Biology subjects

Dongol, S.

Publications and source records attributed to Dongol, S..

4 recordsLinked to original sources

bioRxiv2022

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

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.

bioinformatics↗

bioRxiv2022

Perspectives of pharmacy employees on an inappropriate use of antimicrobials in Kathmandu, Nepal

BackgroundUnregulated antimicrobial use is common in both hospital and community settings of low- and middle-income countries (LMICs). However, discrete data regarding the use/misuse of antimicrobials at pharmacies in LMICs are limited. This study was conducted to understand the knowledge, attitude, and practice of pharmacy employees on antimicrobial dispensing in Nepal. MethodsWe conducted a cross-sectional survey using a structured questionnaire on 801 pharmacy employees working in community and hospital pharmacies located in Lalitpur metropolitan city (LMC) of Kathmandu, Nepal between April 2017 and March 2019. ResultsNot all respondents replied to all questions asked. A majority (92%, 738/801) of respondents agreed that the demand for non-prescription antimicrobials was common. Sixty nine percent (437/635) of participants responded that they would ask of prescription before dispensing. Suspected respiratory tract infection was the most common reason demanding for non-prescription antimicrobials, identified by 68% (535/792) of respondents. Azithromycin was the most commonly prescribed and sold antimicrobials, as reported by 46%, (361/787) and 48% (377/779) of participants respectively. A majority (87%; 696/800) of respondents agreed on antimicrobial resistance (AMR) to be a global public health threat; 54% (429/796) perceived antimicrobial misuse to be an important driver of AMR, while only 39% (315/801) replied that judicious dispensing of antimicrobials can help curb AMR. ConclusionOur study revealed that the unfounded dispensing and use of antimicrobials is prevalent among pharmacies in Kathmandu, Nepal. This overreliance on antimicrobials, notably azithromycin, may escalated the burden of AMR. We identified several drivers of inappropriate antimicrobial dispensing practice in pharmacies, which will aid public health authorities in addressing these issues. Further studies considering the role of other stakeholders, such as physicians, veterinarians, general public, and policy makers are required to obtain a more holistic perspectives on the practices of antimicrobial use so to curb the extant AMR crisis.

scientific communication and education↗

bioRxiv2020

The genetic signatures of Salmonella Typhi carriage in the human gallbladder

Despite recent gains in typhoid fever control, asymptomatic carriage of Salmonella Typhi in the gallbladder remains an enigma. Aiming to understand if S. Typhi in the gallbladder are vital for transmission and/or adapted for long-term colonisation we performed whole genome sequencing on a collection of S. Typhi isolated from the gallbladders of typhoid carriers. These sequences were compared to contemporaneous sequences from organisms isolated from the blood of acute patients.S. Typhi carriage was not restricted to any particular genotype or conformation of antimicrobial resistance genes but reflective of the general population. However, gallbladder isolates had a higher genetic variability than acute isolates, with median pairwise SNP distances of 21 and 13 SNPs (p=2.8x10-9), respectively. This variation was associated with a higher prevalence of nonsense mutations in the gallbladder isolates in the predominant genotype. Notably, gallbladder isolates displayed a higher frequency of non-synonymous mutations in genes encoding hypothetical proteins, membrane lipoproteins, transport/binding proteins, surface antigens, and carbohydrate degradation. Particularly, we identified several gallbladder-specific non-synonymous mutations involved in LPS synthesis and modification, with some isolates lacking the Vi capsular polysaccharide vaccine target due to a 134Kb deletion. Long-term gallbladder carriage of S. Typhi results in atypically long branch lengths that can distinguish between carriage and acute infection. Our data strongly suggests typhoid carriers are unlikely to play a principal role in disease transmission in endemic settings, but that the hostile environment of the human gallbladder may generate new antigenic variants through immune selection.

microbiology↗

bioRxiv2018

Diagnostic host gene signature to accurately distinguish enteric fever from other febrile diseases

Misdiagnosis of enteric fever is a major global health problem resulting in patient mismanagement, antimicrobial misuse and inaccurate disease burden estimates. Applying a machine-learning algorithm to host gene expression profiles, we identified a diagnostic signature which could accurately distinguish culture-confirmed enteric fever cases from other febrile illnesses (AUROC<95%). Applying this signature to a culture-negative suspected enteric fever cohort in Nepal identified a further 12.6% as likely true cases. Our analysis highlights the power of data-driven approaches to identify host-response patterns for the diagnosis of febrile illnesses. Expression signatures were validated using qPCR highlighting their utility as PCR-based diagnostic for use in endemic settings.

molecular biology↗