To date, ancient genome analyses have been largely confined to the study of single nucleotide polymorphisms (SNPs). Copy number variants (CNVs) are a major contributor of disease and of evolutionary ...adaptation, but identifying CNVs in ancient shotgun-sequenced genomes is hampered by typical low genome coverage (<1×) and short fragments (<80 bps), precluding standard CNV detection software to be effectively applied to ancient genomes. Here we present CONGA, tailored for genotyping CNVs at low coverage. Simulations and down-sampling experiments suggest that CONGA can genotype deletions >1 kbps with F-scores >0.75 at ≥1×, and distinguish between heterozygous and homozygous states. We used CONGA to genotype 10,002 outgroup-ascertained deletions across a heterogenous set of 71 ancient human genomes spanning the last 50,000 years, produced using variable experimental protocols. A fraction of these (21/71) display divergent deletion profiles unrelated to their population origin, but attributable to technical factors such as coverage and read length. The majority of the sample (50/71), despite originating from nine different laboratories and having coverages ranging from 0.44×-26× (median 4×) and average read lengths 52-121 bps (median 69), exhibit coherent deletion frequencies. Across these 50 genomes, inter-individual genetic diversity measured using SNPs and CONGA-genotyped deletions are highly correlated. CONGA-genotyped deletions also display purifying selection signatures, as expected. CONGA thus paves the way for systematic CNV analyses in ancient genomes, despite the technical challenges posed by low and variable genome coverage.
Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights ...into the determinants of microbial succession in disease has been a formidable challenge.
Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients.
These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of "dysbiosis" that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.
A major challenge in zooarchaeology is to morphologically distinguish closely related species’ remains, especially using small bone fragments. Shotgun sequencing aDNA from archeological remains and ...comparative alignment to the candidate species’ reference genomes will only apply when reference nuclear genomes of comparable quality are available, and may still fail when coverages are low. Here, we propose an alternative method, MTaxi, that uses highly accessible mitochondrial DNA (mtDNA) to distinguish between pairs of closely related species from ancient DNA sequences. MTaxi utilises mtDNA transversion-type substitutions between pairs of candidate species, assigns reads to either species, and performs a binomial test to determine the sample taxon. We tested MTaxi on sheep/goat and horse/donkey data, between which zooarchaeological classification can be challenging in ways that epitomise our case. The method performed efficiently on simulated ancient genomes down to 0.3x mitochondrial coverage for both sheep/goat and horse/donkey, with no false positives. Trials on n=18 ancient sheep/goat samples and n=10 horse/donkey samples of known species identity also yielded 100% accuracy. Overall, MTaxi provides a straightforward approach to classify closely related species that are difficult to distinguish through zooarchaeological methods using low coverage aDNA data, especially when similar quality reference genomes are unavailable. MTaxi is freely available at
https://github.com/goztag/MTaxi
.
New technologies and analysis methods are enabling genomic structural variants (SVs) to be detected with ever-increasing accuracy, resolution and comprehensiveness. To help translate these methods to ...routine research and clinical practice, we developed a sequence-resolved benchmark set for identification of both false-negative and false-positive germline large insertions and deletions. To create this benchmark for a broadly consented son in a Personal Genome Project trio with broadly available cells and DNA, the Genome in a Bottle Consortium integrated 19 sequence-resolved variant calling methods from diverse technologies. The final benchmark set contains 12,745 isolated, sequence-resolved insertion (7,281) and deletion (5,464) calls ≥50 base pairs (bp). The Tier 1 benchmark regions, for which any extra calls are putative false positives, cover 2.51 Gbp and 5,262 insertions and 4,095 deletions supported by ≥1 diploid assembly. We demonstrate that the benchmark set reliably identifies false negatives and false positives in high-quality SV callsets from short-, linked- and long-read sequencing and optical mapping.
Genomic variations including single nucleotide polymorphisms (SNPs), small INDELs and structural variations (SVs) are known to have significant phenotypic effects on individuals. Among them, SVs, ...that alter more than 50 nucleotides of DNA, are the major source of complex genetic diseases such as Crohn's, schizophrenia and autism. Additionally, the total number of nucleotides affected by SVs are substantially higher than SNPs (3.5 Mbp SNP, 15-20 Mbp SV). Today, we are able to perform whole genome sequencing (WGS) by utilizing high throughput sequencing technology (HTS) to discover these modifications unimaginably faster, cheaper and more accurate than before. However, as demonstrated in the 1000 Genomes Project, HTS technology still has significant limitations. The major problem lies in the short read lengths (<250 bp) produced by the current sequencing platforms and the fact that most genomes include large amounts of repeats make it very challenging to unambiguously map and accurately characterize genomic variants. Thus, most of the existing SV discovery tools focus on detecting relatively simple types of SVs such as insertions, deletions, and short inversions. In fact, other types of SVs including the complex ones are of crucial importance and several have been associated with genomic disorders. To better understand the contribution of these SVs to human genome, we need new approaches to accurately discover and genotype such variants. Therefore, there is still a need for accurate algorithms to fully characterize a broader spectrum of SVs and thus improve calling accuracy of more simple variants.Here we introduce TARDIS that harbors novel algorithms to accurately characterize various types of SVs including deletions, novel sequence insertions, inversions, transposon insertions, nuclear mitochondria insertions, tandem duplications and interspersed segmental duplications in direct or inverted orientations using short read whole genome sequencing datasets. Within our framework, we make use of multiple sequence signatures including read pair, read depth and split read in order to capture different sequence signatures and increase our SV prediction accuracy. Additionally, we are able to analyze more than one possible mapping location of each read to overcome the problems associated with repeated nature of genomes. Recently, due to the limitations of short-read sequencing technology, newer library preparation techniques emerged and 10x Genomics is one of these initiatives. This technique is regarded as a cost-effective alternative to long read sequencing, which can obtain long range contiguity information. We extended TARDIS to be able to utilize Linked-Read information of 10x Genomics to overcome some of the constraints of short-read sequencing technology.We evaluated the prediction performance of our algorithms through several experiments using both simulated and real data sets. In the simulation experiments, TARDIS achieved 97.67% sensitivity with only 1.12% false discovery rate. For experiments that involve real data, we used two haploid genomes (CHM1 and CHM13) and one human genome (NA12878) from the Illumina Platinum Genomes set. Comparison of our results with orthogonal PacBio call sets from the same genomes revealed higher accuracy for TARDIS than state of the art methods. Furthermore, we showed a surprisingly low false discovery rate of our approach for discovery of tandem, direct and inverted interspersed segmental duplications prediction on CHM1 (less than 5% for the top 50 predictions). The algorithms we describe here are the first to predict insertion location and the various types of new segmental duplications using HTS data.
MOOCs 2.0: THE SOCIAL ERA OF EDUCATION SOYLEV, Arda
The Turkish online journal of distance education TOJDE,
04/2017, Letnik:
18, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The improvements in the Internet technology led an evolution in education. Some students' lives have changed since 2012 when the MOOCs gained popularity among the academia. The students now take ...courses from the top universities all around the world without time limitations and they even earn credits for their courses. They are able to discuss lecture topics not only with their instructors in the class but also with thousands of other online students and can get just-in-time help regarding to their questions from teaching assistants. These are some of the practices from the new era of MOOCs called "social MOOCs" or MOOC 2.0. The concepts of collaboration, blended learning and TAs are the new consequences. In this paper, we review the problems and the current solutions associated with MOOC 1.0 era. In the light of these, we analyze the MOOC 2.0 era and discuss its present and possible future affects to our lives.
A major challenge in zooarchaeology is to morphologically distinguish closely related species’ remains, especially using small bone fragments. Shotgun sequencing aDNA from archeological remains and ...comparative alignment to the candidate species’ reference genomes will only apply when reference nuclear genomes of comparable quality are available, and may still fail when coverages are low. Here, we propose an alternative method, MTaxi, that uses highly accessible mitochondrial DNA (mtDNA) to distinguish between pairs of closely related species from ancient DNA sequences. MTaxi utilises mtDNA transversion-type substitutions between pairs of candidate species, assigns reads to either species, and performs a binomial test to determine the sample taxon. We tested MTaxi on sheep/goat and horse/donkey data, between which zooarchaeological classification can be challenging in ways that epitomise our case. The method performed efficiently on simulated ancient genomes down to 0.3x mitochondrial coverage for both sheep/goat and horse/donkey, with no false positives. Trials on n=18 ancient sheep/goat samples and n=10 horse/donkey samples of known species identity also yielded 100% accuracy. Overall, MTaxi provides a straightforward approach to classify closely related species that are difficult to distinguish through zooarchaeological methods using low coverage aDNA data, especially when similar quality reference genomes are unavailable. MTaxi is freely available at
https://github.com/goztag/MTaxi
.
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