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1.
Genome ; 64(4): v-vii, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1523064
3.
Viruses ; 13(1)2021 Jan 16.
Article in English | MEDLINE | ID: covidwho-1389525

ABSTRACT

Our recent study identified seven key microRNAs (miR-8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) similar between SARS-CoV-2 and the human genome, pointing at miR-related mechanisms in viral entry and the regulatory effects on host immunity. To identify the putative roles of these miRs in zoonosis, we assessed their conservation, compared with humans, in some key wild and domestic animal carriers of zoonotic viruses, including bat, pangolin, pig, cow, rat, and chicken. Out of the seven miRs under study, miR-3611 was the most strongly conserved across all species; miR-5197 was the most conserved in pangolin, pig, cow, bat, and rat; miR-1307 was most strongly conserved in pangolin, pig, cow, bat, and human; miR-3691-3p in pangolin, cow, and human; miR-3934-3p in pig and cow, followed by pangolin and bat; miR-1468 was most conserved in pangolin, pig, and bat; while miR-8066 was most conserved in pangolin and pig. In humans, miR-3611 and miR-1307 were most conserved, while miR-8066, miR-5197, miR-3334-3p and miR-1468 were least conserved, compared with pangolin, pig, cow, and bat. Furthermore, we identified that changes in the miR-5197 nucleotides between pangolin and human can generate three new miRs, with differing tissue distribution in the brain, lung, intestines, lymph nodes, and muscle, and with different downstream regulatory effects on KEGG pathways. This may be of considerable importance as miR-5197 is localized in the spike protein transcript area of the SARS-CoV-2 genome. Our findings may indicate roles for these miRs in viral-host co-evolution in zoonotic hosts, particularly highlighting pangolin, bat, cow, and pig as putative zoonotic carriers, while highlighting the miRs' roles in KEGG pathways linked to viral pathogenicity and host responses in humans. This in silico study paves the way for investigations into the roles of miRs in zoonotic disease.


Subject(s)
Biological Coevolution , MicroRNAs/genetics , SARS-CoV-2/genetics , Animals , COVID-19/transmission , COVID-19/virology , Chickens , Gene Regulatory Networks , Genome/genetics , Host Specificity , Humans , Mammals , MicroRNAs/chemistry , MicroRNAs/metabolism , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Sequence Alignment , Tissue Distribution , Zoonoses/transmission , Zoonoses/virology
5.
Int J Mol Sci ; 22(7)2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1369767

ABSTRACT

According to Darwin's theory, endless evolution leads to a revolution. One such example is the Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-Cas system, an adaptive immunity system in most archaea and many bacteria. Gene editing technology possesses a crucial potential to dramatically impact miscellaneous areas of life, and CRISPR-Cas represents the most suitable strategy. The system has ignited a revolution in the field of genetic engineering. The ease, precision, affordability of this system is akin to a Midas touch for researchers editing genomes. Undoubtedly, the applications of this system are endless. The CRISPR-Cas system is extensively employed in the treatment of infectious and genetic diseases, in metabolic disorders, in curing cancer, in developing sustainable methods for fuel production and chemicals, in improving the quality and quantity of food crops, and thus in catering to global food demands. Future applications of CRISPR-Cas will provide benefits for everyone and will save countless lives. The technology is evolving rapidly; therefore, an overview of continuous improvement is important. In this review, we aim to elucidate the current state of the CRISPR-Cas revolution in a tailor-made format from its discovery to exciting breakthroughs at the application level and further upcoming trends related to opportunities and challenges including ethical concerns.


Subject(s)
CRISPR-Cas Systems , Gene Editing/methods , Genetic Engineering/methods , Animals , Archaea/metabolism , Bacteria/metabolism , Clustered Regularly Interspaced Short Palindromic Repeats , Crops, Agricultural/genetics , Genetic Engineering/history , Genome , History, 20th Century , History, 21st Century , Humans , Livestock
6.
Immunobiology ; 226(5): 152130, 2021 09.
Article in English | MEDLINE | ID: covidwho-1368671

ABSTRACT

In this review, we highlight the interaction of SARS-CoV-2 virus and host genomes, reporting the current studies on the sequence analysis of SARS-CoV-2 isolates and host genomes from diverse world populations. The main genetic variants that are present in both the virus and host genomes were particularly focused on the ACE2 and TMPRSS2 genes, and their impact on the patients' susceptibility to the virus infection and severity of the disease. Finally, the interaction of the virus and host non-coding RNAs is described in relation to their regulatory roles in target genes and/or signaling pathways critically associated with SARS-CoV-2 infection. Altogether, these studies provide a significant contribution to the knowledge of SARS-CoV-2 mechanisms of infection and COVID-19 pathogenesis. The described genetic variants and molecular factors involved in host/virus genome interactions have significantly contributed to defining patient risk groups, beyond those based on patients' age and comorbidities, and they are promising candidates to be potentially targeted in treatment strategies for COVID-19 and other viral infectious diseases.


Subject(s)
COVID-19/genetics , Genome , Host-Pathogen Interactions/genetics , RNA, Untranslated , SARS-CoV-2/genetics , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/therapy , Genes, Viral , Humans , Serine Endopeptidases/genetics
7.
Int J Mol Sci ; 22(7)2021 Mar 26.
Article in English | MEDLINE | ID: covidwho-1299435

ABSTRACT

The importance of gene expression regulation in viruses based upon G-quadruplex may point to its potential utilization in therapeutic targeting. Here, we present analyses as to the occurrence of putative G-quadruplex-forming sequences (PQS) in all reference viral dsDNA genomes and evaluate their dependence on PQS occurrence in host organisms using the G4Hunter tool. PQS frequencies differ across host taxa without regard to GC content. The overlay of PQS with annotated regions reveals the localization of PQS in specific regions. While abundance in some, such as repeat regions, is shared by all groups, others are unique. There is abundance within introns of Eukaryota-infecting viruses, but depletion of PQS in introns of bacteria-infecting viruses. We reveal a significant positive correlation between PQS frequencies in dsDNA viruses and corresponding hosts from archaea, bacteria, and eukaryotes. A strong relationship between PQS in a virus and its host indicates their close coevolution and evolutionarily reciprocal mimicking of genome organization.


Subject(s)
Computational Biology/methods , DNA/genetics , G-Quadruplexes , Genome, Viral , Viral Proteins/genetics , Archaea/virology , Bacteria/virology , Gene Expression Regulation , Genome , Humans , Viruses/genetics
8.
Angew Chem Int Ed Engl ; 60(35): 19191-19200, 2021 08 23.
Article in English | MEDLINE | ID: covidwho-1279344

ABSTRACT

SARS-CoV-2 contains a positive single-stranded RNA genome of approximately 30 000 nucleotides. Within this genome, 15 RNA elements were identified as conserved between SARS-CoV and SARS-CoV-2. By nuclear magnetic resonance (NMR) spectroscopy, we previously determined that these elements fold independently, in line with data from in vivo and ex-vivo structural probing experiments. These elements contain non-base-paired regions that potentially harbor ligand-binding pockets. Here, we performed an NMR-based screening of a poised fragment library of 768 compounds for binding to these RNAs, employing three different 1 H-based 1D NMR binding assays. The screening identified common as well as RNA-element specific hits. The results allow selection of the most promising of the 15 RNA elements as putative drug targets. Based on the identified hits, we derive key functional units and groups in ligands for effective targeting of the RNA of SARS-CoV-2.


Subject(s)
Genome , RNA, Viral/metabolism , SARS-CoV-2/genetics , Small Molecule Libraries/metabolism , Drug Evaluation, Preclinical , Ligands , Molecular Structure , Nucleic Acid Conformation , Proton Magnetic Resonance Spectroscopy , RNA, Viral/chemistry , Small Molecule Libraries/chemistry
9.
Pharmacogenomics ; 22(10): 603-618, 2021 07.
Article in English | MEDLINE | ID: covidwho-1278319

ABSTRACT

Aim: Numerous drugs are being widely prescribed for COVID-19 treatment without any direct evidence for the drug safety/efficacy in patients across diverse ethnic populations. Materials & methods: We analyzed whole genomes of 1029 Indian individuals (IndiGen) to understand the extent of drug-gene (pharmacogenetic), drug-drug and drug-drug-gene interactions associated with COVID-19 therapy in the Indian population. Results: We identified 30 clinically significant pharmacogenetic variants and 73 predicted deleterious pharmacogenetic variants. COVID-19-associated pharmacogenes were substantially overlapped with those of metabolic disorder therapeutics. CYP3A4, ABCB1 and ALB are the most shared pharmacogenes. Fifteen COVID-19 therapeutics were predicted as likely drug-drug interaction candidates when used with four CYP inhibitor drugs. Conclusion: Our findings provide actionable insights for future validation studies and improved clinical decisions for COVID-19 therapy in Indians.


Subject(s)
COVID-19/drug therapy , COVID-19/genetics , Antiviral Agents/therapeutic use , Drug Interactions/genetics , Genome/genetics , Genotype , Humans , India , Pharmacogenetics/methods , Pharmacogenomic Testing/methods , Pharmacogenomic Variants/genetics , SARS-CoV-2/drug effects
11.
Molecules ; 26(6)2021 Mar 23.
Article in English | MEDLINE | ID: covidwho-1154456

ABSTRACT

Bats are unique in their potential to serve as reservoir hosts for intracellular pathogens. Recently, the impact of COVID-19 has relegated bats from biomedical darkness to the frontline of public health as bats are the natural reservoir of many viruses, including SARS-Cov-2. Many bat genomes have been sequenced recently, and sequences coding for antimicrobial peptides are available in the public databases. Here we provide a structural analysis of genome-predicted bat cathelicidins as components of their innate immunity. A total of 32 unique protein sequences were retrieved from the NCBI database. Interestingly, some bat species contained more than one cathelicidin. We examined the conserved cysteines within the cathelin-like domain and the peptide portion of each sequence and revealed phylogenetic relationships and structural dissimilarities. The antibacterial, antifungal, and antiviral activity of peptides was examined using bioinformatic tools. The peptides were modeled and subjected to docking analysis with the region binding domain (RBD) region of the SARS-CoV-2 Spike protein. The appearance of multiple forms of cathelicidins verifies the complex microbial challenges encountered by these species. Learning more about antiviral defenses of bats and how they drive virus evolution will help scientists to investigate the function of antimicrobial peptides in these species.


Subject(s)
Cathelicidins/chemistry , Cathelicidins/pharmacology , Chiroptera/genetics , Spike Glycoprotein, Coronavirus/metabolism , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Binding Sites , Cathelicidins/genetics , Cathelicidins/metabolism , Computational Biology/methods , Computer Simulation , Genome , Molecular Docking Simulation , Phylogeny
13.
Perspect Health Inf Manag ; 18(Winter): 1l, 2021.
Article in English | MEDLINE | ID: covidwho-1103043

ABSTRACT

The notion of health information privacy has evolved over time as the healthcare industry has embraced technology. Where once individuals were concerned about the privacy of their conversations and financial information, the digitization of health data has created new challenges for those responsible for ensuring that patient information remains secure and private. Coupled with the lack of updated, overarching legislation, a critical gap exists between advancements in technology, consumer informatics tools and privacy regulations. Almost twenty years after the HIPAA (Health Insurance Portability and Accountability Act) compliance date, the healthcare industry continues to seek solutions to privacy challenges absent formal contemporary law. Since HIPAA, a few attempts have been made to control specific aspects of health information including genetic information and use of technology however none were visionary enough to address issues seen in today's digital data focused healthcare environment. The proliferation of digital health data, trends in data use, increased use of telehealth applications due to COVID-19 pandemic and the consumer's participatory role in healthcare all create new challenges not covered by the existing legal framework. Modern efforts to address this dilemma have emerged in state and international law though the United States healthcare industry continues to operate under a law written two decades ago. As technology continues to advance at a rapid pace along with consumers playing a greater role in the management of their healthcare through digital health the privacy guidance provided by federal law must also shift to reflect the new reality.


Subject(s)
Confidentiality/legislation & jurisprudence , Health Insurance Portability and Accountability Act , Telemedicine/legislation & jurisprudence , COVID-19 , Genome , Humans , SARS-CoV-2 , United States
14.
J Mol Biol ; 433(11): 166835, 2021 05 28.
Article in English | MEDLINE | ID: covidwho-1062478

ABSTRACT

FunCoup (https://funcoup.sbc.su.se) is one of the most comprehensive functional association networks of genes/proteins available. Functional associations are inferred by integrating different types of evidence using a redundancy-weighted naïve Bayesian approach, combined with orthology transfer. FunCoup's high coverage comes from using eleven different types of evidence, and extensive transfer of information between species. Since the latest update of the database, the availability of source data has improved drastically, and user expectations on a tool for functional associations have grown. To meet these requirements, we have made a new release of FunCoup with updated source data and improved functionality. FunCoup 5 now includes 22 species from all domains of life, and the source data for evidences, gold standards, and genomes have been updated to the latest available versions. In this new release, directed regulatory links inferred from transcription factor binding can be visualized in the network viewer for the human interactome. Another new feature is the possibility to filter by genes expressed in a certain tissue in the network viewer. FunCoup 5 further includes the SARS-CoV-2 proteome, allowing users to visualize and analyze interactions between SARS-CoV-2 and human proteins in order to better understand COVID-19. This new release of FunCoup constitutes a major advance for the users, with updated sources, new species and improved functionality for analysis of the networks.


Subject(s)
Databases, Factual , Gene Regulatory Networks , Organ Specificity , Protein Interaction Maps , Bayes Theorem , COVID-19/metabolism , COVID-19/virology , Genome , Host Microbial Interactions , Humans , Protein Binding , Proteins , Proteome , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Transcription Factors
15.
Genome Biol ; 22(1): 31, 2021 01 11.
Article in English | MEDLINE | ID: covidwho-1035070
16.
Nucleic Acids Res ; 49(D1): D981-D987, 2021 01 08.
Article in English | MEDLINE | ID: covidwho-1010406

ABSTRACT

The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the community model organism knowledgebase for the laboratory mouse, a widely used animal model for comparative studies of the genetic and genomic basis for human health and disease. MGD is the authoritative source for biological reference data related to mouse genes, gene functions, phenotypes and mouse models of human disease. MGD is the primary source for official gene, allele, and mouse strain nomenclature based on the guidelines set by the International Committee on Standardized Nomenclature for Mice. MGD's biocuration scientists curate information from the biomedical literature and from large and small datasets contributed directly by investigators. In this report we describe significant enhancements to the content and interfaces at MGD, including (i) improvements in the Multi Genome Viewer for exploring the genomes of multiple mouse strains, (ii) inclusion of many more mouse strains and new mouse strain pages with extended query options and (iii) integration of extensive data about mouse strain variants. We also describe improvements to the efficiency of literature curation processes and the implementation of an information portal focused on mouse models and genes for the study of COVID-19.


Subject(s)
COVID-19/prevention & control , Databases, Genetic , Genome/genetics , Genomics/methods , Knowledge Bases , SARS-CoV-2/genetics , Animals , COVID-19/epidemiology , COVID-19/virology , Data Curation/methods , Disease Models, Animal , Epidemics , Gene Ontology , Humans , Information Storage and Retrieval/methods , Internet , Mice , SARS-CoV-2/physiology
17.
Front Public Health ; 8: 590412, 2020.
Article in English | MEDLINE | ID: covidwho-1004711

ABSTRACT

During air travel, flight crew (flight attendants, pilots) can be exposed to numerous flight-related environmental DNA damaging agents that may be at the root of an excess risk of cancer and other diseases. This already complex mix of exposures is now joined by SARS-CoV-2, the virus that causes COVID-19. The complex exposures experienced during air travel present a challenge to public health research, but also provide an opportunity to consider new strategies for understanding and countering their health effects. In this article, we focus on threats to genomic integrity that occur during air travel and discuss how these threats and our ability to respond to them may influence the risk of SARS-CoV-2 infection and the development of range of severity of the symptoms. We also discuss how the virus itself may lead to compromised genome integrity. We argue that dauntingly complex public health problems, such as the challenge of protecting flight crews from COVID-19, must be met with interdisciplinary research teams that include epidemiologists, engineers, and mechanistic biologists.


Subject(s)
Air Travel/statistics & numerical data , COVID-19/genetics , COVID-19/transmission , DNA Damage , Disease Resistance/genetics , Genome , Occupational Exposure/statistics & numerical data , Adult , Female , Humans , Male , Middle Aged , Risk Factors , SARS-CoV-2
18.
Nucleic Acids Res ; 49(D1): D981-D987, 2021 01 08.
Article in English | MEDLINE | ID: covidwho-941569

ABSTRACT

The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the community model organism knowledgebase for the laboratory mouse, a widely used animal model for comparative studies of the genetic and genomic basis for human health and disease. MGD is the authoritative source for biological reference data related to mouse genes, gene functions, phenotypes and mouse models of human disease. MGD is the primary source for official gene, allele, and mouse strain nomenclature based on the guidelines set by the International Committee on Standardized Nomenclature for Mice. MGD's biocuration scientists curate information from the biomedical literature and from large and small datasets contributed directly by investigators. In this report we describe significant enhancements to the content and interfaces at MGD, including (i) improvements in the Multi Genome Viewer for exploring the genomes of multiple mouse strains, (ii) inclusion of many more mouse strains and new mouse strain pages with extended query options and (iii) integration of extensive data about mouse strain variants. We also describe improvements to the efficiency of literature curation processes and the implementation of an information portal focused on mouse models and genes for the study of COVID-19.


Subject(s)
COVID-19/prevention & control , Databases, Genetic , Genome/genetics , Genomics/methods , Knowledge Bases , SARS-CoV-2/genetics , Animals , COVID-19/epidemiology , COVID-19/virology , Data Curation/methods , Disease Models, Animal , Epidemics , Gene Ontology , Humans , Information Storage and Retrieval/methods , Internet , Mice , SARS-CoV-2/physiology
19.
Nucleic Acids Res ; 49(D1): D1046-D1057, 2021 01 08.
Article in English | MEDLINE | ID: covidwho-939577

ABSTRACT

For more than two decades, the UCSC Genome Browser database (https://genome.ucsc.edu) has provided high-quality genomics data visualization and genome annotations to the research community. As the field of genomics grows and more data become available, new modes of display are required to accommodate new technologies. New features released this past year include a Hi-C heatmap display, a phased family trio display for VCF files, and various track visualization improvements. Striving to keep data up-to-date, new updates to gene annotations include GENCODE Genes, NCBI RefSeq Genes, and Ensembl Genes. New data tracks added for human and mouse genomes include the ENCODE registry of candidate cis-regulatory elements, promoters from the Eukaryotic Promoter Database, and NCBI RefSeq Select and Matched Annotation from NCBI and EMBL-EBI (MANE). Within weeks of learning about the outbreak of coronavirus, UCSC released a genome browser, with detailed annotation tracks, for the SARS-CoV-2 RNA reference assembly.


Subject(s)
COVID-19/prevention & control , Computational Biology/methods , Databases, Genetic , Genome/genetics , Genomics/methods , SARS-CoV-2/genetics , Animals , COVID-19/epidemiology , COVID-19/virology , Data Curation/methods , Epidemics , Humans , Internet , Mice , Molecular Sequence Annotation/methods , SARS-CoV-2/physiology , Software
20.
Nucleic Acids Res ; 49(D1): D373-D379, 2021 01 08.
Article in English | MEDLINE | ID: covidwho-917704

ABSTRACT

OMA is an established resource to elucidate evolutionary relationships among genes from currently 2326 genomes covering all domains of life. OMA provides pairwise and groupwise orthologs, functional annotations, local and global gene order conservation (synteny) information, among many other functions. This update paper describes the reorganisation of the database into gene-, group- and genome-centric pages. Other new and improved features are detailed, such as reporting of the evolutionarily best conserved isoforms of alternatively spliced genes, the inferred local order of ancestral genes, phylogenetic profiling, better cross-references, fast genome mapping, semantic data sharing via RDF, as well as a special coronavirus OMA with 119 viruses from the Nidovirales order, including SARS-CoV-2, the agent of the COVID-19 pandemic. We conclude with improvements to the documentation of the resource through primers, tutorials and short videos. OMA is accessible at https://omabrowser.org.


Subject(s)
Algorithms , Databases, Genetic , Gene Order/genetics , Genome/genetics , Animals , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Chromosome Mapping , Evolution, Molecular , Gene Ontology , Humans , Internet , Pandemics , Phylogeny , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Species Specificity , Synteny
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