68,316 research outputs found
An integrated software for virus community sequencing data analysis
BACKGROUND: A virus community is the spectrum of viral strains populating an infected host, which plays a key role in pathogenesis and therapy response in viral infectious diseases. However automatic and dedicated pipeline for interpreting virus community sequencing data has not been developed yet.RESULTS: We developed Quasispecies Analysis Package (QAP), an integrated software platform to address the problems associated with making biological interpretations from massive viral population sequencing data. QAP provides quantitative insight into virus ecology by first introducing the definition "virus OTU" and supports a wide range of viral community analyses and results visualizations. Various forms of QAP were developed in consideration of broader users, including a command line, a graphical user interface and a web server. Utilities of QAP were thoroughly evaluated with high-throughput sequencing data from hepatitis B virus, hepatitis C virus, influenza virus and human immunodeficiency virus, and the results showed highly accurate viral quasispecies characteristics related to biological phenotypes.CONCLUSIONS: QAP provides a complete solution for virus community high throughput sequencing data analysis, and it would facilitate the easy analysis of virus quasispecies in clinical applications.</p
Fast individual ancestry inference from DNA sequence data leveraging allele frequencies for multiple populations.
BackgroundEstimation of individual ancestry from genetic data is useful for the analysis of disease association studies, understanding human population history and interpreting personal genomic variation. New, computationally efficient methods are needed for ancestry inference that can effectively utilize existing information about allele frequencies associated with different human populations and can work directly with DNA sequence reads.ResultsWe describe a fast method for estimating the relative contribution of known reference populations to an individual's genetic ancestry. Our method utilizes allele frequencies from the reference populations and individual genotype or sequence data to obtain a maximum likelihood estimate of the global admixture proportions using the BFGS optimization algorithm. It accounts for the uncertainty in genotypes present in sequence data by using genotype likelihoods and does not require individual genotype data from external reference panels. Simulation studies and application of the method to real datasets demonstrate that our method is significantly times faster than previous methods and has comparable accuracy. Using data from the 1000 Genomes project, we show that estimates of the genome-wide average ancestry for admixed individuals are consistent between exome sequence data and whole-genome low-coverage sequence data. Finally, we demonstrate that our method can be used to estimate admixture proportions using pooled sequence data making it a valuable tool for controlling for population stratification in sequencing based association studies that utilize DNA pooling.ConclusionsOur method is an efficient and versatile tool for estimating ancestry from DNA sequence data and is available from https://sites.google.com/site/vibansal/software/iAdmix
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Are providers prepared for genomic medicine: interpretation of Direct-to-Consumer genetic testing (DTC-GT) results and genetic self-efficacy by medical professionals.
BACKGROUND:Precision medicine is set to deliver a rich new data set of genomic information. However, the number of certified specialists in the United States is small, with only 4244 genetic counselors and 1302 clinical geneticists. We conducted a national survey of 264 medical professionals to evaluate how they interpret genetic test results, determine their confidence and self-efficacy of interpreting genetic test results with patients, and capture their opinions and experiences with direct-to-consumer genetic tests (DTC-GT). METHODS:Participants were grouped into two categories, genetic specialists (genetic counselors and clinical geneticists) and medical providers (primary care, internists, physicians assistants, advanced nurse practitioners, etc.). The survey (full instrument can be found in the Additional file 1) presented three genetic test report scenarios for interpretation: a genetic risk for diabetes, genomic sequencing for symptoms report implicating a potential HMN7B: distal hereditary motor neuropathy VIIB diagnosis, and a statin-induced myopathy risk. Participants were also asked about their opinions on DTC-GT results and rank their own perceived level of preparedness to review genetic test results with patients. RESULTS:The rates of correctly interpreting results were relatively high (74.4% for the providers compared to the specialist's 83.4%) and age, prior genetic test consultation experience, and level of trust assigned to the reports were associated with higher correct interpretation rates. The self-selected efficacy and the level of preparedness to consult on a patient's genetic results were higher for the specialists than the provider group. CONCLUSION:Specialists remain the best group to assist patients with DTC-GT, however, primary care providers may still provide accurate interpretation of test results when specialists are unavailable
GENETIC TESTING PRACTICES OF GENETIC COUNSELORS, GENETICISTS, AND PEDIATRIC NEUROLOGISTS WITH REGARD TO CHILDHOOD-ONSET NEUROGENETIC CONDITIONS
Identifying genetic diagnoses for neurological conditions with a considerable hereditary component, such as autism spectrum disorder (ASD), intellectual disability, and epilepsy, is critical to providing proper medical management for these patients and their families. However, many patients with these conditions are not tested appropriately or receive no genetic testing at all. The current study was designed to characterize the genetic testing practices of the providers most likely to evaluate or order genetic testing for these patients: pediatric neurologists, geneticists, and genetic counselors. The study noted significant variance between the testing strategies selected by pediatric neurologists compared to those of geneticists and genetic counselors and supports the need for updated guidelines that are consistent across specialties. Pediatric neurologists report lower confidence with ordering genetic testing and a need and desire for further education regarding genetic testing. This study proposes that the continued integration of genetic counselors into pediatric neurology clinics may improve utilization of genetic testing while reducing the burden on neurologists
Next-generation conservation genetics and biodiversity monitoring
This special issue of Evolutionary Applications consists of 10 publications investigating
the use of next-generation
tools and techniques in population genetic analyses and
biodiversity assessment. The special issue stems from a 2016 Next Generation
Genetic Monitoring Workshop, hosted by the National Institute for Mathematical
and Biological Synthesis (NIMBioS) in Tennessee, USA. The improved accessibility of
next-generation
sequencing platforms has allowed molecular ecologists to rapidly
produce large amounts of data. However, with the increased availability of new
genomic markers and mathematical techniques, care is needed in selecting appropriate
study designs, interpreting results in light of conservation concerns, and determining
appropriate management actions. This special issue identifies key attributes
of successful genetic data analyses in biodiversity evaluation and suggests ways to
improve analyses and their application in current population and conservation genetics
research
Analysis of Microsatellite Variation in Drosophila melanogaster with Population-Scale Genome Sequencing
Genome sequencing technologies promise to revolutionize our understanding of genetics, evolution, and disease by making it feasible to survey a broad spectrum of sequence variation on a population scale. However, this potential can only be realized to the extent that methods for extracting and interpreting distinct forms of variation can be established. The error profiles and read length limitations of early versions of next-generation sequencing technologies rendered them ineffective for some sequence variant types, particularly microsatellites and other tandem repeats, and fostered the general misconception that such variants are inherently inaccessible to these platforms. At the same time, tandem repeats have emerged as important sources of functional variation. Tandem repeats are often located in and around genes, and frequent mutations in their lengths exert quantitative effects on gene function and phenotype, rapidly degrading linkage disequilibrium between markers and traits. Sensitive identification of these variants in large-scale next-gen sequencing efforts will enable more comprehensive association studies capable of revealing previously invisible associations. We present a population-scale analysis of microsatellite repeats using whole-genome data from 158 inbred isolates from the Drosophila Genetics Reference Panel, a collection of over 200 extensively phenotypically characterized isolates from a single natural population, to uncover processes underlying repeat mutation and to enable associations with behavioral, morphological, and life-history traits. Analysis of repeat variation from next-generation sequence data will also enhance studies of genome stability and neurodegenerative diseases
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A high-resolution map of human evolutionary constraint using 29 mammals.
The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease
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Patterns of Oral Microbiota Diversity in Adults and Children: A Crowdsourced Population Study.
Oral microbiome dysbiosis has been associated with various local and systemic human diseases such as dental caries, periodontal disease, obesity, and cardiovascular disease. Bacterial composition may be affected by age, oral health, diet, and geography, although information about the natural variation found in the general public is still lacking. In this study, citizen-scientists used a crowdsourcing model to obtain oral bacterial composition data from guests at the Denver Museum of Nature & Science to determine if previously suspected oral microbiome associations with an individual's demographics, lifestyle, and/or genetics are robust and generalizable enough to be detected within a general population. Consistent with past research, we found bacterial composition to be more diverse in youth microbiomes when compared to adults. Adult oral microbiomes were predominantly impacted by oral health habits, while youth microbiomes were impacted by biological sex and weight status. The oral pathogen Treponema was detected more commonly in adults without recent dentist visits and in obese youth. Additionally, oral microbiomes from participants of the same family were more similar to each other than to oral microbiomes from non-related individuals. These results suggest that previously reported oral microbiome associations are observable in a human population containing the natural variation commonly found in the general public. Furthermore, these results support the use of crowdsourced data as a valid methodology to obtain community-based microbiome data
Population history from the Neolithic to present on the Mediterranean island of Sardinia: an ancient DNA perspective
Recent ancient DNA studies of western Eurasia have revealed a dynamic history of admixture, with evidence for major migrations during the Neolithic and Bronze Age. The population of the Mediterranean island of Sardinia has been notable in these studies –} Neolithic individuals from mainland Europe cluster more closely with Sardinian individuals than with all other present-day Europeans. The current model to explain this result is that Sardinia received an initial influx of Neolithic ancestry and then remained relatively isolated from expansions in the later Neolithic and Bronze Age that took place in continental Europe. To test this model, we generated genome-wide capture data (approximately 1.2 million variants) for 43 ancient Sardinian individuals spanning the Neolithic through the Bronze Age, including individuals from Sardinia{’}s Nuragic culture, which is known for the construction of numerous large stone towers throughout the island. We analyze these new samples in the context of previously generated genome-wide ancient DNA data from 972 ancient individuals across western Eurasia and whole-genome sequence data from approximately 1,500 modern individuals from Sardinia. The ancient Sardinian individuals show a strong affinity to western Mediterranean Neolithic populations and we infer a high degree of genetic continuity on the island from the Neolithic (around fifth millennium BCE) through the Nuragic period (second millennium BCE). In particular, during the Bronze Age in Sardinia, we do not find significant levels of the {“}Steppe{” ancestry that was spreading in many other parts of Europe at that time. We also characterize subsequent genetic influx between the Nuragic period and the present. We detect novel, modest signals of admixture between 1,000 BCE and present-day, from ancestry sources in the eastern and northern Mediterranean. Within Sardinia, we confirm that populations from the more geographically isolated mountainous provinces have experienced elevated levels of genetic drift and that northern and southwestern regions of the island received more gene flow from outside Sardinia. Overall, our genetic analysis sheds new light on the origin of Neolithic settlement on Sardinia, reinforces models of genetic continuity on the island, and provides enhanced power to detect post-Bronze-Age gene flow. Together, these findings offer a refined demographic model for future medical genetic studies in Sardinia
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