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1. Identification of Snails and Schistosoma of Medical Importance via Convolutional Neural Networks: A Proof-of-Concept Application for Human Schistosomiasis

   https://doi.org/10.3389/fpubh.2021.642895  

   Tallam, Krti ; Liu, Zac Yung-Chun ; Chamberlin, Andrew J. ; Jones, Isabel J. ; Shome, Pretom ; Riveau, Gilles ; Ndione, Raphael A. ; Bandagny, Lydie ; Jouanard, Nicolas ; Eck, Paul Van ; et al ( July 2021 , Frontiers in Public Health)

   null (Ed.)

   In recent decades, computer vision has proven remarkably effective in addressing diverse issues in public health, from determining the diagnosis, prognosis, and treatment of diseases in humans to predicting infectious disease outbreaks. Here, we investigate whether convolutional neural networks (CNNs) can also demonstrate effectiveness in classifying the environmental stages of parasites of public health importance and their invertebrate hosts. We used schistosomiasis as a reference model. Schistosomiasis is a debilitating parasitic disease transmitted to humans via snail intermediate hosts. The parasite affects more than 200 million people in tropical and subtropical regions. We trained our CNN, a feed-forward neural network, on a limited dataset of 5,500 images of snails and 5,100 images of cercariae obtained from schistosomiasis transmission sites in the Senegal River Basin, a region in western Africa that is hyper-endemic for the disease. The image set included both images of two snail genera that are relevant to schistosomiasis transmission – that is, Bulinus spp. and Biomphalaria pfeifferi – as well as snail images that are non-component hosts for human schistosomiasis. Cercariae shed from Bi. pfeifferi and Bulinus spp. snails were classified into 11 categories, of which only two, S. haematobium and S. mansoni , are major etiological agents of human schistosomiasis. The algorithms, trained on 80% of the snail and parasite dataset, achieved 99% and 91% accuracy for snail and parasite classification, respectively, when used on the hold-out validation dataset – a performance comparable to that of experienced parasitologists. The promising results of this proof-of-concept study suggests that this CNN model, and potentially similar replicable models, have the potential to support the classification of snails and parasite of medical importance. In remote field settings where machine learning algorithms can be deployed on cost-effective and widely used mobile devices, such as smartphones, these models can be a valuable complement to laboratory identification by trained technicians. Future efforts must be dedicated to increasing dataset sizes for model training and validation, as well as testing these algorithms in diverse transmission settings and geographies. 

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2. A Solanum lycopersicoides reference genome facilitates insights into tomato specialized metabolism and immunity

   https://doi.org/10.1111/tpj.15770  

   Powell, Adrian F. ; Feder, Ari ; Li, Jie ; Schmidt, Maximilian H. ‐W. ; Courtney, Lance ; Alseekh, Saleh ; Jobson, Emma M. ; Vogel, Alexander ; Xu, Yimin ; Lyon, David ; et al ( May 2022 , The Plant Journal)

   Wild relatives of tomato are a valuable source of natural variation in tomato breeding, as many can be hybridized to the cultivated species (Solanum lycopersicum). Several, includingSolanum lycopersicoides, have been crossed toS. lycopersicumfor the development of ordered introgression lines (ILs), facilitating breeding for desirable traits. Despite the utility of these wild relatives and their associated ILs, few finished genome sequences have been produced to aid genetic and genomic studies. Here we report a chromosome‐scale genome assembly forS. lycopersicoidesLA2951, which contains 37 938 predicted protein‐coding genes. With the aid of this genome assembly, we have precisely delimited the boundaries of theS. lycopersicoidesintrogressions in a set ofS. lycopersicumcv. VF36 × LA2951 ILs. We demonstrate the usefulness of the LA2951 genome by identifying several quantitative trait loci for phenolics and carotenoids, including underlying candidate genes, and by investigating the genome organization and immunity‐associated function of the clusteredPtogene family. In addition, syntenic analysis of R2R3MYB genes sheds light on the identity of theAuberginelocus underlying anthocyanin production. The genome sequence and IL map provide valuable resources for studying fruit nutrient/quality traits, pathogen resistance, and environmental stress tolerance. We present a new genome resource for the wild speciesS. lycopersicoides, which we use to shed light on theAuberginelocus responsible for anthocyanin production. We also provide IL boundary mappings, which facilitated identifying novel carotenoid quantitative trait loci of which one was likely driven by an uncharacterized lycopene β‐cyclase whose function we demonstrate.

    

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3. Example of Adverse Outcome Pathway Concept Enabling Genome-to-Phenome Discovery in Toxicology

   https://doi.org/10.1093/icb/icaa064  

   Gust, Kurt A ; Ji, Qing ; Luo, Xiao ( June 2020 , Integrative and Comparative Biology)

   Synopsis The following article represents a mini-review of an intensive 10-year progression of genome-to-phenome (G2P) discovery guided by the adverse outcome pathway (AOP) concept. This example is presented as a means to stimulate crossover of this toxicological concept to enhance G2P discovery within the broader biological sciences community. The case study demonstrates the benefits of the AOP approach for establishing causal linkages across multiple levels of biological organization ultimately linking molecular initiation (often at the genomic scale) to organism-level phenotypes of interest. The case study summarizes a US military effort to identify the mechanism(s) underlying toxicological phenotypes of lethargy and weight loss in response to nitroaromatic munitions exposures, such as 2,4,6-trinitrotoluene. Initial key discoveries are described including the toxicogenomic results that nitrotoluene exposures inhibited expression within the peroxisome proliferator activated receptor α (PPARα) pathway. We channeled the AOP concept to test the hypothesis that inhibition of PPARα signaling in nitrotoluene exposures impacted lipid metabolic processes, thus affecting systemic energy budgets, ultimately resulting in body weight loss. Results from a series of transcriptomic, proteomic, lipidomic, in vitro PPARα nuclear signaling, and PPARα knock-out investigations ultimately supported various facets of this hypothesis. Given these results, we next proceeded to develop a formalized AOP description of PPARα antagonism leading to body weight loss. This AOP was refined through intensive literature review and polished through multiple rounds of peer-review leading to final international acceptance as an Organisation for Economic Cooperation and Development-approved AOP. Briefly, that AOP identifies PPARα antagonist binding as the molecular initiating event (MIE) leading to a series of key events including inhibition of nuclear transactivation for genes controlling lipid metabolism and ketogenesis, inhibition of fatty acid beta-oxidation and ketogenesis dynamics, negative energy budget, and ultimately the adverse outcome (AO) of body-weight loss. Given that the PPARα antagonism MIE represented a reliable indicator of AO progression within the pathway, a phylogenetic analysis was conducted which indicated that PPARα amino acid relatedness generally tracked species relatedness. Additionally, PPARα amino acid relatedness analysis using the Sequence Alignment to Predict Across Species Susceptibility predicted susceptibility to the MIE across vertebrates providing context for AOP extrapolation across species. Overall, we hope this illustrative example of how the AOP concept has benefited toxicology sows a seed within the broader biological sciences community to repurpose the concept to facilitate enhanced G2P discovery in biology. 

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4. Genome Investigation of Urinary Gardnerella Strains and Their Relationship to Isolates of the Vaginal Microbiota

   https://doi.org/10.1128/mSphere.00154-21  

   Putonti, Catherine ; Thomas-White, Krystal ; Crum, Elias ; Hilt, Evann E. ; Price, Travis K. ; Wolfe, Alan J. ( June 2021 , mSphere)

   Rao, Krishna (Ed.)

   ABSTRACT Gardnerella is a frequent member of the urogenital microbiota. Given the association between Gardnerella vaginalis and bacterial vaginosis (BV), significant efforts have been focused on characterizing this species in the vaginal microbiota. However, Gardnerella also is a frequent member of the urinary microbiota. In an effort to characterize the bacterial species of the urinary microbiota, we present here 10 genomes of urinary Gardnerella isolates from women with and without lower urinary tract symptoms. These genomes complement those of 22 urinary Gardnerella strains previously isolated and sequenced by our team. We included these genomes in a comparative genome analysis of all publicly available Gardnerella genomes, which include 33 urinary isolates, 78 vaginal isolates, and 2 other isolates. While once this genus was thought to consist of a single species, recent comparative genome analyses have revealed 3 new species and an additional 9 groups within Gardnerella . Based upon our analysis, we suggest a new group for the species. We also find that distinction between these Gardnerella species/groups is possible only when considering the core or whole-genome sequence, as neither the sialidase nor vaginolysin genes are sufficient for distinguishing between species/groups despite their clinical importance. In contrast to the vaginal microbiota, we found that only five Gardnerella species/groups have been detected within the lower urinary tract. Although we found no association between a particular Gardnerella species/group(s) and urinary symptoms, further sequencing of urinary Gardnerella isolates is needed for both comprehensive taxonomic characterization and etiological classification of Gardnerella in the urinary tract. IMPORTANCE Prior research into the bacterium Gardnerella vaginalis has largely focused on its association with bacterial vaginosis (BV). However, G. vaginalis is also frequently found within the urinary microbiota of women with and without lower urinary tract symptoms as well as individuals with chronic kidney disease, interstitial cystitis, and BV. This prompted our investigation into Gardnerella from the urinary microbiota and all publicly available Gardnerella genomes from the urogenital tract. Our work suggests that while some Gardnerella species can survive in both the urinary tract and vagina, others likely cannot. This study provides the foundation for future studies of Gardnerella within the urinary tract and its possible contribution to lower urinary tract symptoms. 

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5. The genome of the stable fly, Stomoxys calcitrans, reveals potential mechanisms underlying reproduction, host interactions, and novel targets for pest control

   https://doi.org/10.1186/s12915-021-00975-9  

   Olafson, Pia U. ; Aksoy, Serap ; Attardo, Geoffrey M. ; Buckmeier, Greta ; Chen, Xiaoting ; Coates, Craig J. ; Davis, Megan ; Dykema, Justin ; Emrich, Scott J. ; Friedrich, Markus ; et al ( March 2021 , BMC Biology)

   The stable fly,Stomoxys calcitrans, is a major blood-feeding pest of livestock that has near worldwide distribution, causing an annual cost of over $2 billion for control and product loss in the USA alone. Control of these flies has been limited to increased sanitary management practices and insecticide application for suppressing larval stages. Few genetic and molecular resources are available to help in developing novel methods for controlling stable flies.

   This study examines stable fly biology by utilizing a combination of high-quality genome sequencing and RNA-Seq analyses targeting multiple developmental stages and tissues. In conjunction, 1600 genes were manually curated to characterize genetic features related to stable fly reproduction, vector host interactions, host-microbe dynamics, and putative targets for control. Most notable was characterization of genes associated with reproduction and identification of expanded gene families with functional associations to vision, chemosensation, immunity, and metabolic detoxification pathways.

   The combined sequencing, assembly, and curation of the male stable fly genome followed by RNA-Seq and downstream analyses provide insights necessary to understand the biology of this important pest. These resources and new data will provide the groundwork for expanding the tools available to control stable fly infestations. The close relationship ofStomoxysto other blood-feeding (horn flies andGlossina) and non-blood-feeding flies (house flies, medflies,Drosophila) will facilitate understanding of the evolutionary processes associated with development of blood feeding among the Cyclorrhapha.

    

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