scholarly journals Large-scale population analysis of SARS-CoV-2 whole genome sequences reveals host-mediated viral evolution with emergence of mutations in the viral Spike protein associated with elevated mortality rates

2020 ◽  
Author(s):  
Carlos Farkas ◽  
Andy Mella ◽  
Jody J. Haigh
Keyword(s):  
Large Scale ◽  
Population Analysis ◽  
Viral Evolution ◽  
Population Level ◽  
Spike Protein ◽  
Host Immune System ◽  
Sequencing Data ◽  
Scale Population ◽  
Significant Public Health ◽  
Viral Sequences

AbstractBackgroundWe aimed to further characterize and analyze in depth intra-host variation and founder variants of SARS-CoV-2 worldwide up until August 2020, by examining in excess of 94,000 SARS-CoV-2 viral sequences in order to understand SARS-CoV-2 variant evolution, how these variants arose and identify any increased mortality associated with these variants.Methods and FindingsWe combined worldwide sequencing data from GISAID and Sequence Read Archive (SRA) repositories and discovered SARS-CoV-2 hypermutation occurring in less than 2% of COVID19 patients, likely caused by host mechanisms involved APOBEC3G complexes and intra-host microdiversity. Most of this intra-host variation occurring in SARS-CoV-2 are predicted to change viral proteins with defined variant signatures, demonstrating that SARS-CoV-2 can be actively shaped by the host immune system to varying degrees. At the global population level, several SARS-CoV-2 proteins such as Nsp2, 3C-like proteinase, ORF3a and ORF8 are under active evolution, as evidenced by their increased πN/πS ratios per geographical region. Importantly, two emergent variants: V1176F in co-occurrence with D614G mutation in the viral Spike protein, and S477N, located in the Receptor Binding Domain (RBD) of the Spike protein, are associated with high fatality rates and are increasingly spreading throughout the world. The S477N variant arose quickly in Australia and experimental data support that this variant increases Spike protein fitness and its binding to ACE2.ConclusionsSARS-CoV-2 is evolving non-randomly, and human hosts shape emergent variants with positive fitness that can easily spread into the population. We propose that V1776F and S477N variants occurring in the Spike protein are two novel mutations occurring in SARS-CoV-2 and may pose significant public health concerns in the future.

scholarly journals Population analysis of retrotransposons in giraffe genomes supports RTE decline and widespread LINE1 activity in Giraffidae

Mobile DNA ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Malte Petersen ◽  
Sven Winter ◽  
Raphael Coimbra ◽  
Menno J. de Jong ◽  
Vladimir V. Kapitonov ◽  
...  
Keyword(s):  
Large Scale ◽  
Population Analysis ◽  
Model Organism ◽  
Population Level ◽  
Data Sets ◽  
Ltr Retrotransposons ◽  
Scale Population ◽  
Mammalian Genomes ◽  
Genome Assemblies ◽  
First Time

Abstract Background The majority of structural variation in genomes is caused by insertions of transposable elements (TEs). In mammalian genomes, the main TE fraction is made up of autonomous and non-autonomous non-LTR retrotransposons commonly known as LINEs and SINEs (Long and Short Interspersed Nuclear Elements). Here we present one of the first population-level analysis of TE insertions in a non-model organism, the giraffe. Giraffes are ruminant artiodactyls, one of the few mammalian groups with genomes that are colonized by putatively active LINEs of two different clades of non-LTR retrotransposons, namely the LINE1 and RTE/BovB LINEs as well as their associated SINEs. We analyzed TE insertions of both types, and their associated SINEs in three giraffe genome assemblies, as well as across a population level sampling of 48 individuals covering all extant giraffe species. Results The comparative genome screen identified 139,525 recent LINE1 and RTE insertions in the sampled giraffe population. The analysis revealed a drastically reduced RTE activity in giraffes, whereas LINE1 is still actively propagating in the genomes of extant (sub)-species. In concert with the extremely low activity of the giraffe RTE, we also found that RTE-dependent SINEs, namely Bov-tA and Bov-A2, have been virtually immobile in the last 2 million years. Despite the high current activity of the giraffe LINE1, we did not find evidence for the presence of currently active LINE1-dependent SINEs. TE insertion heterozygosity rates differ among the different (sub)-species, likely due to divergent population histories. Conclusions The horizontally transferred RTE/BovB and its derived SINEs appear to be close to inactivation and subsequent extinction in the genomes of extant giraffe species. This is the first time that the decline of a TE family has been meticulously analyzed from a population genetics perspective. Our study shows how detailed information about past and present TE activity can be obtained by analyzing large-scale population-level genomic data sets.

scholarly journals The single-cell eQTLGen consortium

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
MGP van der Wijst ◽  
DH de Vries ◽  
HE Groot ◽  
G Trynka ◽  
CC Hon ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Large Scale ◽  
Cell Types ◽  
Eqtl Analysis ◽  
Sequencing Data ◽  
Scale Population ◽  
Trait Locus ◽  
Different Cell Types ◽  
Affect Gene Expression

In recent years, functional genomics approaches combining genetic information with bulk RNA-sequencing data have identified the downstream expression effects of disease-associated genetic risk factors through so-called expression quantitative trait locus (eQTL) analysis. Single-cell RNA-sequencing creates enormous opportunities for mapping eQTLs across different cell types and in dynamic processes, many of which are obscured when using bulk methods. Rapid increase in throughput and reduction in cost per cell now allow this technology to be applied to large-scale population genetics studies. To fully leverage these emerging data resources, we have founded the single-cell eQTLGen consortium (sc-eQTLGen), aimed at pinpointing the cellular contexts in which disease-causing genetic variants affect gene expression. Here, we outline the goals, approach and potential utility of the sc-eQTLGen consortium. We also provide a set of study design considerations for future single-cell eQTL studies.

scholarly journals Reliability of the NIH toolbox cognitive battery in children and adolescents: a 3-year longitudinal examination

2020 ◽  
pp. 1-10
Author(s):  
Brittany K. Taylor ◽  
Michaela R. Frenzel ◽  
Jacob A. Eastman ◽  
Alex I. Wiesman ◽  
Yu-Ping Wang ◽  
...  
Keyword(s):  
Large Scale ◽  
Intraclass Correlation ◽  
Temporal Stability ◽  
Correlation Coefficients ◽  
Population Level ◽  
Clinical Applications ◽  
Intraclass Correlation Coefficients ◽  
Scale Population ◽  
Longitudinal Examination

Abstract Background The Cognitive Battery of the National Institutes of Health Toolbox (NIH-TB) is a collection of assessments that have been adapted and normed for administration across the lifespan and is increasingly used in large-scale population-level research. However, despite increasing adoption in longitudinal investigations of neurocognitive development, and growing recommendations that the Toolbox be used in clinical applications, little is known about the long-term temporal stability of the NIH-TB, particularly in youth. Methods The present study examined the long-term temporal reliability of the NIH-TB in a large cohort of youth (9–15 years-old) recruited across two data collection sites. Participants were invited to complete testing annually for 3 years. Results Reliability was generally low-to-moderate, with intraclass correlation coefficients ranging between 0.31 and 0.76 for the full sample. There were multiple significant differences between sites, with one site generally exhibiting stronger temporal stability than the other. Conclusions Reliability of the NIH-TB Cognitive Battery was lower than expected given early work examining shorter test-retest intervals. Moreover, there were very few instances of tests meeting stability requirements for use in research; none of the tests exhibited adequate reliability for use in clinical applications. Reliability is paramount to establishing the validity of the tool, thus the constructs assessed by the NIH-TB may vary over time in youth. We recommend further refinement of the NIH-TB Cognitive Battery and its norming procedures for children before further adoption as a neuropsychological assessment. We also urge researchers who have already employed the NIH-TB in their studies to interpret their results with caution.

Learnings from Large-Scale, Population-Level Implementation of Parenting Support

2017 ◽  
pp. 419-421
Author(s):  
Trevor G. Mazzucchelli
Keyword(s):  
Large Scale ◽  
Best Practice ◽  
Systems Approach ◽  
Positive Impact ◽  
Population Level ◽  
The United States ◽  
Parenting Support ◽  
Scale Population ◽  
The Many ◽  
Learning Principles

There is considerable evidence supporting the efficacy and effectiveness of parenting interventions based on social learning principles for a range of social, emotional, and health problems, involving different types of families and through a variety of delivery systems. The challenge now is “going to scale” in order to have a positive impact at a population level. This chapter introduces three best practice exemplars that have taken place in the United States, Ireland, and Australia, where a full multilevel systems approach to parenting support has been applied and evaluated. These applications provide important lessons regarding the barriers and facilitators that can influence an initiative’s success and degree of impact. By illustrating how these approaches have involved different populations, behavioral targets, evaluation designs, and means of assessing outcome, they also hint at the many possibilities that are available in future dissemination efforts.

scholarly journals Screening for multi-drug-resistant Gram-negative bacteria: what is effective and justifiable?

2020 ◽  
Vol 38 (S1) ◽  
pp. 72-90 ◽  
Author(s):  
Niels Nijsingh ◽  
Christian Munthe ◽  
Anna Lindblom ◽  
Christina Åhrén
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Large Scale ◽  
Population Level ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
Screening Programs ◽  
Scale Population ◽  
Current Screening

AbstractEffectiveness is a key criterion in assessing the justification of antibiotic resistance interventions. Depending on an intervention’s effectiveness, burdens and costs will be more or less justified, which is especially important for large scale population-level interventions with high running costs and pronounced risks to individuals in terms of wellbeing, integrity and autonomy. In this paper, we assess the case of routine hospital screening for multi-drug-resistant Gram-negative bacteria (MDRGN) from this perspective. Utilizing a comparison to screening programs for Methicillin-Resistant Staphylococcus aureus (MRSA) we argue that current screening programmes for MDRGN in low endemic settings should be reconsidered, as its effectiveness is in doubt, while general downsides to screening programs remain. To accomplish justifiable antibiotic stewardship, MDRGN screening should not be viewed as a separate measure, but rather as part of a comprehensive approach. The program should be redesigned to focus on those at risk of developing symptomatic infections with MDRGN rather than merely detecting those colonised.

scholarly journals Reveel: large-scale population genotyping using low-coverage sequencing data

2015 ◽  
Vol 32 (11) ◽  
pp. 1686-1696 ◽  
Author(s):  
Lin Huang ◽  
Bo Wang ◽  
Ruitang Chen ◽  
Sivan Bercovici ◽  
Serafim Batzoglou
Keyword(s):  
Large Scale ◽  
Sequencing Data ◽  
Scale Population ◽  
Low Coverage

scholarly journals Predicting functional effect of missense variants using graph attention neural networks

2021 ◽  
Author(s):  
Haicang Zhang ◽  
Michelle S. Xu ◽  
Wendy K. Chung ◽  
Yufeng Shen
Keyword(s):  
Neural Networks ◽  
Large Scale ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Loss Of Function ◽  
Sequencing Data ◽  
Missense Variants ◽  
Scale Population ◽  
Scan Data ◽  
Main Component

AbstractAccurate prediction of damaging missense variants is critically important for interpretating genome sequence. While many methods have been developed, their performance has been limited. Recent progress in machine learning and availability of large-scale population genomic sequencing data provide new opportunities to significantly improve computational predictions. Here we describe gMVP, a new method based on graph attention neural networks. Its main component is a graph with nodes capturing predictive features of amino acids and edges weighted by coevolution strength, which enables effective pooling of information from local protein sequence context and functionally correlated distal positions. Evaluated by deep mutational scan data, gMVP outperforms published methods in identifying damaging variants in TP53, PTEN, BRCA1, and MSH2. Additionally, it achieves the best separation of de novo missense variants in neurodevelopmental disorder cases from the ones in controls. Finally, the model supports transfer learning to optimize gain- and loss-of-function predictions in sodium and calcium channels. In summary, we demonstrate that gMVP can improve interpretation of missense variants in clinical testing and genetic studies.

scholarly journals The scope of culture in chimpanzees, humans and ancestral apes

2011 ◽  
Vol 366 (1567) ◽  
pp. 997-1007 ◽  
Author(s):  
Andrew Whiten
Keyword(s):  
Comparative Analysis ◽  
Social Learning ◽  
Large Scale ◽  
Common Ancestor ◽  
Population Level ◽  
Last Common Ancestor ◽  
Learning Mechanisms ◽  
Scale Population

More studies have focused on aspects of chimpanzee behaviour and cognition relevant to the evolution of culture than on any other species except our own. Accordingly, analysis of the features shared by chimpanzees and humans is here used to infer the scope of cultural phenomena in our last common ancestor, at the same time clarifying the nature of the special characteristics that advanced further in the hominin line. To do this, culture is broken down into three major aspects: the large scale, population-level patterning of traditions; social learning mechanisms; and the behavioural and cognitive contents of culture. Each of these is further dissected into subcomponents. Shared features, as well as differences, are identified in as many as a dozen of these, offering a case study for the comparative analysis of culture across animal taxa and a deeper understanding of the roots of our own cultural capacities.

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