Biology subjects

Johnson, L. R.

Publications and source records attributed to Johnson, L. R..

3 recordsLinked to original sources

bioRxiv2018

A tutorial on Bayesian parameter inference for dynamic energy budget models

Mechanistic representations of individual life-history trajectories are powerful tools for the prediction of organismal growth, reproduction and survival under novel environmental conditions. Dynamic energy budget (DEB) theory provides compact models to describe the acquisition and allocation of energy by organisms over their full life cycle. However, estimating DEB model parameters, and their associated uncertainties and covariances, is not trivial. Bayesian inference provides a coherent way to estimate parameter uncertainty, and propagate it through the model, while also making use of prior information to constrain the parameter space. We outline a Bayesian inference approach for energy budget models and provide two case studies - based on a simplified DEBkiss model, and the standard DEB model - detailing the implementation of such inference procedures using the open-source software package deBInfer. We demonstrate how DEB and DEBkiss parameters can be estimated in a Bayesian framework, but our results also highlight the difficulty of identifying DEB model parameters which serves as a reminder that fitting these models requires statistical caution.

physiology↗

bioRxiv2017

Transmission Expression Signature in Nascent Plasmodium vivax Blood Stage Infection

The lack of a continuous in vitro culture system for Plasmodium vivax severely limits our knowledge of pathophysiology of the most widespread malaria parasite. To gain direct understanding of P. vivax human infections, we used Next Generation Sequencing data mining to unravel parasite in vivo expression profiles for P. vivax, and P. falciparum as comparison. We performed cloud and local computing to extract parasite transcriptomes from publicly available raw data of human blood samples. We developed a Poisson Modelling (PM) method to confidently identify parasite derived transcripts in mixed RNAseq signals of infected host tissues. We successfully retrieved and reconstructed parasite transcriptomes from infected patient blood as early as the first blood stage cycle; and the same methodology did not recover any significant signal from controls. Surprisingly, these first generation blood parasites already show strong signature of transmission, which indicates the commitment from asexual-to-sexual stages. Further, we develop mathematical models for P. vivax and P. falciparum to assess the epidemiological impact of possible 7-day early stage transmission and P. vivax complex life cycle. The study uncovers the earliest onset of P. vivax blood pathogenesis and highlights the challenges of P. vivax eradication programs.\n\nAuthor summaryWe discovered that P. vivax in vivo parasitemia is associated with gametocytogenesis expression signature within the first blood stage cycle, that is, eight days from a mosquito bite. Our results suggest that asexual-to-sexual commitment may happen with first generation merozoite infection. This allows for the possibility of transmission at this early stage, much earlier than for P. falciparum. Our novel mathematical model accounts for multiple unique aspects of P. vivax biology to advance our understanding of expected disease prevalence, and compares the results to those of P. falciparum. We demonstrate that given the presence of asymptotical carriers and the possibility of relapses, earlier parasite transmission is capable of increasing the spread of disease within human populations. In summary, P. vivax gametogenesis has the potential to fast track the transmission cycle, which will drive enhanced propagation of the disease during the transmission season and clinical relapses.

systems biology↗

bioRxiv2017

Climate change drives uncertain global shifts in potential distribution and seasonal risk of Aedes-transmitted viruses

AbstractForecasting the impacts of climate change on Aedes-borne viruses--especially dengue, chikungunya, and Zika--is a key component of public health preparedness. We apply an empirically parameterized Bayesian transmission model of Aedes-borne viruses for the two vectors Aedes aegypti and Ae. albopictus as a function of temperature to predict cumulative monthly global transmission risk in current climates, and compare with projected risk in 2050 and 2080 based on general circulation models (GCMs). Our results show that if mosquito range shifts track optimal temperatures for transmission (26-29 {degrees}C), we can expect poleward shifts in Aedes-borne virus distributions. However, the differing thermal niches of the two vectors produce different patterns of shifts under climate change. More severe climate change scenarios produce proportionally worse population exposures from Ae. aegypti, but not from Ae. albopictus in the most extreme cases. Expanding risk of transmission from both mosquitoes will likely be a serious problem, even in the short term, for most of Europe; but significant reductions are also expected for Aedes albopictus, most noticeably in southeast Asia and west Africa. Within the next century, nearly a billion people are threatened with new exposure to both Aedes spp. in the worst-case scenario; but massive net losses in risk are noticeable for Ae. albopictus, especially in terms of year-round transmission, marking a global shift towards more seasonal risk across regions. Many other complicating factors (like mosquito range limits and viral evolution) exist, but overall our results indicate that while climate change will lead to both increased and new exposures to vector-borne disease, the most extreme increases in Ae. albopictus transmission are predicted to occur at intermediate climate change scenarios.\n\nAuthor SummaryThe established scientific consensus indicates that climate change will severely exacerbate the risk and burden of Aedes-transmitted viruses, including dengue, chikungunya, Zika, West Nile virus, and other significant threats to global health security. Here, we show that the story is more complicated, first and foremost due to differences between the more heat-tolerant Aedes aegypti and the more heat-limited Ae. albopictus. Almost a billion people could face their first exposure to viral transmission from either mosquito in the worst-case scenario, especially in Europe and high-elevation tropical and subtropical regions. On the other hand, while year-round transmission potential from Ae. aegypti is likely to expand (especially in south Asia and sub-Saharan Africa), Ae. albopictus loses significant ground in the tropics, marking a global shift towards seasonal risk as the tropics eventually become too hot for transmission by Ae. albopictus. Complete mitigation of climate change to a pre-industrial baseline could protect almost a billion people from arbovirus range expansions; but middle-of-the-road mitigation may actually produce the greatest expansion in the potential for viral transmission by Ae. albopictus. In any scenario, mitigating climate change also shifts the burden of both dengue and chikungunya (and potentially other Aedes transmitted viruses) from higher-income regions back onto the tropics, where transmission might otherwise start to be curbed by rising temperatures.

epidemiology↗