ODBAE: a high-performance model identifying complex phenotypes in high-dimensional biological datasets

Identifying complex phenotypes from high-dimensional biological data is challenging due to the intricate interdependencies among different physiological indicators. Traditional approaches often focus on detecting outliers in single variables, overlooking the broader network of interactions that cont...

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Vydané v:	Communications biology Ročník 8; číslo 1; s. 1415 - 19
Hlavní autori:	Shen, Yafei, Zhang, Tao, Liu, Zhiwei, Kostelidou, Kalliopi, Xu, Ying, Yang, Ling
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 02.10.2025 Nature Publishing Group Nature Portfolio
Predmet:	631/1647/48 631/1647/794 Animals Biomedical and Life Sciences Datasets Disease Genes Genetic engineering Homeostasis Life Sciences Machine Learning Metabolism Mice Mice, Knockout Performance evaluation Phenotype Phenotypes Phenotyping Physiology
ISSN:	2399-3642, 2399-3642
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Abstract	Identifying complex phenotypes from high-dimensional biological data is challenging due to the intricate interdependencies among different physiological indicators. Traditional approaches often focus on detecting outliers in single variables, overlooking the broader network of interactions that contribute to phenotype emergence. Here, we introduce ODBAE (Outlier Detection using Balanced Autoencoders), a machine learning method designed to uncover both subtle and extreme outliers by capturing latent relationships among multiple physiological parameters. ODBAE’s revised loss function enhances its ability to detect two key types of outliers: influential points (IP), which disrupt latent correlations between dimensions, and high leverage points (HLP), which deviate from the norm but go undetected by traditional autoencoder-based methods. Using data from the International Mouse Phenotyping Consortium (IMPC), we show that ODBAE can identify knockout mice with complex, multi-indicator phenotypes—normal in individual traits, but abnormal when considered together. In addition, this method reveals novel metabolism-related genes and uncovers coordinated abnormalities across metabolic indicators. Our results highlight the utility of ODBAE in detecting joint abnormalities and advancing our understanding of homeostatic perturbations in biological systems. ODBAE offers a powerful approach for detecting complex anomalies and characterizing unknown phenotypes within biological systems.
AbstractList	Identifying complex phenotypes from high-dimensional biological data is challenging due to the intricate interdependencies among different physiological indicators. Traditional approaches often focus on detecting outliers in single variables, overlooking the broader network of interactions that contribute to phenotype emergence. Here, we introduce ODBAE (Outlier Detection using Balanced Autoencoders), a machine learning method designed to uncover both subtle and extreme outliers by capturing latent relationships among multiple physiological parameters. ODBAE's revised loss function enhances its ability to detect two key types of outliers: influential points (IP), which disrupt latent correlations between dimensions, and high leverage points (HLP), which deviate from the norm but go undetected by traditional autoencoder-based methods. Using data from the International Mouse Phenotyping Consortium (IMPC), we show that ODBAE can identify knockout mice with complex, multi-indicator phenotypes-normal in individual traits, but abnormal when considered together. In addition, this method reveals novel metabolism-related genes and uncovers coordinated abnormalities across metabolic indicators. Our results highlight the utility of ODBAE in detecting joint abnormalities and advancing our understanding of homeostatic perturbations in biological systems. Abstract Identifying complex phenotypes from high-dimensional biological data is challenging due to the intricate interdependencies among different physiological indicators. Traditional approaches often focus on detecting outliers in single variables, overlooking the broader network of interactions that contribute to phenotype emergence. Here, we introduce ODBAE (Outlier Detection using Balanced Autoencoders), a machine learning method designed to uncover both subtle and extreme outliers by capturing latent relationships among multiple physiological parameters. ODBAE’s revised loss function enhances its ability to detect two key types of outliers: influential points (IP), which disrupt latent correlations between dimensions, and high leverage points (HLP), which deviate from the norm but go undetected by traditional autoencoder-based methods. Using data from the International Mouse Phenotyping Consortium (IMPC), we show that ODBAE can identify knockout mice with complex, multi-indicator phenotypes—normal in individual traits, but abnormal when considered together. In addition, this method reveals novel metabolism-related genes and uncovers coordinated abnormalities across metabolic indicators. Our results highlight the utility of ODBAE in detecting joint abnormalities and advancing our understanding of homeostatic perturbations in biological systems. Identifying complex phenotypes from high-dimensional biological data is challenging due to the intricate interdependencies among different physiological indicators. Traditional approaches often focus on detecting outliers in single variables, overlooking the broader network of interactions that contribute to phenotype emergence. Here, we introduce ODBAE (Outlier Detection using Balanced Autoencoders), a machine learning method designed to uncover both subtle and extreme outliers by capturing latent relationships among multiple physiological parameters. ODBAE’s revised loss function enhances its ability to detect two key types of outliers: influential points (IP), which disrupt latent correlations between dimensions, and high leverage points (HLP), which deviate from the norm but go undetected by traditional autoencoder-based methods. Using data from the International Mouse Phenotyping Consortium (IMPC), we show that ODBAE can identify knockout mice with complex, multi-indicator phenotypes—normal in individual traits, but abnormal when considered together. In addition, this method reveals novel metabolism-related genes and uncovers coordinated abnormalities across metabolic indicators. Our results highlight the utility of ODBAE in detecting joint abnormalities and advancing our understanding of homeostatic perturbations in biological systems.ODBAE offers a powerful approach for detecting complex anomalies and characterizing unknown phenotypes within biological systems. Identifying complex phenotypes from high-dimensional biological data is challenging due to the intricate interdependencies among different physiological indicators. Traditional approaches often focus on detecting outliers in single variables, overlooking the broader network of interactions that contribute to phenotype emergence. Here, we introduce ODBAE (Outlier Detection using Balanced Autoencoders), a machine learning method designed to uncover both subtle and extreme outliers by capturing latent relationships among multiple physiological parameters. ODBAE’s revised loss function enhances its ability to detect two key types of outliers: influential points (IP), which disrupt latent correlations between dimensions, and high leverage points (HLP), which deviate from the norm but go undetected by traditional autoencoder-based methods. Using data from the International Mouse Phenotyping Consortium (IMPC), we show that ODBAE can identify knockout mice with complex, multi-indicator phenotypes—normal in individual traits, but abnormal when considered together. In addition, this method reveals novel metabolism-related genes and uncovers coordinated abnormalities across metabolic indicators. Our results highlight the utility of ODBAE in detecting joint abnormalities and advancing our understanding of homeostatic perturbations in biological systems. ODBAE offers a powerful approach for detecting complex anomalies and characterizing unknown phenotypes within biological systems. Identifying complex phenotypes from high-dimensional biological data is challenging due to the intricate interdependencies among different physiological indicators. Traditional approaches often focus on detecting outliers in single variables, overlooking the broader network of interactions that contribute to phenotype emergence. Here, we introduce ODBAE (Outlier Detection using Balanced Autoencoders), a machine learning method designed to uncover both subtle and extreme outliers by capturing latent relationships among multiple physiological parameters. ODBAE's revised loss function enhances its ability to detect two key types of outliers: influential points (IP), which disrupt latent correlations between dimensions, and high leverage points (HLP), which deviate from the norm but go undetected by traditional autoencoder-based methods. Using data from the International Mouse Phenotyping Consortium (IMPC), we show that ODBAE can identify knockout mice with complex, multi-indicator phenotypes-normal in individual traits, but abnormal when considered together. In addition, this method reveals novel metabolism-related genes and uncovers coordinated abnormalities across metabolic indicators. Our results highlight the utility of ODBAE in detecting joint abnormalities and advancing our understanding of homeostatic perturbations in biological systems.Identifying complex phenotypes from high-dimensional biological data is challenging due to the intricate interdependencies among different physiological indicators. Traditional approaches often focus on detecting outliers in single variables, overlooking the broader network of interactions that contribute to phenotype emergence. Here, we introduce ODBAE (Outlier Detection using Balanced Autoencoders), a machine learning method designed to uncover both subtle and extreme outliers by capturing latent relationships among multiple physiological parameters. ODBAE's revised loss function enhances its ability to detect two key types of outliers: influential points (IP), which disrupt latent correlations between dimensions, and high leverage points (HLP), which deviate from the norm but go undetected by traditional autoencoder-based methods. Using data from the International Mouse Phenotyping Consortium (IMPC), we show that ODBAE can identify knockout mice with complex, multi-indicator phenotypes-normal in individual traits, but abnormal when considered together. In addition, this method reveals novel metabolism-related genes and uncovers coordinated abnormalities across metabolic indicators. Our results highlight the utility of ODBAE in detecting joint abnormalities and advancing our understanding of homeostatic perturbations in biological systems.
ArticleNumber	1415
Author	Xu, Ying Liu, Zhiwei Kostelidou, Kalliopi Shen, Yafei Yang, Ling Zhang, Tao
Author_xml	– sequence: 1 givenname: Yafei surname: Shen fullname: Shen, Yafei organization: School of Mathematical Sciences, Soochow University, Center for Systems Biology, Soochow University – sequence: 2 givenname: Tao surname: Zhang fullname: Zhang, Tao organization: Jiangsu Province Engineering Research Center of Development and Translation of Key Technologies for Chronic Disease Prevention and Control, Suzhou Vocational Health College – sequence: 3 givenname: Zhiwei surname: Liu fullname: Liu, Zhiwei organization: Cambridge-Suda Genomic Research Center, Suzhou Medical College of Soochow University – sequence: 4 givenname: Kalliopi surname: Kostelidou fullname: Kostelidou, Kalliopi organization: KTL Research Acceleration LTD – sequence: 5 givenname: Ying orcidid: 0000-0002-6689-7768 surname: Xu fullname: Xu, Ying email: yingxu@suda.edu.cn organization: Cambridge-Suda Genomic Research Center, Suzhou Medical College of Soochow University, Jiangsu Key Laboratory of Neuropsychiatric Diseases, Suzhou Medical College of Soochow University – sequence: 6 givenname: Ling orcidid: 0000-0002-4045-7457 surname: Yang fullname: Yang, Ling email: lyang@suda.edu.cn organization: School of Mathematical Sciences, Soochow University, Center for Systems Biology, Soochow University
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Snippet	Identifying complex phenotypes from high-dimensional biological data is challenging due to the intricate interdependencies among different physiological... Abstract Identifying complex phenotypes from high-dimensional biological data is challenging due to the intricate interdependencies among different...
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SubjectTerms	631/1647/48 631/1647/794 Animals Biomedical and Life Sciences Datasets Disease Genes Genetic engineering Homeostasis Life Sciences Machine Learning Metabolism Mice Mice, Knockout Performance evaluation Phenotype Phenotypes Phenotyping Physiology
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Title	ODBAE: a high-performance model identifying complex phenotypes in high-dimensional biological datasets
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