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2.
Genome Res ; 29(1): 116-124, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30523036

RESUMO

Emerging Linked-Read technologies (aka read cloud or barcoded short-reads) have revived interest in short-read technology as a viable approach to understand large-scale structures in genomes and metagenomes. Linked-Read technologies, such as the 10x Chromium system, use a microfluidic system and a specialized set of 3' barcodes (aka UIDs) to tag short DNA reads sourced from the same long fragment of DNA; subsequently, the tagged reads are sequenced on standard short-read platforms. This approach results in interesting compromises. Each long fragment of DNA is only sparsely covered by reads, no information about the ordering of reads from the same fragment is preserved, and 3' barcodes match reads from roughly 2-20 long fragments of DNA. However, compared to long-read technologies, the cost per base to sequence is far lower, far less input DNA is required, and the per base error rate is that of Illumina short-reads. In this paper, we formally describe a particular algorithmic issue common to Linked-Read technology: the deconvolution of reads with a single 3' barcode into clusters that represent single long fragments of DNA. We introduce Minerva, a graph-based algorithm that approximately solves the barcode deconvolution problem for metagenomic data (where reference genomes may be incomplete or unavailable). Additionally, we develop two demonstrations where the deconvolution of barcoded reads improves downstream results, improving the specificity of taxonomic assignments and of k-mer-based clustering. To the best of our knowledge, we are the first to address the problem of barcode deconvolution in metagenomics.


Assuntos
Algoritmos , Metagenoma , Metagenômica/métodos , Análise de Sequência de DNA/métodos , Software
3.
J Biomol Tech ; 30(Suppl): S47, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31896984

RESUMO

The majority of the world's population lives in cities, yet our understanding of the dynamics and distribution of bacteria, viruses, and antimicrobial resistance (AMR) genes in urban built environments is limited. Cities and urban transport hubs like metro stations and airports represent the sites of highest human population density, and are thus hotspot areas for microbial and genetic exchange in both developing and developed countries. Moreover, most inhabitants, visitors and passenger carry a mobile phone, which serves as a molecular echo of the travel history of a person as well as a representation of his or her personal microbiome. Through leveraging next-generation sequencing (NGS) and metagenome sequencing methods, combined with rapid computational analysis, we can reveal the microbial and genetic profiles, AMR gene content, localization, and movement patterns imprinted on phones and city surfaces, as readily as for clinical samples. International Consortium for Metagenomics of Subways and Urban Biomes (MetaSUB) at Weill Cornell Medicine, which is funded by the NIH, WorldQuant, and the Bill and Melinda Gates Foundation. We are currently analyzing >5.000 whole-genome shotgun metagenomes using samples collected in the subways (15000 samples total of more than 85 cities in 21 different countries). In parallel we analyzed for interrogating microbiomes obtained from > 2000 mobile phone surfaces, which we showcased during several international conferences. To our knowledge this is the first study investigating a comprehensive and worldwide view of urban microbiomes and AMR exchange. To complement our knowledge, we are comparing the generated metagenomes with data collected by the Extreme Microbiome Project and microbial isolates collected at the ISS by NASA during the last 11 years. Furthermore, to evaluate our findings and improve the accuracy of microbiome analyses, we developed novel protocols for metagenomic linked-DNA genomic sequencing (using 10X Genomics Chromium) and long-read sequencing (using Oxford Nanopore MinION and PromethION sequencers).

4.
Food Addit Contam Part B Surveill ; 11(4): 302-308, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30102133

RESUMO

Heavy-metal content (arsenic, cadmium, lead and mercury) was investigated and evaluated in shellfish, oysters and squids. The samples were collected weekly for 20 weeks from a fishery product market in Hungary. The concentration of heavy metals was measured by Inductively Coupled Plasma Optical Emission Spectrometer (ICP-OES) analysis after sample preparation. The results were analysed statistically by one-way ANOVA method. The average concentration of arsenic (3.01 ± 1.46 mg kg-1) in shellfish was significantly higher (p < 0.001) compared to oysters (2.88 ± 1.12 mg kg-1) and squids (1.28 ± 0.52 mg kg-1). The level of mercury was below the limit of detection (0.5 mg kg-1) in each sample and there was no statistical significance in the concentrations of cadmium (p = 0.351) and lead (p = 0.412) in the species investigated. The provisional tolerable intake values were also calculated. Based on the obtained results of the heavy-metal content of the investigated samples, the seafood is considered to be safe for human consumption. However, prolonged ingestion of oysters and squids at these levels may contribute to the consumers' cadmium burden.


Assuntos
Comércio , Exposição Ambiental/análise , Pesqueiros , Contaminação de Alimentos/análise , Metais Pesados/análise , Alimentos Marinhos/análise , Animais , Arsênico/análise , Cádmio/análise , Decapodiformes/química , Humanos , Hungria , Chumbo/análise , Mercúrio/análise , Ostreidae/química , Frutos do Mar/análise
5.
Gates Open Res ; 2: 3, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29630066

RESUMO

The Microbe Directory is a collective research effort to profile and annotate more than 7,500 unique microbial species from the MetaPhlAn2 database that includes bacteria, archaea, viruses, fungi, and protozoa. By collecting and summarizing data on various microbes' characteristics, the project comprises a database that can be used downstream of large-scale metagenomic taxonomic analyses, allowing one to interpret and explore their taxonomic classifications to have a deeper understanding of the microbial ecosystem they are studying. Such characteristics include, but are not limited to: optimal pH, optimal temperature, Gram stain, biofilm-formation, spore-formation, antimicrobial resistance, and COGEM class risk rating. The database has been manually curated by trained student-researchers from Weill Cornell Medicine and CUNY-Hunter College, and its analysis remains an ongoing effort with open-source capabilities so others can contribute. Available in SQL, JSON, and CSV (i.e. Excel) formats, the Microbe Directory can be queried for the aforementioned parameters by a microorganism's taxonomy. In addition to the raw database, The Microbe Directory has an online counterpart ( https://microbe.directory/) that provides a user-friendly interface for storage, retrieval, and analysis into which other microbial database projects could be incorporated. The Microbe Directory was primarily designed to serve as a resource for researchers conducting metagenomic analyses, but its online web interface should also prove useful to any individual who wishes to learn more about any particular microbe.

6.
Expert Rev Pharmacoecon Outcomes Res ; 17(6): 519-521, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28946800

RESUMO

The Pharmacoeconomics Section of the Pharmaceutical Association of Serbia organised a one day international conference on the value of innovation in decision-making in health care in Central and Eastern Europe. The focus of the conference was on reimbursement decisions for medicines using health technology assessment and the use of managed entry agreements (MEAs). The objectives of this conference were firstly to discuss the challenges and opportunities with the use of MEAs in Central and Eastern European countries; secondly the role of patient registries especially with outcome based schemes, and finally new approaches to improve accessibility to new medicines including better managing their entry.


Assuntos
Tomada de Decisões , Assistência à Saúde/métodos , Farmacoeconomia , Assistência à Saúde/economia , Europa Oriental , Humanos , Mecanismo de Reembolso , Avaliação da Tecnologia Biomédica
7.
Genome Biol ; 18(1): 182, 2017 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-28934964

RESUMO

BACKGROUND: One of the main challenges in metagenomics is the identification of microorganisms in clinical and environmental samples. While an extensive and heterogeneous set of computational tools is available to classify microorganisms using whole-genome shotgun sequencing data, comprehensive comparisons of these methods are limited. RESULTS: In this study, we use the largest-to-date set of laboratory-generated and simulated controls across 846 species to evaluate the performance of 11 metagenomic classifiers. Tools were characterized on the basis of their ability to identify taxa at the genus, species, and strain levels, quantify relative abundances of taxa, and classify individual reads to the species level. Strikingly, the number of species identified by the 11 tools can differ by over three orders of magnitude on the same datasets. Various strategies can ameliorate taxonomic misclassification, including abundance filtering, ensemble approaches, and tool intersection. Nevertheless, these strategies were often insufficient to completely eliminate false positives from environmental samples, which are especially important where they concern medically relevant species. Overall, pairing tools with different classification strategies (k-mer, alignment, marker) can combine their respective advantages. CONCLUSIONS: This study provides positive and negative controls, titrated standards, and a guide for selecting tools for metagenomic analyses by comparing ranges of precision, accuracy, and recall. We show that proper experimental design and analysis parameters can reduce false positives, provide greater resolution of species in complex metagenomic samples, and improve the interpretation of results.


Assuntos
Benchmarking/métodos , Mapeamento de Sequências Contíguas/métodos , Código de Barras de DNA Taxonômico/métodos , Metagenoma , Análise de Sequência de DNA/métodos , Software , Benchmarking/normas , Mapeamento de Sequências Contíguas/normas , Código de Barras de DNA Taxonômico/normas , Humanos , Microbiota , Filogenia , Análise de Sequência de DNA/normas
8.
Pharmacoeconomics ; 35(12): 1271-1285, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28836222

RESUMO

BACKGROUND: Managed entry agreements (MEAs) are a set of instruments to facilitate access to new medicines. This study surveyed the implementation of MEAs in Central and Eastern Europe (CEE) where limited comparative information is currently available. METHOD: We conducted a survey on the implementation of MEAs in CEE between January and March 2017. RESULTS: Sixteen countries participated in this study. Across five countries with available data on the number of different MEA instruments implemented, the most common MEAs implemented were confidential discounts (n = 495, 73%), followed by paybacks (n = 92, 14%), price-volume agreements (n = 37, 5%), free doses (n = 25, 4%), bundle and other agreements (n = 19, 3%), and payment by result (n = 10, >1%). Across seven countries with data on MEAs by therapeutic group, the highest number of brand names associated with one or more MEA instruments belonged to the Anatomical Therapeutic Chemical (ATC)-L group, antineoplastic and immunomodulating agents (n = 201, 31%). The second most frequent therapeutic group for MEA implementation was ATC-A, alimentary tract and metabolism (n = 87, 13%), followed by medicines for neurological conditions (n = 83, 13%). CONCLUSIONS: Experience in implementing MEAs varied substantially across the region and there is considerable scope for greater transparency, sharing experiences and mutual learning. European citizens, authorities and industry should ask themselves whether, within publicly funded health systems, confidential discounts can still be tolerated, particularly when it is not clear which country and party they are really benefiting. Furthermore, if MEAs are to improve access, countries should establish clear objectives for their implementation and a monitoring framework to measure their performance, as well as the burden of implementation.


Assuntos
Indústria Farmacêutica/organização & administração , Farmacoeconomia , Acesso aos Serviços de Saúde , Preparações Farmacêuticas/economia , Assistência à Saúde/economia , Assistência à Saúde/organização & administração , Indústria Farmacêutica/economia , Europa (Continente) , Europa Oriental , Humanos , Preparações Farmacêuticas/administração & dosagem , Inquéritos e Questionários
9.
J Mark Access Health Policy ; 5(1): 1355190, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28804602

RESUMO

In 2014, balanced assessment systems (BAS) were proposed as a resource-conscious, 'fit-for-purpose' form of health technology assessment for middle-income countries which lack resources and competences necessary for resource-intensive health technology assessment models. BAS has undergone extensive policy debate in the period since its publication but it has not been critically assessed in a structured form yet. This article aims to describe both the contributions and the weak spots of the original framework and to reflect on them with the intention of further developing the model.

10.
Cell Syst ; 1(2): 130-140, 2015 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-26436140

RESUMO

Many data sets exhibit well-defined structure that can be exploited to design faster search tools, but it is not always clear when such acceleration is possible. Here we introduce a framework for similarity search based on characterizing a data set's entropy and fractal dimension. We prove that searching scales in time with metric entropy (number of covering hyperspheres), if the fractal dimension of the data set is low, and scales in space with the sum of metric entropy and information-theoretic entropy (randomness of the data). Using these ideas, we present accelerated versions of standard tools, with no loss in specificity and little loss in sensitivity, for use in three domains-high-throughput drug screening (Ammolite, 150x speedup), metagenomics (MICA, 3.5x speedup of DIAMOND (3700x BLASTX)), and protein structure search (esFragBag, 10x speedup of FragBag). Our framework can be used to achieve 'compressive omics,' and the general theory can be readily applied to data science problems outside of biology. Source code: http://gems.csail.mit.edu.

11.
Artigo em Inglês | MEDLINE | ID: mdl-27226832

RESUMO

Because of significant differences in institutional contexts, health technology assessment (HTA) systems that are in place in core pharmaceutical markets may not be suitable, fully or in part, for middle-income countries (MICs) and for other noncore markets. Particular challenges may arise when systems based on the economic evaluation paradigm are conceptualized and implemented in MICs, sometimes with an insufficient level of awareness of the local institutional factors that influence pricing and reimbursement decision making. Focusing on pharmaceuticals, this article investigates possible development directions for HTA systems in MICs and noncore markets bearing similar institutional characteristics, and it provides recommendations for a balanced assessment system (BAS). For this, the main paradigms of HTA have also been reviewed briefly and factors influencing HTA and pricing and reimbursement decisions in MICs and in similar noncore countries have been summarized. The proposed BAS framework takes into account available resources and capabilities and is supposed to facilitate access to new pharmaceuticals while ensuring the transparency of decision-making processes and the stability of the pharmaceutical budget.

12.
Biotechnol Biotechnol Equip ; 28(6): 1181-1189, 2014 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-26019605

RESUMO

Countries in the Balkan region use pharmaco-economic data for decisions about the inclusion of new pharmaceuticals into their positive drug lists, but no predefined frameworks are used and resources for health technology assessment (HTA) are limited. The goal of this analysis is to investigate into possible development directions for the HTA system in the region, and provide some practical recommendations for a sustainable model. For this purpose, the main factors currently influencing HTA in Balkan countries are briefly presented, and possible development strategies are compared. A resource-saving balanced assessment approach is proposed. It is aligned with available resources and capabilities, and helps access to new pharmaceuticals while ensuring the transparency of decision-making processes and the stability of the pharmaceutical budget.

13.
Orv Hetil ; 153(34): 1341-9, 2012 Aug 26.
Artigo em Húngaro | MEDLINE | ID: mdl-22913916

RESUMO

Long-term success in solid organ transplantation strongly depends on the optimal use of maintenance immunosuppressive treatment. Cyclosporin and tacrolimus are the most frequently administered immunosuppressants and they are designed to narrow therapeutic index drugs. The substitution of the branded formulation by their generic counterparts may lead to economic benefit only if equivalent clinical outcomes can be achieved. There is no published evidence to date on the guarantee of their long-term therapeutic equivalence and cases of therapeutic failures have been reported due to inadvertent drug conversion. The disadvantageous clinical consequences of a non medical, mechanistic forced switch from the original to generic formulation of tacrolimus and the estimated loss of the payer's presumed savings are presented in a kidney transplant recipient population. Special problems related to pediatric patients, drug interactions with concurrent medications and the burden of additional therapeutic drug monitoring and follow up visits are also discussed. The authors are convinced that the implementation of the European Society of Organ Transplantation guidelines on generic substitution may provide a safe way for patients and healthcare payers.


Assuntos
Custos de Medicamentos , Substituição de Medicamentos , Medicamentos Genéricos/efeitos adversos , Medicamentos Genéricos/economia , Imunossupressores/administração & dosagem , Imunossupressores/economia , Transplante de Órgãos , Análise Custo-Benefício , Ciclosporina/administração & dosagem , Ciclosporina/economia , Preparações de Ação Retardada , Interações de Medicamentos , Monitoramento de Medicamentos , Substituição de Medicamentos/efeitos adversos , Substituição de Medicamentos/economia , Medicamentos Genéricos/administração & dosagem , Humanos , Hungria , Imunossupressores/efeitos adversos , Transplante de Rim , Tacrolimo/administração & dosagem , Tacrolimo/economia , Equivalência Terapêutica
14.
Orv Hetil ; 153 Suppl: 3-38, 2012 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-23687666

Assuntos
Alphapapillomavirus , Vacinas Anticâncer , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Neoplasias/prevenção & controle , Neoplasias/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Saúde Pública , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Condiloma Acuminado/prevenção & controle , Condiloma Acuminado/virologia , Neoplasias Esofágicas/prevenção & controle , Neoplasias Esofágicas/virologia , Feminino , Neoplasias dos Genitais Femininos/prevenção & controle , Neoplasias dos Genitais Femininos/virologia , Neoplasias dos Genitais Masculinos/prevenção & controle , Neoplasias dos Genitais Masculinos/virologia , Saúde Global , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Humanos , Hungria/epidemiologia , Masculino , Vacinação em Massa , Modelos Teóricos , Neoplasias/economia , Neoplasias/epidemiologia , Neoplasias/imunologia , Neoplasias Orofaríngeas/prevenção & controle , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/economia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Vacinas contra Papillomavirus/imunologia , Prevenção Primária , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/virologia , Prevenção Secundária , Esfregaço Vaginal
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