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3 results on '"STRATAA Study Group"'

1. Direct inference and control of genetic population structure from RNA sequencing data

Author

Muhamad Fachrul, Abhilasha Karkey, Mila Shakya, Louise M. Judd, Taylor Harshegyi, Kar Seng Sim, Susan Tonks, Sabina Dongol, Rajendra Shrestha, Agus Salim, STRATAA study group, Stephen Baker, Andrew J. Pollard, Chiea Chuen Khor, Christiane Dolecek, Buddha Basnyat, Sarah J. Dunstan, Kathryn E. Holt, and Michael Inouye

Subjects
Biology (General), QH301-705.5
Abstract

Abstract RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset. In differential gene expression analysis, we found that inclusion of RG-PCs as covariates reduced test statistic inflation. Our paper demonstrates that genetic population structure can be directly inferred and controlled for using RNAseq data, thus facilitating improved retrospective and future analyses of transcriptomic data.

Published
2023
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2. Pathogen diversity and antimicrobial resistance transmission of Salmonella enterica serovars Typhi and Paratyphi A in Bangladesh, Nepal, and Malawi: a genomic epidemiological study.

Author

Dyson, ZA, Ashton, PM, Khanam, F, Chunga Chirambo, A, Shakya, M, Meiring, JE, Tonks, S, Karkey, A, Msefula, C, Clemens, JD, Dunstan, SJ, Baker, S, Dougan, G, Pitzer, VE, Basnyat, B, Qadri, F, Heyderman, RS, Gordon, MA, Pollard, AJ, Holt, KE, STRATAA Study Group, Dyson, ZA, Ashton, PM, Khanam, F, Chunga Chirambo, A, Shakya, M, Meiring, JE, Tonks, S, Karkey, A, Msefula, C, Clemens, JD, Dunstan, SJ, Baker, S, Dougan, G, Pitzer, VE, Basnyat, B, Qadri, F, Heyderman, RS, Gordon, MA, Pollard, AJ, Holt, KE, and STRATAA Study Group

Abstract

BACKGROUND: Enteric fever is a serious public health concern. The causative agents, Salmonella enterica serovars Typhi and Paratyphi A, frequently have antimicrobial resistance (AMR), leading to limited treatment options and poorer clinical outcomes. We investigated the genomic epidemiology, resistance mechanisms, and transmission dynamics of these pathogens at three urban sites in Africa and Asia. METHODS: S Typhi and S Paratyphi A bacteria isolated from blood cultures of febrile children and adults at study sites in Dhaka (Bangladesh), Kathmandu (Nepal), and Blantyre (Malawi) during STRATAA surveillance were sequenced. Isolates were charactered in terms of their serotypes, genotypes (according to GenoTyphi and Paratype), molecular determinants of AMR, and population structure. We used phylogenomic analyses incorporating globally representative genomic data from previously published surveillance studies and ancestral state reconstruction to differentiate locally circulating from imported pathogen AMR variants. Clusters of sequences without any single-nucleotide variants in their core genome were identified and used to explore spatiotemporal patterns and transmission dynamics. FINDINGS: We sequenced 731 genomes from isolates obtained during surveillance across the three sites between Oct 1, 2016, and Aug 31, 2019 (24 months in Dhaka and Kathmandu and 34 months in Blantyre). S Paratyphi A was present in Dhaka and Kathmandu but not Blantyre. S Typhi genotype 4.3.1 (H58) was common in all sites, but with different dominant variants (4.3.1.1.EA1 in Blantyre, 4.3.1.1 in Dhaka, and 4.3.1.2 in Kathmandu). Multidrug resistance (ie, resistance to chloramphenicol, co-trimoxazole, and ampicillin) was common in Blantyre (138 [98%] of 141 cases) and Dhaka (143 [32%] of 452), but absent from Kathmandu. Quinolone-resistance mutations were common in Dhaka (451 [>99%] of 452) and Kathmandu (123 [89%] of 138), but not in Blantyre (three [2%] of 141). Azithromycin-resistance mutations

Published
2024

3. A Bayesian approach for estimating typhoid fever incidence from large-scale facility-based passive surveillance data

Author

Phillips, Maile T, Meiring, James E, Voysey, Merryn, Warren, Joshua L, Baker, Stephen, Basnyat, Buddha, Clemens, John D, Dolecek, Christiane, Dunstan, Sarah J, Dougan, Gordon, Gordon, Melita A, Thindwa, Deus, Heyderman, Robert S, Holt, Kathryn E, Qadri, Firdausi, Pollard, Andrew J, Pitzer, Virginia E, STRATAA Study Group, Phillips, Maile T [0000-0001-6952-0440], and Apollo - University of Cambridge Repository

Subjects
passive surveillance, reporting pyramid, Malawi, Nepal, incidence estimation, Incidence, Humans, Bayes Theorem, Typhoid Fever
Abstract

Funder: Public Health Research Programme; Id: http://dx.doi.org/10.13039/501100001921, Decisions about typhoid fever prevention and control are based on estimates of typhoid incidence and their uncertainty. Lack of specific clinical diagnostic criteria, poorly sensitive diagnostic tests, and scarcity of accurate and complete datasets contribute to difficulties in calculating age-specific population-level typhoid incidence. Using data from the Strategic Typhoid Alliance across Africa and Asia program, we integrated demographic censuses, healthcare utilization surveys, facility-based surveillance, and serological surveillance from Malawi, Nepal, and Bangladesh to account for under-detection of cases. We developed a Bayesian approach that adjusts the count of reported blood-culture-positive cases for blood culture detection, blood culture collection, and healthcare seeking-and how these factors vary by age-while combining information from prior published studies. We validated the model using simulated data. The ratio of observed to adjusted incidence rates was 7.7 (95% credible interval [CrI]: 6.0-12.4) in Malawi, 14.4 (95% CrI: 9.3-24.9) in Nepal, and 7.0 (95% CrI: 5.6-9.2) in Bangladesh. The probability of blood culture collection led to the largest adjustment in Malawi, while the probability of seeking healthcare contributed the most in Nepal and Bangladesh; adjustment factors varied by age. Adjusted incidence rates were within or below the seroincidence rate limits of typhoid infection. Estimates of blood-culture-confirmed typhoid fever without these adjustments results in considerable underestimation of the true incidence of typhoid fever. Our approach allows each phase of the reporting process to be synthesized to estimate the adjusted incidence of typhoid fever while correctly characterizing uncertainty, which can inform decision-making for typhoid prevention and control.

Published
2021

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