Estimating the potential risk of transmission of arboviruses in the Americas and Europe: a modelling study.

BACKGROUND: Estimates of the spatiotemporal distribution of different mosquito vector species and the associated risk of transmission of arboviruses are key to design adequate policies for preventing local outbreaks and reducing the number of human infections in endemic areas. In this study, we quantified the abundance of Aedes albopictus and Aedes aegypti and the local transmission potential for three arboviral infections at an unprecedented spatiotemporal resolution in areas where no entomological surveillance is available. METHODS: We developed a computational model to quantify the daily abundance of Aedes mosquitoes, leveraging temperature and precipitation records. The model was calibrated on mosquito surveillance data collected in 115 locations in Europe and the Americas between 2007 and 2018. Model estimates were used to quantify the reproduction number of dengue virus, Zika virus, and chikungunya in Europe and the Americas, at a high spatial resolution. FINDINGS: In areas colonised by both Aedes species, A aegypti was estimated to be the main vector for the transmission of dengue virus, Zika virus, and chikungunya, being associated with a higher estimate of R0 when compared with A albopictus. Our estimates highlighted that these arboviruses were endemic in tropical and subtropical countries, with the highest risks of transmission found in central America, Venezuela, Colombia, and central-east Brazil. A non-negligible potential risk of transmission was also estimated for Florida, Texas, and Arizona (USA). The broader ecological niche of A albopictus could contribute to the emergence of chikungunya outbreaks and clusters of dengue autochthonous cases in temperate areas of the Americas, as well as in mediterranean Europe (in particular, in Italy, southern France, and Spain). INTERPRETATION: Our results provide a comprehensive overview of the transmission potential of arboviral diseases in Europe and the Americas, highlighting areas where surveillance and mosquito control capacities should be prioritised. FUNDING: EU and Ministero dell'Università e della Ricerca, Italy (Piano Nazionale di Ripresa e Resilienza Extended Partnership initiative on Emerging Infectious Diseases); EU (Horizon 2020); Ministero dell'Università e della Ricerca, Italy (Progetti di ricerca di Rilevante Interesse Nazionale programme); Brazilian National Council of Science, Technology and Innovation; Ministry of Health, Brazil; and Foundation of Research for Minas Gerais, Brazil.

A temporally and spatially explicit, data-driven estimation of airborne ragweed pollen concentrations across Europe.

Ongoing and future climate change driven expansion of aeroallergen-producing plant species comprise a major human health problem across Europe and elsewhere. There is an urgent need to produce accurate, temporally dynamic maps at the continental level, especially in the context of climate uncertainty. This study aimed to restore missing daily ragweed pollen data sets for Europe, to produce phenological maps of ragweed pollen, resulting in the most complete and detailed high-resolution ragweed pollen concentration maps to date. To achieve this, we have developed two statistical procedures, a Gaussian method (GM) and deep learning (DL) for restoring missing daily ragweed pollen data sets, based on the plant's reproductive and growth (phenological, pollen production and frost-related) characteristics. DL model performances were consistently better for estimating seasonal pollen integrals than those of the GM approach. These are the first published modelled maps using altitude correction and flowering phenology to recover missing pollen information. We created a web page (http://euragweedpollen.gmf.u-szeged.hu/), including daily ragweed pollen concentration data sets of the stations examined and their restored daily data, allowing one to upload newly measured or recovered daily data. Generation of these maps provides a means to track pollen impacts in the context of climatic shifts, identify geographical regions with high pollen exposure, determine areas of future vulnerability, apply spatially-explicit mitigation measures and prioritize management interventions.

Efficient randomization of biological networks while preserving functional characterization of individual nodes.

BACKGROUND: Networks are popular and powerful tools to describe and model biological processes. Many computational methods have been developed to infer biological networks from literature, high-throughput experiments, and combinations of both. Additionally, a wide range of tools has been developed to map experimental data onto reference biological networks, in order to extract meaningful modules. Many of these methods assess results' significance against null distributions of randomized networks. However, these standard unconstrained randomizations do not preserve the functional characterization of the nodes in the reference networks (i.e. their degrees and connection signs), hence including potential biases in the assessment. RESULTS: Building on our previous work about rewiring bipartite networks, we propose a method for rewiring any type of unweighted networks. In particular we formally demonstrate that the problem of rewiring a signed and directed network preserving its functional connectivity (F-rewiring) reduces to the problem of rewiring two induced bipartite networks. Additionally, we reformulate the lower bound to the iterations' number of the switching-algorithm to make it suitable for the F-rewiring of networks of any size. Finally, we present BiRewire3, an open-source Bioconductor package enabling the F-rewiring of any type of unweighted network. We illustrate its application to a case study about the identification of modules from gene expression data mapped on protein interaction networks, and a second one focused on building logic models from more complex signed-directed reference signaling networks and phosphoproteomic data. CONCLUSIONS: BiRewire3 it is freely available at https://www.bioconductor.org/packages/BiRewire/ , and it should have a broad application as it allows an efficient and analytically derived statistical assessment of results from any network biology tool.

A null model for Pearson coexpression networks.

Gene coexpression networks inferred by correlation from high-throughput profiling such as microarray data represent simple but effective structures for discovering and interpreting linear gene relationships. In recent years, several approaches have been proposed to tackle the problem of deciding when the resulting correlation values are statistically significant. This is most crucial when the number of samples is small, yielding a non-negligible chance that even high correlation values are due to random effects. Here we introduce a novel hard thresholding solution based on the assumption that a coexpression network inferred by randomly generated data is expected to be empty. The threshold is theoretically derived by means of an analytic approach and, as a deterministic independent null model, it depends only on the dimensions of the starting data matrix, with assumptions on the skewness of the data distribution compatible with the structure of gene expression levels data. We show, on synthetic and array datasets, that the proposed threshold is effective in eliminating all false positive links, with an offsetting cost in terms of false negative detected edges.

Fast randomization of large genomic datasets while preserving alteration counts.

MOTIVATION: Studying combinatorial patterns in cancer genomic datasets has recently emerged as a tool for identifying novel cancer driver networks. Approaches have been devised to quantify, for example, the tendency of a set of genes to be mutated in a 'mutually exclusive' manner. The significance of the proposed metrics is usually evaluated by computing P-values under appropriate null models. To this end, a Monte Carlo method (the switching-algorithm) is used to sample simulated datasets under a null model that preserves patient- and gene-wise mutation rates. In this method, a genomic dataset is represented as a bipartite network, to which Markov chain updates (switching-steps) are applied. These steps modify the network topology, and a minimal number of them must be executed to draw simulated datasets independently under the null model. This number has previously been deducted empirically to be a linear function of the total number of variants, making this process computationally expensive. RESULTS: We present a novel approximate lower bound for the number of switching-steps, derived analytically. Additionally, we have developed the R package BiRewire, including new efficient implementations of the switching-algorithm. We illustrate the performances of BiRewire by applying it to large real cancer genomics datasets. We report vast reductions in time requirement, with respect to existing implementations/bounds and equivalent P-value computations. Thus, we propose BiRewire to study statistical properties in genomic datasets, and other data that can be modeled as bipartite networks. AVAILABILITY AND IMPLEMENTATION: BiRewire is available on BioConductor at http://www.bioconductor.org/packages/2.13/bioc/html/BiRewire.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The reciprocal interaction of NK cells with plasmacytoid or myeloid dendritic cells profoundly affects innate resistance functions.

A reciprocal activating interaction between NK cells and dendritic cells (DC) has been suggested to play a role in the functional regulation of these cells in immunity, but it has been studied only using in vitro generated bone marrow- or monocyte-derived DC. We report that human peripheral blood plasmacytoid DC (pDC) and myeloid DC are necessary to induce NK cell function depending on the type of microbial stimulus. pDC and myeloid DC are required for strongly increased NK cytolytic activity and CD69 expression, in response to inactivated influenza virus or CpG-containing oligonucleotides and poly(I:C), respectively. Secreted type I IFN is required and sufficient for the augmentation of NK cell cytolytic activity in the coculture with pDC or myeloid DC, whereas CD69 expression is dependent on both type I IFN and TNF. In addition, in response to poly(I:C), myeloid DC induce NK cells to produce IFN-gamma through a mechanism dependent on both IL-12 secretion and cell contact between NK cells and myeloid DC, but independent of type I IFN. IL-2-activated NK cells have little to no cytolytic activity for immature myeloid DC and pDC, but are able to induce maturation of these cells. Moreover, IL-2-activated NK cells induce, in the presence of a suboptimal concentration of CpG-containing oligonucleotides, a strong IFN-alpha and TNF production. These data suggest that the reciprocal functional interaction between NK cells and either pDC or myeloid DC may play an important physiological role in the regulation of both innate resistance and adaptive immunity to infections.