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.

CRESSP: a comprehensive pipeline for prediction of immunopathogenic SARS-CoV-2 epitopes using structural properties of proteins.

The development of autoimmune diseases following SARS-CoV-2 infection, including multisystem inflammatory syndrome, has been reported, and several mechanisms have been suggested, including molecular mimicry. We developed a scalable, comparative immunoinformatics pipeline called cross-reactive-epitope-search-using-structural-properties-of-proteins (CRESSP) to identify cross-reactive epitopes between a collection of SARS-CoV-2 proteomes and the human proteome using the structural properties of the proteins. Overall, by searching 4 911 245 proteins from 196 352 SARS-CoV-2 genomes, we identified 133 and 648 human proteins harboring potential cross-reactive B-cell and CD8+ T-cell epitopes, respectively. To demonstrate the robustness of our pipeline, we predicted the cross-reactive epitopes of coronavirus spike proteins, which were recognized by known cross-neutralizing antibodies. Using single-cell expression data, we identified PARP14 as a potential target of intermolecular epitope spreading between the virus and human proteins. Finally, we developed a web application (https://ahs2202.github.io/3M/) to interactively visualize our results. We also made our pipeline available as an open-source CRESSP package (https://pypi.org/project/cressp/), which can analyze any two proteomes of interest to identify potentially cross-reactive epitopes between the proteomes. Overall, our immunoinformatic resources provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune and chronic inflammatory diseases following COVID-19.

The effects of super spreading events and movement control measures on the COVID-19 pandemic in Malaysia.

This paper aims to develop an automated web application to generate validated daily effective reproduction numbers (Rt) which can be used to examine the effects of super-spreading events due to mass gatherings and the effectiveness of the various Movement Control Order (MCO) stringency levels on the outbreak progression of COVID-19 in Malaysia. The effective reproduction number, Rt, was estimated by adopting and modifying an Rt estimation algorithm using a validated distribution mean of 3.96 and standard deviation of 4.75 with a seven-day sliding window. The Rt values generated were validated using thea moving window SEIR model with a negative binomial likelihood fitted using methods from the Bayesian inferential framework. A Pearson's correlation between the Rt values estimated by the algorithm and the SEIR model was r = 0.70, p < 0.001 and r = 0.81, p < 0.001 during the validation period The Rt increased to reach the highest values at 3.40 (95% CI 1.47, 6.14) and 1.72 (95% CI 1.54, 1.90) due to the Sri Petaling and Sabah electoral process during the second and third waves of COVID-19 respectively. The MCOs was able to reduce the Rt values by 63.2 to 77.1% and 37.0 to 47.0% during the second and third waves of COVID-19, respectively. Mass gathering events were one of the important drivers of the COVID-19 outbreak in Malaysia. However, COVID-19 transmission can be fuelled by noncompliance to Standard Operating Procedure, population mobility, ventilation and environmental factors.

Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2.

Genomic epidemiology is important to study the COVID-19 pandemic, and more than two million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a node-picking rendering strategy. In total, 1,002,739 high-quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, highly efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and ongoing positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB was written in Java and JavaScript. It not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.

Laypeople's activity for seeking telephone number of EMS before and during the COVID-19 outbreak: An analysis of web search data.

OBJECTIVE: To explore trends and patterns of laypeople's activity for seeking telephone number of emergency medical services (EMS) based on analysis of online search traffic, including changes of the search activity with onset of the coronavirus disease 2019 (COVID-19) outbreak, in five countries - the United States of America (USA), India, Brazil, the United Kingdom (UK) and Russia. METHODS: Google Trends (GT) country-level data on weekly relative search volumes (RSV) for top queries to seek EMS number were examined for January 2018-October 2021, including a comparison of RSVs between pre-COVID-19 period (January 2018-October 2019) and COVID-19 period (January 2020-October 2021), and evaluation of temporal associations of RSVs with weekly numbers of new COVID-19 cases. RESULTS: The countries demonstrated diverse patterns of the search activity with significantly different mean RSVs (the USA 1.76, India 10.20, Brazil 2.51, the UK 6.42, Russia 56.79; p < 0.001). For all countries excepting the USA mean RSVs of the COVID-19 period were significantly higher compared with the pre-COVID-19 ones (India +74%, Brazil +148%, the UK +22%, Russia +9%; p ≤ 0.034), and exhibited positive correlations with numbers of new COVID-19 cases, more pronounced for 2021 (India rS = 0.538, Brazil 0.307, the UK 0.434, Russia 0.639; p ≤ 0.045). CONCLUSION: Laypeople's activity for seeking EMS telephone number greatly varies between countries. It clearly responds to the spread of COVID-19 and could be reflective of public need for obtaining emergency help. Further studies are required to establish the role of GT for conducting real-time surveillance of population demand for EMS.

RAPID: A Rep-Seq Dataset Analysis Platform With an Integrated Antibody Database.

The antibody repertoire is a critical component of the adaptive immune system and is believed to reflect an individual's immune history and current immune status. Delineating the antibody repertoire has advanced our understanding of humoral immunity, facilitated antibody discovery, and showed great potential for improving the diagnosis and treatment of disease. However, no tool to date has effectively integrated big Rep-seq data and prior knowledge of functional antibodies to elucidate the remarkably diverse antibody repertoire. We developed a Rep-seq dataset Analysis Platform with an Integrated antibody Database (RAPID; https://rapid.zzhlab.org/), a free and web-based tool that allows researchers to process and analyse Rep-seq datasets. RAPID consolidates 521 WHO-recognized therapeutic antibodies, 88,059 antigen- or disease-specific antibodies, and 306 million clones extracted from 2,449 human IGH Rep-seq datasets generated from individuals with 29 different health conditions. RAPID also integrates a standardized Rep-seq dataset analysis pipeline to enable users to upload and analyse their datasets. In the process, users can also select set of existing repertoires for comparison. RAPID automatically annotates clones based on integrated therapeutic and known antibodies, and users can easily query antibodies or repertoires based on sequence or optional keywords. With its powerful analysis functions and rich set of antibody and antibody repertoire information, RAPID will benefit researchers in adaptive immune studies.

The UCSC Genome Browser database: 2022 update.

The UCSC Genome Browser, https://genome.ucsc.edu, is a graphical viewer for exploring genome annotations. The website provides integrated tools for visualizing, comparing, analyzing, and sharing both publicly available and user-generated genomic datasets. Data highlights this year include a collection of easily accessible public hub assemblies on new organisms, now featuring BLAT alignment and PCR capabilities, and new and updated clinical tracks (gnomAD, DECIPHER, CADD, REVEL). We introduced a new Track Sets feature and enhanced variant displays to aid in the interpretation of clinical data. We also added a tool to rapidly place new SARS-CoV-2 genomes in a global phylogenetic tree enabling researchers to view the context of emerging mutations in our SARS-CoV-2 Genome Browser. Other new software focuses on usability features, including more informative mouseover displays and new fonts.

The Ensembl COVID-19 resource: ongoing integration of public SARS-CoV-2 data.

The COVID-19 pandemic has seen unprecedented use of SARS-CoV-2 genome sequencing for epidemiological tracking and identification of emerging variants. Understanding the potential impact of these variants on the infectivity of the virus and the efficacy of emerging therapeutics and vaccines has become a cornerstone of the fight against the disease. To support the maximal use of genomic information for SARS-CoV-2 research, we launched the Ensembl COVID-19 browser; the first virus to be encompassed within the Ensembl platform. This resource incorporates a new Ensembl gene set, multiple variant sets, and annotation from several relevant resources aligned to the reference SARS-CoV-2 assembly. Since the first release in May 2020, the content has been regularly updated using our new rapid release workflow, and tools such as the Ensembl Variant Effect Predictor have been integrated. The Ensembl COVID-19 browser is freely available at https://covid-19.ensembl.org.

Constructing online concept maps in CMap Cloud collaboratively: Connecting pathways in case scenarios.

Learning metabolic pathways is vital for understanding biochemical processes and all of their implications for life. Their learning in the virtual environment is complex and generative learning strategies, such as the construction of online conceptual maps, can help in this process. This article presents a proposal for the collaborative construction of virtual concept maps on metabolism by students in the CMap Cloud browser application (free). A sequence of steps is suggested, which include online group brainstorming and discussions, peer assessment, and teachers feedback. This proposal is flexible and can be adapted to the didactic and technological reality of each teacher.

LSTM-PHV: prediction of human-virus protein-protein interactions by LSTM with word2vec.

Viral infection involves a large number of protein-protein interactions (PPIs) between human and virus. The PPIs range from the initial binding of viral coat proteins to host membrane receptors to the hijacking of host transcription machinery. However, few interspecies PPIs have been identified, because experimental methods including mass spectrometry are time-consuming and expensive, and molecular dynamic simulation is limited only to the proteins whose 3D structures are solved. Sequence-based machine learning methods are expected to overcome these problems. We have first developed the LSTM model with word2vec to predict PPIs between human and virus, named LSTM-PHV, by using amino acid sequences alone. The LSTM-PHV effectively learnt the training data with a highly imbalanced ratio of positive to negative samples and achieved AUCs of 0.976 and 0.973 and accuracies of 0.984 and 0.985 on the training and independent datasets, respectively. In predicting PPIs between human and unknown or new virus, the LSTM-PHV learned greatly outperformed the existing state-of-the-art PPI predictors. Interestingly, learning of only sequence contexts as words is sufficient for PPI prediction. Use of uniform manifold approximation and projection demonstrated that the LSTM-PHV clearly distinguished the positive PPI samples from the negative ones. We presented the LSTM-PHV online web server and support data that are freely available at http://kurata35.bio.kyutech.ac.jp/LSTM-PHV.

Ultrafast Sample placement on Existing tRees (UShER) enables real-time phylogenetics for the SARS-CoV-2 pandemic.

As the SARS-CoV-2 virus spreads through human populations, the unprecedented accumulation of viral genome sequences is ushering in a new era of 'genomic contact tracing'-that is, using viral genomes to trace local transmission dynamics. However, because the viral phylogeny is already so large-and will undoubtedly grow many fold-placing new sequences onto the tree has emerged as a barrier to real-time genomic contact tracing. Here, we resolve this challenge by building an efficient tree-based data structure encoding the inferred evolutionary history of the virus. We demonstrate that our approach greatly improves the speed of phylogenetic placement of new samples and data visualization, making it possible to complete the placements under the constraints of real-time contact tracing. Thus, our method addresses an important need for maintaining a fully updated reference phylogeny. We make these tools available to the research community through the University of California Santa Cruz SARS-CoV-2 Genome Browser to enable rapid cross-referencing of information in new virus sequences with an ever-expanding array of molecular and structural biology data. The methods described here will empower research and genomic contact tracing for SARS-CoV-2 specifically for laboratories worldwide.

A Synergetic R-Shiny Portal for Modeling and Tracking of COVID-19 Data.

The purpose of this paper is to introduce a useful online interactive dashboard (https://mahdisalehi.shinyapps.io/Covid19Dashboard/) that visualize and follow confirmed cases of COVID-19 in real-time. The dashboard was made publicly available on 6 April 2020 to illustrate the counts of confirmed cases, deaths, and recoveries of COVID-19 at the level of country or continent. This dashboard is intended as a user-friendly dashboard for researchers as well as the general public to track the COVID-19 pandemic, and is generated from trusted data sources and built in open-source R software (Shiny in particular); ensuring a high sense of transparency and reproducibility. The R Shiny framework serves as a platform for visualization and analysis of the data, as well as an advance to capitalize on existing data curation to support and enable open science. Coded analysis here includes logistic and Gompertz growth models, as two mathematical tools for predicting the future of the COVID-19 pandemic, as well as the Moran's index metric, which gives a spatial perspective via heat maps that may assist in the identification of latent responses and behavioral patterns. This analysis provides real-time statistical application aiming to make sense to academic- and public consumers of the large amount of data that is being accumulated due to the COVID-19 pandemic.

2019nCoVAS: Developing the Web Service for Epidemic Transmission Prediction, Genome Analysis, and Psychological Stress Assessment for 2019-nCoV.

Since the COVID-19 epidemic is still expanding around the world and poses a serious threat to human life and health, it is necessary for us to carry out epidemic transmission prediction, whole genome sequence analysis, and public psychological stress assessment for 2019-nCoV. However, transmission prediction models are insufficiently accurate and genome sequence characteristics are not clear, and it is difficult to dynamically assess the public psychological stress state under the 2019-nCoV epidemic. Therefore, this study develops a 2019nCoVAS web service (http://www.combio-lezhang.online/2019ncov/home.html) that not only offers online epidemic transmission prediction and lineage-associated underrepresented permutation (LAUP) analysis services to investigate the spreading trends and genome sequence characteristics, but also provides psychological stress assessments based on such an emotional dictionary that we built for 2019-nCoV. Finally, we discuss the shortcomings and further study of the 2019nCoVAS web service.

BANΔIT: B'-Factor Analysis for Drug Design and Structural Biology.

The analysis of B-factor profiles from X-ray protein structures can be utilized for structure-based drug design since protein mobility changes have been associated with the quality of protein-ligand interactions. With the BANΔIT (B'-factor analysis and ΔB' interpretation toolkit), we have developed a JavaScript-based browser application that provides a graphical user interface for the normalization and analysis of B'-factor profiles. To emphasize the usability for rational drug design applications, we have analyzed a selection of crystallographic protein-ligand complexes and have given exemplary conclusions for further drug optimization including the development of a B'-factor-supported pharmacophore model for SARS CoV-2 main protease inhibitors. BANΔIT is available online at https://bandit.uni-mainz.de. The source code can be downloaded from https://github.com/FBarthels/BANDIT.

A toolkit for the collection of thrombosis-related data elements in COVID-19 clinical studies.

Thrombosis has emerged as an important complication of coronavirus disease 2019 (COVID-19), particularly among individuals with severe illness. However, the precise incidence of thrombotic events remains uncertain due to differences in study design, patient populations, outcome ascertainment, event definitions, and reporting. In an effort to overcome some of these challenges and promote standardized data collection and reporting in clinical studies, the American Society of Hematology Research Collaborative COVID-19 Non-Malignant Hematology Task Force, in collaboration with the International Society on Thrombosis and Haemostasis COVID-19 Task Force, developed sets of data elements in the following domains: venous thromboembolism, myocardial infarction, stroke/transient ischemic attack, peripheral arterial thrombosis, bleeding, laboratory investigations, and antithrombotic therapy. Data elements in each of these domains were developed with 3 levels of detail to facilitate their incorporation into studies evaluating a range of interventions and outcomes. Previously published data elements were included where possible. The use of standardized variables in a range of clinical studies can enhance the quality of data collection, create efficiency, enhance comparison of results across studies, and facilitate future pooling of data sets.

Global Infodemiology of COVID-19: Analysis of Google Web Searches and Instagram Hashtags.

BACKGROUND: Although "infodemiological" methods have been used in research on coronavirus disease (COVID-19), an examination of the extent of infodemic moniker (misinformation) use on the internet remains limited. OBJECTIVE: The aim of this paper is to investigate internet search behaviors related to COVID-19 and examine the circulation of infodemic monikers through two platforms-Google and Instagram-during the current global pandemic. METHODS: We have defined infodemic moniker as a term, query, hashtag, or phrase that generates or feeds fake news, misinterpretations, or discriminatory phenomena. Using Google Trends and Instagram hashtags, we explored internet search activities and behaviors related to the COVID-19 pandemic from February 20, 2020, to May 6, 2020. We investigated the names used to identify the virus, health and risk perception, life during the lockdown, and information related to the adoption of COVID-19 infodemic monikers. We computed the average peak volume with a 95% CI for the monikers. RESULTS: The top six COVID-19-related terms searched in Google were "coronavirus," "corona," "COVID," "virus," "corona virus," and "COVID-19." Countries with a higher number of COVID-19 cases had a higher number of COVID-19 queries on Google. The monikers "coronavirus ozone," "coronavirus laboratory," "coronavirus 5G," "coronavirus conspiracy," and "coronavirus bill gates" were widely circulated on the internet. Searches on "tips and cures" for COVID-19 spiked in relation to the US president speculating about a "miracle cure" and suggesting an injection of disinfectant to treat the virus. Around two thirds (n=48,700,000, 66.1%) of Instagram users used the hashtags "COVID-19" and "coronavirus" to disperse virus-related information. CONCLUSIONS: Globally, there is a growing interest in COVID-19, and numerous infodemic monikers continue to circulate on the internet. Based on our findings, we hope to encourage mass media regulators and health organizers to be vigilant and diminish the use and circulation of these infodemic monikers to decrease the spread of misinformation.

Telemedicine in myocarditis: Evolution of a mutidisciplinary "disease unit" at the time of COVID-19 pandemic.

Myocarditis Disease Unit (MDU) is a functional multidisciplinary network designed to offer multidisciplinary assistance to patients with myocarditis. More than 300 patients coming from the whole Country are currently followed up at a specialized multidisciplinary outpatient clinic. Following the pandemic outbreak of the SARS-CoV-2 infection in Italy, we present how the MDU rapidly evolved to a "tele-MDU", via a dedicated multitasking digital health platform.

Retrospective analysis of the possibility of predicting the COVID-19 outbreak from Internet searches and social media data, China, 2020.

The peak of Internet searches and social media data about the coronavirus disease 2019 (COVID-19) outbreak occurred 10-14 days earlier than the peak of daily incidences in China. Internet searches and social media data had high correlation with daily incidences, with the maximum r > 0.89 in all correlations. The lag correlations also showed a maximum correlation at 8-12 days for laboratory-confirmed cases and 6-8 days for suspected cases.