Browsing by Author "Treangen, Todd"
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Item Accurate and fast estimation of taxonomic profiles from metagenomic shotgun sequences(Springer Nature, 2011-07-27) Liu, Bo; Gibbons, Theodore; Ghodsi, Mohammad; Treangen, Todd; Pop, MihaiA major goal of metagenomics is to characterize the microbial composition of an environment. The most popular approach relies on 16S rRNA sequencing, however this approach can generate biased estimates due to differences in the copy number of the gene between even closely related organisms, and due to PCR artifacts. The taxonomic composition can also be determined from metagenomic shotgun sequencing data by matching individual reads against a database of reference sequences. One major limitation of prior computational methods used for this purpose is the use of a universal classification threshold for all genes at all taxonomic levels. We propose that better classification results can be obtained by tuning the taxonomic classifier to each matching length, reference gene, and taxonomic level. We present a novel taxonomic classifier MetaPhyler (http://metaphyler.cbcb.umd.edu), which uses phylogenetic marker genes as a taxonomic reference. Results on simulated datasets demonstrate that MetaPhyler outperforms other tools commonly used in this context (CARMA, Megan and PhymmBL). We also present interesting results by analyzing a real metagenomic dataset. We have introduced a novel taxonomic classification method for analyzing the microbial diversity from whole-metagenome shotgun sequences. Compared with previous approaches, MetaPhyler is much more accurate in estimating the phylogenetic composition. In addition, we have shown that MetaPhyler can be used to guide the discovery of novel organisms from metagenomic samples.Item Complete Columbian mammoth mitogenome suggests interbreeding with woolly mammoths(Springer Nature, 2011-05-31) Enk, Jacob; Devault, Alison; Debruyne, Regis; King, Christine E; Treangen, Todd; O'Rourke, Dennis; Salzberg, Steven L; Fisher, Daniel; MacPhee, Ross; Poinar, HendrikLate Pleistocene North America hosted at least two divergent and ecologically distinct species of mammoth: the periglacial woolly mammoth (Mammuthus primigenius) and the subglacial Columbian mammoth (Mammuthus columbi). To date, mammoth genetic research has been entirely restricted to woolly mammoths, rendering their genetic evolution difficult to contextualize within broader Pleistocene paleoecology and biogeography. Here, we take an interspecific approach to clarifying mammoth phylogeny by targeting Columbian mammoth remains for mitogenomic sequencing. We sequenced the first complete mitochondrial genome of a classic Columbian mammoth, as well as the first complete mitochondrial genome of a North American woolly mammoth. Somewhat contrary to conventional paleontological models, which posit that the two species were highly divergent, the M. columbi mitogenome we obtained falls securely within a subclade of endemic North American M. primigenius. Though limited, our data suggest that the two species interbred at some point in their evolutionary histories. One potential explanation is that woolly mammoth haplotypes entered Columbian mammoth populations via introgression at subglacial ecotones, a scenario with compelling parallels in extant elephants and consistent with certain regional paleontological observations. This highlights the need for multi-genomic data to sufficiently characterize mammoth evolutionary history. Our results demonstrate that the use of next-generation sequencing technologies holds promise in obtaining such data, even from non-cave, non-permafrost Pleistocene depositional contexts.Item MetaCarvel: linking assembly graph motifs to biological variants(Springer Nature, 2019-08-26) Ghurye, Jay; Treangen, Todd; Fedarko, Marcus; Hervey, W. Judson IV; Pop, MihaiReconstructing genomic segments from metagenomics data is a highly complex task. In addition to general challenges, such as repeats and sequencing errors, metagenomic assembly needs to tolerate the uneven depth of coverage among organisms in a community and differences between nearly identical strains. Previous methods have addressed these issues by smoothing genomic variants. We present a variant-aware metagenomic scaffolder called MetaCarvel, which combines new strategies for repeat detection with graph analytics for the discovery of variants. We show that MetaCarvel can accurately reconstruct genomic segments from complex microbial mixtures and correctly identify and characterize several classes of common genomic variants.Item A new rhesus macaque assembly and annotation for next-generation sequencing analyses(Springer Nature, 2014-10-14) Zimin, Aleksey V; Cornish, Adam S; Maudhoo, Mnirnal D; Gibbs, Robert M; Zhang, Xiongfei; Pandey, Sanjit; Meehan, Daniel T; Wipfler, Kristin; Bosinger, Steven E; Johnson, Zachary P; Tharp, Gregory K; Marçais, Guillaume; Roberts, Michael; Ferguson, Betsy; Fox, Howard S; Treangen, Todd; Salzberg, Steven L; Yorke, James A; Norgren, Robert B JrThe rhesus macaque (Macaca mulatta) is a key species for advancing biomedical research. Like all draft mammalian genomes, the draft rhesus assembly (rheMac2) has gaps, sequencing errors and misassemblies that have prevented automated annotation pipelines from functioning correctly. Another rhesus macaque assembly, CR_1.0, is also available but is substantially more fragmented than rheMac2 with smaller contigs and scaffolds. Annotations for these two assemblies are limited in completeness and accuracy. High quality assembly and annotation files are required for a wide range of studies including expression, genetic and evolutionary analyses. We report a new de novo assembly of the rhesus macaque genome (MacaM) that incorporates both the original Sanger sequences used to assemble rheMac2 and new Illumina sequences from the same animal. MacaM has a weighted average (N50) contig size of 64 kilobases, more than twice the size of the rheMac2 assembly and almost five times the size of the CR_1.0 assembly. The MacaM chromosome assembly incorporates information from previously unutilized mapping data and preliminary annotation of scaffolds. Independent assessment of the assemblies using Ion Torrent read alignments indicates that MacaM is more complete and accurate than rheMac2 and CR_1.0. We assembled messenger RNA sequences from several rhesus tissues into transcripts which allowed us to identify a total of 11,712 complete proteins representing 9,524 distinct genes. Using a combination of our assembled rhesus macaque transcripts and human transcripts, we annotated 18,757 transcripts and 16,050 genes with complete coding sequences in the MacaM assembly. Further, we demonstrate that the new annotations provide greatly improved accuracy as compared to the current annotations of rheMac2. Finally, we show that the MacaM genome provides an accurate resource for alignment of reads produced by RNA sequence expression studies.