Anomaly identification during polymerase chain reaction for detecting SARS-cov-2 using artificial intelligence trained from simulated data
Real-time reverse transcription (RT) PCR is the gold standard for detecting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), owing to its sensitivity and specificity, thereby meeting the demand for the rising number of cases. The scarcity of trained molecular biologists for analyzing PC...
- Autores:
-
Villarreal-González, Reynaldo
Acosta-Hoyos, Antonio J.
Garzón-Ochoa, Jaime A.
Galán-Freyle, Nataly J.
Amar-Sepúlveda, Paola
Pacheco-Londoño, Leonardo C.
- Tipo de recurso:
- Fecha de publicación:
- 2021
- Institución:
- Universidad Simón Bolívar
- Repositorio:
- Repositorio Digital USB
- Idioma:
- eng
- OAI Identifier:
- oai:bonga.unisimon.edu.co:20.500.12442/9229
- Acceso en línea:
- https://hdl.handle.net/20.500.12442/9229
https://dx.doi.org/10.3390/molecules26010020
https://www.mdpi.com/journal/molecules
- Palabra clave:
- SARS-CoV-2
Artificial intelligence
Polymerase chain reaction
COVID-19
Simulated data
- Rights
- restrictedAccess
- License
- Attribution-NonCommercial-NoDerivatives 4.0 Internacional
id |
USIMONBOL2_9cd6828c1815f2db261581646f546029 |
---|---|
oai_identifier_str |
oai:bonga.unisimon.edu.co:20.500.12442/9229 |
network_acronym_str |
USIMONBOL2 |
network_name_str |
Repositorio Digital USB |
repository_id_str |
|
dc.title.eng.fl_str_mv |
Anomaly identification during polymerase chain reaction for detecting SARS-cov-2 using artificial intelligence trained from simulated data |
title |
Anomaly identification during polymerase chain reaction for detecting SARS-cov-2 using artificial intelligence trained from simulated data |
spellingShingle |
Anomaly identification during polymerase chain reaction for detecting SARS-cov-2 using artificial intelligence trained from simulated data SARS-CoV-2 Artificial intelligence Polymerase chain reaction COVID-19 Simulated data |
title_short |
Anomaly identification during polymerase chain reaction for detecting SARS-cov-2 using artificial intelligence trained from simulated data |
title_full |
Anomaly identification during polymerase chain reaction for detecting SARS-cov-2 using artificial intelligence trained from simulated data |
title_fullStr |
Anomaly identification during polymerase chain reaction for detecting SARS-cov-2 using artificial intelligence trained from simulated data |
title_full_unstemmed |
Anomaly identification during polymerase chain reaction for detecting SARS-cov-2 using artificial intelligence trained from simulated data |
title_sort |
Anomaly identification during polymerase chain reaction for detecting SARS-cov-2 using artificial intelligence trained from simulated data |
dc.creator.fl_str_mv |
Villarreal-González, Reynaldo Acosta-Hoyos, Antonio J. Garzón-Ochoa, Jaime A. Galán-Freyle, Nataly J. Amar-Sepúlveda, Paola Pacheco-Londoño, Leonardo C. |
dc.contributor.author.none.fl_str_mv |
Villarreal-González, Reynaldo Acosta-Hoyos, Antonio J. Garzón-Ochoa, Jaime A. Galán-Freyle, Nataly J. Amar-Sepúlveda, Paola Pacheco-Londoño, Leonardo C. |
dc.subject.spa.fl_str_mv |
SARS-CoV-2 |
topic |
SARS-CoV-2 Artificial intelligence Polymerase chain reaction COVID-19 Simulated data |
dc.subject.eng.fl_str_mv |
Artificial intelligence Polymerase chain reaction COVID-19 Simulated data |
description |
Real-time reverse transcription (RT) PCR is the gold standard for detecting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), owing to its sensitivity and specificity, thereby meeting the demand for the rising number of cases. The scarcity of trained molecular biologists for analyzing PCR results makes data verification a challenge. Artificial intelligence (AI) was designed to ease verification, by detecting atypical profiles in PCR curves caused by contamination or artifacts. Four classes of simulated real-time RT-PCR curves were generated, namely, positive, early, no, and abnormal amplifications. Machine learning (ML) models were generated and tested using small amounts of data from each class. The best model was used for classifying the big data obtained by the Virology Laboratory of Simon Bolivar University from real-time RT-PCR curves for SARS-CoV-2, and the model was retrained and implemented in a software that correlated patient data with test and AI diagnoses. The best strategy for AI included a binary classification model, which was generated from simulated data, where data analyzed by the first model were classified as either positive or negative and abnormal. To differentiate between negative and abnormal, the data were reevaluated using the second model. In the first model, the data required preanalysis through a combination of prepossessing. The early amplification class was eliminated from the models because the numbers of cases in big data was negligible. ML models can be created from simulated data using minimum available information. During analysis, changes or variations can be incorporated by generating simulated data, avoiding the incorporation of large amounts of experimental data encompassing all possible changes. For diagnosing SARS-CoV-2, this type of AI is critical for optimizing PCR tests because it enables rapid diagnosis and reduces false positives. Our method can also be used for other types of molecular analyses. |
publishDate |
2021 |
dc.date.accessioned.none.fl_str_mv |
2021-12-13T15:11:26Z |
dc.date.available.none.fl_str_mv |
2021-12-13T15:11:26Z |
dc.date.issued.none.fl_str_mv |
2021 |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.spa.spa.fl_str_mv |
Artículo científico |
dc.identifier.citation.spa.fl_str_mv |
Villarreal-González, R.; Acosta- Hoyos, A.J.; Garzon-Ochoa, J.A.; Galán- Freyle, N.J.; Amar-Sepúlveda, P.; Pacheco- Londoño, L.C. Anomaly Identification during Polymerase Chain Reaction for Detecting SARS-CoV-2 Using Artificial Intelligence Trained from Simulated Data. Molecules 2021, 26, 20. https://dx.doi.org/10.3390/ molecules26010020 |
dc.identifier.issn.none.fl_str_mv |
1420-3049 |
dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/20.500.12442/9229 |
dc.identifier.doi.none.fl_str_mv |
https://dx.doi.org/10.3390/molecules26010020 |
dc.identifier.url.none.fl_str_mv |
https://www.mdpi.com/journal/molecules |
identifier_str_mv |
Villarreal-González, R.; Acosta- Hoyos, A.J.; Garzon-Ochoa, J.A.; Galán- Freyle, N.J.; Amar-Sepúlveda, P.; Pacheco- Londoño, L.C. Anomaly Identification during Polymerase Chain Reaction for Detecting SARS-CoV-2 Using Artificial Intelligence Trained from Simulated Data. Molecules 2021, 26, 20. https://dx.doi.org/10.3390/ molecules26010020 1420-3049 |
url |
https://hdl.handle.net/20.500.12442/9229 https://dx.doi.org/10.3390/molecules26010020 https://www.mdpi.com/journal/molecules |
dc.language.iso.eng.fl_str_mv |
eng |
language |
eng |
dc.rights.*.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_16ec |
dc.rights.uri.*.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/restrictedAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ http://purl.org/coar/access_right/c_16ec |
eu_rights_str_mv |
restrictedAccess |
dc.format.mimetype.spa.fl_str_mv |
pdf |
dc.publisher.spa.fl_str_mv |
MDPI Facultad de Ingenierías |
dc.source.eng.fl_str_mv |
Revista Molecules |
dc.source.none.fl_str_mv |
Vol. 26, No. 1 (2021) |
institution |
Universidad Simón Bolívar |
bitstream.url.fl_str_mv |
https://bonga.unisimon.edu.co/bitstreams/1a367f00-9d95-45e6-9d0f-0a96c7dd6567/download https://bonga.unisimon.edu.co/bitstreams/67d565b4-3c62-4513-96d0-b82cca7307e9/download https://bonga.unisimon.edu.co/bitstreams/0bc116d9-145e-4e97-9fd2-50552d2c137a/download https://bonga.unisimon.edu.co/bitstreams/8ba9b1a5-dc04-41d0-a0f4-e564188e6ead/download https://bonga.unisimon.edu.co/bitstreams/ec78b626-8c12-43c2-9b4d-906f059fe7bb/download https://bonga.unisimon.edu.co/bitstreams/d92277b3-48c7-4a27-bc26-9692d58ca66e/download https://bonga.unisimon.edu.co/bitstreams/989d4106-9add-4454-be06-f7bbad5ab92d/download https://bonga.unisimon.edu.co/bitstreams/80822da5-df09-41e4-b475-4267c599dfac/download https://bonga.unisimon.edu.co/bitstreams/a62932dc-549e-459c-a8f5-1d9b8997fb7e/download |
bitstream.checksum.fl_str_mv |
19357b71028b49cf6ffd65a219cc71bc 4460e5956bc1d1639be9ae6146a50347 2a1661e5960a7bab4fd8dda692fb677c a3eb6a334df157d7c851370f0d53e202 c1859f95aef2509c1be33d7edc7b8752 c1859f95aef2509c1be33d7edc7b8752 f547975df7c83161c80f029c45c86c88 c0d4a2fe7bd269c0cc176a80c08847c5 c0d4a2fe7bd269c0cc176a80c08847c5 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio Digital Universidad Simón Bolívar |
repository.mail.fl_str_mv |
repositorio.digital@unisimon.edu.co |
_version_ |
1814076096030703616 |
spelling |
Villarreal-González, Reynaldo0b64215d-5c8b-4e4d-b796-746ffe6b54feAcosta-Hoyos, Antonio J.6b712d95-7eef-4f3a-ba0b-6647f66d0749Garzón-Ochoa, Jaime A.f746f206-45a5-4bcf-b417-09305bbc3035Galán-Freyle, Nataly J.cd16040f-2e16-4535-a75e-0b661dae889fAmar-Sepúlveda, Paola89dc4721-af40-451f-8e88-d27fc35f1bf8Pacheco-Londoño, Leonardo C.6b1ffce2-eacd-4bef-ac33-027cc8b3ddb22021-12-13T15:11:26Z2021-12-13T15:11:26Z2021Villarreal-González, R.; Acosta- Hoyos, A.J.; Garzon-Ochoa, J.A.; Galán- Freyle, N.J.; Amar-Sepúlveda, P.; Pacheco- Londoño, L.C. Anomaly Identification during Polymerase Chain Reaction for Detecting SARS-CoV-2 Using Artificial Intelligence Trained from Simulated Data. Molecules 2021, 26, 20. https://dx.doi.org/10.3390/ molecules260100201420-3049https://hdl.handle.net/20.500.12442/9229https://dx.doi.org/10.3390/molecules26010020https://www.mdpi.com/journal/moleculesReal-time reverse transcription (RT) PCR is the gold standard for detecting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), owing to its sensitivity and specificity, thereby meeting the demand for the rising number of cases. The scarcity of trained molecular biologists for analyzing PCR results makes data verification a challenge. Artificial intelligence (AI) was designed to ease verification, by detecting atypical profiles in PCR curves caused by contamination or artifacts. Four classes of simulated real-time RT-PCR curves were generated, namely, positive, early, no, and abnormal amplifications. Machine learning (ML) models were generated and tested using small amounts of data from each class. The best model was used for classifying the big data obtained by the Virology Laboratory of Simon Bolivar University from real-time RT-PCR curves for SARS-CoV-2, and the model was retrained and implemented in a software that correlated patient data with test and AI diagnoses. The best strategy for AI included a binary classification model, which was generated from simulated data, where data analyzed by the first model were classified as either positive or negative and abnormal. To differentiate between negative and abnormal, the data were reevaluated using the second model. In the first model, the data required preanalysis through a combination of prepossessing. The early amplification class was eliminated from the models because the numbers of cases in big data was negligible. ML models can be created from simulated data using minimum available information. During analysis, changes or variations can be incorporated by generating simulated data, avoiding the incorporation of large amounts of experimental data encompassing all possible changes. For diagnosing SARS-CoV-2, this type of AI is critical for optimizing PCR tests because it enables rapid diagnosis and reduces false positives. Our method can also be used for other types of molecular analyses.pdfengMDPIFacultad de IngenieríasAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/restrictedAccesshttp://purl.org/coar/access_right/c_16ecRevista MoleculesVol. 26, No. 1 (2021)SARS-CoV-2Artificial intelligencePolymerase chain reactionCOVID-19Simulated dataAnomaly identification during polymerase chain reaction for detecting SARS-cov-2 using artificial intelligence trained from simulated datainfo:eu-repo/semantics/articleArtículo científicohttp://purl.org/coar/resource_type/c_2df8fbb1Mashamba-Thompson, T.P.; Crayton, E.D. Blockchain and artificial intelligence technology for novel coronavirus disease 2019 self-testing. Diagnostics 2020, 10, 198.Huang, L.; Zhang, H.; Deng, D.; Zhao, K.; Liu, K.; Hendrix, D.A.; Mathews, D.H. LinearFold: Linear-time approximate RNA folding by 50-to-30 dynamic programming and beam search. Bioinformatics 2019, 35, i295–i304.Jumper, J.; Tunyasuvunakool, K.; Kohli, P.; Hassabis, D.; Team, A. Computational Predictions of Protein Structures Associated with COVID-19. Available online: https://deepmind.com/research/open-source/computational-predictions-of-protein-structuresassociated- with-COVID-19 (accessed on 28 July 2020).Robson, B. Computers and viral diseases. Preliminary bioinformatics studies on the design of a synthetic vaccine and a preventative peptidomimetic antagonist against the SARS-CoV-2 (2019-nCoV, COVID-19) coronavirus. Comput. Biol. Med. 2020, 119, 103670.Cai, C.Z.; Han, L.Y.; Chen, X.; Cao, Z.W.; Chen, Y.Z. Prediction of functional class of the SARS coronavirus proteins by a statistical learning method. J. Proteome Res. 2005, 4, 1855–1862.Ahuja, A.S.; Reddy, V.P.; Marques, O. Artificial intelligence and COVID-19: A multidisciplinary approach. Integr. Med. Res. 2020, 9, 100434.Allam, Z.; Dey, G.; Jones, D.S. Artificial Intelligence (AI) provided early detection of the Coronavirus (COVID-19) in China and will influence future urban health policy internationally. AI 2020, 1, 156–165.Fusco, A.; Dicuonzo, G.; Dell’Atti, V.; Tatullo,M. Blockchain in healthcare: Insights on COVID-19. Int. J. Environ. Res. Public Health 2020, 17, 7167.Rakib, A.; Paul, A.; Chy, M.N.U.; Sami, S.A.; Baral, S.K.; Majumder, M.; Tareq, A.M.; Amin, M.N.; Shahriar, A.; Uddin, M.Z.; et al. Biochemical and computational approach of selected phytocompounds from tinospora crispa in the management of COVID-19. Molecules 2020, 25, 3936.Galán-Freyle, N.J.; Ospina-Castro, M.L.; Medina-González, A.R.; Villarreal-González, R.; Hernández-Rivera, S.P.; Pacheco- Londoño, L.C. Artificial intelligence assisted mid-infrared laser spectroscopy in situ detection of petroleum in soils. Appl. Sci. 2020, 10, 1319.Pacheco-Londoño, L.C.; Warren, E.; Galán-Freyle, N.J.; Villarreal-González, R.; Aparicio-Bolaño, J.A.; Ospina-Castro, M.L.; Shih, W.C.; Hernández-Rivera, S.P. Mid-infrared laser spectroscopy detection and quantification of explosives in soils using multivariate analysis and artificial intelligence. Appl. Sci. 2020, 10, 4178.Hammad, M.; Maher, A.; Wang, K.; Jiang, F.; Amrani, M. Detection of abnormal heart conditions based on characteristics of ECG signals. Measurement 2018, 125, 634–644.Alghamdi, A.S.; Polat, K.; Alghoson, A.; Alshdadi, A.A.; Abd El-Latif, A.A. A novel blood pressure estimation method based on the classification of oscillometric waveforms using machine-learning methods. Appl. Acoust. 2020, 164, 107279.Khalil, H.; El-Hag, N.; Sedik, A.; El-Shafie, W.; Mohamed, A.E.N.; Khalaf, A.A.M.; El-Banby, G.M.; Abd El-Samie, F.I.; El-Fishawy, A.S. Classification of diabetic retinopathy types based on Convolution Neural Network (CNN). Menoufia J. Electron. Eng. Res. 2019, 28, 126–153.Haggag, N.T.; Sedik, A.; Elbanby, G.M.; El-Fishawy, A.S.; Khalaf, A.A. Classification of Corneal Pattern Based on Convolutional LSTM Neural Network. Menoufia J. Electr. Eng. Res. 2019, 28, 158–162.Sedik, A.; Iliyasu, A.M.; Abd El-Rahiem, B.; Abdel Samea, M.E.; Abdel-Raheem, A.; Hammad, M.; Peng, J.; Abd El-Samie, F.E.; Abd El-Latif, A.A. Deploying machine and deep learning models for efficient data-augmented detection of COVID-19 infections. Viruses 2020, 12, 769.Zhavoronkov, A. Artificial intelligence for drug discovery, biomarker development, and generation of novel chemistry. Mol. Pharm. 2018, 15, 4311–4313.Yan, L.; Zhang, H.T.; Xiao, Y.; Wang, M.; Sun, C.; Liang, J.; Li, S.; Zhang, M.; Guo, Y.; Xiao, Y.; et al. Prediction of criticality in patients with severe Covid-19 infection using three clinical features: A machine learning-based prognostic model with clinical data in Wuhan. medRxiv 2020.Kriegova, E.; Fillerova, R.; Kvapil, P. Direct-RT-qPCR detection of SARS-CoV-2 without RNA extraction as part of a COVID-19 testing strategy: From sample to result in one hour. Diagnostics 2020, 10, 605.Carter, L.J.; Garner, L.V.; Smoot, J.W.; Li, Y.; Zhou, Q.; Saveson, C.J.; Sasso, J.M.; Gregg, A.C.; Soares, D.J.; Beskid, T.R.; et al. Assay techniques and test development for COVID-19 diagnosis. ACS Cent. Sci. 2020, 6, 591–605.Yip, C.C.Y.; Sridhar, S.; Leung, K.H.; Ng, A.C.K.; Chan, K.H.; Chan, J.F.W.; Tsang, O.T.Y.; Hung, I.F.N.; Cheng, V.C.C.; Yuen, K.Y.; et al. Development and evaluation of novel and highly sensitive single-tube nested real-time RT-PCR assays for SARS-CoV-2 detection. Int. J. Mol. Sci. 2020, 21, 5674.Chow, F.W.N.; Chan, T.T.Y.; Tam, A.R.; Zhao, S.; Yao, W.; Fung, J.; Cheng, F.K.K.; Lo, G.C.S.; Chu, S.; Aw-Yong, K.L.; et al. A rapid, simple, inexpensive, and mobile colorimetric assay COVID-19-LAMP for mass on-site screening of COVID-19. Int. J. Mol. Sci. 2020, 21, 5380.Allam, M.; Cai, S.; Ganesh, S.; Venkatesan, M.; Doodhwala, S.; Song, Z.; Hu, T.; Kumar, A.; Heit, J.; Coskun, A.F.; et al. COVID-19 diagnostics, tools, and prevention. Diagnostics 2020, 10, 409.Yuan, X.; Yang, C.; He, Q.; Chen, J.; Yu, D.; Li, J.; Zhai, S.; Qin, Z.; Du, K.; Chu, Z.; et al. Current and perspective diagnostic techniques for COVID-19. ACS Infect. Dis. 2020, 6, 1998–2016.Chauhan, D.S.; Prasad, R.; Srivastava, R.; Jaggi, M.; Chauhan, S.C.; Yallapu, M.M. Comprehensive review on current interventions, diagnostics, and nanotechnology perspectives against SARS-CoV-2. Bioconjug. Chem. 2020, 31, 2021–2045.Epanechnikov, V.A. Non-parametric estimation of a multivariate probability density. Theory Probab. Its Appl. 1969, 14, 153–158.Rosenblatt, M. Remarks on some nonparametric estimates of a density function. Ann. Math. Stat. 1956, 27, 832–837.Parzen, E. On estimation of a probability density function and mode. Ann. Math. Stat. 1962, 33, 1065–1076.Fabian Pedregosa, G.V.; Gramfort, A.; Michel, V.; Thirion, B.; Grisel, O.; Blondel, M.; Prettenhofer, P.; Weiss, R.; Dubourg, V.; Vanderplas, J.; et al. Scikit-learn: Machine learning in Python. J. Mach. Learn. Res. 2011, 12, 2825–2830.Bergstra, J.; Bengio, Y. Random search for hyper-parameter optimization. J. Mach. Learn. Res. 2012, 13, 281–305.Corman, V.M.; Landt, O.; Kaiser, M.; Molenkamp, R.; Meijer, A.; Chu, D.K.; Bleicker, T.; Brünink, S.; Schneider, J.; Schmidt, M.L.; et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Eurosurveillance 2020, 25, 2000045.Buitinck, L.; Louppe, G.; Blondel, M.; Pedregosa, F.; Mueller, A.; Grisel, O.; Niculae, V.; Prettenhofer, P.; Gramfort, A.; Grobler, J.; et al. API design for machine learning software: Experiences from the scikit-learn project. In Proceedings of the European Conference on Machine Learning and Principles and Practices of Knowledge Discovery in Databases, Prague, Czech Republic, 23 September 2013.Sede BarranquillaMaestría en Gestión y Emprendimiento TecnológicoORIGINALPDF.pdfPDF.pdfapplication/pdf3097160https://bonga.unisimon.edu.co/bitstreams/1a367f00-9d95-45e6-9d0f-0a96c7dd6567/download19357b71028b49cf6ffd65a219cc71bcMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805https://bonga.unisimon.edu.co/bitstreams/67d565b4-3c62-4513-96d0-b82cca7307e9/download4460e5956bc1d1639be9ae6146a50347MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-83000https://bonga.unisimon.edu.co/bitstreams/0bc116d9-145e-4e97-9fd2-50552d2c137a/download2a1661e5960a7bab4fd8dda692fb677cMD53TEXTAnomaly_Identification_During_Polymerase_Chain_Reaction_Detecting_Artículo.pdf.txtAnomaly_Identification_During_Polymerase_Chain_Reaction_Detecting_Artículo.pdf.txtExtracted texttext/plain56914https://bonga.unisimon.edu.co/bitstreams/8ba9b1a5-dc04-41d0-a0f4-e564188e6ead/downloada3eb6a334df157d7c851370f0d53e202MD54PDF.txtPDF.txtExtracted texttext/plain61147https://bonga.unisimon.edu.co/bitstreams/ec78b626-8c12-43c2-9b4d-906f059fe7bb/downloadc1859f95aef2509c1be33d7edc7b8752MD56PDF.pdf.txtPDF.pdf.txtExtracted texttext/plain61147https://bonga.unisimon.edu.co/bitstreams/d92277b3-48c7-4a27-bc26-9692d58ca66e/downloadc1859f95aef2509c1be33d7edc7b8752MD58THUMBNAILAnomaly_Identification_During_Polymerase_Chain_Reaction_Detecting_Artículo.pdf.jpgAnomaly_Identification_During_Polymerase_Chain_Reaction_Detecting_Artículo.pdf.jpgGenerated Thumbnailimage/jpeg23632https://bonga.unisimon.edu.co/bitstreams/989d4106-9add-4454-be06-f7bbad5ab92d/downloadf547975df7c83161c80f029c45c86c88MD55PDF.jpgPDF.jpgGenerated Thumbnailimage/jpeg5807https://bonga.unisimon.edu.co/bitstreams/80822da5-df09-41e4-b475-4267c599dfac/downloadc0d4a2fe7bd269c0cc176a80c08847c5MD57PDF.pdf.jpgPDF.pdf.jpgGenerated Thumbnailimage/jpeg5807https://bonga.unisimon.edu.co/bitstreams/a62932dc-549e-459c-a8f5-1d9b8997fb7e/downloadc0d4a2fe7bd269c0cc176a80c08847c5MD5920.500.12442/9229oai:bonga.unisimon.edu.co:20.500.12442/92292024-08-14 21:52:01.484http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internacionalrestrictedhttps://bonga.unisimon.edu.coRepositorio Digital Universidad Simón Bolívarrepositorio.digital@unisimon.edu.co |