Author
M. Coon
Bio: M. Coon is an academic researcher from Wayne State University. The author has contributed to research in topics: Physics & Xenon. The author has an hindex of 9, co-authored 13 publications receiving 6676 citations.
Topics: Physics, Xenon, Scintillation, Genome, Time projection chamber
Papers
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TL;DR: It appears that the 5′ and 3′ UTRs are reservoirs for genetic variations that changes the termini of proteins during evolution of the Drosophila genus.
Abstract: We describe a new computer program, SnpEff, for rapidly categorizing the effects of variants in genome sequences. Once a genome is sequenced, SnpEff annotates variants based on their genomic locations and predicts coding effects. Annotated genomic locations include intronic, untranslated region, upstream, downstream, splice site, or intergenic regions. Coding effects such as synonymous or non-synonymous amino acid replacement, start codon gains or losses, stop codon gains or losses, or frame shifts can be predicted. Here the use of SnpEff is illustrated by annotating ~356,660 candidate SNPs in ~117 Mb unique sequences, representing a substitution rate of ~1/305 nucleotides, between the Drosophila melanogaster w1118; iso-2; iso-3 strain and the reference y1; cn1 bw1 sp1 strain. We show that ~15,842 SNPs are synonymous and ~4,467 SNPs are non-synonymous (N/S ~0.28). The remaining SNPs are in other categories, such as stop codon gains (38 SNPs), stop codon losses (8 SNPs), and start codon gains (297 SNPs) in...
8,017 citations
TL;DR: It is demonstrated that combining SnpEff and SnpSift can expedite the identification of candidate phenotype-causative mutations in chemically mutagenized Drosophila strains and can also be used to characterize the variety of mutations generated by genotoxic chemicals.
Abstract: This paper describes a new program SnpSift for filtering differential DNA sequence variants between two or more experimental genomes after genotoxic chemical exposure. Here, we illustrate how SnpSift can be used to identify candidate phenotype-relevant variants including single nucleotide polymorphisms, multiple nucleotide polymorphisms, insertions, and deletions (InDels) in mutant strains isolated from genome-wide chemical mutagenesis of Drosophila melanogaster. First, the genomes of two independently isolated mutant fly strains that are allelic for a novel recessive male-sterile locus generated by genotoxic chemical exposure were sequenced using the Illumina next-generation DNA sequencer to obtain 20- to 29-fold coverage of the euchromatic sequences. The sequencing reads were processed and variants were called using standard bioinformatic tools. Next, SnpEff was used to annotate all sequence variants and their potential mutational effects on associated genes. Then, SnpSift was used to filter and select differential variants that potentially disrupt a common gene in the two allelic mutant strains. The potential causative DNA lesions were partially validated by capillary sequencing of polymerase chain reaction-amplified DNA in the genetic interval as defined by meiotic mapping and deletions that remove defined regions of the chromosome. Of the five candidate genes located in the genetic interval, the Pka-like gene CG12069 was found to carry a separate pre-mature stop codon mutation in each of the two allelic mutants whereas the other four candidate genes within the interval have wild-type sequences. The Pka-like gene is therefore a strong candidate gene for the male-sterile locus. These results demonstrate that combining SnpEff and SnpSift can expedite the identification of candidate phenotype-causative mutations in chemically mutagenized Drosophila strains. This technique can also be used to characterize the variety of mutations generated by genotoxic chemicals.
746 citations
TL;DR: Cytosine hydroxymethylation at non-CG sites might have more functional significance than previously appreciated, and in honey bees these modifications might be related to the regulation of alternative mRNA splicing by defining the locations of the introns.
Abstract: Previous whole-genome shotgun bisulfite sequencing experiments showed that DNA cytosine methylation in the honey bee (Apis mellifera) is almost exclusively at CG dinucleotides in exons. However, the most commonly used method, bisulfite sequencing, cannot distinguish 5-methylcytosine from 5-hydroxymethylcytosine, an oxidized form of 5-methylcytosine that is catalyzed by the TET family of dioxygenases. Furthermore, some analysis software programs under-represent non-CG DNA methylation and hydryoxymethylation for a variety of reasons. Therefore, we used an unbiased analysis of bisulfite sequencing data combined with molecular and bioinformatics approaches to distinguish 5-methylcytosine from 5-hydroxymethylcytosine. By doing this, we have performed the first whole genome analyses of DNA modifications at non-CG sites in honey bees and correlated the effects of these DNA modifications on gene expression and alternative mRNA splicing. We confirmed, using unbiased analyses of whole-genome shotgun bisulfite sequencing (BS-seq) data, with both new data and published data, the previous finding that CG DNA methylation is enriched in exons in honey bees. However, we also found evidence that cytosine methylation and hydroxymethylation at non-CG sites is enriched in introns. Using antibodies against 5-hydroxmethylcytosine, we confirmed that DNA hydroxymethylation at non-CG sites is enriched in introns. Additionally, using a new technique, Pvu-seq (which employs the enzyme PvuRts1l to digest DNA at 5-hydroxymethylcytosine sites followed by next-generation DNA sequencing), we further confirmed that hydroxymethylation is enriched in introns at non-CG sites. Cytosine hydroxymethylation at non-CG sites might have more functional significance than previously appreciated, and in honey bees these modifications might be related to the regulation of alternative mRNA splicing by defining the locations of the introns.
64 citations
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TL;DR: The projected performance and detector configuration of nEXO are described in this pre-Conceptual Design Report (pCDR) in this article, with a projected half-life sensitivity of approximately $10^{28}$ years.
Abstract: The projected performance and detector configuration of nEXO are described in this pre-Conceptual Design Report (pCDR). nEXO is a tonne-scale neutrinoless double beta ($0
u\beta\beta$) decay search in $^{136}$Xe, based on the ultra-low background liquid xenon technology validated by EXO-200. With $\simeq$ 5000 kg of xenon enriched to 90% in the isotope 136, nEXO has a projected half-life sensitivity of approximately $10^{28}$ years. This represents an improvement in sensitivity of about two orders of magnitude with respect to current results. Based on the experience gained from EXO-200 and the effectiveness of xenon purification techniques, we expect the background to be dominated by external sources of radiation. The sensitivity increase is, therefore, entirely derived from the increase of active mass in a monolithic and homogeneous detector, along with some technical advances perfected in the course of a dedicated R&D program. Hence the risk which is inherent to the construction of a large, ultra-low background detector is reduced, as the intrinsic radioactive contamination requirements are generally not beyond those demonstrated with the present generation $0
u\beta\beta$ decay experiments. Indeed, most of the required materials have been already assayed or reasonable estimates of their properties are at hand. The details described herein represent the base design of the detector configuration as of early 2018. Where potential design improvements are possible, alternatives are discussed.
This design for nEXO presents a compelling path towards a next generation search for $0
u\beta\beta$, with a substantial possibility to discover physics beyond the Standard Model.
55 citations
TL;DR: Chambers et al. as mentioned in this paper used a focused laser across a solid xenon matrix to image and count individual atoms of barium in a solid noble element, and then used this information to identify the Ba daughter atom from double beta decay in the nEXO experiment.
Abstract: Author(s): Chambers, C; Walton, T; Fairbank, D; Craycraft, A; Yahne, DR; Todd, J; Iverson, A; Fairbank, W; Alamare, A; Albert, JB; Anton, G; Arnquist, IJ; Badhrees, I; Barbeau, PS; Beck, D; Belov, V; Bhatta, T; Bourque, F; Brodsky, JP; Brown, E; Brunner, T; Burenkov, A; Cao, GF; Cao, L; Cen, WR; Charlebois, SA; Chiu, M; Cleveland, B; Coon, M; Cree, W; Cote, M; Dalmasson, J; Daniels, T; Darroch, L; Daugherty, SJ; Daughhetee, J; Delaquis, S; Mesrobian-Kabakian, A Der; DeVoe, R; Dilling, J; Ding, YY; Dolinski, MJ; Dragone, A; Echevers, J; Fabris, L; Farine, J; Feyzbakhsh, S; Fontaine, R; Fudenberg, D; Giacomini, G; Gornea, R; Gratta, G; Hansen, EV; Heffner, M; Hoppe, EW; Hosl, J; House, A; Hufschmidt, P; Hughes, M; Ito, Y; Jamil, A; Jessiman, C; Jewell, MJ; Jiang, XS; Karelin, A; Kaufman, LJ; Kodroff, D; Koffas, T; Kravitz, S; Krucken, R; Kuchenkov, A; Kumar, KS; Lan, Y; Larson, A; Leonard, DS; Li, G; Li, S; Li, Z; Licciardi, C; Lin, YH; Lv, P; MacLellan, R; Michel, T; Mong, B; Moore, DC | Abstract: The search for neutrinoless double beta decay probes the fundamental properties of neutrinos, including whether or not the neutrino and antineutrino are distinct. Double beta detectors are large and expensive, so background reduction is essential for extracting the highest sensitivity. The identification, or 'tagging', of the $^{136}$Ba daughter atom from double beta decay of $^{136}$Xe provides a technique for eliminating backgrounds in the nEXO neutrinoless double beta decay experiment. The tagging scheme studied in this work utilizes a cryogenic probe to trap the barium atom in solid xenon, where the barium atom is tagged via fluorescence imaging in the solid xenon matrix. Here we demonstrate imaging and counting of individual atoms of barium in solid xenon by scanning a focused laser across a solid xenon matrix deposited on a sapphire window. When the laser sits on an individual atom, the fluorescence persists for $\sim$30~s before dropping abruptly to the background level, a clear confirmation of one-atom imaging. No barium fluorescence persists following evaporation of a barium deposit to a limit of $\leq$0.16\%. This is the first time that single atoms have been imaged in solid noble element. It establishes the basic principle of a barium tagging technique for nEXO.
25 citations
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: It appears that the 5′ and 3′ UTRs are reservoirs for genetic variations that changes the termini of proteins during evolution of the Drosophila genus.
Abstract: We describe a new computer program, SnpEff, for rapidly categorizing the effects of variants in genome sequences. Once a genome is sequenced, SnpEff annotates variants based on their genomic locations and predicts coding effects. Annotated genomic locations include intronic, untranslated region, upstream, downstream, splice site, or intergenic regions. Coding effects such as synonymous or non-synonymous amino acid replacement, start codon gains or losses, stop codon gains or losses, or frame shifts can be predicted. Here the use of SnpEff is illustrated by annotating ~356,660 candidate SNPs in ~117 Mb unique sequences, representing a substitution rate of ~1/305 nucleotides, between the Drosophila melanogaster w1118; iso-2; iso-3 strain and the reference y1; cn1 bw1 sp1 strain. We show that ~15,842 SNPs are synonymous and ~4,467 SNPs are non-synonymous (N/S ~0.28). The remaining SNPs are in other categories, such as stop codon gains (38 SNPs), stop codon losses (8 SNPs), and start codon gains (297 SNPs) in...
8,017 citations
TL;DR: The Ensembl Variant Effect Predictor can simplify and accelerate variant interpretation in a wide range of study designs.
Abstract: The Ensembl Variant Effect Predictor is a powerful toolset for the analysis, annotation, and prioritization of genomic variants in coding and non-coding regions. It provides access to an extensive collection of genomic annotation, with a variety of interfaces to suit different requirements, and simple options for configuring and extending analysis. It is open source, free to use, and supports full reproducibility of results. The Ensembl Variant Effect Predictor can simplify and accelerate variant interpretation in a wide range of study designs.
4,658 citations
Icahn School of Medicine at Mount Sinai1, Carnegie Mellon University2, Harvard University3, University of Toronto4, Wellcome Trust Sanger Institute5, University of Pittsburgh6, Nagoya University7, University of Freiburg8, King's College London9, Vanderbilt University10, University of Santiago de Compostela11, King Abdulaziz University12, University of Utah13, Duke University14, Memorial University of Newfoundland15, Trinity College, Dublin16, University of Pennsylvania17, University of Illinois at Chicago18, Boston Children's Hospital19, Columbia University20, German Cancer Research Center21, University College London22, Kaiser Permanente23, Broad Institute24, Cardiff University25, Complutense University of Madrid26, Newcastle University27, Baylor College of Medicine28, University of California, San Francisco29, RWTH Aachen University30, National Health Service31, McMaster University32, Saarland University33, Karolinska Institutet34, National Institutes of Health35, University of Helsinki36, Emory University37
TL;DR: Using exome sequencing, it is shown that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate of < 0.05, plus a set of 107 genes strongly enriched for those likely to affect risk (FDR < 0.30).
Abstract: The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.
2,228 citations
TL;DR: The genomic landscape of 496 PTCs is described and a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties is proposed, which has the potential to improve their pathological classification and better inform the management of the disease.
2,096 citations