scholarly journals AcrHub: an integrative hub for investigating, predicting and mapping anti-CRISPR proteins

2020 ◽  
Vol 49 (D1) ◽  
pp. D630-D638
Author(s):  
Jiawei Wang ◽  
Wei Dai ◽  
Jiahui Li ◽  
Qi Li ◽  
Ruopeng Xie ◽  
...  
Keyword(s):  
Paradigm Shift ◽  
Gene Editing ◽  
Phage Therapy ◽  
State Of The Art ◽  
Sequence Data ◽  
Diverse Range ◽  
Adaptive Immune ◽  
Depth Analysis ◽  
Domains Of Life ◽  
Adaptive Immune Systems

Abstract Anti-CRISPR (Acr) proteins naturally inhibit CRISPR-Cas adaptive immune systems across bacterial and archaeal domains of life. This emerging field has caused a paradigm shift in the way we think about the CRISPR-Cas system, and promises a number of useful applications from gene editing to phage therapy. As the number of verified and predicted Acrs rapidly expands, few online resources have been developed to deal with this wealth of information. To overcome this shortcoming, we developed AcrHub, an integrative database to provide an all-in-one solution for investigating, predicting and mapping Acr proteins. AcrHub catalogs 339 non-redundant experimentally validated Acrs and over 70 000 predicted Acrs extracted from genome sequence data from a diverse range of prokaryotic organisms and their viruses. It integrates state-of-the-art predictors to predict potential Acrs, and incorporates three analytical modules: similarity analysis, phylogenetic analysis and homology network analysis, to analyze their relationships with known Acrs. By interconnecting all modules as a platform, AcrHub presents enriched and in-depth analysis of known and potential Acrs and therefore provides new and exciting insights into the future of Acr discovery and validation. AcrHub is freely available at http://pacrispr.erc.monash.edu/AcrHub/.

Repurposing CRISPR-Cas Systems as Genetic Tools for the Enterobacteriales

EcoSal Plus ◽  
2021 ◽  
Author(s):  
Nicholas Backes ◽  
Gregory J. Phillips
Keyword(s):  
Gene Regulation ◽  
Immune System ◽  
Gene Editing ◽  
Defense Mechanism ◽  
Adaptive Immune System ◽  
Plasmid Curing ◽  
Genetic Tools ◽  
Adaptive Immune ◽  
Domains Of Life ◽  
Eukaryotic Genomes

Over the last decade, the study of CRISPR-Cas systems has progressed from a newly discovered bacterial defense mechanism to a diverse suite of genetic tools that have been applied across all domains of life. While the initial applications of CRISPR-Cas technology fulfilled a need to more precisely edit eukaryotic genomes, creative “repurposing” of this adaptive immune system has led to new approaches for genetic analysis of microorganisms, including improved gene editing, conditional gene regulation, plasmid curing and manipulation, and other novel uses.

scholarly journals Understanding Dendritic Cells and Their Role in Cutaneous Carcinoma and Cancer Immunotherapy

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Valerie R. Yanofsky ◽  
Hiroshi Mitsui ◽  
Diane Felsen ◽  
John A. Carucci
Keyword(s):  
Dendritic Cells ◽  
Complex Nature ◽  
Adaptive Immune ◽  
Depth Analysis ◽  
New Strategy ◽  
Antigen Presenting ◽  
Cancer Immunotherapies ◽  
Adaptive Immune Systems ◽  
Epidermal Langerhans Cells ◽  
The Ideal

Dendritic cells (DC) represent a diverse group of professional antigen-presenting cells that serve to link the innate and adaptive immune systems. Their capacity to initiate a robust and antigen-specific immune response has made them the ideal candidates for cancer immunotherapies. To date, the clinical impact of DC immunotherapy has been limited, which may, in part, be explained by the complex nature of DC biology. Multiple distinct subsets of DCs have been identified in the skin, where they can be broadly subcategorized into epidermal Langerhans cells (LC), myeloid-derived dermal dendritic cells (mDC) and plasmacytoid dendritic cells (pDC). Each subset is functionally unique and may activate alternate branches of the immune system. This may be relevant for the treatment of squamous cell carcinoma, where we have shown that the tumor microenvironment may preferentially suppress the activity of mDCs, while LCs remain potent stimulators of immunity. Here, we provide an in depth analysis of DC biology, with a particular focus on skin DCs and their role in cutaneous carcinoma. We further explore the current approaches to DC immunotherapy and provide evidence for the targeting of LCs as a promising new strategy in the treatment of skin cancer.

scholarly journals CRISPR systems: what’s new, where next?

2021 ◽  
Author(s):  
Ashley Parkes ◽  
Fiona Kemm ◽  
Liu He ◽  
Tom Killelea
Keyword(s):  
Dna Repair ◽  
Immune System ◽  
Genetic Engineering ◽  
Gene Editing ◽  
Adaptive Immune System ◽  
Feature Article ◽  
Adaptive Immune ◽  
The Past ◽  
Domains Of Life ◽  
Made In

The genetic signature of natural CRISPR-Cas systems were first noted in a 1989 publication and were characterized in detail from 2002 to 2007, culminating in the first report of a prokaryotic adaptive immune system. Since then, CRISPR-Cas enzymes have been adapted into molecular biology tools that have transformed genetic engineering across domains of life. In this feature article, we describe origins, uses and futures of CRISPR-Cas enzymes in genetic engineering: we highlight advances made in the past 10 years. Central to these advances is appreciation of interplay between CRISPR engineering and DNA repair. We highlight how this relationship has been manipulated to create further advances in the development of gene editing.

scholarly journals MetaCRAST: Reference-guided extraction of CRISPR spacers from unassembled metagenomes

2016 ◽  
Author(s):  
Abraham G Moller ◽  
Chun Liang
Keyword(s):  
De Novo ◽  
Sequence Data ◽  
Direct Repeat ◽  
Detection Methods ◽  
Direct Repeats ◽  
Metagenomic Sequence ◽  
Adaptive Immune ◽  
Adaptive Immune Systems ◽  
Metagenomic Sequence Data ◽  
Better Than

Summary: Clustered regularly interspaced palindromic repeat (CRISPR) systems are prokaryotic adaptive immune systems against phage infection. CRISPR spacer sequences can provide valuable ecological insights by linking environmental viruses to their microbial hosts. Despite this importance, metagenomic CRISPR detection remains a major challenge. Here we present a reference-guided CRISPR detection tool (Metagenomic CRISPR Reference-Aided Search Tool - MetaCRAST) that constrains searches based on user-specified direct repeats. These DRs could be expected from assembly or taxonomic profiles of metagenomic sequence data. Our evaluation shows MetaCRAST improves CRISPR spacer detection in real metagenomes compared to de novo detection methods. Simulations show it performs better than comparable tools when analyzing Illumina metagenomes. Availability and implementation: MetaCRAST is implemented in Perl and takes metagenomic sequence reads and direct repeat queries in FASTA format as input. It is freely available for download at https://github.com/molleraj/MetaCRAST .

Diversity and Integration in Private International Law

2019 ◽  
Keyword(s):  
South America ◽  
International Law ◽  
Value Systems ◽  
Private International Law ◽  
Diverse Range ◽  
Cross Border ◽  
Wide Range ◽  
Depth Analysis ◽  
And Shifts ◽  
Substantive Law

This book opens a cross-regional dialogue and shifts the Eurocentric discussion on diversity and integration to a more inclusive engagement with South America in private international law issues. It promotes a contemporary vision of private international law as a discipline enabling legal interconnectivity, with the potential to transcend its disciplinary boundaries to further promote the reality of cross-border integration, with its focus on the ever-increasing cross-border mobility of individuals. Private international law embraces legal diversity and pluralism. Different legal traditions continue to meet, interact and integrate in different forms, at the national, regional and international levels. Different systems of substantive law couple with divergent systems of private international law (designed to accommodate the former in cross-border situations). This complex legal landscape impacts individuals and families in cross-border scenarios, and international commerce broadly conceived. Private international law methodologies and techniques offer means for the coordination of this constellation of legal orders and value systems in cross-border situations. Bringing together world-renowned academics and experienced private international lawyers from a wide range of jurisdictions in Europe and South America, this edited collection focuses on the connective capabilities of private international law in bridging and balancing legal diversity as a corollary for the development of integration. The book provides in-depth analysis of the role of private international law in dealing with legal diversity across a diverse range of topics and jurisdictions.

Data science in economics: comprehensive review of advanced machine learning and deep learning methods

2020 ◽  
Author(s):  
Saeed Nosratabadi ◽  
Amir Mosavi ◽  
Puhong Duan ◽  
Pedram Ghamisi ◽  
Ferdinand Filip ◽  
...  
Keyword(s):  
Machine Learning ◽  
Deep Learning ◽  
Data Science ◽  
State Of The Art ◽  
Science Methods ◽  
Learning Models ◽  
Diverse Range ◽  
Hybrid Machine ◽  
Economics Research

This paper provides a state-of-the-art investigation of advances in data science in emerging economic applications. The analysis was performed on novel data science methods in four individual classes of deep learning models, hybrid deep learning models, hybrid machine learning, and ensemble models. Application domains include a wide and diverse range of economics research from the stock market, marketing, and e-commerce to corporate banking and cryptocurrency. Prisma method, a systematic literature review methodology, was used to ensure the quality of the survey. The findings reveal that the trends follow the advancement of hybrid models, which, based on the accuracy metric, outperform other learning algorithms. It is further expected that the trends will converge toward the advancements of sophisticated hybrid deep learning models.

scholarly journals Security assurance cases—state of the art of an emerging approach

2021 ◽  
Vol 26 (4) ◽  
Author(s):  
Mazen Mohamad ◽  
Jan-Philipp Steghöfer ◽  
Riccardo Scandariato
Keyword(s):  
State Of The Art ◽  
Tool Support ◽  
Security Assurance ◽  
The Past ◽  
Depth Analysis ◽  
Structured Argumentation ◽  
Security Properties ◽  
Standards And Regulations ◽  
Assurance Cases ◽  
Security Standards

AbstractSecurity Assurance Cases (SAC) are a form of structured argumentation used to reason about the security properties of a system. After the successful adoption of assurance cases for safety, SAC are getting significant traction in recent years, especially in safety-critical industries (e.g., automotive), where there is an increasing pressure to be compliant with several security standards and regulations. Accordingly, research in the field of SAC has flourished in the past decade, with different approaches being investigated. In an effort to systematize this active field of research, we conducted a systematic literature review (SLR) of the existing academic studies on SAC. Our review resulted in an in-depth analysis and comparison of 51 papers. Our results indicate that, while there are numerous papers discussing the importance of SAC and their usage scenarios, the literature is still immature with respect to concrete support for practitioners on how to build and maintain a SAC. More importantly, even though some methodologies are available, their validation and tool support is still lacking.

scholarly journals An Evolutionary Link between Natural Transformation and CRISPR Adaptive Immunity

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Peter Jorth ◽  
Marvin Whiteley
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Bacterial Diversity ◽  
Natural Transformation ◽  
Bacterial Species ◽  
Comparative Genomic ◽  
Content Type ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Adaptive Immune Systems

ABSTRACTNatural transformation by competent bacteria is a primary means of horizontal gene transfer; however, evidence that competence drives bacterial diversity and evolution has remained elusive. To test this theory, we used a retrospective comparative genomic approach to analyze the evolutionary history ofAggregatibacter actinomycetemcomitans, a bacterial species with both competent and noncompetent sister strains. Through comparative genomic analyses, we reveal that competence is evolutionarily linked to genomic diversity and speciation. Competence loss occurs frequently during evolution and is followed by the loss of clustered regularly interspaced short palindromic repeats (CRISPRs), bacterial adaptive immune systems that protect against parasitic DNA. Relative to noncompetent strains, competent bacteria have larger genomes containing multiple rearrangements. In contrast, noncompetent bacterial genomes are extremely stable but paradoxically susceptible to infective DNA elements, which contribute to noncompetent strain genetic diversity. Moreover, incomplete noncompetent strain CRISPR immune systems are enriched for self-targeting elements, which suggests that the CRISPRs have been co-opted for bacterial gene regulation, similar to eukaryotic microRNAs derived from the antiviral RNA interference pathway.IMPORTANCEThe human microbiome is rich with thousands of diverse bacterial species. One mechanism driving this diversity is horizontal gene transfer by natural transformation, whereby naturally competent bacteria take up environmental DNA and incorporate new genes into their genomes. Competence is theorized to accelerate evolution; however, attempts to test this theory have proved difficult. Through genetic analyses of the human periodontal pathogenAggregatibacter actinomycetemcomitans, we have discovered an evolutionary connection between competence systems promoting gene acquisition and CRISPRs (clustered regularly interspaced short palindromic repeats), adaptive immune systems that protect bacteria against genetic parasites. We show that competentA. actinomycetemcomitansstrains have numerous redundant CRISPR immune systems, while noncompetent bacteria have lost their CRISPR immune systems because of inactivating mutations. Together, the evolutionary data linking the evolution of competence and CRISPRs reveals unique mechanisms promoting genetic heterogeneity and the rise of new bacterial species, providing insight into complex mechanisms underlying bacterial diversity in the human body.

Persistent memory hash indexes

2021 ◽  
Vol 14 (5) ◽  
pp. 785-798
Author(s):  
Daokun Hu ◽  
Zhiwen Chen ◽  
Jianbing Wu ◽  
Jianhua Sun ◽  
Hao Chen
Keyword(s):  
Future Development ◽  
High Performance ◽  
Performance Metrics ◽  
Comprehensive Evaluation ◽  
State Of The Art ◽  
Hash Tables ◽  
Trade Offs ◽  
Depth Analysis ◽  
Persistent Memory ◽  
Memory Modules

Persistent memory (PM) is increasingly being leveraged to build hash-based indexing structures featuring cheap persistence, high performance, and instant recovery, especially with the recent release of Intel Optane DC Persistent Memory Modules. However, most of them are evaluated on DRAM-based emulators with unreal assumptions, or focus on the evaluation of specific metrics with important properties sidestepped. Thus, it is essential to understand how well the proposed hash indexes perform on real PM and how they differentiate from each other if a wider range of performance metrics are considered. To this end, this paper provides a comprehensive evaluation of persistent hash tables. In particular, we focus on the evaluation of six state-of-the-art hash tables including Level hashing, CCEH, Dash, PCLHT, Clevel, and SOFT, with real PM hardware. Our evaluation was conducted using a unified benchmarking framework and representative workloads. Besides characterizing common performance properties, we also explore how hardware configurations (such as PM bandwidth, CPU instructions, and NUMA) affect the performance of PM-based hash tables. With our in-depth analysis, we identify design trade-offs and good paradigms in prior arts, and suggest desirable optimizations and directions for the future development of PM-based hash tables.

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