Utility of genetic sequencing in the diagnosis of a very large orbital tumor

Abstract Background The all-electronic Single Molecule Break Junction (SMBJ) method is an emerging alternative to traditional polymerase chain reaction (PCR) techniques for genetic sequencing and identification. Existing work indicates that the current spectra recorded from SMBJ experimentations contain unique signatures to identify known sequences from a dataset. However, the spectra are typically extremely noisy due to the stochastic and complex interactions between the substrate, sample, environment, and the measuring system, necessitating hundreds or thousands of experimentations to obtain reliable and accurate results. Results This article presents a DNA sequence identification system based on the current spectra of ten short strand sequences, including a pair that differs by a single mismatch. By employing a gradient boosted tree classifier model trained on conductance histograms, we demonstrate that extremely high accuracy, ranging from approximately 96 % for molecules differing by a single mismatch to 99.5 % otherwise, is possible. Further, such accuracy metrics are achievable in near real-time with just twenty or thirty SMBJ measurements instead of hundreds or thousands. We also demonstrate that a tandem classifier architecture, where the first stage is a multiclass classifier and the second stage is a binary classifier, can be employed to boost the single mismatched pair’s identification accuracy to 99.5 %. Conclusions A monolithic classifier, or more generally, a multistage classifier with model specific parameters that depend on experimental current spectra can be used to successfully identify DNA strands.

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The Liquid Biopsy for Lung Cancer: State of the Art, Limitations and Future Developments

Cancers ◽

10.3390/cancers13163923 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3923

Author(s):

Daniel Di Capua ◽

Dara Bracken-Clarke ◽

Karine Ronan ◽

Anne-Marie Baird ◽

Stephen Finn

Keyword(s):

Lung Cancer ◽

Lung Carcinoma ◽

Targeted Therapies ◽

Liquid Biopsy ◽

Genetic Alterations ◽

Rapid Progression ◽

Liquid Biopsies ◽

Cell Lung Carcinoma ◽

Genetic Sequencing ◽

Tissue Biopsy

Lung cancer is a leading cause of cancer-related deaths, contributing to 18.4% of cancer deaths globally. Treatment of non-small cell lung carcinoma has seen rapid progression with targeted therapies tailored to specific genetic drivers. However, identifying genetic alterations can be difficult due to lack of tissue, inaccessible tumors and the risk of complications for the patient with serial tissue sampling. The liquid biopsy provides a minimally invasive method which can obtain circulating biomarkers shed from the tumor and could be a safer alternative to tissue biopsy. While tissue biopsy remains the gold standard, liquid biopsies could be very beneficial where serial sampling is required, such as monitoring disease progression or development of resistance mutations to current targeted therapies. Liquid biopsies also have a potential role in identifying patients at risk of relapse post treatment and as a component of future lung cancer screening protocols. Rapid developments have led to multiple platforms for isolating circulating tumor cells (CTCs) and detecting circulating tumor DNA (ctDNA); however, standardization is lacking, especially in lung carcinoma. Additionally, clonal hematopoiesis of uncertain clinical significance must be taken into consideration in genetic sequencing, as it introduces the potential for false positives. Various biomarkers have been investigated in liquid biopsies; however, in this review, we will concentrate on the current use of ctDNA and CTCs, focusing on the clinical relevance, current and possible future applications and limitations of each.

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Evaluating the potential of novel genetic approaches for the treatment of Duchenne muscular dystrophy

European Journal of Human Genetics ◽

10.1038/s41431-021-00811-2 ◽

2021 ◽

Author(s):

Vratko Himič ◽

Kay E. Davies

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Structural Integrity ◽

Viral Vector ◽

Exon Skipping ◽

Dystrophin Gene ◽

Pharmacological Treatments ◽

Genetic Sequencing ◽

Reading Frame ◽

Target Effects

AbstractDuchenne muscular dystrophy (DMD) is an X-linked progressive muscle-wasting disorder that is caused by a lack of functional dystrophin, a cytoplasmic protein necessary for the structural integrity of muscle. As variants in the dystrophin gene lead to a disruption of the reading frame, pharmacological treatments have only limited efficacy; there is currently no effective therapy and consequently, a significant unmet clinical need for DMD. Recently, novel genetic approaches have shown real promise in treating DMD, with advancements in the efficacy and tropism of exon skipping and surrogate gene therapy. CRISPR-Cas9 has the potential to be a ‘one-hit’ curative treatment in the coming decade. The current limitations of gene editing, such as off-target effects and immunogenicity, are in fact partly constraints of the delivery method itself, and thus research focus has shifted to improving the viral vector. In order to halt the loss of ambulation, early diagnosis and treatment will be pivotal. In an era where genetic sequencing is increasingly utilised in the clinic, genetic therapies will play a progressively central role in DMD therapy. This review delineates the relative merits of cutting-edge genetic approaches, as well as the challenges that still need to be overcome before they become clinically viable.

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A multi-institutional outbreak of New Delhi metallo-β-lactamase–producing Escherichia coli with subsequent acquisition of the Klebsiella pneumoniae carbapenemase gene

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.1361 ◽

2020 ◽

pp. 1-4

Author(s):

Ester Solter ◽

Jason C. Kwong ◽

Aaron Walton ◽

Norelle Sherry ◽

Benjamin P. Howden ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Common Ancestor ◽

Sequence Type ◽

Second Phase ◽

New Delhi ◽

Genetic Sequencing ◽

Klebsiella Pneumoniae Carbapenemase ◽

Carbapenemase Gene

Abstract We characterized 57 isolates from a 2-phase clonal outbreak of New Delhi metallo-β-lactamase–producing Eschericha coli, involving 9 Israeli hospitals; all but 1 isolate belonged to sequence-type (ST) 410. Most isolates in the second phase harbored blaKPC-2 in addition to blaNDM-5. Genetic sequencing revealed most dual-carbapenemase–producing isolates to be monophyletically derived from a common ancestor.

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From wood to vent: first cocculinid limpet associated with hydrothermal activity discovered in the Weddell Sea

Antarctic Science ◽

10.1017/s095410202000022x ◽

2020 ◽

Vol 32 (5) ◽

pp. 354-366

Author(s):

Chong Chen ◽

Katrin Linse

Keyword(s):

Hydrothermal Vents ◽

Deep Ocean ◽

First Record ◽

Hydrothermal Activity ◽

Integrative Taxonomy ◽

Weddell Sea ◽

Anatomical Reconstruction ◽

Cold Seeps ◽

Evolutionary Trajectory ◽

Genetic Sequencing

AbstractLush ‘oases’ of life seen in chemosynthetic ecosystems such as hot vents and cold seeps represent rare, localized exceptions to the generally oligotrophic deep ocean floor. Organic falls, best known from sunken wood and whale carcasses, are additional sources of such oases. Kemp Caldera (59°42'S, 28°20'W) in the Weddell Sea exhibits active hydrothermal vents and a natural whale fall in close proximity, where an undescribed cocculinid limpet was found living in both types of chemosynthetic habitats. This represents the first member of the gastropod order Cocculinida discovered from hot vents, and also the first record from the Southern Ocean. Here, we applied an integrative taxonomy framework incorporating traditional dissection, electron microscopy, genetic sequencing and 3D anatomical reconstruction through synchrotron computed tomography in order to characterize this species. Together, our data revealed an unusual member of the genus Cocculina with a highly modified radula for feeding on bacterial film, described herein as Cocculina enigmadonta n. sp. Its phylogenetically derived position within the largely wood-inhabiting Cocculina indicates that it probably evolved from an ancestor adapted to living on sunken wood, providing a compelling case of the ‘stepping stone’ evolutionary trajectory from organic falls to seeps and vents.

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Uncovering two phases of early intercontinental COVID-19 transmission dynamics

Journal of Travel Medicine ◽

10.1093/jtm/taaa200 ◽

2020 ◽

Vol 27 (8) ◽

Author(s):

Jing Yang ◽

Juan Li ◽

Shengjie Lai ◽

Corrine W Ruktanonchai ◽

Weijia Xing ◽

...

Keyword(s):

Phylogenetic Analyses ◽

International Travel ◽

Contact Tracing ◽

Genetic Sequencing ◽

Response Strategies ◽

The World ◽

Containment Measures ◽

The Usa ◽

Community Transmission ◽

Two Phases

Abstract Background The COVID-19 pandemic has posed an ongoing global crisis, but how the virus spread across the world remains poorly understood. This is of vital importance for informing current and future pandemic response strategies. Methods We performed two independent analyses, travel network-based epidemiological modelling and Bayesian phylogeographic inference, to investigate the intercontinental spread of COVID-19. Results Both approaches revealed two distinct phases of COVID-19 spread by the end of March 2020. In the first phase, COVID-19 largely circulated in China during mid-to-late January 2020 and was interrupted by containment measures in China. In the second and predominant phase extending from late February to mid-March, unrestricted movements between countries outside of China facilitated intercontinental spread, with Europe as a major source. Phylogenetic analyses also revealed that the dominant strains circulating in the USA were introduced from Europe. However, stringent restrictions on international travel across the world since late March have substantially reduced intercontinental transmission. Conclusions Our analyses highlight that heterogeneities in international travel have shaped the spatiotemporal characteristics of the pandemic. Unrestricted travel caused a large number of COVID-19 exportations from Europe to other continents between late February and mid-March, which facilitated the COVID-19 pandemic. Targeted restrictions on international travel from countries with widespread community transmission, together with improved capacity in testing, genetic sequencing and contact tracing, can inform timely strategies for mitigating and containing ongoing and future waves of COVID-19 pandemic.

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Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives

International Journal of Molecular Sciences ◽

10.3390/ijms22126360 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6360

Author(s):

Giulia Di Donato ◽

Debora Mariarita d’Angelo ◽

Luciana Breda ◽

Francesco Chiarelli

Keyword(s):

Innate Immune ◽

Sterile Inflammation ◽

Autoinflammatory Diseases ◽

Clinical Aspects ◽

Genetic Sequencing ◽

Regulatory Pathways ◽

Interferon Pathway ◽

Mediterranean Fever ◽

Encoding Gene ◽

Nf Kappab

Systemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic background, with mutations in single genes involved in inflammation. Therefore, they can derive from different pathogenic mechanisms at any level, such as dysregulated inflammasome-mediated production of cytokines, intracellular stress, defective regulatory pathways, altered protein folding, enhanced NF-kappaB signalling, ubiquitination disorders, interferon pathway upregulation and complement activation. Since the discover of pathogenic mutations of the pyrin-encoding gene MEFV in Familial Mediterranean Fever, more than 50 monogenic autoinflammatory diseases have been discovered thanks to the advances in genetic sequencing: the advent of new genetic analysis techniques and the discovery of genes involved in autoinflammatory diseases have allowed a better understanding of the underlying innate immunologic pathways and pathogenetic mechanisms, thus opening new perspectives in targeted therapies. Moreover, this field of research has become of great interest, since more than a hundred clinical trials for autoinflammatory diseases are currently active or recently concluded, allowing us to hope for considerable acquisitions for the next few years. General paediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in order to guide further examinations and refer the patient to a specialist rheumatologist. Here we resume the pathogenesis, clinical aspects and diagnosis of the most important autoinflammatory diseases in children.

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Aromatic Profile Variation of Essential Oil from Dried Makwhaen Fruit and Related Species

Plants ◽

10.3390/plants10040803 ◽

2021 ◽

Vol 10 (4) ◽

pp. 803

Author(s):

Trid Sriwichai ◽

Jiratchaya Wisetkomolmat ◽

Tonapha Pusadee ◽

Korawan Sringarm ◽

Kiattisak Duangmal ◽

...

Keyword(s):

Cluster Analysis ◽

Essential Oil ◽

Related Species ◽

Phenotypic Characteristic ◽

Genetic Sequencing ◽

Dried Fruits ◽

Profile Variation ◽

Chemical Profiles ◽

The Relationship ◽

Different Sources

The aim of this research is to evaluate the relationship between genotype, phenotype, and chemical profiles of essential oil obtained from available Zanthoxylum spp. Three specimens of makhwaen (MK) distributed in Northern Thailand were genetically and morphologically compared with other Zanthoxylum spices, known locally as huajiao (HJ) and makwoung (MKO), respectively. HJ was taxonomically confirmed as Z. armatum while MKO and MK were identified as Z. rhetsa and Z. myriacanthum. Genetic sequencing distributed these species into three groups accordingly to their confirmed species. Essential oil of the dried fruits from these samples was extracted and analyzed for their chemical and physical properties. Cluster analysis of their volatile compositions separated MKO and MK apart from HJ with L-limonene, terpinen-4-ol, β-phellandrene, and β-philandrene. By using odor attributes, the essential oil of MKO and MK were closely related possessing fruity, woody, and citrus aromas, while the HJ was distinctive. Overall, the phenotypic characteristic can be used to elucidate the species among makhwaen fruits of different sources. The volatile profiling was nonetheless dependent on the genotypes but makwoung and makhwaen showed similar profiles.

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Implementing and using finite automata toolkits

Natural Language Engineering ◽

10.1017/s135132499700154x ◽

1996 ◽

Vol 2 (4) ◽

pp. 295-302 ◽

Cited By ~ 14

Author(s):

BRUCE W. WATSON

Keyword(s):

Flight Control ◽

Program Verification ◽

Finite Automata ◽

Circuit Simulation ◽

Implementation Strategies ◽

Digital Circuit ◽

General Purpose ◽

Genetic Sequencing ◽

Java Program ◽

Fire Engine

Finite automata and various extensions of them, such as transducers, are used in areas as diverse as compilers, spelling checking, natural language grammar checking, communication protocol design, digital circuit simulation, digital flight control, speech recognition and synthesis, genetic sequencing, and Java program verification. Unfortunately, as the number of applications has grown, so has the variety of implementations and implementation techniques. Typically, programmers will be confused enough to resort to their text books for the most elementary algorithms. Recently, advances have been made in taxonomizing algorithms for constructing and minimizing automata and in evaluating various implementation strategies Watson 1995. Armed with this, a number of general-purpose toolkits have been developed at universities and companies. One of these, FIRE Lite, was developed at the Eindhoven University of Technology, while its commercial successor, FIRE Engine II, has been developed at Ribbit Software Systems Inc. Both of these toolkits provide implementations of all of the known algorithms for constructing automata from regular expressions, and all of the known algorithms for minimizing deterministic finite automata. While the two toolkits have a great deal in common, we will concentrate on the structure and use of the noncommercial FIRE Lite. The prototype version of FIRE Lite was designed with compilers in mind. More recently, computation linguists and communications protocol designers have become interested in using the toolkit. This has led to the development of a much more general interface to FIRE Lite, including the support of both Mealy and Moore regular transducers. While such a toolkit may appear extremely complex, there are only a few choices to be made. We also consider a ‘recipe’ for making good use of the toolkits. Lastly, we consider the future of FIRE Lite. While FIRE Engine II has obvious commercial value, we are committed to maintaining a version which is freely available for academic use.

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