DeepPBI-KG: a deep learning method for the prediction of phage-bacteria interactions based on key genes.

Phages, the natural predators of bacteria, were discovered more than 100 years ago. However, increasing antimicrobial resistance rates have revitalized phage research. Methods that are more time-consuming and efficient than wet-laboratory experiments are needed to help screen phages quickly for therapeutic use. Traditional computational methods usually ignore the fact that phage-bacteria interactions are achieved by key genes and proteins. Methods for intraspecific prediction are rare since almost all existing methods consider only interactions at the species and genus levels. Moreover, most strains in existing databases contain only partial genome information because whole-genome information for species is difficult to obtain. Here, we propose a new approach for interaction prediction by constructing new features from key genes and proteins via the application of K-means sampling to select high-quality negative samples for prediction. Finally, we develop DeepPBI-KG, a corresponding prediction tool based on feature selection and a deep neural network. The results show that the average area under the curve for prediction reached 0.93 for each strain, and the overall AUC and area under the precision-recall curve reached 0.89 and 0.92, respectively, on the independent test set; these values are greater than those of other existing prediction tools. The forward and reverse validation results indicate that key genes and key proteins regulate and influence the interaction, which supports the reliability of the model. In addition, intraspecific prediction experiments based on Klebsiella pneumoniae data demonstrate the potential applicability of DeepPBI-KG for intraspecific prediction. In summary, the feature engineering and interaction prediction approaches proposed in this study can effectively improve the robustness and stability of interaction prediction, can achieve high generalizability, and may provide new directions and insights for rapid phage screening for therapy.

SARS-CoV-2 intra-host single-nucleotide variants associated with disease severity.

Variants of severe acute respiratory syndrome coronavirus 2 frequently arise within infected individuals. Here, we explored the level and pattern of intra-host viral diversity in association with disease severity. Then, we analyzed information underlying these nucleotide changes to infer the impetus including mutational signatures and immune selection from neutralizing antibody or T-cell recognition. From 23 January to 31 March 2020, a set of cross-sectional samples were collected from individuals with homogeneous founder virus regardless of disease severity. Intra-host single-nucleotide variants (iSNVs) were enumerated using deep sequencing. Human leukocyte antigen (HLA) alleles were genotyped by Sanger sequencing. Medical records were collected and reviewed by attending physicians. A total of 836 iSNVs (3-106 per sample) were identified and distributed in a highly individualized pattern. The number of iSNVs paced with infection duration peaked within days and declined thereafter. These iSNVs did not stochastically arise due to a strong bias toward C > U/G > A and U > C/A > G substitutions in reciprocal proportion with escalating disease severity. Eight nonsynonymous iSNVs in the receptor-binding domain could escape from neutralization, and eighteen iSNVs were significantly associated with specific HLA alleles. The level and pattern of iSNVs reflect the in vivo viral-host interaction and the disease pathogenesis.

Changing legislative thinking in China to better protect wild animals and human health.

The COVID-19 pandemic has exposed the inadequacy of China's legal protection of wildlife. Long-standing illegal wildlife trade in China and worldwide increases the risk of zoonotic infectious diseases. We sought to improve the understanding of China' legal system for the protection of wildlife, which has at its core the wildlife protection law, by systematically evaluating the laws and regulations of China's Wildlife Protection Framework. We examined how existing legal documents (e.g., the Wildlife Protection Law 2018) are directly or indirectly related to wildlife conservation. The inherent defects of wildlife protection legislation include a narrow scope of protection, insufficient public participation, and inconsistent enforcement among responsible agencies. Solutions to improve China's Wildlife Protection Law include expanding the legal protection of wildlife, and improving monitoring of wildlife protection. Strengthening legislation will be the basis for effective regulation of the use of wild animals. We advocate the establishment of a sound wildlife protection legal system for resolving conflicts between humans and wild animals and preventing zoonotic disease, such a system will have a profound impact on the sustainable development of China's wildlife resources.

Cambios en el Pensamiento Legislativo en China para Mejorar la Protección a los Animales Silvestres y la Salud Humana Resumen La pandemia de COVID-19 ha expuesto la insuficiencia de la protección legal de la fauna en China. El prolongado mercado ilegal de fauna en China y en todo el mundo incrementa el riesgo de enfermedades zoonóticas infecciosas. Buscamos mejorar el entendimiento del sistema legal de China para la protección de la fauna, el cual tiene como núcleo la ley de protección de fauna, mediante la evaluación sistemática de las leyes y regulaciones del Marco de Protección a la Fauna de China. Examinamos cómo los documentos legales existentes (p. ej.: la Ley de Protección de Fauna 2018) están relacionados directa o indirectamente con la conservación de la fauna. Los defectos inherentes de la legislación para la protección de fauna incluyen una visión reducida de la protección, una participación pública insuficiente y el cumplimiento inconsistente entre las agencias responsables. Las soluciones para mejorar la Ley de Protección de Fauna incluyen la expansión de la protección legal de fauna y el aumento al monitoreo de la protección de fauna. El fortalecimiento de la legislación será la base para la regulación efectiva del uso de animales silvestres. Abogamos por el establecimiento de un firme sistema legal de protección a la fauna para resolver los conflictos entre los humanos y los animales silvestres y también para prevenir las enfermedades zoonóticas. Dicho sistema tendrá un impacto profundo sobre el desarrollo sustentable de los recursos faunísticos de China.