scholarly journals Dynamics of a Dual SARS-CoV-2 Lineage Co-Infection on a Prolonged Viral Shedding COVID-19 Case: Insights into Clinical Severity and Disease Duration

2021 ◽  
Vol 9 (2) ◽  
pp. 300
Author(s):  
Nicole Pedro ◽  
Cláudio N. Silva ◽  
Ana C. Magalhães ◽  
Bruno Cavadas ◽  
Ana M. Rocha ◽  
...  
Keyword(s):  
Clinical Severity ◽  
Risk Scores ◽  
Portuguese Population ◽  
Normal Distributions ◽  
Viral Shedding ◽  
Genome Wide ◽  
Multiple Component ◽  
Old Portuguese ◽  
Serial Samples

A few molecularly proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding coronavirus disease 2019 (COVID-19) case in a 17-year-old Portuguese female. She had two hospitalizations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days. The viral genome was sequenced in seven serial samples and in the diagnostic sample from her infected mother. A human genome-wide array (>900 K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples. The patient had co-infection by two SARS-CoV-2 lineages, which were affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with the patient’s mother), but nine days later, the 20B lineage had 3% frequency, and two months later, the 20B lineage had 100% frequency. The 900 K profiles confirmed the identity of the patient in the serial samples, and they allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort. The early-on dynamic co-infection may have contributed to the severity of COVID-19 in this otherwise healthy young patient, and to her prolonged SARS-CoV-2 shedding profile.

scholarly journals Dynamics of a dual SARS-CoV-2 strain co-infection on a prolonged viral shedding COVID-19 case: insights into clinical severity and disease duration

2020 ◽  
Author(s):  
Nicole Pedro ◽  
Cláudio N. Silva ◽  
Ana C. Magalhães ◽  
Bruno Cavadas ◽  
Ana M. Rocha ◽  
...  
Keyword(s):  
Clinical Severity ◽  
Risk Scores ◽  
Close Relative ◽  
Portuguese Population ◽  
Normal Distributions ◽  
Viral Shedding ◽  
Genome Wide ◽  
Multiple Component ◽  
Serial Samples

AbstractObjectivesA few molecularly proven SARS-CoV-2 cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding COVID-19 case in a teenager Portuguese female. She had two hospitalisations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days.MethodsThe viral genome was sequenced in seven serial samples and in the diagnostic sample from an infected close relative. A human genome-wide array (>900K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples.ResultsThe patient had co-infection by two SARS-CoV-2 strains, affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with a cohabitating relative), but nine days later the 20B lineage had 3% frequency, and two months later the 20B lineage had 100% frequency. The 900K profiles confirmed the identity of the patient in the serial samples, and allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort.ConclusionsThe early-on dynamic co-infection was the probable cause for the severity of COVID-19 in this otherwise healthy young patient, and for her prolonged SARS-CoV-2 shedding profile.

scholarly journals Strain variation in Clostridioides difficile toxin activity associated with genomic variation at both PaLoc and non-PaLoc loci

2021 ◽  
Author(s):  
Katie Saund ◽  
Ali Pirani ◽  
Borden Lacy ◽  
Philip C Hanna ◽  
Evan S Snitkin
Keyword(s):  
Evolutionary History ◽  
Genome Wide Association Study ◽  
Bacterial Genome ◽  
Genomic Variation ◽  
Clinical Severity ◽  
Clostridioides Difficile ◽  
Genome Wide ◽  
Net Method ◽  
Human Infections

Clinical disease from Clostridioides difficile infection can be mediated by two toxins and their neighboring regulatory genes encoded within the five-gene pathogenicity locus (PaLoc). We provide several lines of evidence that the toxin activity of C. difficile may be modulated by genomic variants outside of the PaLoc. We used a phylogenetic tree-based approach to demonstrate discordance between toxin activity and PaLoc evolutionary history, an elastic net method to show the insufficiency of PaLoc variants alone to model toxin activity, and a convergence-based bacterial genome-wide association study (GWAS) to identify correlations between non-PaLoc loci with changes in toxin activity. Combined, these data support a model of C. difficile disease wherein toxin activity may be strongly affected by many non-PaLoc loci. Additionally, we characterize multiple other in vitro phenotypes relevant to human infections including germination and sporulation. These phenotypes vary greatly in their clonality, variability, convergence, and concordance with genomic variation. Lastly, we highlight the intersection of loci identified by GWAS for different phenotypes and clinical severity. This strategy to identify the overlapping loci can facilitate the identification of genetic variation linking phenotypic variation to clinical outcomes.

scholarly journals Genome-Wide Transcriptomic Identification and Functional Insight of Lily WRKY Genes Responding to Botrytis Fungal Disease

Plants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 776
Author(s):  
Shipra Kumari ◽  
Bashistha Kumar Kanth ◽  
Ju young Ahn ◽  
Jong Hwa Kim ◽  
Geung-Joo Lee
Keyword(s):  
Abiotic Stress ◽  
Biotic Stress ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Lilium Longiflorum ◽  
Biotic And Abiotic Stress ◽  
Biotic Stresses ◽  
Genome Wide

Genome-wide transcriptome analysis using RNA-Seq of Lilium longiflorum revealed valuable genes responding to biotic stresses. WRKY transcription factors are regulatory proteins playing essential roles in defense processes under environmental stresses, causing considerable losses in flower quality and production. Thirty-eight WRKY genes were identified from the transcriptomic profile from lily genotypes, exhibiting leaf blight caused by Botrytis elliptica. Lily WRKYs have a highly conserved motif, WRKYGQK, with a common variant, WRKYGKK. Phylogeny of LlWRKYs with homologous genes from other representative plant species classified them into three groups- I, II, and III consisting of seven, 22, and nine genes, respectively. Base on functional annotation, 22 LlWRKY genes were associated with biotic stress, nine with abiotic stress, and seven with others. Sixteen unique LlWRKY were studied to investigate responses to stress conditions using gene expression under biotic and abiotic stress treatments. Five genes—LlWRKY3, LlWRKY4, LlWRKY5, LlWRKY10, and LlWRKY12—were substantially upregulated, proving to be biotic stress-responsive genes in vivo and in vitro conditions. Moreover, the expression patterns of LlWRKY genes varied in response to drought, heat, cold, and different developmental stages or tissues. Overall, our study provides structural and molecular insights into LlWRKY genes for use in the genetic engineering in Lilium against Botrytis disease.

scholarly journals Shedding Light on the African Enigma: In Vitro Testing of Homo sapiens-Helicobacter pylori Coevolution

2021 ◽  
Vol 9 (2) ◽  
pp. 240
Author(s):  
Bruno Cavadas ◽  
Marina Leite ◽  
Nicole Pedro ◽  
Ana C. Magalhães ◽  
Joana Melo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Host Response ◽  
Homo Sapiens ◽  
European Ancestry ◽  
Genome Wide ◽  
Expression Host ◽  
H Pylori ◽  
Human Ancestry

The continuous characterization of genome-wide diversity in population and case–cohort samples, allied to the development of new algorithms, are shedding light on host ancestry impact and selection events on various infectious diseases. Especially interesting are the long-standing associations between humans and certain bacteria, such as the case of Helicobacter pylori, which could have been strong drivers of adaptation leading to coevolution. Some evidence on admixed gastric cancer cohorts have been suggested as supporting Homo-Helicobacter coevolution, but reliable experimental data that control both the bacterium and the host ancestries are lacking. Here, we conducted the first in vitro coinfection assays with dual human- and bacterium-matched and -mismatched ancestries, in African and European backgrounds, to evaluate the genome wide gene expression host response to H. pylori. Our results showed that: (1) the host response to H. pylori infection was greatly shaped by the human ancestry, with variability on innate immune system and metabolism; (2) African human ancestry showed signs of coevolution with H. pylori while European ancestry appeared to be maladapted; and (3) mismatched ancestry did not seem to be an important differentiator of gene expression at the initial stages of infection as assayed here.

scholarly journals Nascent RNA sequencing identifies a widespread sigma70-dependent pausing regulated by Gre factors in bacteria

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhe Sun ◽  
Alexander V. Yakhnin ◽  
Peter C. FitzGerald ◽  
Carl E. Mclntosh ◽  
Mikhail Kashlev
Keyword(s):  
Environmental Cues ◽  
Start Site ◽  
Transcription Start ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Vitro Analysis ◽  
In Vitro Analysis

AbstractPromoter-proximal pausing regulates eukaryotic gene expression and serves as checkpoints to assemble elongation/splicing machinery. Little is known how broadly this type of pausing regulates transcription in bacteria. We apply nascent elongating transcript sequencing combined with RNase I footprinting for genome-wide analysis of σ70-dependent transcription pauses in Escherichia coli. Retention of σ70 induces strong backtracked pauses at a 10−20-bp distance from many promoters. The pauses in the 10−15-bp register of the promoter are dictated by the canonical −10 element, 6−7 nt spacer and “YR+1Y” motif centered at the transcription start site. The promoters for the pauses in the 16−20-bp register contain an additional −10-like sequence recognized by σ70. Our in vitro analysis reveals that DNA scrunching is involved in these pauses relieved by Gre cleavage factors. The genes coding for transcription factors are enriched in these pauses, suggesting that σ70 and Gre proteins regulate transcription in response to changing environmental cues.

scholarly journals Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
José Jaime Martínez-Magaña ◽  
Alma Delia Genis-Mendoza ◽  
Jorge Ameth Villatoro Velázquez ◽  
Marycarmen Bustos-Gamiño ◽  
Isela Esther Juárez-Rojop ◽  
...  
Keyword(s):  
Substance Use ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Logistic Models ◽  
Genome Wide Association ◽  
Risk Scores ◽  
Multinomial Models ◽  
Gamma Receptor ◽  
Genome Wide ◽  
A Genome

AbstractThe combination of substance use and psychiatric disorders is one of the most common comorbidities. The objective of this study was to perform a genome-wide association study of this comorbidity (Com), substance use alone (Subs), and psychiatric symptomatology alone (Psych) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (p < 5.00e−05). The SNPs associated with each trait were independent, and the individuals with high PRSs had a higher prevalence of tobacco and alcohol use. In the multinomial models all of the PRSs (Subs-PRS, Com-PRS, and Psych-PRS) were associated with all of the traits. Brain meQTL of the Subs-associated SNPs had an effect on the genes enriched in insulin signaling pathway, and that of the Psych-associated SNPs had an effect on the Fc gamma receptor phagocytosis pathway.

scholarly journals Previous Humoral Immunity to the Endemic Seasonal Alphacoronaviruses NL63 and 229E Is Associated with Worse Clinical Outcome in COVID-19 and Suggests Original Antigenic Sin

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 298
Author(s):  
Daniele Focosi ◽  
Angelo Genoni ◽  
Ersilia Lucenteforte ◽  
Silvia Tillati ◽  
Antonio Tamborini ◽  
...  
Keyword(s):  
Humoral Immunity ◽  
Cross Reactivity ◽  
Clinical Severity ◽  
World Health ◽  
Laboratory Findings ◽  
Cellular And Humoral Immunity ◽  
Rate Ratios ◽  
Original Antigenic Sin

Antibody-dependent enhancement (ADE) of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection has been hypothesized. However, to date, there has been no in vitro or in vivo evidence supporting this. Cross-reactivity exists between SARS CoV-2 and other Coronaviridae for both cellular and humoral immunity. We show here that IgG against nucleocapsid protein of alphacoronavirus NL63 and 229E correlate with the World Health Organization’s (WHO) clinical severity score ≥ 5 (incidence rate ratios was 1.87 and 1.80, respectively, and 1.94 for the combination). These laboratory findings suggest possible ADE of SARS CoV-2 infection by previous alphacoronavirus immunity.

scholarly journals Genome-Wide Binding Analyses of HOXB1 Revealed a Novel DNA Binding Motif Associated with Gene Repression

2021 ◽  
Vol 9 (1) ◽  
pp. 6
Author(s):  
Narendra Pratap Singh ◽  
Bony De Kumar ◽  
Ariel Paulson ◽  
Mark E. Parrish ◽  
Carrie Scott ◽  
...  
Keyword(s):  
Dna Binding ◽  
Target Genes ◽  
Embryonic Stem ◽  
Binding Motif ◽  
Binding Assays ◽  
Histone Marks ◽  
Genome Wide ◽  
Hox Cofactors

Knowledge of the diverse DNA binding specificities of transcription factors is important for understanding their specific regulatory functions in animal development and evolution. We have examined the genome-wide binding properties of the mouse HOXB1 protein in embryonic stem cells differentiated into neural fates. Unexpectedly, only a small number of HOXB1 bound regions (7%) correlate with binding of the known HOX cofactors PBX and MEIS. In contrast, 22% of the HOXB1 binding peaks display co-occupancy with the transcriptional repressor REST. Analyses revealed that co-binding of HOXB1 with PBX correlates with active histone marks and high levels of expression, while co-occupancy with REST correlates with repressive histone marks and repression of the target genes. Analysis of HOXB1 bound regions uncovered enrichment of a novel 15 base pair HOXB1 binding motif HB1RE (HOXB1 response element). In vitro template binding assays showed that HOXB1, PBX1, and MEIS can bind to this motif. In vivo, this motif is sufficient for direct expression of a reporter gene and over-expression of HOXB1 selectively represses this activity. Our analyses suggest that HOXB1 has evolved an association with REST in gene regulation and the novel HB1RE motif contributes to HOXB1 function in part through a repressive role in gene expression.

scholarly journals A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Juliette Coignard ◽  
◽  
Michael Lush ◽  
Jonathan Beesley ◽  
Tracy A. O’Mara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Genome Wide Association Study ◽  
Brca2 Mutation ◽  
Risk Scores ◽  
Genetic Modifiers ◽  
Mutation Carriers ◽  
Genotype Frequencies ◽  
Genome Wide ◽  
Brca1 Brca2

AbstractBreast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.

Sign in / Sign up

Export Citation Format

Share Document