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      Combining machine learning and nanopore construction creates an artificial intelligence nanopore for coronavirus detection

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          Abstract

          High-throughput, high-accuracy detection of emerging viruses allows for the control of disease outbreaks. Currently, reverse transcription-polymerase chain reaction (RT-PCR) is currently the most-widely used technology to diagnose the presence of SARS-CoV-2. However, RT-PCR requires the extraction of viral RNA from clinical specimens to obtain high sensitivity. Here, we report a method for detecting novel coronaviruses with high sensitivity by using nanopores together with artificial intelligence, a relatively simple procedure that does not require RNA extraction. Our final platform, which we call the artificially intelligent nanopore, consists of machine learning software on a server, a portable high-speed and high-precision current measuring instrument, and scalable, cost-effective semiconducting nanopore modules. We show that artificially intelligent nanopores are successful in accurately identifying four types of coronaviruses similar in size, HCoV-229E, SARS-CoV, MERS-CoV, and SARS-CoV-2. Detection of SARS-CoV-2 in saliva specimen is achieved with a sensitivity of 90% and specificity of 96% with a 5-minute measurement.

          Abstract

          Rapid, accurate and specific point-of-care diagnostics can help manage and contain fast-spreading infections. Here, the authors present a nanopore-based system that uses artificial intelligence to discriminate between four coronaviruses in saliva, with little need for sample pre-processing.

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          Most cited references36

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            A Novel Coronavirus from Patients with Pneumonia in China, 2019

            Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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              A pneumonia outbreak associated with a new coronavirus of probable bat origin

              Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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                Author and article information

                Contributors
                taniguti@sanken.osaka-u.ac.jp
                matsuura@biken.osaka-u.ac.jp
                tomono@hp-infect.med.osaka-u.ac.jp
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                17 June 2021
                17 June 2021
                2021
                : 12
                : 3726
                Affiliations
                [1 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, The Institute of Scientific and Industrial Research, , Osaka University, ; Ibaraki, Osaka Japan
                [2 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Research Institute for Microbial Diseases, , Osaka University, ; Suita, Osaka Japan
                [3 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Center for Infectious Diseases Education and Research, , Osaka University, ; Suita, Osaka Japan
                [4 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Graduate School of Medicine, , Osaka University, ; Suita, Osaka Japan
                [5 ]GRID grid.412398.5, ISNI 0000 0004 0403 4283, Osaka University Hospital, Osaka University, ; Suita, Osaka Japan
                [6 ]GRID grid.256642.1, ISNI 0000 0000 9269 4097, Graduate School of Medicine, , Gunma University, ; Maebashi, Gunma Japan
                [7 ]GRID grid.21925.3d, ISNI 0000 0004 1936 9000, Center for Vaccine Research, , University of Pittsburgh, ; Pittsburgh, PA USA
                [8 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, The Research Foundation for Microbial Diseases of Osaka University, ; Suita, Osaka Japan
                [9 ]GRID grid.412398.5, ISNI 0000 0004 0403 4283, Medical Center for Translational and Clinical Research, , Osaka University Hospital, Osaka University, ; Suita, Osaka Japan
                [10 ]GRID grid.471051.6, ISNI 0000 0004 1791 2380, ADVANTEST Corporation, ; Kazo, Saitama Japan
                [11 ]GRID grid.510033.4, Aipore Inc., ; Shibuya, Tokyo Japan
                Author information
                http://orcid.org/0000-0002-0338-8755
                http://orcid.org/0000-0002-9163-787X
                http://orcid.org/0000-0001-9091-8285
                Article
                24001
                10.1038/s41467-021-24001-2
                8211865
                34140500
                6db40abc-dcdc-4e4f-8808-375414864ab4
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 October 2020
                : 28 May 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/100009619, Japan Agency for Medical Research and Development (AMED);
                Award ID: JP20he0722002
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                viral infection,computer science,nanopores
                Uncategorized
                viral infection, computer science, nanopores

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