scholarly journals Genomic search for COVID-19 severity clues

2020 ◽  
Vol 38 (6) ◽  
pp. 657-657
Keyword(s):  
Genomic Search

scholarly journals Potent CRISPR-Cas9 inhibitors fromStaphylococcusgenomes

2020 ◽  
Vol 117 (12) ◽  
pp. 6531-6539 ◽  
Author(s):  
Kyle E. Watters ◽  
Haridha Shivram ◽  
Christof Fellmann ◽  
Rachel J. Lew ◽  
Blake McMahon ◽  
...  
Keyword(s):  
Genome Editing ◽  
Dna Cleavage ◽  
Repeat Sequence ◽  
Inverted Repeat Sequence ◽  
Terminal Sequence ◽  
Dna Targeting ◽  
Small Proteins ◽  
Genomic Search ◽  
Guilt By Association ◽  
Bacterial Genes

Anti-CRISPRs (Acrs) are small proteins that inhibit the RNA-guided DNA targeting activity of CRISPR-Cas enzymes. Encoded by bacteriophage and phage-derived bacterial genes, Acrs prevent CRISPR-mediated inhibition of phage infection and can also block CRISPR-Cas-mediated genome editing in eukaryotic cells. To identify Acrs capable of inhibitingStaphylococcus aureusCas9 (SauCas9), an alternative to the most commonly used genome editing proteinStreptococcus pyogenesCas9 (SpyCas9), we used both self-targeting CRISPR screening and guilt-by-association genomic search strategies. Here we describe three potent inhibitors of SauCas9 that we name AcrIIA13, AcrIIA14, and AcrIIA15. These inhibitors share a conserved N-terminal sequence that is dispensable for DNA cleavage inhibition and have divergent C termini that are required in each case for inhibition of SauCas9-catalyzed DNA cleavage. In human cells, we observe robust inhibition of SauCas9-induced genome editing by AcrIIA13 and moderate inhibition by AcrIIA14 and AcrIIA15. We also find that the conserved N-terminal domain of AcrIIA13–AcrIIA15 binds to an inverted repeat sequence in the promoter of these Acr genes, consistent with its predicted helix-turn-helix DNA binding structure. These data demonstrate an effective strategy for Acr discovery and establish AcrIIA13–AcrIIA15 as unique bifunctional inhibitors of SauCas9.

Implications of a genomic search for autophagy-related genes in trypanosomatids

2005 ◽  
Vol 33 (5) ◽  
pp. 972-974 ◽  
Author(s):  
D.J. Rigden ◽  
M. Herman ◽  
S. Gillies ◽  
P.A.M. Michels
Keyword(s):  
Transport System ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Genomic Analysis ◽  
Genomic Search ◽  
Similarities And Differences ◽  
Related Proteins ◽  
Cellular Components ◽  
Putative Orthologues

Autophagy is the process by which cellular components are directed to and degraded in the vacuole or lysosome and has been studied largely in yeasts. We present here an in silico genomic analysis of trypanosomatid autophagy aimed at highlighting similarities and differences with autophagy in other organisms. Less than half of the yeast autophagy-related proteins examined have certain putative orthologues in trypanosomatids. A cytosol-to-vacuole transport system is clearly lacking in these organisms. Other absences are even more unexpected and have implications for our understanding of the molecular mechanisms of autophagy. The results are consistent with taxon-specific addition of components to a core autophagy machinery during evolution.

scholarly journals Identification of phenol- and p-cresol-producing intestinal bacteria by using media supplemented with tyrosine and its metabolites

2018 ◽  
Vol 94 (9) ◽  
Author(s):  
Yuki Saito ◽  
Tadashi Sato ◽  
Koji Nomoto ◽  
Hirokazu Tsuji
Keyword(s):  
Phylogenetic Analysis ◽  
Intestinal Bacteria ◽  
Acid Decarboxylase ◽  
Rrna Gene ◽  
Bacterial Strains ◽  
16S Rrna Gene Sequences ◽  
Metabolic Intermediates ◽  
Genomic Search ◽  
Tyrosine Phenol Lyase ◽  
The 16S Rrna Gene

AbstractTo identify intestinal bacteria that produce phenols (phenol and p-cresol), we screened 153 strains within 152 species in 44 genera by culture-based assay using broth media supplemented with 200 µM each of tyrosine and its predicted microbial metabolic intermediates (4-hydroxyphenylpyruvate, DL-4-hydroxyphenyllactate, 3-(p-hydroxyphenyl)propionate, 4-hydroxyphenylacetate and 4-hydroxybenzoate). Phenol-producing activity was found in 36 strains and p-cresol-producing activity in 55 strains. Fourteen strains had both types of activity. Phylogenetic analysis based on the 16S rRNA gene sequences of strains that produced 100 µM or more of phenols revealed that 16 phenol producers belonged to the Coriobacteriaceae, Enterobacteriaceae, Fusobacteriaceae and Clostridium clusters I and XIVa; four p-cresol-producing bacteria belonged to the Coriobacteriaceae and Clostridium clusters XI and XIVa; and one strain producing both belonged to the Coriobacteriaceae. A genomic search for protein homologs of enzymes involved in the metabolism of tyrosine to phenols in 10 phenol producers and four p-cresol producers, the draft genomes of which were available in public databases, predicted that phenol producers harbored tyrosine phenol-lyase or hydroxyarylic acid decarboxylase, or both, and p-cresol producers harbored p-hydroxyphenylacetate decarboxylase or tyrosine lyase, or both. These results provide important information about the bacterial strains that contribute to production of phenols in the intestine.

scholarly journals Phylogenomics Provides New Insights into Gains and Losses of Selenoproteins among Archaeplastida

2019 ◽  
Vol 20 (12) ◽  
pp. 3020 ◽  
Author(s):  
Hongping Liang ◽  
Tong Wei ◽  
Yan Xu ◽  
Linzhou Li ◽  
Sunil Kumar Sahu ◽  
...  
Keyword(s):  
Horizontal Gene Transfer ◽  
Evolutionary Dynamics ◽  
Viral Infections ◽  
Land Plants ◽  
Acidic Environment ◽  
Transcriptome Data ◽  
Photosynthetic Eukaryotes ◽  
Redox Active ◽  
Genomic Search ◽  
Gains And Losses

Selenoproteins that contain selenocysteine (Sec) are found in all kingdoms of life. Although they constitute a small proportion of the proteome, selenoproteins play essential roles in many organisms. In photosynthetic eukaryotes, selenoproteins have been found in algae but are missing in land plants (embryophytes). In this study, we explored the evolutionary dynamics of Sec incorporation by conveying a genomic search for the Sec machinery and selenoproteins across Archaeplastida. We identified a complete Sec machinery and variable sizes of selenoproteomes in the main algal lineages. However, the entire Sec machinery was missing in the Bangiophyceae-Florideophyceae clade (BV) of Rhodoplantae (red algae) and only partial machinery was found in three species of Archaeplastida, indicating parallel loss of Sec incorporation in different groups of algae. Further analysis of genome and transcriptome data suggests that all major lineages of streptophyte algae display a complete Sec machinery, although the number of selenoproteins is low in this group, especially in subaerial taxa. We conclude that selenoproteins tend to be lost in Archaeplastida upon adaptation to a subaerial or acidic environment. The high number of redox-active selenoproteins found in some bloom-forming marine microalgae may be related to defense against viral infections. Some of the selenoproteins in these organisms may have been gained by horizontal gene transfer from bacteria.

The Use of a Genetic Algorithm for Simultaneous Mapping of Multiple Interacting Quantitative Trait Loci

Genetics ◽  
2000 ◽  
Vol 155 (4) ◽  
pp. 2003-2010 ◽  
Author(s):  
Örjan Carlborg ◽  
Leif Andersson ◽  
Brian Kinghorn
Keyword(s):  
Genetic Algorithm ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Permutation Tests ◽  
Search Method ◽  
A Genome ◽  
Trait Loci ◽  
Genomic Search ◽  
Empirical Significance ◽  
General Method

AbstractHere we describe a general method for improving computational efficiency in simultaneous mapping of multiple interacting quantitative trait loci (QTL). The method uses a genetic algorithm to search for QTL in the genome instead of an exhaustive enumerative (“step-by-step”) search. It can be used together with any method of QTL mapping based on a genomic search, since it only provides a more efficient way to search the genome for QTL. The computational demand decreases by a factor of ~130 when using genetic algorithm-based mapping instead of an exhaustive enumerative search for two QTL in a genome size of 2000 cM using a resolution of 1 cM. The advantage of using a genetic algorithm increases further for larger genomes, higher resolutions, and searches for more QTL. We show that a genetic algorithm-based search has efficiency higher than or equal to a search method conditioned on previously identified QTL for all epistatic models tested and that this efficiency is comparable to that of an exhaustive search for multiple QTL. The genetic algorithm is thus a powerful and computationally tractable alternative to the exhaustive enumerative search for simultaneous mapping of multiple interacting QTL. The use of genetic algorithms for simultaneous mapping of more than two QTL and for determining empirical significance thresholds using permutation tests is also discussed.

scholarly journals synder: inferring genomic orthologs from synteny maps

2019 ◽  
Author(s):  
Zebulun Arendsee ◽  
Andrew Wilkey ◽  
Urminder Singh ◽  
Jing Li ◽  
Manhoi Hur ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Transcription Factor ◽  
Search Space ◽  
Genomic Feature ◽  
Nuclear Factor ◽  
Genomic Context ◽  
Similar Sequence ◽  
Member Gene ◽  
Genomic Search ◽  
And Function

AbstractOrtholog inference is a key step in understanding the evolution and function of a gene or other genomic feature. Yet often no similar sequence can be identified, or the true ortholog is hidden among false positives. A solution is to consider the sequence’s genomic context. We present the generic program,synder, for tracing features of interest between genomes based on a synteny map. This approach narrows genomic search-space independently of the sequence of the feature of interest. We illustrate the utility ofsynderby finding orthologs for theArabidopsis thaliana13-member gene family of Nuclear Factor YC transcription factor across the Brassicaceae clade.

scholarly journals Potent CRISPR-Cas9 inhibitors from Staphylococcus genomes

2019 ◽  
Author(s):  
Kyle E. Watters ◽  
Haridha Shivram ◽  
Christof Fellmann ◽  
Rachel J. Lew ◽  
Blake McMahon ◽  
...  
Keyword(s):  
Genome Editing ◽  
Dna Cleavage ◽  
Selective Inhibition ◽  
Repeat Sequence ◽  
Terminal Sequence ◽  
Dna Targeting ◽  
Small Proteins ◽  
Genomic Search ◽  
Guilt By Association ◽  
Bacterial Genes

AbstractAnti-CRISPRs (Acrs) are small proteins that inhibit the RNA-guided DNA targeting activity of CRISPR-Cas enzymes. Encoded by bacteriophage and phage-derived bacterial genes, Acrs prevent CRISPR-mediated inhibition of phage infection and can also block CRISPR-Cas-mediated genome editing in eukaryotic cells. To identify Acrs capable of inhibiting Staphylococcus aureus Cas9 (SauCas9), an alternative to the most commonly used genome editing protein Streptococcus pyogenes Cas9 (SpyCas9), we used both self-targeting CRISPR screening and guilt-by-association genomic search strategies. Here we describe three new potent inhibitors of SauCas9 that we name AcrIIA13, AcrIIA14 and AcrIIA15. These inhibitors share a conserved N-terminal sequence that is dispensable for anti-CRISPR function, and have divergent C-termini that are required in each case for selective inhibition of SauCas9-catalyzed DNA cleavage. In human cells, we observe robust and specific inhibition of SauCas9-induced genome editing by AcrIIA13 and moderate inhibition by AcrIIA14 and AcrIIA15. We also find that the conserved N-terminal domain of AcrIIA13-15 binds to an inverted repeat sequence in the promoter of these Acr genes, consistent with its predicted helix-turn-helix DNA binding structure. These data demonstrate an effective strategy for Acr discovery and establish AcrIIA13-15 as unique bifunctional inhibitors of SauCas9.

scholarly journals Identification of In Vivo-Expressed Immunogenic Proteins by Serological Proteome Analysis of the Bacillus anthracis Secretome

2007 ◽  
Vol 75 (6) ◽  
pp. 2841-2852 ◽  
Author(s):  
Theodor Chitlaru ◽  
Orit Gat ◽  
Haim Grosfeld ◽  
Itzhak Inbar ◽  
Yael Gozlan ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Vaccine Development ◽  
Protective Antigen ◽  
Proteome Analysis ◽  
Humoral Response ◽  
Growth Conditions ◽  
Lethal Challenge ◽  
Genomic Search ◽  
Future Evaluation

ABSTRACTIn a previous comparative proteomic study ofBacillus anthracisexamining the influence of the virulence plasmids and of various growth conditions on the composition of the bacterial secretome, we identified 64 abundantly expressed proteins (T. Chitlaru, O. Gat, Y. Gozlan, N. Ariel, and A. Shafferman, J. Bacteriol.188:3551-3571, 2006). Using a battery of sera fromB. anthracis-infected animals, in the present study we demonstrated that 49 of these proteins are immunogenic. Thirty-eightB. anthracisimmunogens are documented in this study for the first time. The relative immunogenicities of the 49 secreted proteins appear to span a >10,000-fold range. The proteins eliciting the highest humoral response in the course of infection include, in addition to the well-established immunogens protective antigen (PA), Sap, and EA1, GroEL (BA0267), AhpC (BA0345), MntA (BA3189), HtrA (BA3660), 2,3-cyclic nucleotide diesterase (BA4346), collagen adhesin (BAS5205), an alanine amidase (BA0898), and an endopeptidase (BA1952), as well as three proteins having unknown functions (BA0796, BA0799, and BA0307). Of these 14 highly potent secreted immunogens, 11 are known to be associated with virulence and pathogenicity inB. anthracisor in other bacterial pathogens. Combining the results reported here with the results of a similar study of the membranal proteome ofB. anthracis(T. Chitlaru, N. Ariel, A. Zvi, M. Lion, B. Velan, A. Shafferman, and E. Elhanany, Proteomics4:677-691, 2004) and the results obtained in a functional genomic search for immunogens (O. Gat, H. Grosfeld, N. Ariel, I. Inbar, G. Zaide, Y. Broder, A. Zvi, T. Chitlaru, Z. Altboum, D. Stein, S. Cohen, and A. Shafferman, Infect. Immun.74:3987-4001, 2006), we generated a list of 84 in vivo-expressed immunogens for future evaluation for vaccine development, diagnostics, and/or therapeutic intervention. In a preliminary study, the efficacies of eight immunogens following DNA immunization of guinea pigs were compared to the efficacy of a PA DNA vaccine. All eight immunogens induced specific high antibody titers comparable to the titers elicited by PA; however, unlike PA, none of them provided protection against a lethal challenge (50 50% lethal doses) of virulentB. anthracisstrain Vollum spores.

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