The virulence factor database (VFDB, http://www.mgc.ac.cn/VFs/) is dedicated to presenting a comprehensive knowledge base and a versatile analysis platform for bacterial virulence factors (VFs). Recent developments in sequencing technologies have led to increasing demands to analyze potential VFs within microbiome data that always consist of many different bacteria. Nevertheless, the current classification of VFs from various pathogens is based on different schemes, which create a chaotic situation and form a barrier for the easy application of the VFDB dataset for future panbacterial metagenomic analyses. Therefore, based on extensive literature mining, we recently proposed a general category of bacterial VFs in the database and reorganized the VFDB dataset accordingly. Thus, all known bacterial VFs from 32 genera of common bacterial pathogens collected in the VFDB are well grouped into 14 basal categories along with over 100 subcategories in a hierarchical architecture. The new coherent and well-defined VFDB dataset will be feasible and applicable for future panbacterial analysis in terms of virulence factors. In addition, we introduced a redesigned JavaScript-independent web interface for the VFDB website to make the database readily accessible to all users with various client settings worldwide.

Strongyloidiasis is a much-neglected soil born helminthiasis caused by the nematode Strongyloides stercoralis. Human derived S. stercoralis can be maintained in dogs in the laboratory and this parasite has been reported to also occur in dogs in the wild. Some authors have considered strongyloidiasis a zoonotic disease while others have argued that the two hosts carry host specialized populations of S. stercoralis and that dogs play a minor role, if any, as a reservoir for zoonotic S. stercoralis infections of humans. We isolated S. stercoralis from humans and their dogs in rural villages in northern Cambodia, a region with a high incidence of strongyloidiasis, and compared the worms derived from these two host species using nuclear and mitochondrial DNA sequence polymorphisms. We found that in dogs there exist two populations of S. stercoralis, which are clearly separated from each other genetically based on the nuclear 18S rDNA, the mitochondrial cox1 locus and whole genome sequence. One population, to which the majority of the worms belong, appears to be restricted to dogs. The other population is indistinguishable from the population of S. stercoralis isolated from humans. Consistent with earlier studies, we found multiple sequence variants of the hypervariable region I of the 18 S rDNA in S. stercoralis from humans. However, comparison of mitochondrial sequences and whole genome analysis suggest that these different 18S variants do not represent multiple genetically isolated subpopulations among the worms isolated from humans. We also investigated the mode of reproduction of the free-living generations of laboratory and wild isolates of S. stercoralis. Contrary to earlier literature on S. stercoralis but similar to other species of Strongyloides, we found clear evidence of sexual reproduction. Overall, our results show that dogs carry two populations, possibly different species of Strongyloides. One population appears to be dog specific but the other one is shared with humans. This argues for the strong potential of dogs as reservoirs for zoonotic transmission of S. stercoralis to humans and suggests that in order to reduce the exposure of humans to infective S. stercoralis larvae, dogs should be treated for the infection along with their owners.

Highlights d eCIS loci are widely distributed among bacteria genomes d eCIS loci encode phage-tail-like proteinaceous machines d eCIS superfamily is grouped into six families with distinct genetic features

During the epidemic period of the novel H7N9 viruses, an influenza A (H9N2) virus was isolated from a 7-year-old boy with influenza-like illness in Yongzhou city of Hunan province in November 2013. To identify the possible source of infection, environmental specimens collected from local live poultry markets epidemiologically linked to the human case in Yongzhou city were tested for influenza type A and its subtypes H5, H7, and H9 using real-time RT-PCR methods as well as virus isolation, and four other H9N2 viruses were isolated. The real-time RT-PCR results showed that the environment was highly contaminated with avian influenza H9 subtype viruses (18.0%). Sequencing analyses revealed that the virus isolated from the patient, which was highly similar (98.5-99.8%) to one of isolates from environment in complete genome sequences, was of avian origin. Based on phylogenetic and antigenic analyses, it belonged to genotype S and Y280 lineage. In addition, the virus exhibited high homology (95.7-99.5%) of all six internal gene lineages with the novel H7N9 and H10N8 viruses which caused epidemic and endemic in China. Meanwhile, it carried several mammalian adapted molecular residues including Q226L in HA protein, L13P in PB1 protein, K356R, S409N in PA protein, V15I in M1 protein, I28V, L55F in M2 protein, and E227K in NS protein. These findings reinforce the significance of continuous surveillance of H9N2 influenza viruses.

Strongyloidiasis is a much-neglected but sometimes fatal soil born helminthiasis. The causing agent, the small intestinal parasitic nematode Strongyloides stercoralis can reproduce sexually through the indirect/heterogonic life cycle, or asexually through the auto-infective or the direct/homogonic life cycles. Usually, among the progeny of the parasitic females both, parthenogenetic parasitic (females only) and sexual free-living (females and males) individuals, are present simultaneously. We isolated S . stercoralis from people living in a village with a high incidence of parasitic helminths, in particular liver flukes ( Clonorchis sinensis ) and hookworms, in the southern Chinese province Guangxi. We determined nuclear and mitochondrial DNA sequences of individual S . stercoralis isolated from this village and from close by hospitals and we compared these S . stercoralis among themselves and with selected published S . stercoralis from other geographic locations. For comparison, we also analyzed the hookworms present in the same location. We found that, compared to earlier studies of S . stercoralis populations in South East Asia, all S . stercoralis sampled in our study area were very closely related, suggesting a recent common source of infection for all patients. In contrast, the hookworms from the same location, while all belonging to the species Necator americanus , showed rather extensive genetic diversity even within host individuals. Different from earlier studies conducted in other geographic locations, almost all S . stercoralis in this study appeared heterozygous for different sequence variants of the 18S rDNA hypervariable regions (HVR) I and IV. In contrast to earlier investigations, except for three males, all S . stercoralis we isolated in this study were infective larvae, suggesting that the sampled population reproduces predominantly, if not exclusively through the clonal life cycles. Consistently, whole genome sequencing of individual worms revealed higher heterozygosity than reported earlier for likely sexual populations of S . stercoralis . Elevated heterozygosity is frequently associated with asexual clonal reproduction.

This paper reviews and advocates against the use of permute-and-predict (PaP) methods for interpreting black box functions. Methods such as the variable importance measures proposed for random forests, partial dependence plots, and individual conditional expectation plots remain popular because they are both model-agnostic and depend only on the pre-trained model output, making them computationally efficient and widely available in software. However, numerous studies have found that these tools can produce diagnostics that are highly misleading, particularly when there is strong dependence among features. The purpose of our work here is to (i) review this growing body of literature, (ii) provide further demonstrations of these drawbacks along with a detailed explanation as to why they occur, and (iii) advocate for alternative measures that involve additional modeling. In particular, we describe how breaking dependencies between features in hold-out data places undue emphasis on sparse regions of the feature space by forcing the original model to extrapolate to regions where there is little to no data. We explore these effects across various model setups and find support for previous claims in the literature that PaP metrics can vastly over-emphasize correlated features in both variable importance measures and partial dependence plots. As an alternative, we discuss and recommend more direct approaches that involve measuring the change in model performance after muting the effects of the features under investigation.

Background As the largest group of mammalian species, which are also widely distributed all over the world, rodents are the natural reservoirs for many diverse zoonotic viruses. A comprehensive understanding of the core virome of diverse rodents should therefore assist in efforts to reduce the risk of future emergence or re-emergence of rodent-borne zoonotic pathogens. Results This study aimed to describe the viral range that could be detected in the lungs of rodents from Mainland Southeast Asia. Lung samples were collected from 3284 rodents and insectivores of the orders Rodentia, Scandentia, and Eulipotyphla in eighteen provinces of Thailand, Lao PDR, and Cambodia throughout 2006–2018. Meta-transcriptomic analysis was used to outline the unique spectral characteristics of the mammalian viruses within these lungs and the ecological and genetic imprints of the novel viruses. Many mammalian- or arthropod-related viruses from distinct evolutionary lineages were reported for the first time in these species, and viruses related to known pathogens were characterized for their genomic and evolutionary characteristics, host species, and locations. Conclusions These results expand our understanding of the core viromes of rodents and insectivores from Mainland Southeast Asia and suggest that a high diversity of viruses remains to be found in rodent species of this area. These findings, combined with our previous virome data from China, increase our knowledge of the viral community in wildlife and arthropod vectors in emerging disease hotspots of East and Southeast Asia.

Soliton frequency combs generate equally-distant frequencies, offering a powerful tool for fast and accurate measurements over broad spectral ranges. The generation of solitons in microresonators can further improve the compactness of comb sources. However the geometry and the material’s inertness of pristine microresonators limit their potential in applications such as gas molecule detection. Here, we realize a two-dimensional-material functionalized microcomb sensor by asymmetrically depositing graphene in an over-modal microsphere. By using one single pump, spectrally trapped Stokes solitons belonging to distinct transverse mode families are co-generated in one single device. Such Stokes solitons with locked repetition rate but different offsets produce ultrasensitive beat notes in the electrical domain, offering unique advantages for selective and individual gas molecule detection. Moreover, the stable nature of the solitons enables us to trace the frequency shift of the dual-soliton beat-note with uncertainty <0.2 Hz and to achieve real-time individual gas molecule detection in vacuum, via an optoelectronic heterodyne detection scheme. This combination of atomically thin materials and microcombs shows the potential for compact photonic sensing with high performances and offers insights toward the design of versatile functionalized microcavity photonic devices.