Biology subjects

Weeratunga, P.

Publications and source records attributed to Weeratunga, P..

3 recordsLinked to original sources

bioRxiv2026

DENcode: A model for haplotype-informed transmission probability of dengue virus

Dengue virus transmission networks are often only partially resolved, due to gaps in sampling, unobserved mosquito-mediated transmission, and using methods (phylogenetics) that describe evolutionary relatedness but not explicit, probabilistic transmission links between individual infections. We developed DENcode, a framework to estimate the relative likelihood of vector-mediated transmission between pairs of dengue cases by combining a temperature- and time-modulated epidemiological kernel, which captures the extrinsic incubation period and human infectiousness, with a phylogenetically informed genetic similarity kernel derived from patristic distances between viral haplotypes or consensus sequences. Validation with a real-life dataset of 90 dengue infections sampled from Colombo, Sri Lanka between 2017 - 2020 and sequenced to resolve within-host haplotypes, DENcode estimates were stable across 100 Monte Carlo iterations, yielding narrow credible intervals (median width <0.001) and consistent top-ranked transmission pairs. Sensitivity analyses using ablation experiments showed that removing either the genetic or epidemiological component substantially altered the distribution of linkage probabilities, indicating that both contribute meaningfully to the inferred transmission structure. Serotype-specific transmission networks constructed from pairwise linkage probabilities from DENcode were analysed using degree- and path-based centrality measures at probability thresholds of 0.1 and 0.5, revealing relative importance of cases to disease transmission within the community. Haplotype-derived networks were more informative than consensus-based networks (x 3.6 and x 1.6 times more edges for DENV2 and 3 respectively). DENcode is a robust framework to explore dengue transmission within a community that provides an output of network of transmission probabilities informed by pathogen genetic similarity and clinical epidemiological parameters. Author summaryTracing epidemics of dengue in setting where dengue transmission happens continuously poses many challenges especially with limited availability of genomic surveillance. Here we introduce a model that uses genomic data together with time and location data to calculate a probability of two cases of dengue being related to each other. Using data from the Colombo dengue study, from 2017 to 2020, Sri Lanka, we evaluated the model. We used haplotype level sequences that correspond to the viral variation within the human host and consensus level sequences that average the data from a single human host into a single sequence. We constructed transmission probability networks for each dengue serotype and were able to identify patients who played key roles in the corresponding networks. We were able to show that this model is robust and will be a valuable tool in the context of dengue control.

bioinformatics↗

bioRxiv2025

Between- and within-host mutation of dengue virus

RNA viruses exhibit high mutation rates due to error-prone polymerases, leading to a diverse pool of viral haplotypes (also referred to as quasi-species) within infected hosts. While haplotypes have been well studied in chronic infections like HIV and HCV, diversity remains under-explored in acute infections like dengue (DENV), which are constrained by a short viremic phase. This study aimed to characterise the mutation hotspots in DENV genomes at both consensus and haplotype levels. Near full length DENV genomes were sequenced using Oxford Nanopore Technology (ONT) from the plasma of Sri Lankan patients with dengue fever recruited between 2017 -2020. Consensus sequences were mapped with Minimap-2, and haplotypes were reconstructed with Nano-Q, a tool designed for estimation of RNA virus haplotypes and their relative abundance. The genomic variability of DENV genomes was assessed by calculating Shannon Entropy (SE). Codons undergoing diversifying selection were identified with three phylogenetics-based algorithms (FEL, MEME, FUBAR) implemented within the Datamonkey suite. From 150 samples tested, both consensus and haplotype sequences were characterised in 90 samples (DENV1: 8, DENV2: 51, DENV3: 31). The genomic variability of consensus sequences measured by SE was higher in DENV2 compared to DENV3, and the reverse was true for haplotypes. At the consensus level, the NS2A gene had the greatest number of mutable sites when adjusted for gene length across all serotypes, while at the haplotype level the NS1 gene had the same. Overall, the haplotypes sequences revealed more sites with high mutability and codons under diversifying selection than those visible at consensus level. This provides proof-in-principle that in acute RNA viruses also have high mutability in haplotypes, which may be inapparent with a consensus-level analysis.

bioinformatics↗

bioRxiv2018

Platypus Induced Pluripotent Stem Cells: the Unique Pluripotency Signature of a Monotreme

Summary StatementThe generation and transcriptome analysis of the first induced pluripotent stem cells from the platypus reveals SOX2 has been a key driver of the expanded pluripotency regulatory network in placental mammals.\n\nABSTRACTThe mechanisms by which pluripotency has evolved remain unclear. To gain insight into the evolution of mammalian pluripotency we have generated induced pluripotent stem cells (piPSCs) from the platypus. Deep sequencing of the piPSC transcriptome revealed that piPSCs robustly express the core eutherian pluripotency factors OCT4, SOX2 and NANOG. Given the more extensive role of SOX3 over SOX2 in avian pluripotency, our data indicate that between 315 million years and 166 million years ago primitive mammals replaced the role of SOX3 in the vertebrate pluripotency network with SOX2. DAX1/NR0B1 is not expressed in piPSCs and an analysis of the platypus DAX1 promoter revealed the absence of a proximal SOX2-binding DNA motif known to be critical for DAX1 expression in eutherian pluripotent stem cells, suggesting that the acquisition of SOX2 responsiveness by DAX1 has facilitated its recruitment into the pluripotency network of eutherians. We further show that the expression ratio of X chromosomes to autosomes (X1-5 X1-5:AA) is approximately equal to 1 indicating that there is no upregulation of X-linked genes and that there is no preference for silencing of maternal or paternal alleles (ie imprinting).

cell biology↗