Browsing by Author "Jjingo, Daudi"
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Item Air pollution and mobility patterns in two Ugandan cities during COVID‑19 mobility restrictions suggest the validity of air quality data as a measure for human mobility(Environmental Science and Pollution Research, 2022) Galiwango, Ronald; Bainomugisha, Engineer; Kivunike, Florence; Kateete, David Patrick; Jjingo, DaudiWe explored the viability of using air quality as an alternative to aggregated location data from mobile phones in the two most populated cities in Uganda. We accessed air quality and Google mobility data collected from 15th February 2020 to 10th June 2021 and augmented them with mobility restrictions implemented during the COVID-19 lockdown. We determined whether air quality data depicted similar patterns to mobility data before, during, and after the lockdown and determined associations between air quality and mobility by computing Pearson correlation coefficients ( R ), conducting multivariable regression with associated confidence intervals (CIs), and visualized the relationships using scatter plots. Residential mobility increased with the stringency of restrictions while both non-residential mobility and air pollution decreased with the stringency of restrictions. In Kampala, PM2.5 was positively correlated with non-residential mobility and negatively correlated with residential mobility. Only correlations between PM2.5 and movement in work and residential places were statistically significant in Wakiso. After controlling for stringency in restrictions, air quality in Kampala was independently correlated with movement in retail and recreation (− 0.55; 95% CI = − 1.01– − 0.10), parks (0.29; 95% CI = 0.03–0.54), transit stations (0.29; 95% CI = 0.16–0.42), work (− 0.25; 95% CI = − 0.43– − 0.08), and residential places (− 1.02; 95% CI = − 1.4– − 0.64). For Wakiso, only the correlation between air quality and residential mobility was statistically significant (− 0.99; 95% CI = − 1.34– − 0.65). These findings suggest that air quality is linked to mobility and thus could be used by public health programs in monitoring movement patterns and the spread of infectious diseases without compromising on individuals’ privacy.Item Airway microbiome signature accurately discriminates Mycobacterium tuberculosis infection status(Elsevier Inc, 2024-06) Kayongo, Alex; Ntayi, Moses Levi; Olweny, Geoffrey; Kyalo, Edward; Ndawula, Josephine; Ssengooba, Willy; Kigozi, Edgar; Kalyesubula, Robert; Munana, Richard; Namaganda, Jesca; Caroline, Musiime; Sekibira, Rogers; Bagaya, Bernard Sentalo; Kateete, David Patrick; Joloba, Moses Lutaakome; Jjingo, Daudi; Sande, Obondo James; Mayanja-Kizza, HarrietAbstract Mycobacterium tuberculosis remains one of the deadliest infectious agents globally. Amidst efforts to control TB, long treatment duration, drug toxicity, and resistance underscore the need for novel therapeutic strategies. Despite advances in understanding the interplay between microbiome and disease in humans, the specific role of the microbiome in predicting disease susceptibility and discriminating infection status in tuberculosis still needs to be fully investigated. We investigated the impact of M.tb infection and M.tb-specific IFNγ immune responses on airway microbiome diversity by performing TB GeneXpert and QuantiFERON-GOLD assays during the follow-up phase of a longitudinal HIV-Lung Microbiome cohort of individuals recruited from two large independent cohorts in rural Uganda. M.tb rather than IFNγ immune response mainly drove a significant reduction in airway microbiome diversity. A microbiome signature comprising Streptococcus, Neisseria, Fusobacterium, Prevotella, Schaalia, Actinomyces, Cutibacterium, Brevibacillus, Microbacterium, and Beijerinckiacea accurately discriminated active TB from Latent TB and M.tb-uninfected individuals. [Display omitted] •M.tb infection drives a significant reduction in airway microbiome diversity•M.tb-specific IFNg does not directly impact airway microbiome diversity•Airway microbiome signature discriminates active TB from LTBI and uninfected states•LTBI and M.tb-uninfected states display similar airway microbiome diversity Microbiology; Bacteriology; MicrobiomeItem Bioinformatics mentorship in a resource limited setting(Briefings in Bioinformatics, 2021) Jjingo, Daudi; Mboowa, Gerald; Sserwadda, Ivan; Kakaire, Robert; Kiberu, Davis; Amujal, Marion; Galiwango, Ronald; Kateete, David; Joloba, Moses; Whalen, Christopher C.The two recent simultaneous developments of high-throughput sequencing and increased computational power have brought bioinformatics to the forefront as an important tool for effective and efficient biomedical research. Consequently, there have been multiple approaches to developing bioinformatics skills. In resource rich environments, it has been possible to develop and implement formal fully accredited graduate degree training programs in bioinformatics. In resource limited settings with a paucity of expert bioinformaticians, infrastructure and financial resources, the task has been approached by delivering short courses on bioinformatics—lasting only a few days to a couple of weeks. Alternatively, courses are offered online, usually over a period of a few months. These approaches are limited by both the lack of sustained in-person trainer–trainee interactions, which is a key part of quality mentorships and short durations which constrain the amount of learning that can be achieved.Item Compound cis-regulatory elements with both boundary and enhancer sequences in the human genome(Bioinformatics, 2013) Jjingo, Daudi; Wang, Jianrong; Conley, Andrew B.; Lunyak, Victoria V.; Jordan, I. KingIt has been suggested that presumably distinct classes of genomic regulatory elements may actually share common sets of features and mechanisms. However, there has been no genome-wide assessment of the prevalence of this phenomenon. Results: To evaluate this possibility, we performed a bioinformatic screen for the existence of compound regulatory elements in the human genome. We identified numerous such colocated boundary and enhancer elements from human CD4þ T cells.We report evidence that such compound regulatory elements possess unique chromatin features and facilitate cell type-specific functions related to inflammation and immune response in CD4þ T cells.Item Designing and delivering bioinformatics project-based learning in East Africa(BioMed Central Ltd, 2024-04) Kibet, Caleb K; Entfellner, Jean-Baka Domelevo; Jjingo, Daudi; de Villiers, Etienne Pierre; de Villiers, Santie; Wambui, Karen; Kinyanjui, Sam; Masiga, DanielThe Eastern Africa Network for Bioinformatics Training (EANBiT) has matured through continuous evaluation, feedback, and codesign. We highlight how the program has evolved to meet challenges and achieve its goals and how experiential learning through mini projects enhances the acquisition of skills and collaboration. We continued to learn and grow through honest feedback and evaluation of the program, trainers, and modules, enabling us to provide robust training even during the Coronavirus disease 2019 (COVID-19) pandemic, when we had to redesign the program due to restricted travel and in person group meetings. In response to the pandemic, we developed a program to maintain "residential" training experiences and benefits remotely. We had to answer the following questions: What must change to still achieve the RT goals? What optimal platforms should be used? How would we manage connectivity and data challenges? How could we avoid online fatigue? Going virtual presented an opportunity to reflect on the essence and uniqueness of the program and its ability to meet the objective of strengthening bioinformatics skills among the cohorts of students using different delivery approaches. It allowed an increase in the number of participants. Evaluating each program component is critical for improvement, primarily when feedback feeds into the program's continuous amendment. Initially, the participants noted that there were too many modules, insufficient time, and a lack of hands-on training as a result of too much focus on theory. In the subsequent iterations, we reduced the number of modules from 27 to five, created a harmonized repository for the materials on GitHub, and introduced project-based learning through the mini projects. We demonstrate that implementing a program design through detailed monitoring and evaluation leads to success, especially when participants who are the best fit for the program are selected on an appropriate level of skills, motivation, and commitment.Item Effect of the Transposable Element Environment of Human Genes on Gene Length and Expression(Genome biology and evolution, 2011) Jjingo, Daudi; Huda, Ahsan; Gundapuneni, Madhumati; Leonardo Mari o-Ramırez, Leonardo Marin˜ o-Ramı´rez3,4, and I. King Jordan; Jordan, I. KingIndependent lines of investigation have documented effects of both transposable elements (TEs) and gene length (GL) on gene expression. However, TE gene fractions are highly correlated with GL, suggesting that they cannot be considered independently. We evaluated the TE environment of human genes and GL jointly in an attempt to tease apart their relative effects. TE gene fractions and GL were compared with the overall level of gene expression and the breadth of expression across tissues. GL is strongly correlated with overall expression level but weakly correlated with the breadth of expression, confirming the selection hypothesis that attributes the compactness of highly expressed genes to selection for economy of transcription. However, TE gene fractions overall, and for the L1 family in particular, show stronger anticorrelations with expression level than GL, indicating that GL may not be the most important target of selection for transcriptional economy. These results suggest a specific mechanism, removal of TEs, by which highly expressed genes are selectively tuned for efficiency. MIR elements are the only family of TEs with gene fractions that show a positive correlation with tissue-specific expression, suggesting that they may provide regulatory sequences that help to control human gene expression. Consistent with this notion, MIR fractions are relatively enriched close to transcription start sites and associated with coexpression in specific sets of related tissues. Our results confirm the overall relevance of the TE environment to gene expression and point to distinct mechanisms by which different TE families may contribute to gene regulation.Item Genetic Diversity of Bundibugyo Ebolavirus from Uganda and the Democratic Republic of Congo(bioRxiv, 2021) Omara, Isaac Emmanuel; Kiwuwa-Muyingo, Sylvia; Balinandi, Stephen; Nyakarahuka, Luke; Kiconco, Jocelyn; Kayiwa, John Timothy; Mboowa, Gerald; Jjingo, Daudi; Lutwama, Julius J.The Ebolavirus is one of the deadliest viral pathogens which was first discovered in the year 1976 during two consecutive outbreaks in the Democratic Republic of Congo and Sudan. Six known strains have been documented. The Bundibugyo Ebolavirus in particular first emerged in the year 2007 in Uganda. This outbreak was constituted with 116 human cases and 39 laboratory confirmed deaths. After 5 years, it re-emerged and caused an epidemic for the first time in the Democratic Republic of Congo in the year 2012 as reported by the WHO. Here, 36 human cases with 13 laboratory confirmed deaths were registered. Despite several research studies conducted in the past, there is still scarcity of knowledge available on the genetic diversity of Bundibugyo Ebolavirus. We undertook a research project to provide insights into the unique variants of Bundibugyo Ebolavirus that circulated in the two epidemics that occurred in Uganda and the Democratic Republic of CongoItem Mammalian-wide interspersed repeat (MIR)-derived enhancers and the regulation of human gene expression(Mobile DNA, 2014) Jjingo, Daudi; Conley, Andrew B.; Wang, Jianrong; Mariño-Ramírez, Leonardo; Lunyak, Victoria V.; Jordan, I. KingMammalian-wide interspersed repeats (MIRs) are the most ancient family of transposable elements (TEs) in the human genome. The deep conservation of MIRs initially suggested the possibility that they had been exapted to play functional roles for their host genomes. MIRs also happen to be the only TEs whose presence in-and-around human genes is positively correlated to tissue-specific gene expression. Similar associations of enhancer prevalence within genes and tissue-specific expression, along with MIRs’ previous implication as providing regulatory sequences, suggested a possible link between MIRs and enhancers. Results: To test the possibility that MIRs contribute functional enhancers to the human genome, we evaluated the relationship between MIRs and human tissue-specific enhancers in terms of genomic location, chromatin environment, regulatory function, and mechanistic attributes. This analysis revealed MIRs to be highly concentrated in enhancers of the K562 and HeLa human cell-types. Significantly more enhancers were found to be linked to MIRs than would be expected by chance, and putative MIR-derived enhancers are characterized by a chromatin environment highly similar to that of canonical enhancers. MIR-derived enhancers show strong associations with gene expression levels, tissue-specific gene expression and tissue-specific cellular functions, including a number of biological processes related to erythropoiesis. MIR-derived enhancers were found to be a rich source of transcription factor binding sites, underscoring one possible mechanistic route for the element sequences co-option as enhancers. There is also tentative evidence to suggest that MIR-enhancer function is related to the transcriptional activity of non-coding RNAs. Conclusions: Taken together, these data reveal enhancers to be an important cis-regulatory platform from which MIRs can exercise a regulatory function in the human genome and help to resolve a long-standing conundrum as to the reason for MIRs’ deep evolutionary conservation.Item On the presence and role of human gene-body DNA methylation(Oncotarget, 2012) Jjingo, Daudi; Conley, Andrew B.; Yi, Soojin V.; Lunyak, Victoria V.; Jordan, I. KingDNA methylation of promoter sequences is a repressive epigenetic mark that down-regulates gene expression. However, DNA methylation is more prevalent within gene-bodies than seen for promoters, and gene-body methylation has been observed to be positively correlated with gene expression levels. This paradox remains unexplained, and accordingly the role of DNA methylation in gene-bodies is poorly understood. We addressed the presence and role of human gene-body DNA methylation using a meta-analysis of human genome-wide methylation, expression and chromatin data sets. Methylation is associated with transcribed regions as genic sequences have higher levels of methylation than intergenic or promoter sequences. We also find that the relationship between gene-body DNA methylation and expression levels is non-monotonic and bell-shaped. Mid-level expressed genes have the highest levels of gene-body methylation, whereas the most lowly and highly expressed sets of genes both have low levels of methylation. While gene-body methylation can be seen to efficiently repress the initiation of intragenic transcription, the vast majority of methylated sites within genes are not associated with intragenic promoters. In fact, highly expressed genes initiate the most intragenic transcription, which is inconsistent with the previously held notion that gene-body methylation serves to repress spurious intragenic transcription to allow for efficient transcriptional elongation. These observations lead us to propose a model to explain the presence of human gene-body methylation. This model holds that the repression of intragenic transcription by gene-body methylation is largely epiphenomenal, and suggests that gene-body methylation levels are predominantly shaped via the accessibility of the DNA to methylating enzyme complexes.Item Phylogenomic analysis of Uganda influenza type-A viruses to assess their relatedness to the vaccine strains and other Africa viruses: a molecular epidemiology study(bioRxiv, 2021) Nabakooza, Grace; Owuor, David Collins; Laurent, Zaydah R. de; Owor, Nicholas; Kayiwa, John Timothy; Jjingo, Daudi; Nyaigoti Agoti, Charles; Nokes, David James; Kateete, David Patrick; Mulindwa Kitayimbwa, John; Frost, Simon David William; Lutwama, Julius JulianGenetic characterisation of circulating influenza viruses is essential for vaccine selection and mitigation of viral transmission. The current scantiness of viral genomic data and underutilisation of advanced molecular analysis methods on influenza viruses circulating in Africa has limited their extensive study and representation in the global influenza ecology. We aimed to sequence influenza type-A viruses (IAVs) that previously circulated in Uganda and characterised their genetic relatedness to the vaccine viruses and publicly available Africa IAVs. Methods: This was an observational study nested to the Uganda national influenza surveillance programme. We used Next-generation sequencing to locally generate genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) viruses collected between 2010 and 2018 from 7 districts across Uganda. A total of 206 hemagglutinin (HA), 207 neuraminidase (NA), and 213 matrix protein (MP) sequences were genetically compared to the WHO-recommended vaccines and other viruses isolated from Africa since 1994. Viral temporal and spatial divergence and circulating genetic clades were characterised using phylogenetic methods. Findings: We successfully generated gene sequences for 91·9% (215/234) viruses. Uganda A(H1N1)pdm09 and A(H3N2) virus HA, NA, and MP proteins had 96·36-99·09%, 96·49-99·39%, and 97·48-99·95% amino acid similarity, respectively, to vaccines recommended from 2010 through 2020. The local viruses incorporated amino acid substitutions (AAS) in their antigenic, receptor binding, and glycosylation sites each year causing them to antigenically drift away from vaccines. For seasons when vaccine formulations differed, Uganda IAV antigenic sites had 1-2 extra AAS relative to the Southern than Northern hemisphere vaccine viruses. All Uganda IAVs carried the adamantine-resistance marker S31N but not the neuraminidase inhibitor (NAI) resistance markers H274Y and H275Y. However, some A(H1N1)pdm09 viruses had permissive substitutions V234I, N369K, and V241I typical of NAI-resistant viruses.Item Prediction of Transposable Element Derived Enhancers Using Chromatin Modification Profiles(PLoS ONE, 2011) Huda, Ahsan; Tyagi, Eishita; Marino-Ramırez, Leonardo; Bowen, Nathan J.; Jjingo, Daudi; Jordan, I. KingExperimentally characterized enhancer regions have previously been shown to display specific patterns of enrichment for several different histone modifications. We modelled these enhancer chromatin profiles in the human genome and used them to guide the search for novel enhancers derived from transposable element (TE) sequences. To do this, a computational approach was taken to analyze the genome-wide histone modification landscape characterized by the ENCODE project in two human hematopoietic cell types, GM12878 and K562. We predicted the locations of 2,107 and 1,448 TE-derived enhancers in the GM12878 and K562 cell lines respectively. A vast majority of these putative enhancers are unique to each cell line; only 3.5% of the TE-derived enhancers are shared between the two. We evaluated the functional effect of TE-derived enhancers by associating them with the cell-type specific expression of nearby genes, and found that the number of TE-derived enhancers is strongly positively correlated with the expression of nearby genes in each cell line. Furthermore, genes that are differentially expressed between the two cell lines also possess a divergent number of TE derived enhancers in their vicinity. As such, genes that are up-regulated in the GM12878 cell line and down-regulated in K562 have significantly more TE-derived enhancers in their vicinity in the GM12878 cell line and vice versa. These data indicate that human TE-derived sequences are likely to be involved in regulating cell-type specific gene expression on a broad scale and suggest that the enhancer activity of TE-derived sequences is mediated by epigenetic regulatory mechanisms.Item QuasiFlow: A Nextflow Pipeline for Analysis of NGS-based HIV-1 Drug Resistance Data(Bioinformatics advances, 2022) Ssekagiri, Alfred; Jjingo, Daudi; Lujumba, Ibra; Bbosa, Nicholas; Bugembe, Daniel L.; Kateete, David P.; Kaleebu, Pontiano; Ssemwanga, DeogratiusNext-generation sequencing (NGS) enables reliable detection of resistance mutations in minority variants of human immunodeficiency virus type 1 (HIV-1). There is paucity of evidence for the association of minority resistance to treatment failure, and this requires evaluation. However, the tools for analyzing HIV-1 drug resistance (HIVDR) testing data are mostly web-based which requires uploading data to webservers. This is a challenge for laboratories with internet connectivity issues and instances with restricted data transfer across networks. We present QuasiFlow, a pipeline for reproducible analysis of NGS-based HIVDR testing data across different computing environments. Since QuasiFlow entirely depends on command-line tools and a local copy of the reference database, it eliminates challenges associated with uploading HIV-1 NGS data onto webservers. The pipeline takes raw sequence reads in FASTQ format as input and generates a user-friendly report in PDF/HTML format. The drug resistance scores obtained using QuasiFlow were 100% and 99.12% identical to those obtained using web-based HIVdb program and HyDRA web respectively at a mutation detection threshold of 20%.Item Transcriptional Activity, Chromosomal Distribution and Expression Effects of Transposable Elements in Coffea Genomes(PLoS One, 2013) Lopes, Fabrıcio R.; Jjingo, Daudi; da Silva, Carlos R. M.; Andrade, Alan C.; Marraccini, Pierre; Teixeira, Joao B.; Carazzolle, Marcelo F.; Pereira, Goncalo A. G.; Pereira, Luiz Filipe P.; Vanzela, Andre´ L. L.; Wang, Lu; Jordan, I. King; Carareto, Claudia M. A.Plant genomes are massively invaded by transposable elements (TEs), many of which are located near host genes and can thus impact gene expression. In flowering plants, TE expression can be activated (de-repressed) under certain stressful conditions, both biotic and abiotic, as well as by genome stress caused by hybridization. In this study, we examined the effects of these stress agents on TE expression in two diploid species of coffee, Coffea canephora and C. eugenioides, and their allotetraploid hybrid C. arabica. We also explored the relationship of TE repression mechanisms to host gene regulation via the effects of exonized TE sequences. Similar to what has been seen for other plants, overall TE expression levels are low in Coffea plant cultivars, consistent with the existence of effective TE repression mechanisms. TE expression patterns are highly dynamic across the species and conditions assayed here are unrelated to their classification at the level of TE class or family. In contrast to previous results, cell culture conditions per se do not lead to the de-repression of TE expression in C. arabica. Results obtained here indicate that differing plant drought stress levels relate strongly to TE repression mechanisms. TEs tend to be expressed at significantly higher levels in non-irrigated samples for the drought tolerant cultivars but in drought sensitive cultivars the opposite pattern was shown with irrigated samples showing significantly higher TE expression. Thus, TE genome repression mechanisms may be finely tuned to the ideal growth and/or regulatory conditions of the specific plant cultivars in which they are active. Analysis of TE expression levels in cell culture conditions underscored the importance of nonsense-mediated mRNA decay (NMD) pathways in the repression of Coffea TEs. These same NMD mechanisms can also regulate plant host gene expression via the repression of genes that bear exonized TE sequences.Item Validity of Air Quality as a Measure of Human Mobility in Uganda. The COVID-19 Context(Research Square, 2022) Galiwango, Ronald; Bainomugisha, Engineer; Kivunike, Florence; Kateete, David Patrick; Jjingo, DaudiMobility patterns are valuable in identifying transmission patterns for infectious diseases and in deriving contact matrices that are used to parametrize mathematical models. Aggregated location data from mobile phones have been the main means of measuring human mobility on a population level. However, these data come with several limitations related to individual privacy, access and restriction of the GPS location by the user that limit their use. Methods We explored the viability of using ground monitored air quality data as an alternative to aggregated location data from mobile phones, as a measure of human mobility in two cities in Uganda. We determined associations between air quality and human mobility; and the effect of mobility restrictions on mobility and air quality using Pearson correlation (R), multivariate regression and visualized these relationships using scatter plots. Results Daily mean levels for PM2.5 in both cities were consistently higher than the WHO guideline limit, with a mean of 77.0μg/m3 (Range = 22.0–309) for Kampala and 60.0μg/m3 (Range = 18.2–331) for Wakiso. PM10 levels had a mean of 84.6μg/m3 (Range = 25.0–318) in Kampala and 67.9μg/m3 (Range = 21.0– 340) in Wakiso. PM2.5 was negatively correlated with the government response stringency index for Kampala (R = -0.31, p < 0.001) and Wakiso (R = -0.21, p < 0.001). In Kampala, PM2.5 was positively associated with movement in grocery and pharmacy (R = 0.24, p < 0.001), parks (R = 0.25, p < 0.001), retail and recreation (R = 0.24, p < 0.001), transit stations (R = 0.3, p < 0.001) and work places (R = 0.2, p < 0.001); and negatively correlated with movement in residential places (R = -0.3, p < 0.001). Only associations between PM2.5 and movement in workplaces and residential places were statistically significant in Wakiso (R = 0.14, p < 0.001 and R = -0.19, p = 0.003 respectively). Conclusions These findings suggest that air quality data are linked to human mobility data and could thus be used to monitor human movement patterns. This work represents a pioneer study to empirically and quantitatively assess the value of air quality data as a surrogate for human mobility in Uganda.