SNPGenie: estimating evolutionary parameters to detect natural selection using pooled next-generation sequencing data

Nelson, Chase W.; Moncla, Louise H.; Hughes, Austin L.

doi:10.1093/bioinformatics/btv449

Cited by 162 publications

(134 citation statements)

References 12 publications

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“…As nonsynonymous polymorphisms are more likely to give rise to functional change than synonymous polymorphisms, the ratio of the presence of nonsynonymous to synonymous polymorphisms provides a measure of the potential for functional diversity (Firnberg & Ostermeier, ; Whitehead et al., ). We present π N / π S , the ratio of nonsynonymous to synonymous diversity, here as a correlate for functional diversity throughout ViVa (Hughes, Green, Garbayo, & Roberts, ; Nelson, Moncla, & Hughes, ). While imperfect, this metric may be suggestive of functional constraint when π N / π S ≫ 1 (Hughes, ).…”

Section: Resultsmentioning

confidence: 99%

Accelerating structure‐function mapping using the ViVa webtool to mine natural variation

et al. 2019

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Thousands of sequenced genomes are now publicly available capturing a significant amount of natural variation within plant species; yet, much of these data remain inaccessible to researchers without significant bioinformatics experience. Here, we present a webtool called ViVa (Visualizing Variation) which aims to empower any researcher to take advantage of the amazing genetic resource collected in the Arabidopsis thaliana 1001 Genomes Project ( http://1001genomes.org ). ViVa facilitates data mining on the gene, gene family, or gene network level. To test the utility and accessibility of ViVa, we assembled a team with a range of expertise within biology and bioinformatics to analyze the natural variation within the well‐studied nuclear auxin signaling pathway. Our analysis has provided further confirmation of existing knowledge and has also helped generate new hypotheses regarding this well‐studied pathway. These results highlight how natural variation could be used to generate and test hypotheses about less‐studied gene families and networks, especially when paired with biochemical and genetic characterization. ViVa is also readily extensible to databases of interspecific genetic variation in plants as well as other organisms, such as the 3,000 Rice Genomes Project ( http://snp-seek.irri.org/ ) and human genetic variation ( https://www.ncbi.nlm.nih.gov/clinvar/ ).

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Section: Resultsmentioning

confidence: 99%

Accelerating structure‐function mapping using the ViVa webtool to mine natural variation

et al. 2019

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“…Patterns of variation were assessed for evidence of purifying (negative) or diversifying (positive) selection using SNPgenie (Nelson et al, 2015). The mean synonymous ( d S ) and nonsynonymous ( d N ) divergence from the reference sequence of the pooled NGS data was determined on a gene by gene basis (Figure 5).…”

Section: Resultsmentioning

confidence: 99%

Modeling the evolution of SIV sooty mangabey progenitor virus towards HIV-2 using humanized mice

et al. 2017

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HIV-2 is thought to have originated from an SIV progenitor native to sooty mangabeys. To model the initial human transmission and understand the sequential viral evolution, humanized mice were infected with SIVsm and serially passaged for five generations. Productive infection was seen by week 3 during the initial challenge followed by chronic viremia and gradual CD4+ T cell decline. Viral loads increased by the 5th generation resulting in more rapid CD4+ T cell decline. Genetic analysis revealed several amino acid substitutions that were nonsynonymous and fixed in multiple hu-mice across each of the 5 generations in the nef, env and vpr regions. The highest rate of substitution occurred in the nef and env regions and most were observed within the first two generations. These data demonstrated the utility of hu-mice in modeling the SIVsm transmission to the human and to evaluate its potential sequential evolution into a human pathogen of HIV-2 lineage.

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“…Aligned sequences were analyzed to determine mean numbers of nonsynonymous and synonymous pairwise differences and sites for each ORF using SNPGenie (Nelson et al, 2015) (https://github.com/chasewnelson/snpgenie), yielding estimates of mean nonsynonymous ( d N ) and mean synonymous ( d S ) nucleotide distance. Codons containing indeterminate nucleotides (N’s) were excluded from analysis.…”

Section: Methodsmentioning

confidence: 99%

HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis

Mirabello

Yeager

et al. 2017

Cell

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SUMMARY Although most cervical human papillomavirus type 16 (HPV16) infections become undetectable within 1–2 years, persistent HPV16 causes half of all cervical cancers. We used a novel HPV whole-genome sequencing technique to evaluate an exceptionally large collection of 5,570 HPV16-infected case-control samples to determine whether viral genetic variation influences risk of cervical precancer and cancer. We observed thousands of unique HPV16 genomes; very few women shared the identical HPV16 sequence, which should stimulate a careful re-evaluation of the clinical implications of HPV mutation rates, transmission, clearance, and persistence. In case-control analyses, HPV16 in the controls had significantly more amino acid changing variants throughout the genome. Strikingly, E7 was devoid of variants in precancers/cancers compared to higher levels in the controls; we confirmed this in cancers from around the world. Strict conservation of the 98 amino acids of E7, which disrupts Rb function, is critical for HPV16 carcinogenesis, presenting a highly specific target for etiologic and therapeutic research.

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SNPGenie: estimating evolutionary parameters to detect natural selection using pooled next-generation sequencing data

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 162 publications

References 12 publications

Accelerating structure‐function mapping using the ViVa webtool to mine natural variation

Accelerating structure‐function mapping using the ViVa webtool to mine natural variation

Modeling the evolution of SIV sooty mangabey progenitor virus towards HIV-2 using humanized mice

HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis

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