Project description:Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this article, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains.
Project description:Despite its economic importance as a bioenergy crop and key role in riparian ecosystems, little is known about genetic diversity and adaptation of the eastern cottonwood (Populus deltoides). Here, we report the first population genomics study for this species, conducted on a sample of 425 unrelated individuals collected in 13 states of the southeastern United States. The trees were genotyped by targeted resequencing of 18,153 genes and 23,835 intergenic regions, followed by the identification of single nucleotide polymorphisms (SNPs). This natural P. deltoides population showed low levels of subpopulation differentiation (FST = 0.022-0.106), high genetic diversity (θW = 0.00100, π = 0.00170), a large effective population size (Ne ≈ 32,900), and low to moderate levels of linkage disequilibrium. Additionally, genomewide scans for selection (Tajima's D), subpopulation differentiation (XTX), and environmental association analyses with eleven climate variables carried out with two different methods (LFMM and BAYENV2) identified genes putatively involved in local adaptation. Interestingly, many of these genes were also identified as adaptation candidates in another poplar species, Populus trichocarpa, indicating possible convergent evolution. This study constitutes the first assessment of genetic diversity and local adaptation in P. deltoides throughout the southern part of its range, information we expect to be of use to guide management and breeding strategies for this species in future, especially in the face of climate change.
Project description:Interactions between environmental factors and complex life-history characteristics of marine organisms produce the genetic diversity and structure observed within species. Our main goal was to test for genetic differentiation among eastern oyster populations from the coastal region of Canadian Maritimes against expected genetic homogeneity caused by historical events, taking into account spatial and environmental (temperature, salinity, turbidity) variation. This was achieved by genotyping 486 individuals originating from 13 locations using RADSeq. A total of 11,321 filtered SNPs were used in a combination of population genomics and environmental association analyses. We revealed significant neutral genetic differentiation (mean F ST = 0.009) between sampling locations, and the occurrence of six major genetic clusters within the studied system. Redundancy analyses (RDAs) revealed that spatial and environmental variables explained 3.1% and 4.9% of the neutral genetic variation and 38.6% and 12.2% of the putatively adaptive genetic variation, respectively. These results indicate that these environmental factors play a role in the distribution of both neutral and putatively adaptive genetic diversity in the system. Moreover, polygenic selection was suggested by genotype-environment association analysis and significant correlations between additive polygenic scores and temperature and salinity. We discuss our results in the context of their conservation and management implications for the eastern oyster.
Project description:Resolving evolutionary relationships and establishing population structure depends on molecular diagnosability that is often limited for closely related taxa. Here, we use 3,200 ddRAD-seq loci across 290 mallards, American black ducks, and putative hybrids to establish population structure and estimate hybridization rates. We test between traditional assignment probability and accumulated recombination events based analyses to assign hybrids to generational classes. For hybrid identification, we report the distribution of recombination events complements ADMIXTURE simulation by extending resolution past F4 hybrid status; however, caution against hybrid assignment based on accumulated recombination events due to an inability to resolve F1 hybrids. Nevertheless, both analyses suggest that there are relatively few backcrossed stages before a lineage's hybrid ancestry is lost and the offspring are effectively parental again. We conclude that despite high rates of observed interspecific hybridization between mallards and black ducks in the middle part of the 20th century, our results do not support the predicted hybrid swarm. Conversely, we report that mallard samples genetically assigned to western and non-western clusters. We indicate that these non-western mallards likely originated from game-farm stock, suggesting landscape level gene flow between domestic and wild conspecifics.
Project description:The application of nanotechnology to medicine promises a wide range of new tools and possibilities, from earlier diagnostics and improved imaging, to better, more efficient, and more targeted therapies. This emerging field could help address obesity, with advances in drug delivery, nutraceuticals, and genetic and epigenetic therapeutics. Its application to obesity is still largely in the development phase. Here, we review the novel angle of nanotech applied to human consumable products and their specific applications to addressing obesity through nutraceuticals, with respect to benefits and limitations of current nanotechnology methods. Further, we review potential future applications to deliver genetic and epigenetic miRNA therapeutics. Finally, we discuss future directions, including theranostics, combinatory therapy, and personalized medicine.
Project description:Leukemia involves different types of blood cancers, which lead to significant mortality and morbidity. Murine models of leukemia have been instrumental in understanding the biology of the disease and identifying therapeutics. However, such models are time consuming and expensive in high throughput genetic and drug screening. Drosophila melanogaster has emerged as an invaluable in vivo model for studying different diseases, including cancer. Fruit flies possess several hematopoietic processes and compartments that are in close resemblance to their mammalian counterparts. A number of studies succeeded in characterizing the fly's response upon the expression of human leukemogenic proteins in hematopoietic and non-hematopoietic tissues. Moreover, some of these studies showed that these models are amenable to genetic screening. However, none were reported to be tested for drug screening. In this review, we describe the Drosophila hematopoietic system, briefly focusing on leukemic diseases in which fruit flies have been used. We discuss myeloid and lymphoid leukemia fruit fly models and we further highlight their roles for future therapeutic screening. In conclusion, fruit fly leukemia models constitute an interesting area which could speed up the process of integrating new therapeutics when complemented with mammalian models.
Project description:This article reviews existing research at the intersection of genetics and economics, presents some new findings that illustrate the state of genoeconomics research, and surveys the prospects of this emerging field. Twin studies suggest that economic outcomes and preferences, once corrected for measurement error, appear to be about as heritable as many medical conditions and personality traits. Consistent with this pattern, we present new evidence on the heritability of permanent income and wealth. Turning to genetic association studies, we survey the main ways that the direct measurement of genetic variation across individuals is likely to contribute to economics, and we outline the challenges that have slowed progress in making these contributions. The most urgent problem facing researchers in this field is that most existing efforts to find associations between genetic variation and economic behavior are based on samples that are too small to ensure adequate statistical power. This has led to many false positives in the literature. We suggest a number of possible strategies to improve and remedy this problem: (a) pooling data sets, (b) using statistical techniques that exploit the greater information content of many genes considered jointly, and (c) focusing on economically relevant traits that are most proximate to known biological mechanisms.
Project description:An ever-increasing body of literature affirms the physical and biological basis for sensitisation of tumours to conventional therapies such as chemotherapy and radiation therapy by mild temperature hyperthermia. This knowledge has fuelled the efforts to attain, maintain, measure and monitor temperature via technological advances. A relatively new entrant in the field of hyperthermia is nanotechnology which capitalises on locally injected or systemically administered nanoparticles that are activated by extrinsic energy sources to generate heat. This review describes the kinds of nanoparticles available for hyperthermia generation, their activation sources, their characteristics, and the unique opportunities and challenges with nanoparticle-mediated hyperthermia.
Project description:A rapidly expanding range of diverse human diseases is now associated with perturbations to the gastrointestinal microbiome. Fecal microbial transplant (FMT) has been used with high rates of efficacy to treat gastrointestinal microbiome perturbation associated with recurrent Clostridium difficile infection, and is now being considered for other indications. Here we discuss the gut microbiome, review published and ongoing studies using FMT as a treatment modality for human disease, consider the regulatory aspects of FMT, and outline some factors that should be considered in patients in whom this therapeutic strategy is being contemplated.