Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy
Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy...
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Veröffentlicht in: | Archives of toxicology 2024-09, Vol.98 (9), p.3049-3061 |
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description | Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed
T
test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using “H2O” autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance. |
doi_str_mv | 10.1007/s00204-024-03803-5 |
format | Article |
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T
test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using “H2O” autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance.</description><identifier>ISSN: 0340-5761</identifier><identifier>ISSN: 1432-0738</identifier><identifier>EISSN: 1432-0738</identifier><identifier>DOI: 10.1007/s00204-024-03803-5</identifier><identifier>PMID: 38879852</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Abnormalities ; Adolescent ; Adult ; Aged ; Algorithms ; Anticonvulsants - adverse effects ; automation ; Bilirubin ; Biomedical and Life Sciences ; Biomedicine ; Chemical and Drug Induced Liver Injury - etiology ; chi-square distribution ; Chi-square test ; Child ; Child, Preschool ; data collection ; Datasets ; Environmental Health ; Epilepsy ; Epilepsy - drug therapy ; Female ; Hepatotoxicity ; Humans ; In Silico ; Learning algorithms ; leukocyte count ; Machine Learning ; Male ; Middle Aged ; Occupational Medicine/Industrial Medicine ; oral administration ; Parameters ; Pharmacology/Toxicology ; Pharmacovigilance ; Prediction models ; Predictions ; Regression analysis ; risk ; t-test ; Transaminase ; Transaminases ; Transaminases - blood ; Valproic Acid ; Young Adult</subject><ispartof>Archives of toxicology, 2024-09, Vol.98 (9), p.3049-3061</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c289t-70662b9f95aa5e1004a6aeba590139bff19f72caf1a40bfb9f98b5d1e5e96e973</cites><orcidid>0000-0002-1661-3261</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00204-024-03803-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00204-024-03803-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38879852$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Hongying</creatorcontrib><creatorcontrib>Huang, Sihui</creatorcontrib><creatorcontrib>Li, Fengxin</creatorcontrib><creatorcontrib>Pang, Zicheng</creatorcontrib><creatorcontrib>Luo, Jian</creatorcontrib><creatorcontrib>Sun, Danfeng</creatorcontrib><creatorcontrib>Liu, Junsong</creatorcontrib><creatorcontrib>Chen, Zhuoming</creatorcontrib><creatorcontrib>Qu, Jian</creatorcontrib><creatorcontrib>Qu, Qiang</creatorcontrib><title>Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy</title><title>Archives of toxicology</title><addtitle>Arch Toxicol</addtitle><addtitle>Arch Toxicol</addtitle><description>Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed
T
test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using “H2O” autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance.</description><subject>Abnormalities</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Algorithms</subject><subject>Anticonvulsants - adverse effects</subject><subject>automation</subject><subject>Bilirubin</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Chemical and Drug Induced Liver Injury - etiology</subject><subject>chi-square distribution</subject><subject>Chi-square test</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>data collection</subject><subject>Datasets</subject><subject>Environmental Health</subject><subject>Epilepsy</subject><subject>Epilepsy - drug therapy</subject><subject>Female</subject><subject>Hepatotoxicity</subject><subject>Humans</subject><subject>In Silico</subject><subject>Learning algorithms</subject><subject>leukocyte count</subject><subject>Machine Learning</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Occupational Medicine/Industrial Medicine</subject><subject>oral administration</subject><subject>Parameters</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacovigilance</subject><subject>Prediction models</subject><subject>Predictions</subject><subject>Regression analysis</subject><subject>risk</subject><subject>t-test</subject><subject>Transaminase</subject><subject>Transaminases</subject><subject>Transaminases - blood</subject><subject>Valproic Acid</subject><subject>Young Adult</subject><issn>0340-5761</issn><issn>1432-0738</issn><issn>1432-0738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1TAQhi0EoofCC7BAltiwCfUljuMlKlepUjd0bU2SSXHl2MF2KvUteGScngISC7BkWR5_849nfkJecvaWM6bPMmOCtQ0TdcueyUY9IgfeStEwLfvH5MBkyxqlO35CnuV8wxgXvZFPyYnse216JQ7kx3u8RR_XBUOhECZ6C95NUFwMNM41QmErcamBkS4wfnMBqUdIwYVrusQJPS2RrgknN1aBIcS0gKcujAkh465REoQMiwv73YW9wppi1YPRTU2pXMGJ4uo8rvnuOXkyg8_44uE8JVcfP3w9_9xcXH76cv7uohlrD6XRrOvEYGajABTWcbTQAQ6gDOPSDPPMzazFCDOHlg3zTvaDmjgqNB0aLU_Jm6Nu_cv3DXOxi8sjeg8B45at5Erqti7xf5R1va5j1jv6-i_0Jm4p1EYqZYRRXAlZKXGkxhRzTjjbNbkF0p3lzO7W2qO1tlpr7621qia9epDehgWn3ym_vKyAPAK5PoVrTH9q_0P2JzuBsQk</recordid><startdate>20240901</startdate><enddate>20240901</enddate><creator>Ma, Hongying</creator><creator>Huang, Sihui</creator><creator>Li, Fengxin</creator><creator>Pang, Zicheng</creator><creator>Luo, Jian</creator><creator>Sun, Danfeng</creator><creator>Liu, Junsong</creator><creator>Chen, Zhuoming</creator><creator>Qu, Jian</creator><creator>Qu, Qiang</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T2</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0002-1661-3261</orcidid></search><sort><creationdate>20240901</creationdate><title>Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy</title><author>Ma, Hongying ; 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This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed
T
test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using “H2O” autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>38879852</pmid><doi>10.1007/s00204-024-03803-5</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-1661-3261</orcidid></addata></record> |
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subjects | Abnormalities Adolescent Adult Aged Algorithms Anticonvulsants - adverse effects automation Bilirubin Biomedical and Life Sciences Biomedicine Chemical and Drug Induced Liver Injury - etiology chi-square distribution Chi-square test Child Child, Preschool data collection Datasets Environmental Health Epilepsy Epilepsy - drug therapy Female Hepatotoxicity Humans In Silico Learning algorithms leukocyte count Machine Learning Male Middle Aged Occupational Medicine/Industrial Medicine oral administration Parameters Pharmacology/Toxicology Pharmacovigilance Prediction models Predictions Regression analysis risk t-test Transaminase Transaminases Transaminases - blood Valproic Acid Young Adult |
title | Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy |
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