Defining objective clusters for rabies virus sequences using affinity propagation clustering

Fischer, Susanne; Freuling, Conrad Martin; Müller, Thomas; Pfaff, Florian; Bodenhofer, Ulrich; Höper, Dirk W.; Fischer, Mareike; Marston, Denise A.; Fooks, Anthony R.; Mettenleiter, Thomas C.; Conraths, Franz Josef; Homeier‐Bachmann, Timo

doi:10.1371/journal.pntd.0006182

Cited by 20 publications

(34 citation statements)

References 53 publications

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“…With the explicit aim to include a broad diversity of RABV isolates, with respect to geographical origin, host species, and genetic background of RABV, we included different genetic lineages of all major genetic clusters [36] from most parts of rabies endemic areas. Unfortunately, none of these parameters provided any correlation to the outcome of the test result.…”

Section: Discussionmentioning

confidence: 99%

Further Evidence of Inadequate Quality in Lateral Flow Devices Commercially Offered for the Diagnosis of Rabies

Fahrion

Finke

Eyngor³

et al. 2020

TropicalMed

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As a neglected zoonotic disease, rabies causes approximately 5.9 × 104 human deaths annually, primarily affecting low- and middle-income countries in Asia and Africa. In those regions, insufficient surveillance is hampering adequate medical intervention and is driving the vicious cycle of neglect. Where resources to provide laboratory disease confirmation are limited, there is a need for user-friendly and low-cost reliable diagnostic tools that do not rely on specialized laboratory facilities. Lateral flow devices (LFD) offer an alternative to conventional diagnostic methods and may strengthen control efforts in low-resource settings. Five different commercially available LFDs were compared in a multi-centered study with respect to their diagnostic sensitivity and their agreement with standard rabies diagnostic techniques. Our evaluation was conducted by several international reference laboratories using a broad panel of samples. The overall sensitivities ranged from 0% up to 62%, depending on the LFD manufacturer, with substantial variation between the different laboratories. Samples with high antigen content and high relative viral load tended to test positive more often in the Anigen/Bionote test, the latter being the one with the best performance. Still, the overall unsatisfactory findings corroborate a previous study and indicate a persistent lack of appropriate test validation and quality control. At present, the tested kits are not suitable for in-field use for rabies diagnosis, especially not for suspect animals where human contact has been identified, as an incorrect negative diagnosis may result in human casualties. This study points out the discrepancy between the enormous need for such a diagnostic tool on the one hand, and on the other hand, a number of already existing tests that are not yet ready for use.

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Section: Discussionmentioning

confidence: 99%

Further Evidence of Inadequate Quality in Lateral Flow Devices Commercially Offered for the Diagnosis of Rabies

Fahrion

Finke

Eyngor³

et al. 2020

TropicalMed

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“…images of faces, genes in a microarray, heavily travelled cities) and identify representative examples of each cluster (Frey and Dueck 2007). The method has been used to cluster strains of rabies viruses (Fischer et al 2017), but has never been used to identify viral OTUs for analyses in the context of community ecology. Here, we show that affinity propagation can be used as a quantitative complement, in congruence with currently defined herpesvirus species, to objectively support current methods of viral OTU delineation.…”

Section: Discussionmentioning

confidence: 99%

“…When inputting the PID matrix of all clones, the number of clusters identified through affinity propagation can be interpreted as an optimal number of viral OTUs. Although this method has been used to define clusters of a single viral species (Fischer et al 2017), this is the first instance in which it has been used to delineate viral "species" for the purpose of communitylevel analyses. To conduct affinity propagation analyses, the apcluster() command was run using the R package apcluster (Bodenhofer et al 2011), with default values of input parameters (input data = NA, input preference = NA, q = 0.5, convits = 100, maxits = 1000, lam = 0.9).…”

Section: Methodsmentioning

confidence: 99%

Quantitative Delineation of Herpesviruses in Bats for use in Ecological Studies

Sjodin

2019

Preprint

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Public health concerns about recent viral epidemics have motivated researchers to seek transdisciplinary understanding of infection in wildlife hosts. With its deep history devoted to explaining the abundance and distribution of organisms, ecology can augment current methods for studying viral dynamics. However, datasets allowing ecological explorations of viral communities are lacking, and common methods for delineating viral operational taxonomic units (OTUs), or "species", are subjective. Here, we comprehensively sampled 1,086 bats from two Puerto Rican caves and tested them for infection with herpesviruses. Using percent identity of nucleotides and a machine learning algorithm, we categorized herpesviruses into 41 OTUs, representing approximately 80% of all herpesviruses in the host community. Although 13 OTUs were detected in multiple host species, OTUs generally exhibited host specificity by infecting a core host species at a significantly higher prevalence than in all other species combined. Only two OTUs showed significantly different prevalence between host sexes. This work is the first exploration of viral community ecology in a community of wildlife hosts. Lipkin WI (2013) A strategy to estimate unknown viral diversity in mammals. mBio 4: e00598-13.

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“…To group bacteria in a phylogenetically related cluster, an application of a data mining technique called affinity propagation clustering (APC) is used. This clustering technique needs no presumptions or supervision, unlike other clustering methods used for bacteria [46]. With these methods, we would like to generate new insight and a new method to cluster bacteria.…”

Section: Clusteringmentioning

confidence: 99%

“…To be independent of presumptions, we have devised a strategy enabling us to resolve phylogenetic cluster of bacteria also independently. The reference independent and alignmentindependent method (affinity propagation clustering-APC) has successfully applied for clustering of bacterial genes and viral (Fischer, 2018) nucleotide sequences but never on whole genomes.…”

Section: Introductionmentioning

confidence: 99%

Using affinity propagation clustering for identifying bacterial clades and subclades with whole-genome sequences of Francisella tularensis

et al. 2020

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By combining a reference-independent SNP analysis and average nucleotide identity (ANI) with affinity propagation clustering (APC), we developed a significantly improved methodology allowing resolving phylogenetic relationships, based on objective criteria. These bioinformatics tools can be used as a general ruler to determine phylogenetic relationships and clustering of bacteria, exemplary done with Francisella (F.) tularensis. Molecular epidemiology of F. tularensis is currently assessed mostly based on laboratory methods and molecular analysis. The high evolutionary stability and the clonal nature makes Francisella ideal for subtyping with single nucleotide polymorphisms (SNPs). Sequencing and real-time PCR can be used to validate the SNP analysis. We investigate whole-genome sequences of 155 F. tularensis subsp. holarctica isolates. Phylogenetic testing was based on SNPs and average nucleotide identity (ANI) as reference independent, alignment-free methods taking small-scale and large-scale differences within the genomes into account. Especially the whole genome SNP analysis with kSNP3.0 allowed deciphering quite subtle signals of systematic differences in molecular variation. Affinity propagation clustering (APC) resulted in three clusters showing the known clades B.4, B.6, and B.12. These data correlated with the results of real-time PCR assays targeting canSNPs loci. Additionally, we detected two subtle sub-clusters. SplitsTree was used with standard-setting using the aligned SNPs from Parsnps. Together APC, HierBAPS, and SplitsTree enabled us to generate hypotheses about epidemiologic relationships between bacterial clusters and describing the distribution of isolates. Our data indicate that the choice of the typing technique can increase our understanding of the pathogenesis and transmission of diseases with the eventual for prevention. This is opening perspectives to be applied to other bacterial species. The data provide evidence that Germany might be the collision zone where the clade B.12, also known as the East European clade, overlaps with the clade B.6, also known as the Iberian clade. Described methods allow generating a new, more detailed perspective for F. tularensis

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Defining objective clusters for rabies virus sequences using affinity propagation clustering

Cited by 20 publications

References 53 publications

Further Evidence of Inadequate Quality in Lateral Flow Devices Commercially Offered for the Diagnosis of Rabies

Further Evidence of Inadequate Quality in Lateral Flow Devices Commercially Offered for the Diagnosis of Rabies

Quantitative Delineation of Herpesviruses in Bats for use in Ecological Studies

Using affinity propagation clustering for identifying bacterial clades and subclades with whole-genome sequences of Francisella tularensis

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