scholarly journals ViralRecall—A Flexible Command-Line Tool for the Detection of Giant Virus Signatures in ‘Omic Data

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 150 ◽  
Author(s):  
Frank O. Aylward ◽  
Mohammad Moniruzzaman

Giant viruses are widespread in the biosphere and play important roles in biogeochemical cycling and host genome evolution. Also known as nucleo-cytoplasmic large DNA viruses (NCLDVs), these eukaryotic viruses harbor the largest and most complex viral genomes known. Studies have shown that NCLDVs are frequently abundant in metagenomic datasets, and that sequences derived from these viruses can also be found endogenized in diverse eukaryotic genomes. The accurate detection of sequences derived from NCLDVs is therefore of great importance, but this task is challenging owing to both the high level of sequence divergence between NCLDV families and the extraordinarily high diversity of genes encoded in their genomes, including some encoding for metabolic or translation-related functions that are typically found only in cellular lineages. Here, we present ViralRecall, a bioinformatic tool for the identification of NCLDV signatures in ‘omic data. This tool leverages a library of giant virus orthologous groups (GVOGs) to identify sequences that bear signatures of NCLDVs. We demonstrate that this tool can effectively identify NCLDV sequences with high sensitivity and specificity. Moreover, we show that it can be useful both for removing contaminating sequences in metagenome-assembled viral genomes as well as the identification of eukaryotic genomic loci that derived from NCLDV. ViralRecall is written in Python 3.5 and is freely available on GitHub: https://github.com/faylward/viralrecall.

2020 ◽  
Author(s):  
Frank O Aylward ◽  
Mohammad Moniruzzaman

Giant viruses are widespread in the biosphere and play important roles in biogeochemical cycling and host genome evolution. Also known as Nucleo-Cytoplasmic Large DNA Viruses (NCLDV), these eukaryotic viruses harbor the largest and most complex viral genomes known. Recent studies have shown that NCLDV are frequently abundant in metagenomic datasets, and that sequences derived from these viruses can also be found endogenized in diverse eukaryotic genomes. The accurate detection of sequences derived from NCLDV is therefore of great importance, but this task is challenging owing to both the high level of sequence divergence between NCLDV families and the extraordinarily high diversity of genes encoded in their genomes, including some encoding for metabolic or translation-related functions that are typically found only in cellular lineages. Here we present ViralRecall, a bioinformatic tool for the identification of NCLDV signatures in omic data. This tool leverages a library of Giant Virus Orthologous Groups (GVOGs) to identify sequences that bear signatures of NCLDV. We demonstrate that this tool can effectively identify NCLDV sequences with high sensitivity and specificity. Moreover, we show that it can be useful both for removing contaminating sequences in metagenome-assembled viral genomes as well as the identification of eukaryotic genomic loci that derived from NCLDV. ViralRecall is written in Python 3.5 and is freely available on GitHub: https://github.com/faylward/viralrecall.


Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 779
Author(s):  
Man Teng ◽  
Yongxiu Yao ◽  
Venugopal Nair ◽  
Jun Luo

In recent years, the CRISPR/Cas9-based gene-editing techniques have been well developed and applied widely in several aspects of research in the biological sciences, in many species, including humans, animals, plants, and even in viruses. Modification of the viral genome is crucial for revealing gene function, virus pathogenesis, gene therapy, genetic engineering, and vaccine development. Herein, we have provided a brief review of the different technologies for the modification of the viral genomes. Particularly, we have focused on the recently developed CRISPR/Cas9-based gene-editing system, detailing its origin, functional principles, and touching on its latest achievements in virology research and applications in vaccine development, especially in large DNA viruses of humans and animals. Future prospects of CRISPR/Cas9-based gene-editing technology in virology research, including the potential shortcomings, are also discussed.


2021 ◽  
pp. 143-165
Author(s):  
V.G. Maralov ◽  
◽  
V.A. Sitarov ◽  

The relevance of the problem is due to the importance of identifying factors that determine the propensity of students to coercion or nonviolence, creating psychological and pedagogical conditions for the formation of the socionomic sphere of nonviolent competencies for future specialists at universities. The theoretical basis of the study was the position of nonviolence as a daily practice of interaction, by which we understand the ability of a person to choose from a number of possible alternatives that carry the least charge of coercion. The aim of the work was to study the influence of irrational beliefs and sensitivity to a person (interest, empathy, understanding and assistance) on the students’ tendency to coercion, manipulation, non-violence and non-interference in the processes of interaction with people. The hypothesis was tested that the tendency of students to coercion, manipulation, and noninterference will be due to expressed irrational beliefs and low level of sensitivity to a person and the tendency to non-violence will be explained by the absence of irrational beliefs and a high level of sensitivity to a person. The study involved 125 students of pedagogical and psychological faculties of the Moscow Humanitarian and Cherepovets State universities. The authors used questionnaires to identify the positions of interaction among students and sensitivity to a person, as well as a list of irrational beliefs proposed by A. Beck and A. Freeman. It is established that the tendency to both coercion and manipulation are determined by the beliefs of anti-social type and low sensitivity to the person. The tendency to manipulate the narcissistic beliefs, high interest in people and understanding them, at the same time the tendency to non-violence and non-interference are determined by beliefs of avoidant and dependent types with a low level of understanding people. And a tendency to non-interference is determined by beliefs of dependent type with unexpressed orientation on helping. The tendency to nonviolence is determined by the high sensitivity to a person and the absence of irrational beliefs of antisocial, passive-aggressive and narcissistic types. As a result, the conclusion is made about the need to form purposefully the ability to nonviolent interaction among students, which should include the work on awareness and overcoming irrational beliefs and the development of sensitivity to a person. The obtained results can be used in practical work with students on the formation of their nonviolent competencies.


2021 ◽  
Author(s):  
Ian M Rambo ◽  
Valerie De Anda ◽  
Marguerite V Langwig ◽  
Brett J Baker

Asgard archaea are newly described microbes that are related to eukaryotes. Asgards are diverse and globally distributed, however, their viruses have not been described. Here we characterize seven viral genomes that infected Lokiarchaeota, Helarchaeota, and Thorarchaeota in deep-sea hydrothermal sediments. These viruses code for structural proteins similar to those in Caudovirales, as well as proteins distinct from those described in archaeal viruses. They also have genes common in eukaryotic nucleocytoplasmic large DNA viruses (NCLDVs), and are predicted to be capable of semi-autonomous genome replication, repair, epigenetic modifications, and transcriptional regulation. Moreover, Helarchaeota viruses may hijack host ubiquitin systems similar to eukaryotic viruses. This first glimpse of Asgard viruses reveals they have features of both prokaryotic and eukaryotic viruses, and provides insights into their roles in the ecology and evolution of these globally distributed microbes.


2020 ◽  
Vol 66 (11) ◽  
pp. 1434-1443
Author(s):  
Daoxia Guo ◽  
Zhengbao Zhu ◽  
Chongke Zhong ◽  
Aili Wang ◽  
Xuewei Xie ◽  
...  

Abstract Background Conventional prognostic risk factors can only partly explain the adverse clinical outcomes after ischemic stroke. We aimed to establish a set of prognostic metrics and evaluate its public health significance on the burden of adverse clinical outcomes of ischemic stroke. Methods All patients were from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). We established prognostic metrics of ischemic stroke from 20 potential biomarkers in a propensity-score-matched extreme case sample (n = 146). Pathway analysis was conducted using Ingenuity Pathway Analysis. In the whole CATIS population (n = 3575), we evaluated effectiveness of these prognostic metrics and estimated their population-attributable fractions (PAFs) related to the risk of clinical outcomes. The primary outcome was a composite outcome of death or major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Results Matrix metalloproteinase-9 (MMP-9), S100A8/A9, high-sensitivity C-reactive protein (hsCRP), and growth differentiation factor-15 (GDF-15) were selected as prognostic metrics for ischemic stroke. Pathway analysis showed significant enrichment in inflammation and atherosclerosis signaling. All 4 prognostic metrics were independently associated with poor prognosis of ischemic stroke. Compared with patients having 1 or 0 high-level prognostic metrics, those with 4 had higher risk of primary outcome (OR: 3.84, 95%CI: 2.67–5.51; PAF: 37.4%, 95%CI: 19.5%–52.9%). Conclusion The set of prognostic metrics, enriching in inflammation and atherosclerosis signaling, could effectively predict the prognosis at 3 months after ischemic stroke and would provide additional information for the burden of adverse clinical outcomes among patients with ischemic stroke.


2019 ◽  
Vol 87 (6) ◽  
Author(s):  
Paul G. Young ◽  
Jeremy M. Raynes ◽  
Jacelyn M. Loh ◽  
Thomas Proft ◽  
Edward N. Baker ◽  
...  

ABSTRACTGroup AStreptococcus(GAS) (Streptococcus pyogenes) is an important human pathogen associated with significant global morbidity and mortality for which there is no safe and efficacious vaccine. The T antigen, a protein that polymerizes to form the backbone of the GAS pilus structure, is a potential vaccine candidate. Previous surveys of theteegene, which encodes the T antigen, have identified 21 differentteetypes and subtypes such that any T antigen-based vaccine must be multivalent and carefully designed to provide broad strain coverage. In this study, the crystal structures of three two-domain T antigens (T3.2, T13, and T18.1) were determined and found to have remarkable structural similarity to the previously reported T1 antigen, despite moderate overall sequence similarity. This has enabled reliable modeling of all major two-domain T antigens to reveal that T antigen sequence variation is distributed along the full length of the protein and shields a highly conserved core. Immunoassays performed with sera from immunized animals and commercial T-typing sera identified a significant cross-reactive antibody response between T18.1, T18.2, T3.2, and T13. The existence of shared epitopes between T antigens, combined with the remarkably conserved structure and high level of surface sequence divergence, has important implications for the design of multivalent T antigen-based vaccines.


2020 ◽  
Vol 36 (10) ◽  
pp. 3263-3265 ◽  
Author(s):  
Lucas Czech ◽  
Pierre Barbera ◽  
Alexandros Stamatakis

Abstract Summary We present genesis, a library for working with phylogenetic data, and gappa, an accompanying command-line tool for conducting typical analyses on such data. The tools target phylogenetic trees and phylogenetic placements, sequences, taxonomies and other relevant data types, offer high-level simplicity as well as low-level customizability, and are computationally efficient, well-tested and field-proven. Availability and implementation Both genesis and gappa are written in modern C++11, and are freely available under GPLv3 at http://github.com/lczech/genesis and http://github.com/lczech/gappa. Supplementary information Supplementary data are available at Bioinformatics online.


2012 ◽  
Vol 108 (10) ◽  
pp. 2641-2652 ◽  
Author(s):  
K. Heimonen ◽  
E.-V. Immonen ◽  
R. V. Frolov ◽  
I. Salmela ◽  
M. Juusola ◽  
...  

In dim light, scarcity of photons typically leads to poor vision. Nonetheless, many animals show visually guided behavior with dim environments. We investigated the signaling properties of photoreceptors of the dark active cockroach ( Periplaneta americana) using intracellular and whole-cell patch-clamp recordings to determine whether they show selective functional adaptations to dark. Expectedly, dark-adapted photoreceptors generated large and slow responses to single photons. However, when light adapted, responses of both phototransduction and the nontransductive membrane to white noise (WN)-modulated stimuli remained slow with corner frequencies ∼20 Hz. This promotes temporal integration of light inputs and maintains high sensitivity of vision. Adaptive changes in dynamics were limited to dim conditions. Characteristically, both step and frequency responses stayed effectively unchanged for intensities >1,000 photons/s/photoreceptor. A signal-to-noise ratio (SNR) of the light responses was transiently higher at frequencies <5 Hz for ∼5 s after light onset but deteriorated to a lower value upon longer stimulation. Naturalistic light stimuli, as opposed to WN, evoked markedly larger responses with higher SNRs at low frequencies. This allowed realistic estimates of information transfer rates, which saturated at ∼100 bits/s at low-light intensities. We found, therefore, selective adaptations beneficial for vision in dim environments in cockroach photoreceptors: large amplitude of single-photon responses, constant high level of temporal integration of light inputs, saturation of response properties at low intensities, and only transiently efficient encoding of light contrasts. The results also suggest that the sources of the large functional variability among different photoreceptors reside mostly in phototransduction processes and not in the properties of the nontransductive membrane.


Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 691 ◽  
Author(s):  
Alice MacQueen ◽  
Dacheng Tian ◽  
Wenhan Chang ◽  
Eric Holub ◽  
Martin Kreitman ◽  
...  

Plant nucleotide-binding domain and leucine-rich repeat containing (NLR) genes provide some of the most extreme examples of polymorphism in eukaryotic genomes, rivalling even the vertebrate major histocompatibility complex. Surprisingly, this is also true in Arabidopsis thaliana, a predominantly selfing species with low heterozygosity. Here, we investigate how gene duplication and intergenic exchange contribute to this extraordinary variation. RPP8 is a three-locus system that is configured chromosomally as either a direct-repeat tandem duplication or as a single copy locus, plus a locus 2 Mb distant. We sequenced 48 RPP8 alleles from 37 accessions of A. thaliana and 12 RPP8 alleles from Arabidopsis lyrata to investigate the patterns of interlocus shared variation. The tandem duplicates display fixed differences and share less variation with each other than either shares with the distant paralog. A high level of shared polymorphism among alleles at one of the tandem duplicates, the single-copy locus and the distal locus, must involve both classical crossing over and intergenic gene conversion. Despite these polymorphism-enhancing mechanisms, the observed nucleotide diversity could not be replicated under neutral forward-in-time simulations. Only by adding balancing selection to the simulations do they approach the level of polymorphism observed at RPP8. In this NLR gene triad, genetic architecture, gene function and selection all combine to generate diversity.


Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1160
Author(s):  
Amanda M. Hewes ◽  
Brett M. Sansbury ◽  
Eric B. Kmiec

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas gene editing systems have enabled molecular geneticists to manipulate prokaryotic and eukaryotic genomes with greater efficiency and precision. CRISPR/Cas provides adaptive immunity in bacterial cells by degrading invading viral genomes. By democratizing this activity into human cells, it is possible to knock out specific genes to disable their function and repair errors. The latter of these activities requires the participation of a single-stranded donor DNA template that provides the genetic information to execute correction in a process referred to as homology directed repair (HDR). Here, we utilized an established cell-free extract system to determine the influence that the donor DNA template length has on the diversity of products from CRISPR-directed gene editing. This model system enables us to view all outcomes of this reaction and reveals that donor template length can influence the efficiency of the reaction and the categories of error-prone products that accompany it. A careful measurement of the products revealed a category of error-prone events that contained the corrected template along with insertions and deletions (indels). Our data provides foundational information for those whose aim is to translate CRISPR/Cas from bench to bedside.


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