{"title":"机器学习识别与马脑炎病毒、创伤性脑损伤和有机磷神经毒剂引起的神经系统疾病相关的基因。","authors":"Liduo Yin, Morgen VanderGiessen, Vinoth Kumar, Benjamin Conacher, Po-Chien Haku Chao, Michelle Theus, Erik Johnson, Kylene Kehn-Hall, Xiaowei Wu, Hehuang Xie","doi":"10.3389/fncom.2025.1529902","DOIUrl":null,"url":null,"abstract":"<p><p>Venezuelan, eastern, and western equine encephalitis viruses (collectively referred to as equine encephalitis viruses---EEV) cause serious neurological diseases and pose a significant threat to the civilian population and the warfighter. Likewise, organophosphorus nerve agents (OPNA) are highly toxic chemicals that pose serious health threats of neurological deficits to both military and civilian personnel around the world. Consequently, only a select few approved research groups are permitted to study these dangerous chemical and biological warfare agents. This has created a significant gap in our scientific understanding of the mechanisms underlying neurological diseases. Valuable insights may be gleaned by drawing parallels to other extensively researched neuropathologies, such as traumatic brain injuries (TBI). By examining combined gene expression profiles, common and unique molecular characteristics may be discovered, providing new insights into medical countermeasures (MCMs) for TBI, EEV infection and OPNA neuropathologies and sequelae. In this study, we collected transcriptomic datasets for neurological disorders caused by TBI, EEV, and OPNA injury, and implemented a framework to normalize and integrate gene expression datasets derived from various platforms. Effective machine learning approaches were developed to identify critical genes that are either shared by or distinctive among the three neuropathologies. With the aid of deep neural networks, we were able to extract important association signals for accurate prediction of different neurological disorders by using integrated gene expression datasets of VEEV, OPNA, and TBI samples. Gene ontology and pathway analyses further identified neuropathologic features with specific gene product attributes and functions, shedding light on the fundamental biology of these neurological disorders. Collectively, we highlight a workflow to analyze published transcriptomic data using machine learning, which can be used for both identification of gene biomarkers that are unique to specific neurological conditions, as well as genes shared across multiple neuropathologies. These shared genes could serve as potential neuroprotective drug targets for conditions like EEV, TBI, and OPNA.</p>","PeriodicalId":12363,"journal":{"name":"Frontiers in Computational Neuroscience","volume":"19 ","pages":"1529902"},"PeriodicalIF":2.1000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106541/pdf/","citationCount":"0","resultStr":"{\"title\":\"Machine learning identifies genes linked to neurological disorders induced by equine encephalitis viruses, traumatic brain injuries, and organophosphorus nerve agents.\",\"authors\":\"Liduo Yin, Morgen VanderGiessen, Vinoth Kumar, Benjamin Conacher, Po-Chien Haku Chao, Michelle Theus, Erik Johnson, Kylene Kehn-Hall, Xiaowei Wu, Hehuang Xie\",\"doi\":\"10.3389/fncom.2025.1529902\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Venezuelan, eastern, and western equine encephalitis viruses (collectively referred to as equine encephalitis viruses---EEV) cause serious neurological diseases and pose a significant threat to the civilian population and the warfighter. Likewise, organophosphorus nerve agents (OPNA) are highly toxic chemicals that pose serious health threats of neurological deficits to both military and civilian personnel around the world. Consequently, only a select few approved research groups are permitted to study these dangerous chemical and biological warfare agents. This has created a significant gap in our scientific understanding of the mechanisms underlying neurological diseases. Valuable insights may be gleaned by drawing parallels to other extensively researched neuropathologies, such as traumatic brain injuries (TBI). By examining combined gene expression profiles, common and unique molecular characteristics may be discovered, providing new insights into medical countermeasures (MCMs) for TBI, EEV infection and OPNA neuropathologies and sequelae. In this study, we collected transcriptomic datasets for neurological disorders caused by TBI, EEV, and OPNA injury, and implemented a framework to normalize and integrate gene expression datasets derived from various platforms. Effective machine learning approaches were developed to identify critical genes that are either shared by or distinctive among the three neuropathologies. With the aid of deep neural networks, we were able to extract important association signals for accurate prediction of different neurological disorders by using integrated gene expression datasets of VEEV, OPNA, and TBI samples. Gene ontology and pathway analyses further identified neuropathologic features with specific gene product attributes and functions, shedding light on the fundamental biology of these neurological disorders. Collectively, we highlight a workflow to analyze published transcriptomic data using machine learning, which can be used for both identification of gene biomarkers that are unique to specific neurological conditions, as well as genes shared across multiple neuropathologies. These shared genes could serve as potential neuroprotective drug targets for conditions like EEV, TBI, and OPNA.</p>\",\"PeriodicalId\":12363,\"journal\":{\"name\":\"Frontiers in Computational Neuroscience\",\"volume\":\"19 \",\"pages\":\"1529902\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-05-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106541/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Computational Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fncom.2025.1529902\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MATHEMATICAL & COMPUTATIONAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Computational Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fncom.2025.1529902","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MATHEMATICAL & COMPUTATIONAL BIOLOGY","Score":null,"Total":0}
Machine learning identifies genes linked to neurological disorders induced by equine encephalitis viruses, traumatic brain injuries, and organophosphorus nerve agents.
Venezuelan, eastern, and western equine encephalitis viruses (collectively referred to as equine encephalitis viruses---EEV) cause serious neurological diseases and pose a significant threat to the civilian population and the warfighter. Likewise, organophosphorus nerve agents (OPNA) are highly toxic chemicals that pose serious health threats of neurological deficits to both military and civilian personnel around the world. Consequently, only a select few approved research groups are permitted to study these dangerous chemical and biological warfare agents. This has created a significant gap in our scientific understanding of the mechanisms underlying neurological diseases. Valuable insights may be gleaned by drawing parallels to other extensively researched neuropathologies, such as traumatic brain injuries (TBI). By examining combined gene expression profiles, common and unique molecular characteristics may be discovered, providing new insights into medical countermeasures (MCMs) for TBI, EEV infection and OPNA neuropathologies and sequelae. In this study, we collected transcriptomic datasets for neurological disorders caused by TBI, EEV, and OPNA injury, and implemented a framework to normalize and integrate gene expression datasets derived from various platforms. Effective machine learning approaches were developed to identify critical genes that are either shared by or distinctive among the three neuropathologies. With the aid of deep neural networks, we were able to extract important association signals for accurate prediction of different neurological disorders by using integrated gene expression datasets of VEEV, OPNA, and TBI samples. Gene ontology and pathway analyses further identified neuropathologic features with specific gene product attributes and functions, shedding light on the fundamental biology of these neurological disorders. Collectively, we highlight a workflow to analyze published transcriptomic data using machine learning, which can be used for both identification of gene biomarkers that are unique to specific neurological conditions, as well as genes shared across multiple neuropathologies. These shared genes could serve as potential neuroprotective drug targets for conditions like EEV, TBI, and OPNA.
期刊介绍:
Frontiers in Computational Neuroscience is a first-tier electronic journal devoted to promoting theoretical modeling of brain function and fostering interdisciplinary interactions between theoretical and experimental neuroscience. Progress in understanding the amazing capabilities of the brain is still limited, and we believe that it will only come with deep theoretical thinking and mutually stimulating cooperation between different disciplines and approaches. We therefore invite original contributions on a wide range of topics that present the fruits of such cooperation, or provide stimuli for future alliances. We aim to provide an interactive forum for cutting-edge theoretical studies of the nervous system, and for promulgating the best theoretical research to the broader neuroscience community. Models of all styles and at all levels are welcome, from biophysically motivated realistic simulations of neurons and synapses to high-level abstract models of inference and decision making. While the journal is primarily focused on theoretically based and driven research, we welcome experimental studies that validate and test theoretical conclusions.
Also: comp neuro