The SARS-CoV-2 subgenome landscape and its novel regulatory features.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global pandemic. CoVs are known to generate negative subgenomes (subgenomic RNAs [sgRNAs]) through transcription-regulating sequence (TRS)-dependent template switching, but the global dynamic landscapes of coronaviral subgenomes and regulatory rules remain unclear. Here, using next-generation sequencing (NGS) short-read and Nanopore long-read poly(A) RNA sequencing in two cell types at multiple time points after infection with SARS-CoV-2, we identified hundreds of template switches and constructed the dynamic landscapes of SARS-CoV-2 subgenomes. Interestingly, template switching could occur in a bidirectional manner, with diverse SARS-CoV-2 subgenomes generated from successive template-switching events. The majority of template switches result from RNA-RNA interactions, including seed and compensatory modes, with terminal pairing status as a key determinant. Two TRS-independent template switch modes are also responsible for subgenome biogenesis. Our findings reveal the subgenome landscape of SARS-CoV-2 and its regulatory features, providing a molecular basis for understanding subgenome biogenesis and developing novel anti-viral strategies.

MVIP: multi-omics portal of viral infection.

Virus infections are huge threats to living organisms and cause many diseases, such as COVID-19 caused by SARS-CoV-2, which has led to millions of deaths. To develop effective strategies to control viral infection, we need to understand its molecular events in host cells. Virus related functional genomic datasets are growing rapidly, however, an integrative platform for systematically investigating host responses to viruses is missing. Here, we developed a user-friendly multi-omics portal of viral infection named as MVIP (https://mvip.whu.edu.cn/). We manually collected available high-throughput sequencing data under viral infection, and unified their detailed metadata including virus, host species, infection time, assay, and target, etc. We processed multi-layered omics data of more than 4900 viral infected samples from 77 viruses and 33 host species with standard pipelines, including RNA-seq, ChIP-seq, and CLIP-seq, etc. In addition, we integrated these genome-wide signals into customized genome browsers, and developed multiple dynamic charts to exhibit the information, such as time-course dynamic and differential gene expression profiles, alternative splicing changes and enriched GO/KEGG terms. Furthermore, we implemented several tools for efficiently mining the virus-host interactions by virus, host and genes. MVIP would help users to retrieve large-scale functional information and promote the understanding of virus-host interactions.

The prediction of contact force networks in granular materials based on graph neural networks.

The contact force network, usually organized inhomogeneously by the inter-particle forces on the bases of the contact network topologies, is essential to the rigidity and stability in amorphous solids. How to capture such a "backbone" is crucial to the understanding of various anomalous properties or behaviors in those materials, which remains a central challenge presently in physics, engineering, or material science. Here, we use a novel graph neural network to predict the contact force network in two-dimensional granular materials under uniaxial compression. With the edge classification model in the framework of the deep graph library, we show that the inter-particle contact forces can be accurately estimated purely from the knowledge of the static microstructures, which can be acquired from a discrete element method or directly visualized from experimental methods. By testing the granular packings with different structural disorders and pressure, we further demonstrate the robustness of the optimized graph neural network to changes in various model parameters. Our research tries to provide a new way of extracting the information about the inter-particle forces, which substantially improves the efficiency and reduces the costs compared to the traditional experiments.

[Detection and Analysis of Human Parainfluenza Virus Infection in Hospitalized Adults with Acute Respiratory Tract Infections].

OBJECTIVE: To investigate the prevalence and gene characteristics of different groups of human parainfluenza virus (HPIV) infection in hospitalized adults with acute respiratory tract infections (ARI). METHODS: RT-PCR was used to detect HPIV hemagglutinin (HA) DNA,which was extracted from sputum samples of 1 039 adult patients with ARI from March,2014 to June,2016. The HA gene amplified from randomly selected positive samples were sequenced to analyze the homology and variation. RESULTS: 10.6% (110/1 039) of these samples were positive for HPIV,including 8 cases of HPIV-1,22 cases of HPIV-2,46 cases of HPIV-3 and 34 cases of HPIV-4. Detectable rate varied among different groups of HPIV according to seasons of the year and ages of patients. No significant differences were found between the positive samples and the reference sequences. Compared with different reference strains of different regions,the genetic distance of nucleotide is the smallest between the strains tested in this study and the reference strains of other provinces and cities in China. CONCLUSION: In Chengdu region,HPIV virus is highly detected in ARI,all subtypes were detected with HPIV-3 being the main subtype.

Estimation of Particle Location in Granular Materials Based on Graph Neural Networks.

Particle locations determine the whole structure of a granular system, which is crucial to understanding various anomalous behaviors in glasses and amorphous solids. How to accurately determine the coordinates of each particle in such materials within a short time has always been a challenge. In this paper, we use an improved graph convolutional neural network to estimate the particle locations in two-dimensional photoelastic granular materials purely from the knowledge of the distances for each particle, which can be estimated in advance via a distance estimation algorithm. The robustness and effectiveness of our model are verified by testing other granular systems with different disorder degrees, as well as systems with different configurations. In this study, we attempt to provide a new route to the structural information of granular systems irrelevant to dimensionality, compositions, or other material properties.

Fear of Missing Out and Irrational Procrastination in the Mobile Social Media Environment: A Moderated Mediation Analysis.

This study explored the relationship between Fear of Missing Out (FoMO) and irrational procrastination in a mobile social media environment and its underlying mechanism: the mediating role of cognitive failure. The study was conducted with 817 college students using the FoMO Scale, Irrational Procrastination Scale, Cognitive Failures Questionnaire, and Self-Control Scale. The results showed that (a) FoMO positively predicted irrational procrastination in the mobile social media environment; (b) cognitive failure had a complete mediating effect on the relationship between FoMO and irrational procrastination; and (c) self-control had a moderating effect on the relationship between FoMO and cognitive failure.

Integrated Analysis of Gene Co-Expression Network and Prediction Model Indicates Immune-Related Roles of the Identified Biomarkers in Sepsis and Sepsis-Induced Acute Respiratory Distress Syndrome.

Sepsis is a series of clinical syndromes caused by immunological response to severe infection. As the most important and common complication of sepsis, acute respiratory distress syndrome (ARDS) is associated with poor outcomes and high medical expenses. However, well-described studies of analysis-based researches, especially related bioinformatics analysis on revealing specific targets and underlying molecular mechanisms of sepsis and sepsis-induced ARDS (sepsis/se-ARDS), still remain limited and delayed despite the era of data-driven medicine. In this report, weight gene co-expression network based on data from a public database was constructed to identify the key modules and screen the hub genes. Functional annotation by enrichment analysis of the modular genes also demonstrated the key biological processes and signaling pathway; among which, extensive immune-involved enrichment was remarkably associated with sepsis/se-ARDS. Based on the differential expression analysis, least absolute shrink and selection operator, and multivariable logistic regression analysis of the screened hub genes, SIGLEC9, TSPO, CKS1B and PTTG3P were identified as the candidate biomarkers for the further analysis. Accordingly, a four-gene-based model for diagnostic prediction assessment was established and then developed by sepsis/se-ARDS risk nomogram, whose efficiency was verified by calibration curves and decision curve analyses. In addition, various machine learning algorithms were also applied to develop extra models based on the four genes. Receiver operating characteristic curve analysis proved the great diagnostic and predictive performance of these models, and the multivariable logistic regression of the model was still found to be the best as further verified again by the internal test, training, and external validation cohorts. During the development of sepsis/se-ARDS, the expressions of the identified biomarkers including SIGLEC9, TSPO, CKS1B and PTTG3P were all regulated remarkably and generally exhibited notable correlations with the stages of sepsis/se-ARDS. Moreover, the expression levels of these four genes were substantially correlated during sepsis/se-ARDS. Analysis of immune infiltration showed that multiple immune cells, neutrophils and monocytes in particular, might be closely involved in the process of sepsis/se-ARDS. Besides, SIGLEC9, TSPO, CKS1B and PTTG3P were considerably correlated with the infiltration of various immune cells including neutrophils and monocytes during sepsis/se-ARDS. The discovery of relevant gene co-expression network and immune signatures might provide novel insights into the pathophysiology of sepsis/se-ARDS.