scholarly journals The Impacts of Low Diversity Sequence Data on Phylodynamic Inference during an Emerging Epidemic

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 79
Author(s):  
Anthony Lam ◽  
Sebastian Duchene

Phylodynamic inference is a pivotal tool in understanding transmission dynamics of viral outbreaks. These analyses are strongly guided by the input of an epidemiological model as well as sequence data that must contain sufficient intersequence variability in order to be informative. These criteria, however, may not be met during the early stages of an outbreak. Here we investigate the impact of low diversity sequence data on phylodynamic inference using the birth–death and coalescent exponential models. Through our simulation study, estimating the molecular evolutionary rate required enough sequence diversity and is an essential first step for any phylodynamic inference. Following this, the birth–death model outperforms the coalescent exponential model in estimating epidemiological parameters, when faced with low diversity sequence data due to explicitly exploiting the sampling times. In contrast, the coalescent model requires additional samples and therefore variability in sequence data before accurate estimates can be obtained. These findings were also supported through our empirical data analyses of an Australian and a New Zealand cluster outbreaks of SARS-CoV-2. Overall, the birth–death model is more robust when applied to datasets with low sequence diversity given sampling is specified and this should be considered for future viral outbreak investigations.

2019 ◽  
Author(s):  
Leo A. Featherstone ◽  
Francesca Di Giallonardo ◽  
Edward C. Holmes ◽  
Timothy G. Vaughan ◽  
Sebastián Duchêne

AbstractPoint 1Phylodynamic models use pathogen genome sequence data to infer epidemiological dynamics. With the increasing genomic surveillance of pathogens, especially amid the SARS-CoV-2 outbreak, new practical questions about their use are emerging.Point 2One such question focuses on the inclusion of un-sequenced case occurrence data alongside sequenced data to improve phylodynamic analyses. This approach can be particularly valuable if sequencing efforts vary over time.Point 3Using simulations, we demonstrate that birth-death phylodynamic models can employ occurrence data to eliminate bias in estimates of the basic reproductive number due to misspecification of the sampling process. In contrast, the coalescent exponential model is robust to such sampling biases, but in the absence of a sampling model it cannot exploit occurrence data. Subsequent analysis of the SARS-CoV-2 epidemic in the northwest USA supports these results.Point 4We conclude that occurrence data are a valuable source of information in combination with birth-death models. These data should be used to bolster phylodynamic analyses of infectious diseases and other rapidly spreading species in the future.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 477-477
Author(s):  
Leah K Treffer ◽  
Edward S Rice ◽  
Anna M Fuller ◽  
Samuel Cutler ◽  
Jessica L Petersen

Abstract Domestic yak (Bos grunniens) are bovids native to the Asian Qinghai-Tibetan Plateau. Studies of Asian yak have revealed that introgression with domestic cattle has contributed to the evolution of the species. When imported to North America (NA), some hybridization with B. taurus did occur. The objective of this study was to use mitochondrial (mt) DNA sequence data to better understand the mtDNA origin of NA yak and their relationship to Asian yak and related species. The complete mtDNA sequence of 14 individuals (12 NA yak, 1 Tibetan yak, 1 Tibetan B. indicus) was generated and compared with sequences of similar species from GeneBank (B. indicus, B. grunniens (Chinese), B. taurus, B. gaurus, B. primigenius, B. frontalis, Bison bison, and Ovis aries). Individuals were aligned to the B. grunniens reference genome (ARS_UNL_BGru_maternal_1.0), which was also included in the analyses. The mtDNA genes were annotated using the ARS-UCD1.2 cattle sequence as a reference. Ten unique NA yak haplotypes were identified, which a haplotype network separated into two clusters. Variation among the NA haplotypes included 93 nonsynonymous single nucleotide polymorphisms. A maximum likelihood tree including all taxa was made using IQtree after the data were partitioned into twenty-two subgroups using PartitionFinder2. Notably, six NA yak haplotypes formed a clade with B. indicus; the other four haplotypes grouped with B. grunniens and fell as a sister clade to bison, gaur and gayal. These data demonstrate two mitochondrial origins of NA yak with genetic variation in protein coding genes. Although these data suggest yak introgression with B. indicus, it appears to date prior to importation into NA. In addition to contributing to our understanding of the species history, these results suggest the two major mtDNA haplotypes in NA yak may functionally differ. Characterization of the impact of these differences on cellular function is currently underway.


2021 ◽  
pp. 216769682110251
Author(s):  
Samantha G. Farris ◽  
Mindy M. Kibbey ◽  
Erick J. Fedorenko ◽  
Angelo M. DiBello

The psychological effect of the pandemic and measures taken in response to control viral spread are not yet well understood in university students; in-depth qualitative analysis can provide nuanced information about the young adult distress experience. Undergraduate students ( N = 624) in an early US outbreak “hotspot” completed an online narrative writing about the impact and distress experienced due to the COVID-19 pandemic. Data were collected April-May 2020. A random selection of 50 cases were sampled for thematic analysis. Nine themes were identified: viral outbreak distress, fear of virus contraction/transmission, proximity to virus, dissatisfaction with public response, physical distancing distress, social distancing distress, academic and school-related distress, disruptive changes in health behavior and routines, financial strain and unemployment, worsening of pre-existing mental health problems, and social referencing that minimizes distress. Future work is needed to understand the persistence of the distress, in addition to developing methods for assessment, monitoring, and mitigation of the distress.


2021 ◽  
Vol 95 (3) ◽  
pp. 1103-1116
Author(s):  
Francesco Marchetti ◽  
Gu Zhou ◽  
Danielle LeBlanc ◽  
Paul A. White ◽  
Andrew Williams ◽  
...  

AbstractThe Organisation for Economic Co-Operation and Development Test Guideline 488 (TG 488) uses transgenic rodent models to generate in vivo mutagenesis data for regulatory submission. The recommended design in TG 488, 28 consecutive daily exposures with tissue sampling three days later (28 + 3d), is optimized for rapidly proliferating tissues such as bone marrow (BM). A sampling time of 28 days (28 + 28d) is considered more appropriate for slowly proliferating tissues (e.g., liver) and male germ cells. We evaluated the impact of the sampling time on mutant frequencies (MF) in the BM of MutaMouse males exposed for 28 days to benzo[a]pyrene (BaP), procarbazine (PRC), isopropyl methanesulfonate (iPMS), or triethylenemelamine (TEM) in dose–response studies. BM samples were collected + 3d, + 28d, + 42d or + 70d post exposure and MF quantified using the lacZ assay. All chemicals significantly increased MF with maximum fold increases at 28 + 3d of 162.9, 6.6, 4.7 and 2.8 for BaP, PRC, iPMS and TEM, respectively. MF were relatively stable over the time period investigated, although they were significantly increased only at 28 + 3d and 28 + 28d for TEM. Benchmark dose (BMD) modelling generated overlapping BMD confidence intervals among the four sampling times for each chemical. These results demonstrate that the sampling time does not affect the detection of mutations for strong mutagens. However, for mutagens that produce small increases in MF, sampling times greater than 28 days may produce false-negative results. Thus, the 28 + 28d protocol represents a unifying protocol for simultaneously assessing mutations in rapidly and slowly proliferating somatic tissues and male germ cells.


2018 ◽  
Vol 35 (14) ◽  
pp. 2492-2494
Author(s):  
Tania Cuppens ◽  
Thomas E Ludwig ◽  
Pascal Trouvé ◽  
Emmanuelle Genin

Abstract Summary When analyzing sequence data, genetic variants are considered one by one, taking no account of whether or not they are found in the same individual. However, variant combinations might be key players in some diseases as variants that are neutral on their own can become deleterious when associated together. GEMPROT is a new analysis tool that allows, from a phased vcf file, to visualize the consequences of the genetic variants on the protein. At the level of an individual, the program shows the variants on each of the two protein sequences and the Pfam functional protein domains. When data on several individuals are available, GEMPROT lists the haplotypes found in the sample and can compare the haplotype distributions between different sub-groups of individuals. By offering a global visualization of the gene with the genetic variants present, GEMPROT makes it possible to better understand the impact of combinations of genetic variants on the protein sequence. Availability and implementation GEMPROT is freely available at https://github.com/TaniaCuppens/GEMPROT. An on-line version is also available at http://med-laennec.univ-brest.fr/GEMPROT/. Supplementary information Supplementary data are available at Bioinformatics online.


2021 ◽  
Vol 2 (1) ◽  
pp. 30-36
Author(s):  
Douglas L. Hatch ◽  
Imam Z. Imam

Countries need teams of well trained epidemiologists with extensive field experience to work with clinicians and laboratory scientists to conduct prompt and effective outbreak investigations of epidemics. To identify these outbreaks of possible emerging or re-emerging problems, existing surveillance must be strengthened and the quality of data validated routinely. In addition, ministry of health officials and international agencies need an open, collaborative, scientific work environment. The best environment to design effective interventions and control measures to limit the impact of these newly identified problems on the public’s health is one of cooperation and collaboration


2020 ◽  
Author(s):  
Brendan N. Reid ◽  
Rachel L. Moran ◽  
Christopher J. Kopack ◽  
Sarah W. Fitzpatrick

AbstractResearchers studying non-model organisms have an increasing number of methods available for generating genomic data. However, the applicability of different methods across species, as well as the effect of reference genome choice on population genomic inference, are still difficult to predict in many cases. We evaluated the impact of data type (whole-genome vs. reduced representation) and reference genome choice on data quality and on population genomic and phylogenomic inference across several species of darters (subfamily Etheostomatinae), a highly diverse radiation of freshwater fish. We generated a high-quality reference genome and developed a hybrid RADseq/sequence capture (Rapture) protocol for the Arkansas darter (Etheostoma cragini). Rapture data from 1900 individuals spanning four darter species showed recovery of most loci across darter species at high depth and consistent estimates of heterozygosity regardless of reference genome choice. Loci with baits spanning both sides of the restriction enzyme cut site performed especially well across species. For low-coverage whole-genome data, choice of reference genome affected read depth and inferred heterozygosity. For similar amounts of sequence data, Rapture performed better at identifying fine-scale genetic structure compared to whole-genome sequencing. Rapture loci also recovered an accurate phylogeny for the study species and demonstrated high phylogenetic informativeness across the evolutionary history of the genus Etheostoma. Low cost and high cross-species effectiveness regardless of reference genome suggest that Rapture and similar sequence capture methods may be worthwhile choices for studies of diverse species radiations.


2005 ◽  
Vol 71 (10) ◽  
pp. 6319-6324 ◽  
Author(s):  
Gene W. Tyson ◽  
Ian Lo ◽  
Brett J. Baker ◽  
Eric E. Allen ◽  
Philip Hugenholtz ◽  
...  

ABSTRACT Analysis of assembled random shotgun sequence data from a low-diversity, subsurface acid mine drainage (AMD) biofilm revealed a single nif operon. This was found on a genome fragment belonging to a member of Leptospirillum group III, a lineage in the Nitrospirae phylum with no cultivated representatives. Based on the prediction that this organism is solely responsible for nitrogen fixation in the community, we pursued a selective isolation strategy to obtain the organism in pure culture. An AMD biofilm sample naturally abundant in Leptospirillum group III cells was homogenized, filtered, and serially diluted into a nitrogen-free liquid medium. The resulting culture in the terminal dilution grew autotrophically to a maximum cell density of ∼106 cells/ml, oxidizing ferrous iron as the sole energy source. 16S rRNA-internal transcribed spacer region clone library analysis confirmed that the isolate is a member of Leptospirillum group III and that the culture is axenic. We propose the name Leptospirillum ferrodiazotrophum sp. nov. for this iron-oxidizing, free-living diazotroph. This study highlights how environmental sequence data can provide insights for culturing previously uncultured microorganisms.


2016 ◽  
Vol 23 (2) ◽  
pp. 448-459 ◽  
Author(s):  
Richard T. Melstrom

This article presents an exponential model of tourist expenditures estimated by a quasi-maximum likelihood (QML) technique. The advantage of this approach is that, unlike conventional OLS and Tobit estimators, it produces consistent parameter estimates under conditions of a corner solution at zero and heteroscedasticity. An application to sportfishing evaluates the role of socioeconomic demographics and species preferences on trip spending. The bias from an inappropriate estimator is illustrated by comparing the results from QML and OLS estimation, which shows that OLS significantly overstates the impact of trip duration on trip expenditures compared with the QML estimator. Both sets of estimates imply that trout and bass anglers spend significantly more on their fishing trips compared with other anglers.


2007 ◽  
Vol 52 (2) ◽  
pp. 215-238 ◽  
Author(s):  
Sylvie Lambert-Tierrafría

Abstract This article examines the case of translation of official documents from Spanish into English in Canada. The article begins by providing some background information about immigration in Canada and in the Ottawa region in particular, and discussing the impact that this is having on translation needs. It then describes the types of official documents that need to be translated (e.g., birth, death, marriage certificates). Next, a type of translation tool known as a Translation Memory is briefly introduced, followed by an explanation of why, contrary to expectations, such a tool is not necessarily suitable for translating official documents. Finally, an alternative strategy that entails the creation and application of templates is presented. This templating approach is being developed and taught in Spanish translation courses at the University of Ottawa in Canada.


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