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1.
Int J Biol Macromol ; 176: 1-12, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33548314

RESUMO

SARS-CoV-2 is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). The main protease of SARS-CoV-2, 3CLpro, is an attractive target for antiviral inhibitors due to its indispensable role in viral replication and gene expression of viral proteins. The search of compounds that can effectively inhibit the crucial activity of 3CLpro, which results to interference of the virus life cycle, is now widely pursued. Here, we report that epigallocatechin-3-gallate (EGCG), an active ingredient of Chinese herbal medicine (CHM), is a potent inhibitor of 3CLpro with half-maximum inhibitory concentration (IC50) of 0.874 ± 0.005 µM. In the study, we retrospectively analyzed the clinical data of 123 cases of COVID-19 patients, and found three effective Traditional Chinese Medicines (TCM) prescriptions. Multiple strategies were performed to screen potent inhibitors of SARS-CoV-2 3CLpro from the active ingredients of TCMs, including network pharmacology, molecular docking, surface plasmon resonance (SPR) binding assay and fluorescence resonance energy transfer (FRET)-based inhibition assay. The SPR assay showed good interaction between EGCG and 3CLpro with KD ~6.17 µM, suggesting a relatively high affinity of EGCG with SARS-CoV-2 3CLpro. Our results provide critical insights into the mechanism of action of EGCG as a potential therapeutic agent against COVID-19.

2.
BMC Biol ; 19(1): 5, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33441133

RESUMO

BACKGROUND: Viruses are ubiquitous biological entities, estimated to be the largest reservoirs of unexplored genetic diversity on Earth. Full functional characterization and annotation of newly discovered viruses requires tools to enable taxonomic assignment, the range of hosts, and biological properties of the virus. Here we focus on prokaryotic viruses, which include phages and archaeal viruses, and for which identifying the viral host is an essential step in characterizing the virus, as the virus relies on the host for survival. Currently, the method for determining the viral host is either to culture the virus, which is low-throughput, time-consuming, and expensive, or to computationally predict the viral hosts, which needs improvements at both accuracy and usability. Here we develop a Gaussian model to predict hosts for prokaryotic viruses with better performances than previous computational methods. RESULTS: We present here Prokaryotic virus Host Predictor (PHP), a software tool using a Gaussian model, to predict hosts for prokaryotic viruses using the differences of k-mer frequencies between viral and host genomic sequences as features. PHP gave a host prediction accuracy of 34% (genus level) on the VirHostMatcher benchmark dataset and a host prediction accuracy of 35% (genus level) on a new dataset containing 671 viruses and 60,105 prokaryotic genomes. The prediction accuracy exceeded that of two alignment-free methods (VirHostMatcher and WIsH, 28-34%, genus level). PHP also outperformed these two alignment-free methods much (24-38% vs 18-20%, genus level) when predicting hosts for prokaryotic viruses which cannot be predicted by the BLAST-based or the CRISPR-spacer-based methods alone. Requiring a minimal score for making predictions (thresholding) and taking the consensus of the top 30 predictions further improved the host prediction accuracy of PHP. CONCLUSIONS: The Prokaryotic virus Host Predictor software tool provides an intuitive and user-friendly API for the Gaussian model described herein. This work will facilitate the rapid identification of hosts for newly identified prokaryotic viruses in metagenomic studies.

3.
Brief Bioinform ; 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33313676

RESUMO

The genus Culicoides includes biting midges, some of which are vectors for viruses that cause diseases in humans and animals. Knowledge of the roles of Culicoides in viral ecology is inadequate. We collected ~300 000 samples of Culicoides and mosquitoes in 15 representative regions within Yunnan, China. Using mosquitoes as reference vectors, we designed a comparative virome strategy to study the viral composition, diversity, hosts and spatiotemporal distribution of Culicoides. A map of viromes in Culicoides and mosquitoes in Yunan province, China, was constructed. At the same locations, Culicoides and mosquitoes usually share a similar viral diversity. At least 10 important pathogenic viruses were detected from Culicoides. Many novel viruses were discovered, including 21 segmented viruses of Flaviviridae, 180 viruses of Monjiviricetes and 130 viruses of Bunyavirales. The findings demonstrate that Culicoides is an important part of viral ecology and should be studied and monitored for potentially emerging viruses.

4.
Brief Bioinform ; 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33333556

RESUMO

African swine fever virus (ASFV) poses serious threats to the pig industry. The multigene family (MGF) proteins are extensively distributed in ASFVs and are generally classified into five families, including MGF-100, MGF-110, MGF-300, MGF-360 and MGF-505. Most MGF proteins, however, have not been well characterized and classified within each family. To bridge this gap, this study first classified MGF proteins into 31 groups based on protein sequence homology and network clustering. A web server for classifying MGF proteins was established and kept available for free at http://www.computationalbiology.cn/MGF/home.html. Results showed that MGF groups of the same family were most similar to each other and had conserved sequence motifs; the genetic diversity of MGF groups varied widely, mainly due to the occurrence of indels. In addition, the MGF proteins were predicted to have large structural and functional diversity, and MGF proteins of the same MGF family tended to have similar structure, location and function. Reconstruction of the ancestral states of MGF groups along the ASFV phylogeny showed that most MGF groups experienced either the copy number variations or the gain-or-loss changes, and most of these changes happened within strains of the same genotype. It is found that the copy number decrease and the loss of MGF groups were much larger than the copy number increase and the gain of MGF groups, respectively, suggesting the ASFV tended to lose MGF proteins in the evolution. Overall, the work provides a detailed classification for MGF proteins and would facilitate further research on MGF proteins.

5.
Brief Bioinform ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33164053

RESUMO

It is of considerable interest to detect somatic mutations in paired tumor and normal sequencing data. A number of callers that are based on statistical or machine learning approaches have been developed to detect somatic small variants. However, they take into consideration only limited information about the reference and potential variant allele in both tumor and normal samples at a candidate somatic site. Also, they differ in how biological and technological noises are addressed. Hence, they are expected to produce divergent outputs. To overcome the drawbacks of existing somatic callers, we develop a deep learning-based tool called DeepSSV, which employs a convolutional neural network (CNN) model to learn increasingly abstract feature representations from the raw data in higher feature layers. DeepSSV creates a spatially oriented representation of read alignments around the candidate somatic sites adapted for the convolutional architecture, which enables it to expand to effectively gather scattered evidence. Moreover, DeepSSV incorporates the mapping information of both reference allele-supporting and variant allele-supporting reads in the tumor and normal samples at a genomic site that are readily available in the pileup format file. Together, the CNN model can process the whole alignment information. Such representational richness allows the model to capture the dependencies in the sequence and identify context-based sequencing artifacts. We fitted the model on ground truth somatic mutations and did benchmarking experiments on simulated and real tumors. The benchmarking results demonstrate that DeepSSV outperforms its state-of-the-art competitors in overall F1 score.

6.
Brief Bioinform ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126244

RESUMO

Accessory proteins play important roles in the interaction between coronaviruses and their hosts. Accordingly, a comprehensive study of the compositional diversity and evolutionary patterns of accessory proteins is critical to understanding the host adaptation and epidemic variation of coronaviruses. Here, we developed a standardized genome annotation tool for coronavirus (CoroAnnoter) by combining open reading frame prediction, transcription regulatory sequence recognition and homologous alignment. Using CoroAnnoter, we annotated 39 representative coronavirus strains to form a compositional profile for all of the accessary proteins. Large variations were observed in the number of accessory proteins of 1-10 for different coronaviruses, with SARS-CoV-2 and SARS-CoV having the most (9 and 10, respectively). The variation between SARS-CoV and SARS-CoV-2 accessory proteins could be traced back to related coronaviruses in other hosts. The genomic distribution of accessory proteins had significant intra-genus conservation and inter-genus diversity and could be grouped into 1, 4, 2 and 1 types for alpha-, beta-, gamma-, and delta-coronaviruses, respectively. Evolutionary analysis suggested that accessory proteins are more conservative locating before the N-terminal of proteins E and M (E-M), while they are more diverse after these proteins. Furthermore, comparison of virus-host interaction networks of SARS-CoV-2 and SARS-CoV accessory proteins showed that they share multiple antiviral signaling pathways, those involved in the apoptotic process, viral life cycle and response to oxidative stress. In summary, our study provides a tool for coronavirus genome annotation and builds a comprehensive profile for coronavirus accessory proteins covering their composition, classification, evolutionary pattern and host interaction.

7.
Biosaf Health ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32905055

RESUMO

Since coronavirus disease 2019 (COVID-19) might circulate in the following seasons, it is essential to understand how COVID-19 influences other respiratory diseases, especially influenza. In this study, we analyzed the influenza activity from mid-November 2019 to March 2020 in mainland China and found that the influenza season ended much earlier than previous seasons for all subtypes and lineages, which may have resulted from the circulation of COVID-19 and measures such as travel control and personal protection. These findings provide rudimentary knowledge of the co-circulation patterns of the two types of viruses.

8.
Nat Commun ; 11(1): 3910, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764693

RESUMO

SARS-CoV-2, a ß-coronavirus, has rapidly spread across the world, highlighting its high transmissibility, but the underlying morphogenesis and pathogenesis remain poorly understood. Here, we characterize the replication dynamics, cell tropism and morphogenesis of SARS-CoV-2 in organotypic human airway epithelial (HAE) cultures. SARS-CoV-2 replicates efficiently and infects both ciliated and secretory cells in HAE cultures. In comparison, HCoV-NL63 replicates to lower titers and is only detected in ciliated cells. SARS-CoV-2 shows a similar morphogenetic process as other coronaviruses but causes plaque-like cytopathic effects in HAE cultures. Cell fusion, apoptosis, destruction of epithelium integrity, cilium shrinking and beaded changes are observed in the plaque regions. Taken together, our results provide important insights into SARS-CoV-2 cell tropism, replication and morphogenesis.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Células Epiteliais/virologia , Morfogênese/fisiologia , Pneumonia Viral/virologia , Sistema Respiratório/virologia , Betacoronavirus/patogenicidade , Linhagem Celular , Células Cultivadas , Efeito Citopatogênico Viral , Células Epiteliais/patologia , Humanos , Pandemias , Sistema Respiratório/patologia , Tropismo , Replicação Viral
9.
Virol Sin ; 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32725480

RESUMO

The virus receptors are key for the viral infection of host cells. Identification of the virus receptors is still challenging at present. Our previous study has shown that human virus receptor proteins have some unique features including high N-glycosylation level, high number of interaction partners and high expression level. Here, a random-forest model was built to identify human virus receptorome from human cell membrane proteins with an accepted accuracy based on the combination of the unique features of human virus receptors and protein sequences. A total of 1424 human cell membrane proteins were predicted to constitute the receptorome of the human-infecting virome. In addition, the combination of the random-forest model with protein-protein interactions between human and viruses predicted in previous studies enabled further prediction of the receptors for 693 human-infecting viruses, such as the enterovirus, norovirus and West Nile virus. Finally, the candidate alternative receptors of the SARS-CoV-2 were also predicted in this study. As far as we know, this study is the first attempt to predict the receptorome for the human-infecting virome and would greatly facilitate the identification of the receptors for viruses.

10.
bioRxiv ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32511312

RESUMO

Background: The 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. Methods: We collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. Results: Systematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. Conclusions: Our studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. One Sentence Summary: Novel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.

12.
Sci Rep ; 10(1): 8591, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32433560

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

13.
Can J Cardiol ; 36(6): 915-930, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32439306

RESUMO

With more than 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. This paper provides a critical review of the available evidence regarding the lessons learned from the Chinese experience with COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits, which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hubei Province and the rest of the country, as well as closure of all schools and nonessential businesses. Other measures included the rapid construction of two new hospitals and the establishment of "Fangcang" shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high-flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin, and convalescent plasma infusions. These measures appeared to provide only moderate success. Although some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers, and contacts and early implementation of quarantine measures with an organised, proactive, and unified strategy at a national level. Delays result in significantly higher death tolls.


Assuntos
Betacoronavirus , Controle de Doenças Transmissíveis , Infecções por Coronavirus , Pandemias , Administração dos Cuidados ao Paciente , Pneumonia Viral , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , China/epidemiologia , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Humanos , Pandemias/prevenção & controle , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/organização & administração , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Pneumonia Viral/transmissão
14.
J Am Soc Nephrol ; 31(6): 1282-1295, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32444356

RESUMO

BACKGROUND: Antiglomerular basement membrane (anti-GBM) disease is associated with HLA-DRB1*1501 (the major predisposing genetic factor in the disease), with α3127-148 as a nephritogenic T and B cell epitope. Although the cause of disease remains unclear, the association of infections with anti-GBM disease has been long suspected. METHODS: To investigate whether microbes might activate autoreactive T and B lymphocytes via molecular mimicry in anti-GBM disease, we used bioinformatic tools, including BLAST, SYFPEITHI, and ABCpred, for peptide searching and epitope prediction. We used sera from patients with anti-GBM disease to assess peptides recognized by antibodies, and immunized WKY rats and a humanized mouse model (HLA-DR15 transgenic mice) with each of the peptide candidates to assess pathogenicity. RESULTS: On the basis of the critical motif, the bioinformatic approach identified 36 microbial peptides that mimic human α3127-148. Circulating antibodies in sera from patients with anti-GBM recognized nine of them. One peptide, B7, derived from Actinomyces species, induced proteinuria, linear IgG deposition on the GBM, and crescent formation when injected into WKY rats. The antibodies to B7 also targeted human and rat α3127-148. B7 induced T cell activation from human α3127-148-immunized rats. T cell responses to B7 were detected in rats immunized by Actinomyces lysate proteins or recombinant proteins. We confirmed B7's pathogenicity in HLA-DR15 transgenic mice that developed kidney injury similar to that observed in α3135-145-immunized mice. CONCLUSIONS: Sera from patients with anti-GBM disease recognized microbial peptides identified through a bioinformatic approach, and a peptide from Actinomyces induced experimental anti-GBM GN by T and B cell crossreactivity. These studies demonstrate that anti-GBM disease may be initiated by immunization with a microbial peptide.

15.
Clin Rev Allergy Immunol ; 59(1): 89-100, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32328954

RESUMO

The COVID-19 pandemic is a significant global event in the history of infectious diseases. The SARS-CoV-2 appears to have originated from bats but is now easily transmissible among humans, primarily through droplet or direct contact. Clinical features of COVID-19 include high fever, cough, and fatigue which may progress to ARDS. Respiratory failure can occur rapidly after this. The primary laboratory findings include lymphopenia and eosinopenia. Elevated D-dimer, procalcitonin, and CRP levels may correlate with disease severity. Imaging findings include ground-glass opacities and patchy consolidation on CT scan. Mortality is higher in patients with hypertension, cardiac disease, diabetes mellitus, cancer, and COPD. Elderly patients are more susceptible to severe disease and death, while children seem to have lower rates of infection and lower mortality. Diagnostic criteria and the identification of persons under investigation have evolved as more data has emerged. However, the approach to diagnosis is still very variable from region to region, country to country, and even among different hospitals in the same city. The importance of a clinical pathway to implement the most effective and relevant diagnostic strategy is of critical importance to establish the control of this virus that is responsible for more and more deaths each day.


Assuntos
Anticorpos Antivirais/imunologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico , RNA Viral/análise , Algoritmos , Betacoronavirus/imunologia , Procedimentos Clínicos , Diagnóstico Precoce , Prática Clínica Baseada em Evidências , Reações Falso-Negativas , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Anamnese , Pandemias , Isolamento de Pacientes , Quarentena , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Testes Sorológicos/métodos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
16.
Cell Metab ; 31(5): 937-955.e7, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32325032

RESUMO

Cell proliferation and inflammation are two metabolically demanding biological processes. How these competing processes are selectively executed in the same cell remains unknown. Here, we report that the enzyme carbamoyl-phosphate synthetase, aspartyl transcarbamoylase, and dihydroorotase (CAD) deamidates the RelA subunit of NF-κB in cancer cells to promote aerobic glycolysis and fuel cell proliferation in tumorigenesis. This post-translational modification switches RelA function from mediating the expression of NF-κB-responsive genes to that of glycolytic enzymes, thus shunting the cell's inflammatory response to aerobic glycolysis. Further, we profiled diverse human cancer cell lines and found that high CAD expression and a subset of RELA mutations correlated with RelA deamidation. And by use of inhibitors of key glycolytic enzymes, we validated the pivotal role of RelA deamidation in tumorigenesis of cancer cell lines. This work illuminates a mechanism by which protein deamidation selectively specifies gene expression and consequent biological processes.

17.
Brief Bioinform ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349124

RESUMO

Circular RNAs (circRNAs) are covalently closed long noncoding RNAs critical in diverse cellular activities and multiple human diseases. Several cancer-related viral circRNAs have been identified in double-stranded DNA viruses (dsDNA), yet no systematic study about the viral circRNAs has been reported. Herein, we have performed a systematic survey of 11 924 circRNAs from 23 viral species by computational prediction of viral circRNAs from viral-infection-related RNA sequencing data. Besides the dsDNA viruses, our study has also revealed lots of circRNAs in single-stranded RNA viruses and retro-transcribing viruses, such as the Zika virus, the Influenza A virus, the Zaire ebolavirus, and the Human immunodeficiency virus 1. Most viral circRNAs had reverse complementary sequences or repeated sequences at the flanking sequences of the back-splice sites. Most viral circRNAs only expressed in a specific cell line or tissue in a specific species. Functional enrichment analysis indicated that the viral circRNAs from dsDNA viruses were involved in KEGG pathways associated with cancer. All viral circRNAs presented in the current study were stored and organized in VirusCircBase, which is freely available at http://www.computationalbiology.cn/ViruscircBase/home.html and is the first virus circRNA database. VirusCircBase forms the fundamental atlas for the further exploration and investigation of viral circRNAs in the context of public health.

18.
PeerJ ; 8: e8855, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32274268

RESUMO

The African swine fever virus (ASFV) has severely influenced the swine industry of the world. Unfortunately, there is currently no effective antiviral drug or vaccine against the virus. Identification of new anti-ASFV drugs is urgently needed. Here, an up-to-date set of protein-protein interactions between ASFV and swine were curated by integration of protein-protein interactions from multiple sources. Thirty-eight swine proteins were observed to interact with ASFVs and were defined as ASFV-interacting swine proteins. The ASFV-interacting swine proteins were found to play a central role in the swine protein-protein interaction network, with significant larger degree, betweenness and smaller shortest path length than other swine proteins. Some of ASFV-interacting swine proteins also interacted with several other viruses and could be taken as potential targets of drugs for broad-spectrum effect, such as HSP90AB1. Finally, the antiviral drugs which targeted ASFV-interacting swine proteins and ASFV proteins were predicted. Several drugs with either broad-spectrum effect or high specificity on ASFV-interacting swine proteins were identified, such as Polaprezinc and Geldanamycin. Structural modeling and molecular dynamics simulation showed that Geldanamycin could bind with swine HSP90AB1 stably. This work could not only deepen our understanding towards the ASFV-swine interactions, but also help for the development of effective antiviral drugs against the ASFVs.

19.
J Autoimmun ; 109: 102434, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32143990

RESUMO

The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002-2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/história , Animais , Betacoronavirus/genética , Betacoronavirus/patogenicidade , China/epidemiologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/economia , Infecções por Coronavirus/prevenção & controle , Genoma Viral , História do Século XXI , Humanos , Disseminação de Informação , Pandemias/economia , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/economia , Pneumonia Viral/prevenção & controle , Piroptose , Quarentena , Síndrome Respiratória Aguda Grave/prevenção & controle , Zoonoses/virologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-32117926

RESUMO

The broad spectrum of intellectual disability (ID) patients' clinical manifestations, the heterogeneity of ID genetic variation, and the diversity of the phenotypic variation represent major challenges for ID diagnosis. By exploiting a manually curated systematic phenotyping cohort of 3803 patients harboring ID, we identified 704 pathogenic genes, 3848 pathogenic sites, and 2075 standard phenotypes for underlying molecular perturbations and their phenotypic impact. We found the positive correlation between the number of phenotypes and that of patients that revealed their extreme heterogeneities, and the relative contribution of multiple determinants to the heterogeneity of ID phenotypes. Nevertheless, despite the extreme heterogeneity in phenotypes, the ID genes had a specific bias of mutation types, and the top 44 genes that ranked by the number of patients accounted for 39.9% of total patients. More interesting, enriched co-occurrent phenotypes and co-occurrent phenotype networks for each gene had the potential for prioritizing ID genes, further exhibited the convergences of ID phenotypes. Then we established a predictor called IDpred using machine learning methods for ID pathogenic genes prediction. Using10-fold cross-validation, our evaluation shows remarkable AUC values for IDpred (auc = 0.978), demonstrating the robustness and reliability of our tool. Besides, we built the most comprehensive database of ID phenotyped cohort to date: IDminer http://218.4.234.74:3100/IDminer/, which included the curated ID data and integrated IDpred tool for both clinical and experimental researchers. The IDminer serves as an important resource and user-friendly interface to help researchers investigate ID data, and provide important implications for the diagnosis and pathogenesis of developmental disorders of cognition.

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