RESUMO
Advances in information technologies (ITs) and operational technologies (OTs) offer high-containment laboratories opportunities to evolve scientific and operational approaches, while increasing efficiency. Emerging technologies steadily introduce changes in data generation and management practices. United States (US) government agencies and partners operate high-containment laboratories that rely on ITs/OTs to provide critical scientific functions that support prevention, detection, response and recovery for catastrophic events. These unique operating environments provide an opportunity for implementation of ITs/OTs that can facilitate both efficiency and deeper or parallel study of disease and associated biological phenomena. Operational study by subject matter experts can aid in identification of requirements and challenges pertaining to emerging ITs/OTs, examination of use cases, refinement of technical specifications and optimisation of workflows. The National Bio and Agro-Defense Facility (NBAF) in the United States of America (USA), slated to be fully operational by 2023, will be a state-of-the-art research and diagnostic facility with Biosafety Level 2, 3 and 4 laboratories for the study of high-consequence transboundary animal pathogens and zoonotic diseases impacting public health. The NBAF will support the diagnosis of emerging diseases, development of countermeasures and transboundary animal disease training. Given the rapid emergence of IT/OT solutions, the authors used a case study approach to analyse and assess real-world, high-containment laboratory functions to help maximise efficiency in mission delivery for the NBAF and the broader high-containment laboratory network. The case study approach described here could be widely adapted to diverse situations characterised by a high rate of change to provide accurate, relevant workflow analyses and optimised recommendations.
Les progrès enregistrés dans les domaines des technologies de l'information (IT) et des technologies opérationnelles (OT) offrent aux laboratoires de confinement à haute sécurité la possibilité de faire évoluer leurs approches scientifiques et opérationnelles tout en gagnant en efficacité. Grâce à ces technologies émergentes, les pratiques de production et de gestion des données sont régulièrement affinées. Les organismes gouvernementaux étatsuniens et leurs partenaires exploitent des laboratoires de confinement à haute sécurité qui font appel aux IT/OT pour mettre en oeuvre des fonctionnalités scientifiques cruciales en appui de la prévention, la détection, l'intervention et le rétablissement en cas de catastrophes. Ces environnements opérationnels uniques offrent la possibilité d'introduire des applications IT/OT afin de faciliter aussi bien l'efficacité des opérations que l'étude plus approfondie ou concomitante d'une maladie et des phénomènes biologiques qui lui sont associés. Des études opérationnelles menées par des spécialistes peuvent contribuer à identifier les exigences et les défis liés aux IT/OT émergentes, à vérifier leurs utilisations concrètes, à affiner les spécifications techniques et à optimiser l'ordonnancement des opérations. Le National Bio and Agro-Defense Facility (NBAF) des états-Unis d'Amérique, qui devrait être pleinement opérationnel d'ici 2023, sera une institution de recherche et de diagnostic de pointe dotée de laboratoires de niveaux de biosécurité 2, 3 et 4 pour l'étude des agents pathogènes responsables de maladies animales transfrontalières à haut risque et des agents zoonotiques à fort impact sur la santé publique. Le NBAF contribuera au diagnostic des maladies émergentes et à l'élaboration de mesures de lutte ; il dispensera également des formations sur les maladies animales transfrontalières. Compte tenu du développement rapide des nouvelles solutions IT/OT, les auteurs ont mis au point une méthode d'études de cas pour l'analyse et l'évaluation des fonctionnalités concrètes des laboratoires de confinement à haute sécurité, destinée à maximiser l'efficacité des prestations du NBAF et du réseau plus large de laboratoires de confinement à haute sécurité. La méthode par études de cas décrite ici pourrait être largement adaptée à diverses situations caractérisées par un niveau élevé de changement, afin de fournir des analyses précises et pertinentes de l'ordonnancement des opérations et d'élaborer des recommandations optimisées.
Los adelantos de las tecnologías de la información (TI) y las tecnologías operativas (TO) ofrecen a los laboratorios de alta contención la posibilidad de transformar sus lógicas y procedimientos de trabajo científico y al mismo tiempo ganar en eficiencia. Progresivamente, a la estela de las nuevas tecnologías, los métodos empleados para generar y gestionar datos van evolucionando. Ciertos organismos públicos estadounidenses administran, junto con entidades colaboradoras, laboratorios de alta contención que dependen de las TI/TO para cumplir una serie de cometidos científicos fundamentales en apoyo de la prevención y detección de sucesos catastróficos, de la respuesta a ellos y de los subsiguientes procesos de recuperación. Estos excepcionales entornos de trabajo ofrecen la posibilidad de implantar TI/TO que a la vez aporten más eficiencia y faciliten un estudio más a fondo o en paralelo de as enfermedades y los fenómenos biológicos asociados a ellas. La realización de estudios operativos a cargo de especialistas en el tema puede ayudar a determinar las necesidades y dificultades que plantean las nuevas TI/TO, a examinar ejemplos de utilización, a afinar las especificaciones técnicas y a optimizar los procesos de trabajo. El órgano nacional de defensa biológica y agrícola (National Bio and Agro-Defense Facility, NBAF) de los Estados Unidos de América, que según las previsiones funcionará a pleno rendimiento en 2023, constituirá un avanzado dispositivo de investigación y diagnóstico al que estarán adscritos laboratorios de nivel 2, 3 y 4 de seguridad biológica para el estudio de agentes patógenos de los animales y enfermedades zoonóticas de carácter transfronterizo y de gran repercusión que afecten a la salud pública. El NBAF secundará el diagnóstico de enfermedades emergentes, la preparación de medidas de lucha y la formación sobre enfermedades animales transfronterizas. Teniendo en cuenta la velocidad a la que surgen soluciones de TI/TO, los autores recurrieron al estudio de ejemplos concretos para analizar y evaluar las funciones que cumplen en el mundo real los laboratorios de alta contención con el objetivo de ayudar al NBAF y a la red general de laboratorios de alta contención a ejercer su cometido con la máxima eficiencia. El método de trabajo aquí descrito, basado en el estudio de casos concretos, podría ser adaptado a diversas situaciones que se caractericen por un alto ritmo de transformaciones para efectuar análisis precisos y pertinentes de los procesos de trabajo y formular recomendaciones optimizadas.
RESUMO
Nanopore sequencing generates noisy electrical signals that need to be converted into a standard string of DNA nucleotide bases using a computational step called basecalling. The performance of basecalling has critical implications for all later steps in genome analysis. Therefore, there is a need to reduce the computation and memory cost of basecalling while maintaining accuracy. We present RUBICON, a framework to develop efficient hardware-optimized basecallers. We demonstrate the effectiveness of RUBICON by developing RUBICALL, the first hardware-optimized mixed-precision basecaller that performs efficient basecalling, outperforming the state-of-the-art basecallers. We believe RUBICON offers a promising path to develop future hardware-optimized basecallers.
Assuntos
Aprendizado Profundo , Nanoporos , Análise de Sequência de DNA , Genômica , Nucleotídeos , DNA/genéticaRESUMO
The COVID-19 pandemic has seen large-scale pathogen genomic sequencing efforts, becoming part of the toolbox for surveillance and epidemic research. This resulted in an unprecedented level of data sharing to open repositories, which has actively supported the identification of SARS-CoV-2 structure, molecular interactions, mutations and variants, and facilitated vaccine development and drug reuse studies and design. The European COVID-19 Data Platform was launched to support this data sharing, and has resulted in the deposition of several million SARS-CoV-2 raw reads. In this paper we describe (1) open data sharing, (2) tools for submission, analysis, visualisation and data claiming (e.g. ORCiD), (3) the systematic analysis of these datasets, at scale via the SARS-CoV-2 Data Hubs as well as (4) lessons learnt. This paper describes a component of the Platform, the SARS-CoV-2 Data Hubs, which enable the extension and set up of infrastructure that we intend to use more widely in the future for pathogen surveillance and pandemic preparedness.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Pandemias , COVID-19/epidemiologia , Genômica , Disseminação de InformaçãoRESUMO
Rapid advances in single-cell genomics sequencing (SCGS) have allowed researchers to characterize tumor heterozygosity with unprecedented resolution and reveal the phylogenetic relationships between tumor cells or clones. However, high sequencing error rates of current SCGS data, i.e., false positives, false negatives, and missing bases, severely limit its application. Here, we present a deep learning framework, RDAClone, to recover genotype matrices from noisy data with an extended robust deep autoencoder, cluster cells into subclones by the Louvain-Jaccard method, and further infer evolutionary relationships between subclones by the minimum spanning tree. Studies on both simulated and real datasets demonstrate its robustness and superiority in data denoising, cell clustering, and evolutionary tree reconstruction, particularly for large datasets.
Assuntos
Genômica/métodos , Neoplasias/genética , Análise de Célula Única/métodos , Algoritmos , Evolução Biológica , Análise por Conglomerados , Análise de Dados , Aprendizado Profundo , FilogeniaRESUMO
Yarrowia lipolytica is one of the most intensively investigated α-ketoglutaric acid (α-KG) producers, and metabolic engineering has proven effective for enhancing production. However, regulation of α-KG metabolism remains poorly understood. Genetic engineering of new strains is accompanied by potential safety concerns in some countries and regions. A series of mutants with varied capacity for α-KG production were obtained using random mutagenesis of Y. lipolytica WSH-Z06. Comparative genomics analysis was implemented to identify genes candidates associated with α-KG production. Manipulation of genes regulating mitochondrial biogenesis and energy metabolism could improve α-KG production, while genes involved in regulating transformation between keto acids and amino acids may decrease production. One gene associated with cell cycle control well represented in all mutants, whereas this gene involved in cell concentration do not appear to influence α-KG production. The results shed light on α-KG production in eukaryotic cells, and pave the way for a high-throughput screening and random mutagenesis method for enhancing α-KG production.