scholarly journals ClusTRace, a bioinformatic pipeline for analyzing clusters in virus phylogenies

2021 ◽  
Author(s):  
Ilya Plyusnin ◽  
Phuoc Thien Truong Nguyen ◽  
Tarja Sironen ◽  
Olli Vapalahti ◽  
Teemu Smura ◽  
...  

Summary: SARS-CoV-2 is the highly transmissible etiologic agent of coronavirus disease 2019 (COVID-19) and has become a global scientific and public health challenge since December 2019. Several new variants of SARS-CoV-2 have emerged globally raising concern about prevention and treatment of COVID-19. Early detection and in depth analysis of the emerging variants allowing pre-emptive alert and mitigation efforts are thus of paramount importance. Here we present ClusTRace, a novel bioinformatic pipeline for a fast and scalable analysis of sequence clusters or clades in large viral phylogenies. ClusTRace offers several high level functionalities including outlier filtering, aligning, phylogenetic tree reconstruction, cluster or clade extraction, variant calling, visualization and reporting. ClusTRace was developed as an aid for COVID-19 transmission chain tracing in Finland and the main emphasis has been on fast and unsupervised screening of phylogenies for markers of super-spreading events and other features of concern, such as high rates of cluster growth and/or accumulation of novel mutations. Availability: All code is freely available from https://bitbucket.org/plyusnin/clustrace/

2005 ◽  
Vol 360 (1454) ◽  
pp. 297-308 ◽  
Author(s):  
M de Heer ◽  
V Kapos ◽  
B.J.E ten Brink

This paper presents a trial of a species population trend indicator for evaluating progress towards the 2010 biodiversity target in Europe, using existing data. The indicator integrates trends on different species (groups), and can be aggregated across habitats and countries. Thus, the indicator can deliver both headline messages for high-level decision-making and detailed information for in-depth analysis, using data from different sources, collected with different methods. International non-governmental organizations mobilized data on over 2800 historical trends in national populations of birds, butterflies and mammals, for a total of 273 species. These were combined by habitat and biogeographical region to generate a pilot pan-European scale indicator. The trial indicator suggests a decline of species populations in nearly all habitats, the largest being in farmland, where species populations declined by an average of 23% between 1970 and 2000. The indicator is potentially useful for monitoring progress towards 2010 biodiversity targets, but constraints include: the limited sensitivity of the historical data, which leads to conservative estimates of species decline; a potential danger of ambiguity because increases in opportunistic species can mask the loss of other species; and failure to account for pre-1970 population declines. We recommend mobilizing additional existing data, particularly for plants and fishes, and elaborating further the criteria for compiling representative sets of species. For a frequent, reliable update of the indicator, sound, sensitive and harmonized biodiversity monitoring programmes are needed in all pan-European countries.


Author(s):  
Elena Vladimirovna Frolova

In terms of its efficiency and accessibility, the health care of Cyprus is not inferior in many ways to the systems of medical care in a number of developed countries of the world. By placing the main emphasis on the organization of preventive care, the Cypriots were able to achieve quite a high level of life expectancy — 85 years for women and 81 years for men. Due to its excellent geographical position and mild climate, the country has a special attraction in terms of medical tourism, the most popular areas of which are plastic cosmetology, dentistry, and reproductive medicine. Foreigners who come for medical services have the opportunity not only to improve their health, but also to have a wonderful rest, enjoy Mediterranean cuisine, golden sandy beaches and blessed sunshine. Fortunately, nature provides all the opportunities for this — scientists say that at least 300 days a year are sunny on this island.


2019 ◽  
Vol 62 (3) ◽  
pp. 406-419 ◽  
Author(s):  
Lili Zheng ◽  
Ning Jiang ◽  
Xiaoyu Sang ◽  
Naiwen Zhang ◽  
Kai Zhang ◽  
...  

2019 ◽  
Author(s):  
Petr Kaniok ◽  
Monika Brusenbauch Meislova

Abstract The aim of the article is to explore how the Czech bicameral parliament has reacted to the process of the United Kingdom's (UK's) withdrawal from the European Union (EU). Drawing upon insights from the theoretical expectations of parliamentary power, the inquiry researches the ways that Czech legislatures have developed in terms of engaging with and influencing the Brexit process. In this regard, the Czech case is exceptionally interesting and worth exploring, since the EU agenda has become a highly politicised issue within the Czech context. The significance of this inquiry has been further highlighted by the high level of party-based Euroscepticism typical of Czech politics as well as the frequent changes that the Czech party system has been undergoing in recent years. Throughout the in-depth analysis of parliamentary scrutiny activities—conceptualised as comprising four aspects: (i) the institutional adjustment; (ii) articulation of priorities; (iii) interactions with the government and (iv) parliamentary party politics—the article considers how these activities compare between both chambers of the Czech Parliament.


2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 124-124
Author(s):  
Hestia S. Mellert ◽  
Leisa Jackson ◽  
Gary Anthony Pestano

124 Background: Treatment of late-stage non-small cell lung cancer has been greatly impacted by the advances in immunotherapy. Molecular biomarkers such as tumor mutation load (TML or TMB) and micro-satellite instability (MSI) may identify patients with NSCLC that are more likely to respond to immune checkpoint inhibitors. In this report, we describe the development of and NGS-based assay for the robust detection of TML and somatic variants simultaneously using a targeted assay that covers 1.7 Mb of the genome. Methods: Initial feasibility included reference control cell-lines, HCC1143 and NIST8398, as well as FFPE (formalin-fixed, paraffin-embedded) samples from lung and colorectal tumors. In development, eight FFPE specimens from patients with late stage cancer and a reference MSI status were evaluated. FFPE slides were extracted using the MagMax FFPE DNA/RNA Ultra kit, and nucleic acid quality was assessed using qPCR. Extracted DNA was processed through the Oncomine TML Assay with a minimum input of 30 ng of DNA per specimen. Automated library and template preparation were performed followed by sequencing on the Ion GeneStudio S5 Plus system using replicate 540 chips. Eight samples with barcoded adapters were multiplexed per chip. Tumor mutation analysis and variant calling was performed using the Oncomine TML v2.0 workflow. Results: The time from FFPE extraction to result was 96 hours, and all samples passed QC metrics. TML scores ranged from 14.4-36.04 mutations/Mb for all samples with MSI-high reference results. A very high level of inter-chip concordance was also observed (R2=0.990). Additionally, the variant caller function within the TML workflow was used to detect BRAF V600E mutations with 100% concordance to reference testing results. Conclusions: The accurate quantification of somatic mutations paired with fast turn-around time and robust automated workflow is ideal for assessing the tumor mutation load as well as hotspot mutations from limited (FFPE) samples.


2021 ◽  
Vol 12 ◽  
Author(s):  
Carlos Farkas ◽  
Andy Mella ◽  
Maxime Turgeon ◽  
Jody J. Haigh

An unprecedented amount of SARS-CoV-2 sequencing has been performed, however, novel bioinformatic tools to cope with and process these large datasets is needed. Here, we have devised a bioinformatic pipeline that inputs SARS-CoV-2 genome sequencing in FASTA/FASTQ format and outputs a single Variant Calling Format file that can be processed to obtain variant annotations and perform downstream population genetic testing. As proof of concept, we have analyzed over 229,000 SARS-CoV-2 viral sequences up until November 30, 2020. We have identified over 39,000 variants worldwide with increased polymorphisms, spanning the ORF3a gene as well as the 3′ untranslated (UTR) regions, specifically in the conserved stem loop region of SARS-CoV-2 which is accumulating greater observed viral diversity relative to chance variation. Our analysis pipeline has also discovered the existence of SARS-CoV-2 hypermutation with low frequency (less than in 2% of genomes) likely arising through host immune responses and not due to sequencing errors. Among annotated non-sense variants with a population frequency over 1%, recurrent inactivation of the ORF8 gene was found. This was found to be present in the newly identified B.1.1.7 SARS-CoV-2 lineage that originated in the United Kingdom. Almost all VOC-containing genomes possess one stop codon in ORF8 gene (Q27∗), however, 13% of these genomes also contains another stop codon (K68∗), suggesting that ORF8 loss does not interfere with SARS-CoV-2 spread and may play a role in its increased virulence. We have developed this computational pipeline to assist researchers in the rapid analysis and characterization of SARS-CoV-2 variation.


2017 ◽  
Vol 5 ◽  
pp. 218-223
Author(s):  
Miroslav Karahuta ◽  
Peter Gallo ◽  
Daniela Matušíková ◽  
Anna Ĺ enková ◽  
Kristína Šambronská

The paper addresses the issue of management decision-making using artificial neural networks and their application in hotel management. Today, the development of tourism is of great importance and plays a very important role in the development of national economy. Balanced ranking and prediction model using financial and non-financial indicators with the application of artificial intelligence, allows us to reach a high level of effectivity and accuracy in evaluation of the financial and non-financial health of companies operating in this segment. This approach improves the manager’s ability to understand complex contexts and make better decisions for further development. It also brings new managerial and scientific point of view of an in-depth analysis of the performance of these facilities. It can help the development of tourism in terms of the application of modern management techniques built on scientific principles and thereby better integrate science and practice.


2018 ◽  
Author(s):  
Md Vasimuddin ◽  
Sanchit Misra ◽  
Srinivas Aluru

AbstractRapid advances in next-generation sequencing technologies are improving the throughput and cost of sequencing at a rate significantly faster than the Moore’s law. This necessitates equivalent rate of acceleration of NGS secondary analysis that assembles reads into full genomes and identifies variants between genomes. Conventional improvement in hardware can at best help accelerate this according to the Moore’s law. Moreover, a majority of the software tools used for secondary analysis do not use the hardware efficiently. Therefore, we need hardware that is designed taking into account the computational requirements of secondary analysis, along with software tools that use it efficiently. Here, we take the first step towards these goals by identifying the computational requirements of secondary analysis. We surveyed dozens of software tools from all the three major problems in secondary analysis – sequence mapping, De novo assembly, and variant calling – to select seven popular tools and a workflow for an in-depth analysis. We performed runtime profiling of the tools using multiple real datasets to find that the majority of the runtime is dominated by just four building blocks – Smith-Waterman alignment, FM-index based sequence search, Debruijn graph construction and traversal, and pairwise hidden markov model algorithm – covering 80.5%-98.2%, 63.9%-99.4% and 72%-93% of the runtime, respectively, for sequence mapping, De novo assembly, and variant calling. The key outcome of this result is that by just targeting software and hardware optimizations to these building blocks, major performance improvements for NGS secondary analysis can be achieved.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kelly Conde-Pérez ◽  
Juan C. Vázquez-Ucha ◽  
Laura Álvarez-Fraga ◽  
Lucía Ageitos ◽  
Soraya Rumbo-Feal ◽  
...  

Acinetobacter baumannii is a multidrug-resistant pathogen that represents a serious threat to global health. A. baumannii possesses a wide range of virulence factors that contribute to the bacterial pathogenicity. Among them, the siderophore acinetobactin is one of the most important, being essential for the development of the infection. In this study we performed an in-depth analysis of the acinetobactin cluster in the strain A. baumannii ATCC 17978. For this purpose, nineteen individual isogenic mutant strains were generated, and further phenotypical analysis were performed. Individual mutants lacking the biosynthetic genes entA, basG, basC, basD, and basB showed a significant loss in virulence, due to the disruption in the acinetobactin production. Similarly, the gene bauA, coding for the acinetobactin receptor, was also found to be crucial for the bacterial pathogenesis. In addition, the analysis of the ΔbasJ/ΔfbsB double mutant strain demonstrated the high level of genetic redundancy between siderophores where the role of specific genes of the acinetobactin cluster can be fulfilled by their fimsbactin redundant genes. Overall, this study highlights the essential role of entA, basG, basC, basD, basB and bauA in the pathogenicity of A. baumannii and provides potential therapeutic targets for the design of new antivirulence agents against this microorganism.


1999 ◽  
Vol 67 (10) ◽  
pp. 5106-5116 ◽  
Author(s):  
Brian J. Morrow ◽  
James E. Graham ◽  
Roy Curtiss

ABSTRACT Salmonella typhi, the etiologic agent of typhoid fever, is adapted to the human host and unable to infect nonprimate species. The genetic basis for host specificity in S. typhi is unknown. The avirulence of S. typhi in animal hosts may result from a lack of genes present in the broad-host-range pathogenSalmonella typhimurium. Genomic subtractive hybridization was successfully employed to isolate S. typhimurium genomic sequences which are absent from the S. typhi genome. These genomic subtracted sequences mapped to 17 regions distributed throughout the S. typhimurium chromosome. A positive cDNA selection method was then used to identify subtracted sequences which were transcribed by S. typhimurium following macrophage phagocytosis. A novel putative transcriptional regulator of the LysR family was identified as transcribed by intramacrophage S. typhimurium. This putative transcriptional regulator was absent from the genomes of the human-adapted serovars S. typhi andSalmonella paratyphi A. Mutations within this gene did not alter the level of S. typhimurium survival within macrophages or virulence within mice. A subtracted genomic fragment derived from the ferrichrome operon also hybridized to the intramacrophage cDNA. Nucleotide sequence analysis of S. typhimurium and S. typhi chromosomal sequences flanking the ferrichrome operon identified a novel S. typhimurium fimbrial operon with a high level of similarity to sequences encoding Proteus mirabilis mannose-resistant fimbriae. The novel fimbrial operon was absent from the S. typhi genome. The absence of specific genes may have allowedS. typhi to evolve as a highly invasive, systemic human pathogen.


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