12 research outputs found
In vivo NMR as a tool for probing molecular structure and dynamics in intact Chlamydomonas reinhardtii cells
GO biological process enrichment for the 882 deletion strains below the threshold of detection by microarray in the BCprot relative to the gene universe of strains present in at least one deletion collectio
Post-COVID symptoms are associated with endotypes reflecting poor inflammatory and hemostatic modulation
IntroductionPersistent symptoms after COVID-19 infection (âlong COVIDâ) negatively affects almost half of COVID-19 survivors. Despite its prevalence, its pathophysiology is poorly understood, with multiple host systems likely affected. Here, we followed patients from hospital to discharge and used a systems-biology approach to identify mechanisms of long COVID.MethodsRNA-seq was performed on whole blood collected early in hospital and 4-12 weeks after discharge from 24 adult COVID-19 patients (10 reported post-COVID symptoms after discharge). Differential gene expression analysis, pathway enrichment, and machine learning methods were used to identify underlying mechanisms for post-COVID symptom development.ResultsCompared to patients with post-COVID symptoms, patients without post-COVID symptoms had larger temporal gene expression changes associated with downregulation of inflammatory and coagulation genes over time. Patients could also be separated into three patient endotypes with differing mechanistic trajectories, which was validated in another published patient cohort. The âResolvedâ endotype (lowest rate of post-COVID symptoms) had robust inflammatory and hemostatic responses in hospital that resolved after discharge. Conversely, the inflammatory/hemostatic responses of âSuppressiveâ and âUnresolvedâ endotypes (higher rates of patients with post-COVID symptoms) were persistently dampened and activated, respectively. These endotypes were accurately defined by specific blood gene expression signatures (6-7 genes) for potential clinical stratification.DiscussionThis study allowed analysis of long COVID whole blood transcriptomics trajectories while accounting for the issue of patient heterogeneity. Two of the three identified and externally validated endotypes (âUnresolvedâ and âSuppressiveâ) were associated with higher rates of post-COVID symptoms and either persistently activated or suppressed inflammation and coagulation processes. Gene biomarkers in blood could potentially be used clinically to stratify patients into different endotypes, paving the way for personalized long COVID treatment
The TESS-Keck Survey II: An Ultra-Short Period Rocky Planet and its Siblings Transiting the Galactic Thick-Disk Star TOI-561
We report the discovery of TOI-561, a multi-planet system in the galactic
thick disk that contains a rocky, ultra-short period planet (USP). This bright
() star hosts three small transiting planets identified in photometry
from the NASA TESS mission: TOI-561 b (TOI-561.02, P=0.44 days, ), c (TOI-561.01, P=10.8 days,
), and d (TOI-561.03, P=16.3 days,
). The star is chemically ([Fe/H],
[/H]) and kinematically consistent with the galactic
thick disk population, making TOI-561 one of the oldest (Gyr) and
most metal-poor planetary systems discovered yet. We dynamically confirm
planets b and c with radial velocities from the W. M. Keck Observatory High
Resolution Echelle Spectrometer. Planet b has a mass and density of
and gcm, consistent with
a rocky composition. Its lower-than-average density is consistent with an
iron-poor composition, although an Earth-like iron-to-silicates ratio is not
ruled out. Planet c is and gcm,
consistent with an interior rocky core overlaid with a low-mass volatile
envelope. Several attributes of the photometry for planet d (which we did not
detect dynamically) complicate the analysis, but we vet the planet with
high-contrast imaging, ground-based photometric follow-up and radial
velocities. TOI-561 b is the first rocky world around a galactic thick-disk
star confirmed with radial velocities and one of the best rocky planets for
thermal emission studies.Comment: Accepted at The Astronomical Journal; 25 pages, 10 figure
Genotype-specific phenotypic behaviour of auxotrophic and prototrophic yeast gene deletion collections
The Yeast Knockout (YKO) collection has provided functional annotations from thousands of genome-wide screens. As an unintended consequence however, ~90% of gene annotations are derived from a single genotype. The nutritional auxotrophies in the YKO are of particular concern as they have phenotypic consequences. To address this issue, repaired âprototrophicâ versions of the YKO collection have been constructed; the first by introducing an ARS-CEN plasmid carrying wildtype copies of the auxotrophic markers (Plasmid-Borne, PBprot), and the second by backcrossing (Backcrossed, BCprot) to a strain wildtype for the auxotrophies. To systematically assess the impact of the auxotrophies, genome-wide fitness profiles of the prototrophic and auxotrophic YKO collections were compared across a diverse set of drug and environmental conditions. Comparative fitness profiling for the prototrophic collections revealed genotypic and strain-construction-specific phenotypes. The PBprot collection exhibited fitness defects associated with plasmid maintenance, while the BCprot collectionâs fitness profiles were compromised due to strain loss resulting from nutrient selection steps during strain construction. The repaired prototrophic versions of the YKO collection did not restore wildtype behaviour and had additional experimental liabilities. Neither prototrophic collection compensated for gaps in gene annotation resulting from the auxotrophic YKO genetic background. To remove marker bias and expand the experimental scope of current deletion libraries, construction of a bona fide prototrophic collection from a wildtype strain will be required.Science, Faculty ofGraduat
Validation of reference gene stability for miRNA quantification by reverse transcription quantitative PCR in the peripheral blood of patients with COVID-19 critical illness.
The COVID-19 pandemic has created an urgency to study the host gene response that leads to variable clinical presentations of the disease, particularly the critical illness response. miRNAs have been implicated in the mechanism of host immune dysregulation and thus hold potential as biomarkers and/or therapeutic agents with clinical application. Hence, further analyses of their altered expression in COVID-19 is warranted. An important basis for this is identifying appropriate reference genes for high quality expression analysis studies. In the current report, NanoString technology was used to study the expression of 798 miRNAs in the peripheral blood of 24 critically ill patients, 12 had COVID-19 and 12 were COVID-19 negative. A list of potentially stable candidate reference genes was generated that included ten miRNAs. The top six were analyzed using reverse transcription quantitative polymerase chain reaction (RT-qPCR) in a total of 41 patients so as to apply standard computational algorithms for validating reference genes, namely geNorm, NormFinder, BestKeeper and RefFinder. There was general agreement among all four algorithms in the ranking of four stable miRNAs: miR-186-5p, miR-148b-3p, miR-194-5p and miR-448. A detailed analysis of their output rankings led to the conclusion that miR-186-5p and miR-148b-3p are appropriate reference genes for miRNA expression studies using PaxGene tubes in the peripheral blood of patients critically ill with COVID-19 disease
The Impact of Migration on the Gut Metagenome of South Asian Canadians
South Asian (SA) Canadian immigrants have a higher risk of developing certain immune-mediated inflammatory diseases compared to non-migrant SAs. We sought to investigate the effect of migration on the gut metagenome and to identify microbiological associations between migration and conditions that may influence the development of immune-mediated inflammatory diseases. Metagenomic analysis of 58 first-generation (GEN1) SA immigrants and 38 unrelated Canadian born children-of-immigrants (GEN2) determined that the time lived in Canada was associated with continued changes in gut microbial communities. Migration of GEN1 to Canada early in life results in a gut community with similarities to GEN2 SA Canadians and non-SA North Americans. Conversely, GEN1 immigrants who arrived recently to Canada exhibited pronounced differences from GEN2, while displaying microbial similarities to a non-migrating SA cohort. Multivariate analysis identified that community composition was primarily influenced by high abundance taxa. Prevotella copri dominated in GEN1 and non-migrant SAs. Clostridia and functionally related Bacteroidia spp. replaced P. copri dominance over generations in Canada. Mutually exclusive Dialister species occurred at differing relative abundances over time and generations in Canada. This shift in species composition is accompanied by a change in genes associated with carbohydrate utilization and short-chain fatty acid production. Total energy derived from carbohydrates compared to protein consumption was significantly higher for GEN1 recent immigrants, which may influence the functional requirements of the gut community. This study demonstrates the associations between migration and the gut microbiome, which may be further associated with the altered risk of immune-mediated inflammatory diseases observed for SA Canadians
Average log2ratios for all conditions tested by Bar-seq from Comparative functional genomic screens of three yeast deletion collections reveal unexpected effects of genotype in response to diverse stress
For Bar-Seq data generated for each deletion collection and drug or environmental experimental condition relative to its control, average log2ratios for condition replicates are given
Supplemental figure legends, additional files and references from Comparative functional genomic screens of three yeast deletion collections reveal unexpected effects of genotype in response to diverse stress
Supplemental figure legends, additional files and reference
GO enrichment of deletion strains present in the HLU signature from Comparative functional genomic screens of three yeast deletion collections reveal unexpected effects of genotype in response to diverse stress
GO biological process enrichment for the 73 deletion strains present in the HLU deletion signature