmental Exposure statistics & numerical data, Environmental Monitoring, Female, Humans, Hydrocarbons, Chlorinated analysis, Maternal Exposure, Risk Assessment, Tanzania, Dioxins analysis, Eggs analysis, Environmental Exposure analysis, Environmental Pollutants analysis, Flame Retardants analysis, Pesticides analysis, Polychlorinated Biphenyls analysis
- Abstract
The environment in the northern part of Tanzania is influenced by rapid population growth, and increased urbanization. Urban agriculture is common and of economic value for low income families. In Arusha, many households sell eggs from free-ranging backyard chicken. In 2011, 159 eggs from different households in five different locations in Arusha were collected, homogenized, pooled into 28 composite samples and analyzed for a wide selection of POPs. Levels of POPs varied widely within and between the locations. The levels of dieldrin and ΣDDT ranged between 2 and 98,791 and 2 and 324ng/g lipid weight (lw), respectively. EU MRLs of 0.02mg/kg dieldrin for eggs were exceeded in 4/28 samples. PCBs, HCHs, chlordanes, toxaphenes and endosulfanes were found at lower frequency and levels. Brominated flame retardants (BFRs), e.g polybrominated diphenylethers (PBDEs), hexabromocyclododecane (HBCD) and 1,2-bis(2,4,6-tribromphenoxy)ethane (BTBPE) were present in 100%, 60% and 46% of the composite samples, respectively. Octa-and deca-BDEs were the dominating PBDEs and BDE 209 levels ranged between
- Published
- 2016
- Full Text
- View/download PDF
31. Identifying copy number variation of the dominant virulence factors msa and p22 within genomes of the fish pathogen Renibacterium salmoninarum .
- Author
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Brynildsrud O, Gulla S, Feil EJ, Nørstebø SF, and Rhodes LD
- Subjects
- Animals, North America, Norway, Phylogeny, Bacterial Proteins genetics, DNA Copy Number Variations, Micrococcaceae genetics, Virulence Factors genetics
- Abstract
Renibacterium salmoninarum is the causative agent of bacterial kidney disease, an important disease of farmed and wild salmonid fish worldwide. Despite the wide spatiotemporal distribution of this disease and habitat pressures ranging from the natural environment to aquaculture and rivers to marine environments, little variation has been observed in the R. salmoninarum genome. Here we use the coverage depth from genomic sequencing corroborated by real-time quantitative PCR to detect copy number variation (CNV) among the genes of R. salmoninarum . CNV was primarily limited to the known dominant virulence factors msa and p22 . Among 68 isolates representing the UK, Norway and North America, the msa gene ranged from two to five identical copies and the p22 gene ranged from one to five copies. CNV for these two genes co-occurred, suggesting they may be functionally linked. Isolates carrying CNV were phylogenetically restricted and originated predominantly from sites in North America, rather than the UK or Norway. Although both phylogenetic relationship and geographical origin were found to correlate with CNV status, geographical origin was a much stronger predictor than phylogeny, suggesting a role for local selection pressures in the repeated emergence and maintenance of this trait.
- Published
- 2016
- Full Text
- View/download PDF
32. Brominated flame retardants (BFRs) in breast milk and associated health risks to nursing infants in Northern Tanzania.
- Author
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Müller MH, Polder A, Brynildsrud OB, Lie E, Løken KB, Manyilizu WB, Mdegela RH, Mokiti F, Murtadha M, Nonga HE, Skaare JU, and Lyche JL
- Subjects
- Female, Humans, Infant, Maternal Exposure adverse effects, Risk, Tanzania, Breast Feeding, Flame Retardants analysis, Halogenated Diphenyl Ethers analysis, Milk, Human chemistry
- Abstract
The main aim of this study was to assess brominated flame retardants (BFRs) in breast milk in the Northern parts of Tanzania. Ninety-five colostrum samples from healthy, primiparous mothers at Mount Meru Regional Referral Hospital (MMRRH), Arusha Tanzania, were analyzed for polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), hexabromobenzene (HBB), (2,3-dibromopropyl) (2,4,6-tribromophenyl) ether (DPTE), pentabromoethylbenzene (PBEB) and 2,3,4,5,6-pentabromotoluene (PBT). The Ʃ7PBDE (BDE 28, 47, 99, 100, 153, 154, 183) ranged from below level of detection (
- Published
- 2016
- Full Text
- View/download PDF
33. CNOGpro: detection and quantification of CNVs in prokaryotic whole-genome sequencing data.
- Author
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Brynildsrud O, Snipen LG, and Bohlin J
- Subjects
- Base Composition, Genome, Archaeal, Genomics methods, High-Throughput Nucleotide Sequencing, Internet, Sequence Analysis, DNA, DNA Copy Number Variations, Genome, Bacterial, Software
- Abstract
Motivation: The explosion of whole-genome sequencing (WGS) as a tool in the mapping and understanding of genomes has been accompanied by an equally massive report of tools and pipelines for the analysis of DNA copy number variation (CNV). Most currently available tools are designed specifically for human genomes, with comparatively little literature devoted to CNVs in prokaryotic organisms. However, there are several idiosyncrasies in prokaryotic WGS data. This work proposes a step-by-step approach for detection and quantification of copy number variants specifically aimed at prokaryotes., Results: After aligning WGS reads to a reference genome, we count the individual reads in a sliding window and normalize these counts for bias introduced by differences in GC content. We then investigate the coverage in two fundamentally different ways: (i) Employing a Hidden Markov Model and (ii) by repeated sampling with replacement (bootstrapping) on each individual gene. The latter bypasses the complex problem of breakpoint determination. To demonstrate our method, we apply it to real and simulated WGS data and benchmark it against two popular methods for CNV detection. The proposed methodology will in some cases represent a significant jump in accuracy from other current methods., Availability and Implementation: CNOGpro is written entirely in the R programming language and is available from the CRAN repository (http://cran.r-project.org) under the GNU General Public License., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2015
- Full Text
- View/download PDF
34. Positive correlations between genomic %AT and genome size within strains of bacterial species.
- Author
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Bohlin J, Sekse C, Skjerve E, and Brynildsrud O
- Subjects
- Bacteria genetics, Base Composition, Genome Size, Genome, Bacterial
- Abstract
Genomic %AT has been found to correlate negatively with genome size in microbes. While microbes with large genomes are often GC rich and free living, AT-rich bacteria tend to be host associated with smaller genomes. With over 2000 fully sequenced and assembled microbial genomes available, we explored the relationship among genomic %AT, genome size, relative entropy (a measure associated with genetic drift) and fraction of genome islands (GIs) in microbial species with the genomes of more than 10 strains available. A negative correlation with genome size was found in six out of 12 phylogenetic groups and subphyla and a positive correlation in only two. At the species level, we found a trend of positive correlations between genomic %AT and genome size in eight out of 20 species, while only four showed a negative correlation. Estimated chromosomal fractions of GIs were found to correlate positively with genome size in the strains of 14 out of 18 species and genomic %AT in the strains of seven species (two correlated negatively). Although GIs explain most of the observed positive correlations between genomic %AT and size, Chlamydia trachomatis seem to be an exception; therefore, these findings needs to be further explored., (© 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.)
- Published
- 2014
- Full Text
- View/download PDF
35. Microevolution of Renibacterium salmoninarum: evidence for intercontinental dissemination associated with fish movements.
- Author
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Brynildsrud O, Feil EJ, Bohlin J, Castillo-Ramirez S, Colquhoun D, McCarthy U, Matejusova IM, Rhodes LD, Wiens GD, and Verner-Jeffreys DW
- Subjects
- Animals, DNA, Bacterial genetics, Micrococcaceae isolation & purification, Norway, Polymorphism, Single Nucleotide genetics, Population Dynamics, Time, Actinomycetales Infections microbiology, Fish Diseases microbiology, Micrococcaceae classification, Micrococcaceae genetics, Phylogeny, Salmonidae microbiology, Salmonidae physiology
- Abstract
Renibacterium salmoninarum is the causative agent of bacterial kidney disease, a major pathogen of salmonid fish species worldwide. Very low levels of intra-species genetic diversity have hampered efforts to understand the transmission dynamics and recent evolutionary history of this Gram-positive bacterium. We exploited recent advances in the next-generation sequencing technology to generate genome-wide single-nucleotide polymorphism (SNP) data from 68 diverse R. salmoninarum isolates representing broad geographical and temporal ranges and different host species. Phylogenetic analysis robustly delineated two lineages (lineage 1 and lineage 2); futhermore, dating analysis estimated that the time to the most recent ancestor of all the isolates is 1239 years ago (95% credible interval (CI) 444-2720 years ago). Our data reveal the intercontinental spread of lineage 1 over the last century, concurrent with anthropogenic movement of live fish, feed and ova for aquaculture purposes and stocking of recreational fisheries, whilst lineage 2 appears to have been endemic in wild Eastern Atlantic salmonid stocks before commercial activity. The high resolution of the SNP-based analyses allowed us to separate closely related isolates linked to neighboring fish farms, indicating that they formed part of single outbreaks. We were able to demonstrate that the main lineage 1 subgroup of R. salmoninarum isolated from Norway and the UK likely represent an introduction to these areas ~40 years ago. This study demonstrates the promise of this technology for analysis of micro and medium scale evolutionary relationships in veterinary and environmental microorganisms, as well as human pathogens.
- Published
- 2014
- Full Text
- View/download PDF
36. Amino acid usage is asymmetrically biased in AT- and GC-rich microbial genomes.
- Author
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Bohlin J, Brynildsrud O, Vesth T, Skjerve E, and Ussery DW
- Subjects
- Bias, Codon genetics, Entropy, Models, Genetic, Mutation genetics, Principal Component Analysis, Prokaryotic Cells metabolism, Regression Analysis, Amino Acids genetics, Base Composition genetics, Genome, Microbial genetics
- Abstract
Introduction: Genomic base composition ranges from less than 25% AT to more than 85% AT in prokaryotes. Since only a small fraction of prokaryotic genomes is not protein coding even a minor change in genomic base composition will induce profound protein changes. We examined how amino acid and codon frequencies were distributed in over 2000 microbial genomes and how these distributions were affected by base compositional changes. In addition, we wanted to know how genome-wide amino acid usage was biased in the different genomes and how changes to base composition and mutations affected this bias. To carry this out, we used a Generalized Additive Mixed-effects Model (GAMM) to explore non-linear associations and strong data dependences in closely related microbes; principal component analysis (PCA) was used to examine genomic amino acid- and codon frequencies, while the concept of relative entropy was used to analyze genomic mutation rates., Results: We found that genomic amino acid frequencies carried a stronger phylogenetic signal than codon frequencies, but that this signal was weak compared to that of genomic %AT. Further, in contrast to codon usage bias (CUB), amino acid usage bias (AAUB) was differently distributed in AT- and GC-rich genomes in the sense that AT-rich genomes did not prefer specific amino acids over others to the same extent as GC-rich genomes. AAUB was also associated with relative entropy; genomes with low AAUB contained more random mutations as a consequence of relaxed purifying selection than genomes with higher AAUB., Conclusion: Genomic base composition has a substantial effect on both amino acid- and codon frequencies in bacterial genomes. While phylogeny influenced amino acid usage more in GC-rich genomes, AT-content was driving amino acid usage in AT-rich genomes. We found the GAMM model to be an excellent tool to analyze the genomic data used in this study.
- Published
- 2013
- Full Text
- View/download PDF
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