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Background: A high-quality genome sequence of any model organism is an essential starting point for genetic and other studies. Older clone-based methods are slow and expensive, whereas faster, cheaper short-read-only assemblies can be incomplete and highly fragmented, which minimizes their usefulness. The last few years have seen the introduction of many new technologies for genome assembly. These new technologies and associated new algorithms are typically benchmarked on microbial genomes or, if they scale appropriately, on larger (e.g., human) genomes. However, plant genomes can be much more repetitive and larger than the human genome, and plant biochemistry often makes obtaining high-quality DNA that is free from contaminants difficult. Reflecting their challenging nature, we observe that plant genome assembly statistics are typically poorer than for vertebrates., Results: Here, we compare Illumina short read, Pacific Biosciences long read, 10x Genomics linked reads, Dovetail Hi-C, and BioNano Genomics optical maps, singly and combined, in producing high-quality long-range genome assemblies of the potato species Solanum verrucosum. We benchmark the assemblies for completeness and accuracy, as well as DNA compute requirements and sequencing costs., Conclusions: The field of genome sequencing and assembly is reaching maturity, and the differences we observe between assemblies are surprisingly small. We expect that our results will be helpful to other genome projects, and that these datasets will be used in benchmarking by assembly algorithm developers., (© The Author(s) 2019. Published by Oxford University Press.)

The concept of a pan-genome refers to intraspecific diversity in genome content and structure, encompassing both genes and intergenic space. Pan-genomic studies employ a combination of de novo sequence assembly and reference-based alignment to discover and genotype structural variants. The large size and complex structure of Triticeae genomes were for a long time an obstacle for genomic research in barley and its relatives. Now that a reference genome is available, computational pipelines for high-quality sequence assembly are in place, and sequence costs continue to drop, investigations into the structural diversity of the barley genome seem within reach. Here, we review the recent progress on pan-genomics in the model grass Brachypodium distachyon, and the cereal crops rice and maize, and devise a multi-tiered strategy for a pan-genome project in barley. Our design involves: (1) the construction of high-quality de novo sequence assemblies for a small core set of representative genotypes, (2) short-read sequencing of a large diversity panel of genebank accessions to medium coverage and (3) the use of complementary methods such as chromosome-conformation capture sequencing and k-mer-based association genetics. The in silico representation of the barley pan-genome may inform about the mechanisms of structural genome evolution in the Triticeae and supplement quantitative genetics models of crop performance for better accuracy and predictive ability.

Affordable, high-throughput DNA sequencing has accelerated the pace of genome assembly over the past decade. Genome assemblies from high-throughput, short-read sequencing, however, are often not as contiguous as the first generation of genome assemblies. Whereas early genome assembly projects were often aided by clone maps or other mapping data, many current assembly projects forego these scaffolding data and only assemble genomes into smaller segments. Recently, new technologies have been invented that allow chromosome-scale assembly at a lower cost and faster speed than traditional methods. Here, we give an overview of the problem of chromosome-scale assembly and traditional methods for tackling this problem. We then review new technologies for chromosome-scale assembly and recent genome projects that used these technologies to create highly contiguous genome assemblies at low cost.

Genomic sequencing is rapidly transitioning into clinical practice, and implementation into healthcare systems has been supported by substantial government investment, totaling over US$4 billion, in at least 14 countries. These national genomic-medicine initiatives are driving transformative change under real-life conditions while simultaneously addressing barriers to implementation and gathering evidence for wider adoption. We review the diversity of approaches and current progress made by national genomic-medicine initiatives in the UK, France, Australia, and US and provide a roadmap for sharing strategies, standards, and data internationally to accelerate implementation., (Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Next-generation sequencing (NGS)-based mutation panels profile multiple genes simultaneously, allowing the reporting of numerous genes while saving labor and resources. However, one drawback of using NGS is that the turnaround time is often longer than conventional single gene tests. This delay can be problematic if molecular results are required to guide therapy in patients with clinically aggressive diseases, such as acute myeloid leukemia. To overcome this limitation, we developed a novel custom platform designated as Ultra-rapid Reporting of GENomic Targets (URGENTseq), an integrated solution that includes workflow optimization and an innovative custom bioinformatics pipeline to provide targeted NGS results on fresh peripheral blood and bone marrow samples within an actionable time period. URGENTseq was validated for clinical use by determining mutant allelic frequency and minimum coverage in silico to achieve 100% concordance for all positive and negative calls between the URGENTseq and conventional sequencing approach. URGENTseq enables the reporting of selected genes useful for immediate diagnosis (CALR, CSF3R, JAK2, KRAS, MPL, NPM1, NRAS, SF3B1) and treatment decisions (IDH1, IDH2) in hematologic malignancies within 48 hours of specimen collection. In addition, we summarize the molecular findings of the first 272 clinical test results performed using the URGENTseq platform., (Copyright © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Personalized medicine promises to advance and improve health by targeting the right medication to the right person at the right time, thus maximizing the proportion of treated patients who achieve an effective response to therapy. This Comment article makes the complementary argument that equally important benefits will derive from negative prediction, namely by identifying those individuals who are either not actually in need of, or unlikely to respond to, a drug. Reduction of unnecessary prescription could conceivably save health-care systems many billions of dollars with very little detrimental impact on outcomes.

Background: Reducing ultraviolet radiation (UV) exposure and improving early detection may reduce melanoma incidence, mortality and health system costs. This study aims to evaluate the efficacy and cost-effectiveness of providing information on personal genomic risk of melanoma in reducing UV exposure at 12 months, according to low and high traditional risk., Methods: In this randomized controlled trial, participants (target sample = 892) will be recruited from the general population, and randomized (1:1 ratio, intervention versus control). Intervention arm participants provide a saliva sample, receive personalized melanoma genomic risk information, a genetic counselor phone call, and an educational booklet on melanoma prevention. Control arm participants receive only the educational booklet. Eligible participants are aged 18-69 years, have European ancestry and no personal history of melanoma. All participants will complete a questionnaire and wear a UV dosimeter to objectively measure their sun exposure at baseline, 1- and 12-month time-points, except 1-month UV dosimetry will be limited to ~250 participants. The primary outcome is total daily Standard Erythemal Doses at 12 months. Secondary outcomes include objectively measured UV exposure for specific time periods (e.g. midday hours), self-reported sun protection and skin-examination behaviors, psycho-social outcomes, and ethical considerations surrounding offering genomic testing at a population level. A within-trial and modelled economic evaluation will be undertaken from an Australian health system perspective to assess the intervention costs and outcomes., Discussion: This trial will inform the clinical and personal utility of introducing genomic testing into the health system for melanoma prevention and early detection at a population-level., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12617000691347., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Developments in next-generation sequencing technologies have driven the clinical application of diagnostic tests that interrogate the whole genome, which offer the chance to diagnose rare inherited diseases or inform the targeting of therapies. New genomic diagnostic tests compete with traditional approaches to diagnosis, including the genetic testing of single genes and other clinical strategies, for finite health-care budgets. In this context, decision analytic model-based cost-effectiveness analysis is a useful method to help evaluate the costs versus consequences of introducing new health-care interventions. This Perspective presents key methodological, technical, practical and organizational challenges that must be considered by decision-makers responsible for the allocation of health-care resources to obtain robust and timely information about the relative cost-effectiveness of the increasing numbers of emerging genomic tests.

Standard Illumina libraries are biased toward sequences of intermediate GC-content. This results in an underrepresentation of GC-rich regions in sequencing projects of genomes with heterogeneous base composition, such as mammals and birds. We developed a simple, cost-effective protocol to enrich sheared genomic DNA in its GC-rich fraction by subtracting AT-rich DNA. This was achieved by heating DNA up to 90 °C before applying Illumina library preparation. We tested the new approach on chicken DNA and found that heated DNA increased average coverage in the GC-richest chromosomes by a factor up to six. Using a Taq polymerase supposedly appropriate for PCR amplification of GC-rich sequences had a much weaker effect. Our protocol should greatly facilitate sequencing and resequencing of the GC-richest regions of heterogeneous genomes, in combination with standard short-read and long-read technologies., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Obtaining high-quality samples from wild animals is a major obstacle for genomic studies of many taxa, particularly at the population level, as collection methods for such samples are typically invasive. DNA from feces is easy to obtain noninvasively, but is dominated by bacterial and other non-host DNA. The high proportion of non-host DNA drastically reduces the efficiency of high-throughput sequencing for host animal genomics. To address this issue, we developed an inexpensive capture method for enriching host DNA from noninvasive fecal samples. Our method exploits natural differences in CpG-methylation density between vertebrate and bacterial genomes to preferentially bind and isolate host DNA from majority-bacterial samples. We demonstrate that the enrichment is robust, efficient, and compatible with downstream library preparation methods useful for population studies (e.g., RADseq). Compared to other enrichment strategies, our method is quick and inexpensive, adding only a negligible cost to sample preparation. In combination with downstream methods such as RADseq, our approach allows for cost-effective and customizable genomic-scale genotyping that was previously feasible in practice only with invasive samples. Because feces are widely available and convenient to collect, our method empowers researchers to explore genomic-scale population-level questions in organisms for which invasive sampling is challenging or undesirable.

This article traces the emergence of lean principles in genomics research and connects this new way of doing science with many of the current pitfalls of precision medicine in its attempts at improving population health outcomes. Precision medicine has a history of public funding, yet the benefits in clinical settings are very slowly being realized due to a variety of factors, such as uncertainty regarding relevant treatments after identifying disease risk, lack of cost-effectiveness studies for general population-level interventions, and letting a culture of "over promise and under deliver" permeate some areas of genomics research. The article concludes with insights into the challenges and opportunities that will need careful consideration and consultation with the wider society in order to decide whether to turn off the "tap" for investment of public funds in research on genomics and other "omics." Ultimately, this article argues for a moderate course correction in how public funds are invested to truly improve the health of all of us, and not just some of us.

Large-scale genomic analyses of human cancers have cataloged somatic point mutations thought to initiate tumor development and sustain cancer growth. However, determining the functional significance of specific alterations remains a major bottleneck in our understanding of the genetic determinants of cancer. Here, we present a platform that integrates multiplexed AAV/Cas9-mediated homology-directed repair (HDR) with DNA barcoding and high-throughput sequencing to simultaneously investigate multiple genomic alterations in de novo cancers in mice. Using this approach, we introduce a barcoded library of non-synonymous mutations into hotspot codons 12 and 13 of Kras in adult somatic cells to initiate tumors in the lung, pancreas, and muscle. High-throughput sequencing of barcoded Kras HDR alleles from bulk lung and pancreas reveals surprising diversity in Kras variant oncogenicity. Rapid, cost-effective, and quantitative approaches to simultaneously investigate the function of precise genomic alterations in vivo will help uncover novel biological and clinically actionable insights into carcinogenesis.

Genomic medicine has greatly matured in terms of its technical capabilities, but the diffusion of genomic innovations worldwide faces significant barriers beyond mere access to technology. New global development strategies are sorely needed for biotechnologies such as genomics and their applications toward precision medicine without borders. Moreover, diffusion of genomic medicine globally cannot adhere to a "one-size-fits-all-countries" development strategy, in the same way that drug treatments should be customized. This begs a timely, difficult but crucial question: How should developing countries, and the resource-limited regions of developed countries, invest in genomic medicine? Although a full-scale investment in infrastructure from discovery to the translational implementation of genomic science is ideal, this may not always be feasible in all countries at all times. A simple "transplantation of genomics" from developed to developing countries is unlikely to be feasible. Nor should developing countries be seen as simple recipients and beneficiaries of genomic medicine developed elsewhere because important advances in genomic medicine have materialized in developing countries as well. There are several noteworthy examples of genomic medicine success stories involving resource-limited settings that are contextualized and described in this global genomic medicine innovation analysis. In addition, we outline here a new long-term development strategy for global genomic medicine in a way that recognizes the individual country's pressing public health priorities and disease burdens. We term this approach the "Fast-Second Winner" model of innovation that supports innovation commencing not only "upstream" of discovery science but also "mid-stream," building on emerging highly promising biomarker and diagnostic candidates from the global science discovery pipeline, based on the unique needs of each country. A mid-stream entry into innovation can enhance collective learning from other innovators' mistakes upstream in discovery science and boost the probability of success for translation and implementation when resources are limited. This à la carte model of global innovation and development strategy offers multiple entry points into the global genomics innovation ecosystem for developing countries, whether or not extensive and expensive discovery infrastructures are already in place. Ultimately, broadening our thinking beyond the linear model of innovation will help us to enable the vision and practice of genomics without borders in both developed and resource-limited settings.

Summary: The decreasing cost in high-throughput technologies led to a number of sequencing projects consisting of thousands of whole genomes. The paradigm shift from exome to whole genome brings a significant increase in the size of output files. Most of the existing tools which are developed to analyse exome files are not adequate for larger VCF files produced by whole genome studies. In this work we present VCF-Explorer, a variant analysis software capable of handling large files. Memory efficiency and avoiding computationally costly pre-processing step enable to carry out the analysis to be performed with ordinary computers. VCF-Explorer provides an easy to use environment where users can define various types of queries based on variant and sample genotype level annotations. VCF-Explorer can be run in different environments and computational platforms ranging from a standard laptop to a high performance server., Availability and Implementation: VCF-Explorer is freely available at: http://vcfexplorer.sourceforge.net/., Contact: mete.akgun@tubitak.gov.tr., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Introduction and Method: Africa is currently host to a number of international genomics research and biobanking consortia, each with a mandate to advance genomics research and biobanking in Africa. Whilst most of these consortia promise to transform the way international health research is done in Africa, few have articulated exactly how they propose to go about this. In this paper, we report on a qualitative interviewing study in which we involved 17 genomics researchers in Africa. We describe their perceptions and expectations of international genomics research and biobanking initiatives in Africa., Results: All interviewees were of the view that externally funded genomics research and biobanking initiatives in Africa, have played a critical role in building capacity for genomics research and biobanking in Africa and in providing an opportunity for researchers in Africa to collaborate and network with other researchers. Whilst the opportunity to collaborate was seen as a benefit, some interviewees stressed the importance of recognizing that these collaborations carry mutual benefits for all partners, including their collaborators in HICs. They also voiced two major concerns of being part of these collaborative initiatives: the possibility of exploitation of African researchers and the non-sustainability of research capacity building efforts. As a way of minimising exploitation, researchers in Africa recommended that genuine efforts be made to create transparent and equitable international health research partnerships. They suggested that this could be achieved through,: having rules of engagement, enabling African researchers to contribute to the design and conduct of international health projects in Africa, and mutual and respectful exchange of experience and capacity between research collaborators. These were identified as hallmarks to equitable international health research collaborations in Africa., Conclusion: Genomics research and biobanking initiatives in Africa such as H3Africa have gone some way in defining aspects of fair and equitable research collaborations in Africa. However, they will need to strive at achieving equitable health research collaborations if they truly aim at setting a gold standard for how international health research should be conducted in Africa.

Clinical implementation of pharmacogenomics (PGx) leads to personalized medicine, which improves the efficacy, safety, and cost-effectiveness of treatments. Although PGx-based research has been conducted for more than a decade, several barriers have slowed down its widespread implementation in clinical practice. Globally, there is an imbalance in programs and solutions required to empower the clinical implementation of PGx between countries. Therefore, we aimed to review these issues comprehensively, determine the major barriers, and find the best solutions. Through an extensive review of ongoing clinical implementation programs, scientific, educational, ethical, legal, and social issues, information technology, and reimbursement were identified as the key barriers. The pace of global implementation of genomic medicine coincided with the resource limitations of each country. The key solutions identified for the earlier mentioned barriers are as follows: building of secure and suitable information technology infrastructure with integrated clinical decision support systems along with increasing PGx evidence, more regulations, reimbursement strategies for stakeholder's acceptance, incorporation of PGx education in all institutions and clinics, and PGx promotion to all health care professionals and patients. In conclusion, this review will be helpful for the better understanding of common barriers and solutions pertaining to the clinical application of PGx., (Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Third generation sequencing technologies, with sequencing reads in the tens- of kilo-bases, facilitate genome assembly by spanning ambiguous regions and improving continuity. This has been critical for plant genomes, which are difficult to assemble due to high repeat content, gene family expansions, segmental and tandem duplications, and polyploidy. Recently, high-throughput mapping and scaffolding strategies have further improved continuity. Together, these long-range technologies enable quality draft assemblies of complex genomes in a cost-effective and timely manner., Results: Here, we present high quality genome assemblies of the model legume plant, Medicago truncatula (R108) using PacBio, Dovetail Chicago (hereafter, Dovetail) and BioNano technologies. To test these technologies for plant genome assembly, we generated five assemblies using all possible combinations and ordering of these three technologies in the R108 assembly. While the BioNano and Dovetail joins overlapped, they also showed complementary gains in continuity and join numbers. Both technologies spanned repetitive regions that PacBio alone was unable to bridge. Combining technologies, particularly Dovetail followed by BioNano, resulted in notable improvements compared to Dovetail or BioNano alone. A combination of PacBio, Dovetail, and BioNano was used to generate a high quality draft assembly of R108, a M. truncatula accession widely used in studies of functional genomics. As a test for the usefulness of the resulting genome sequence, the new R108 assembly was used to pinpoint breakpoints and characterize flanking sequence of a previously identified translocation between chromosomes 4 and 8, identifying more than 22.7 Mb of novel sequence not present in the earlier A17 reference assembly., Conclusions: Adding Dovetail followed by BioNano data yielded complementary improvements in continuity over the original PacBio assembly. This strategy proved efficient and cost-effective for developing a quality draft assembly compared to traditional reference assemblies.

Computational modelling of proteins has been a major catalyst in structural biology. Bioinformatics groups have exploited the repositories of known structures to predict high-quality structural models with high efficiency at low cost. This article provides an overview of comparative modelling, reviews recent developments and describes resources dedicated to large-scale comparative modelling of genome sequences. The value of subclustering protein domain superfamilies to guide the template-selection process is investigated. Some recent cases in which structural modelling has aided experimental work to determine very large macromolecular complexes are also cited.

Today's short-read sequencing instruments can generate read lengths between 50 bp and 700 bp depending on the specific instrument. These high-throughput sequencing approaches have revolutionized genomic science, allowing hundreds of thousands of full genomes to be sequenced, and have become indispensable tools for many researchers. With greater insight has come the revelation that many genomes are much more complicated than originally thought and include many rearrangements and copy-number variations. Unfortunately, short-read sequencing technologies are not well suited for identifying many of these types of events. Long-read sequencing technologies can read contiguous fragments of DNA in excess of 10 kb and are much better suited for detecting large structural events. The newest long-read sequencing instrument is the MinION device from Oxford Nanopore. The rapid sequencing speed and low upfront instrument cost are features drawing interest in this device from the genomics community. This unit provides a representative protocol for carrying out human genome sequencing on the Oxford Nanopore MinION. © 2017 by John Wiley & Sons, Inc., (Copyright © 2017 John Wiley & Sons, Inc.)

The United States' ambitious Precision Medicine Initiative proposes to accelerate exponentially the adoption of precision medicine, an approach to health care that tailors disease diagnosis, treatment, and prevention to individual variability in genes, environment, and lifestyle. It aims to achieve this by creating a cohort of volunteers for precision medicine research, accelerating biomedical research innovation, and adopting policies geared toward patients' empowerment. As strategies to implement the PMI are formulated, critical consideration of the initiative's ethical and sociopolitical dimensions is needed. Drawing on scholarship of nationalism and democracy, we discuss the PMI's construction of what we term "genomic citizenship"; the possible normative obligations arising therefrom; and the ethical, legal, and social challenges that will ensue. Although the PMI is a work in progress, discussion of the existing and emerging issues can facilitate the development of policies, structures, and procedures that can maximize the initiative's ability to produce equitable and socially sensitive outcomes. Our analysis can also be applied to other population-based, precision medicine research programs., (© 2017 The Hastings Center.)

An estimated U.S. $300 billion is spent each year on medical research. What proportion of this goes to genomics and genetics research in Africa? Until recently, this type of question was nearly impossible to answer. The World RePORT database, sponsored by the Heads of International Research Organizations (HIRO) and managed by the National Institutes of Health (NIH), provides a first attempt at answering questions on the distribution of research funding by geography and research organization. In this journal issue on the Human Heredity and Health in Africa (H3Africa), we explore the geography of biomedical research funding in the genomics field with special emphasis on Africa. Using World RePORT, we identified 185 research projects in genetics and genomics in Africa in 2015 with total funding exceeding U.S. $216 million. These numbers are likely incomplete and more efforts at collating data from funder organizations is needed. A comprehensive snapshot of funders' portfolios will be invaluable to research investigators and policy makers in the identification of research gaps and analysis of allocation priorities to facilitate evidence-based decision-making for public-research-funding organizations., (Published by Elsevier B.V.)

Background: Controversy exists regarding the effectiveness of early adjuvant versus salvage radiation therapy after prostatectomy for prostate cancer. Estimates of prostate cancer progression from the Decipher genomic classifier (GC) could guide informed decision-making and improve the outcomes for patients., Materials and Methods: We developed a Markov model to compare the costs and quality-adjusted life years (QALYs) associated with GC-based treatment decisions regarding adjuvant therapy after prostatectomy with those of 2 control strategies: usual care (determined from patterns of care studies) and the alternative of 100% adjuvant radiation therapy. Using the bootstrapping method of sampling with replacement, the cases of 10,000 patients were simulated during a 10-year time horizon, with each subject having individual estimates for cancer progression (according to GC findings) and noncancer mortality (according to age)., Results: GC-based care was more effective and less costly than 100% adjuvant radiation therapy and resulted in cost savings up to an assay cost of $11,402. Compared with usual care, GC-based care resulted in more QALYs. Assuming a $4000 assay cost, the incremental cost-effectiveness ratio was $90,833 per QALY, assuming a 7% usage rate of adjuvant radiation therapy. GC-based care was also associated with a 16% reduction in the percentage of patients with distant metastasis at 5 years compared with usual care., Conclusion: The Decipher GC could be a cost-effective approach for genomics-driven cancer treatment decisions after prostatectomy, with improvements in estimated clinical outcomes compared with usual care. The individualized decision analytic framework applied in the present study offers a flexible approach to estimate the potential utility of genomic assays for personalized cancer medicine., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The ubiquity of DNA sequencing and the advent of medical imaging, electronic health records, and "omics" technologies have produced a deluge of data. Making meaning of those data-creating scientific knowledge and useful clinical information-will vastly exceed the capacity of even the largest institutions. Data must be shared to achieve the promises of genomic science and precision medicine., (© 2017 Cook-Deegan and McGuire; Published by Cold Spring Harbor Laboratory Press.)

Recent advances in cellular profiling have demonstrated substantial heterogeneity in the behaviour of cells once deemed 'identical', challenging fundamental notions of cell 'type' and 'state'. Not surprisingly, these findings have elicited substantial interest in deeply characterizing the diversity, interrelationships and plasticity among cellular phenotypes. To explore these questions, experimental platforms are needed that can extensively and controllably profile many individual cells. Here, microfluidic structures - whether valve-, droplet- or nanowell-based - have an important role because they can facilitate easy capture and processing of single cells and their components, reducing labour and costs relative to conventional plate-based methods while also improving consistency. In this article, we review the current state-of-the-art methodologies with respect to microfluidics for mammalian single-cell 'omics' and discuss challenges and future opportunities.

Whole-genome sequencing (WGS) is being applied within research settings across Europe to develop genomic WGS-based diagnostic tests. The focus of this perspective paper is to describe if, and how, current approaches of health technology assessment could be applied to WGS-based diagnostic tests. This perspective draws on the collective view from a trans-European multidisciplinary consortium of methodologists, clinicians and scientists. Specific challenges can be described by using the PICO (population, intervention, comparator, outcome) framework to inform health technology assessment. Practical solutions are suggested which require joined-up, multidisciplinary working across healthcare systems using existing expert networks so that emergent issues for the health technology assessment of WGS can be met in a timely fashion.

Background: Next-generation sequencing (NGS) allows ultra-deep sequencing of nucleic acids. The use of sequence-independent amplification of viral nucleic acids without utilization of target-specific primers provides advantages over traditional sequencing methods and allows detection of unsuspected variants and co-infecting agents. However, NGS is not widely used for small RNA viruses because of incorrectly perceived cost estimates and inefficient utilization of freely available bioinformatics tools., Methods: In this study, we have utilized NGS-based random sequencing of total RNA combined with barcode multiplexing of libraries to quickly, effectively and simultaneously characterize the genomic sequences of multiple avian paramyxoviruses. Thirty libraries were prepared from diagnostic samples amplified in allantoic fluids and their total RNAs were sequenced in a single flow cell on an Illumina MiSeq instrument. After digital normalization, data were assembled using the MIRA assembler within a customized workflow on the Galaxy platform., Results: Twenty-eight avian paramyxovirus 1 (APMV-1), one APMV-13, four avian influenza and two infectious bronchitis virus complete or nearly complete genome sequences were obtained from the single run. The 29 avian paramyxovirus genomes displayed 99.6% mean coverage based on bases with Phred quality scores of 30 or more. The lower and upper quartiles of sample median depth per position for those 29 samples were 2984 and 6894, respectively, indicating coverage across samples sufficient for deep variant analysis. Sample processing and library preparation took approximately 25-30 h, the sequencing run took 39 h, and processing through the Galaxy workflow took approximately 2-3 h. The cost of all steps, excluding labor, was estimated to be 106 USD per sample., Conclusions: This work describes an efficient multiplexing NGS approach, a detailed analysis workflow, and customized tools for the characterization of the genomes of RNA viruses. The combination of multiplexing NGS technology with the Galaxy workflow platform resulted in a fast, user-friendly, and cost-efficient protocol for the simultaneous characterization of multiple full-length viral genomes. Twenty-nine full-length or near-full-length APMV genomes with a high median depth were successfully sequenced out of 30 samples. The applied de novo assembly approach also allowed identification of mixed viral populations in some of the samples.

The progress of next-generation sequencing has a major impact on medical and genomic research. This high-throughput technology can now produce billions of short DNA or RNA fragments in excess of a few terabytes of data in a single run. This leads to massive datasets used by a wide range of applications including personalized cancer treatment and precision medicine. In addition to the hugely increased throughput, the cost of using high-throughput technologies has been dramatically decreasing. A low sequencing cost of around US$1000 per genome has now rendered large population-scale projects feasible. However, to make effective use of the produced data, the design of big data algorithms and their efficient implementation on modern high performance computing systems is required., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Analysing the genomic data of pathogens with the help of next-generation sequencing (NGS) is an increasingly important part of disease outbreak investigations and helps guide responses. While this technology has already been successfully employed to elucidate and control disease outbreaks, wider implementation of NGS also depends on its cost-effectiveness. COMPARE - short for 'Collaborative Management Platform for detection and Analyses of (Re-) emerging and foodborne outbreaks' - is a major project, funded by the European Union, to develop a global platform for sharing and analysing NGS data and thereby improve the rapid identification, containment and mitigation of emerging infectious diseases and foodborne outbreaks. This article introduces the project and presents the results of a review of the literature, composed of previous relevant cost-benefit and cost-effectiveness analyses. The authors also outline the implications for a methodological framework to assess the costeffectiveness of COMPARE and similar systems.

While the cost of genome sequencing has come way down and the uses of that information to improve patient care have taken an enormous leap forward, only a few pioneering healthcare systems are putting that knowledge to work.

Biosynthetic pathways provide an enzymatic route from inexpensive renewable resources to valuable metabolic products such as pharmaceuticals and plastics. Designing these pathways is challenging due to the complexities of biology. Advances in the design and construction of genetic variants has enabled billions of cells, each possessing a slightly different metabolic design, to be rapidly generated. However, our ability to measure the quality of these designs lags by several orders of magnitude. Recent research has enabled cells to report their own success in chemical production through the use of genetically encoded biosensors. A new engineering discipline is emerging around the creation and application of biosensors. Biosensors, implemented in selections and screens to identify productive cells, are paving the way for a new era of biotechnological progress., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Of the approximately two hundred sequenced plant genomes, how many and which ones were sequenced motivated by strictly or largely scientific considerations, and how many by chiefly economic, in a wide sense, incentives? And how large a role does publication opportunity play?, Results: In an integration of multiple disparate databases and other sources of information, we collect and analyze data on the size (number of species) in the plant orders and families containing sequenced genomes, on the trade value of these species, and of all the same-family or same-order species, and on the publication priority within the family and order. These data are subjected to multiple regression and other statistical analyses. We find that despite the initial importance of model organisms, it is clearly economic considerations that outweigh others in the choice of genome to be sequenced., Conclusions: This has important implications for generalizations about plant genomes, since human choices of plants to harvest (and cultivate) will have incurred many biases with respect to phenotypic characteristics and hence of genomic properties, and recent genomic evolution will also have been affected by human agricultural practices.

Next-generation sequencing has evolved technically and economically into the method of choice for interrogating the genome in cancer and inherited disorders. The introduction of procedural code sets for whole-exome and genome sequencing is a milestone toward financially sustainable clinical implementation; however, achieving reimbursement is currently a major challenge. As part of a prospective quality-improvement initiative to implement the new code sets, we adopted Agile, a development methodology originally devised in software development. We implemented eight functionally distinct modules (request review, cost estimation, preauthorization, accessioning, prebilling, testing, reporting, and reimbursement consultation) and obtained feedback via an anonymous survey. We managed 50 clinical requests (January to June 2015). The fraction of pursued-to-requested cases (n = 15/50; utilization management fraction, 0.3) aimed for a high rate of preauthorizations. In 13 of 15 patients the insurance plan required preauthorization, which we obtained in 70% and ultimately achieved reimbursement in 50%. Interoperability enabled assessment of 12 different combinations of modules that underline the importance of an adaptive workflow and policy tailoring to achieve higher yields of reimbursement. The survey confirmed a positive attitude toward self-organizing teams. We acknowledge the individuals and their interactions and termed the infrastructure: human pipeline. Nontechnical barriers currently are limiting the scope and availability of clinical genomic sequencing. The presented human pipeline is one approach toward long-term financial sustainability of clinical genomics., (Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Scientific outreach delivers science to the people. But it can also deliver people to the science. In this work, we report our experience from a large-scale public engagement project promoting genomic literacy among Danish high school students with the additional benefit of collecting data for studying the genetic makeup of the Danish population. Not only did we confirm that students have a great interest in their genetic past, but we were also gratified to see that, with the right motivation, adolescents can provide high-quality data for genetic studies., Competing Interests: The authors have declared that no competing interests exist.