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Exploring and Identifying Prognostic Phenotypes of Patients with Heart Failure Guided by Explainable Machine Learning

Identifying patient prognostic phenotypes facilitates precision medicine. This study aimed to explore phenotypes of patients with heart failure (HF) corresponding to prognostic condition (risk of mortality) and identify the phenotype of new patients by machine learning (ML). A unsupervised ML was ap...

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Autores principales: Zhou, Xue, Nakamura, Keijiro, Sahara, Naohiko, Asami, Masako, Toyoda, Yasutake, Enomoto, Yoshinari, Hara, Hidehiko, Noro, Mahito, Sugi, Kaoru, Moroi, Masao, Nakamura, Masato, Huang, Ming, Zhu, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224610/
https://www.ncbi.nlm.nih.gov/pubmed/35743806
http://dx.doi.org/10.3390/life12060776
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author Zhou, Xue
Nakamura, Keijiro
Sahara, Naohiko
Asami, Masako
Toyoda, Yasutake
Enomoto, Yoshinari
Hara, Hidehiko
Noro, Mahito
Sugi, Kaoru
Moroi, Masao
Nakamura, Masato
Huang, Ming
Zhu, Xin
author_facet Zhou, Xue
Nakamura, Keijiro
Sahara, Naohiko
Asami, Masako
Toyoda, Yasutake
Enomoto, Yoshinari
Hara, Hidehiko
Noro, Mahito
Sugi, Kaoru
Moroi, Masao
Nakamura, Masato
Huang, Ming
Zhu, Xin
author_sort Zhou, Xue
collection PubMed
description Identifying patient prognostic phenotypes facilitates precision medicine. This study aimed to explore phenotypes of patients with heart failure (HF) corresponding to prognostic condition (risk of mortality) and identify the phenotype of new patients by machine learning (ML). A unsupervised ML was applied to explore phenotypes of patients in a derivation dataset (n = 562) based on their medical records. Thereafter, supervised ML models were trained on the derivation dataset to classify these identified phenotypes. Then, the trained classifiers were further validated on an independent validation dataset (n = 168). Finally, Shapley additive explanations were used to interpret decision making of phenotype classification. Three patient phenotypes corresponding to stratified mortality risk (high, low, and intermediate) were identified. Kaplan–Meier survival curves among the three phenotypes had significant difference (pairwise comparison p < 0.05). Hazard ratio of all-cause mortality between patients in phenotype 1 (n = 91; high risk) and phenotype 3 (n = 329; intermediate risk) was 2.08 (95%CI 1.29–3.37, p = 0.003), and 0.26 (95%CI 0.11–0.61, p = 0.002) between phenotype 2 (n = 142; low risk) and phenotype 3. For phenotypes classification by random forest, AUCs of phenotypes 1, 2, and 3 were 0.736 ± 0.038, 0.815 ± 0.035, and 0.721 ± 0.03, respectively, slightly better than the decision tree. Then, the classifier effectively identified the phenotypes for new patients in the validation dataset with significant difference on survival curves and hazard ratios. Finally, age and creatinine clearance rate were identified as the top two most important predictors. ML could effectively identify patient prognostic phenotypes, facilitating reasonable management and treatment considering prognostic condition.
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spelling pubmed-92246102022-06-24 Exploring and Identifying Prognostic Phenotypes of Patients with Heart Failure Guided by Explainable Machine Learning Zhou, Xue Nakamura, Keijiro Sahara, Naohiko Asami, Masako Toyoda, Yasutake Enomoto, Yoshinari Hara, Hidehiko Noro, Mahito Sugi, Kaoru Moroi, Masao Nakamura, Masato Huang, Ming Zhu, Xin Life (Basel) Article Identifying patient prognostic phenotypes facilitates precision medicine. This study aimed to explore phenotypes of patients with heart failure (HF) corresponding to prognostic condition (risk of mortality) and identify the phenotype of new patients by machine learning (ML). A unsupervised ML was applied to explore phenotypes of patients in a derivation dataset (n = 562) based on their medical records. Thereafter, supervised ML models were trained on the derivation dataset to classify these identified phenotypes. Then, the trained classifiers were further validated on an independent validation dataset (n = 168). Finally, Shapley additive explanations were used to interpret decision making of phenotype classification. Three patient phenotypes corresponding to stratified mortality risk (high, low, and intermediate) were identified. Kaplan–Meier survival curves among the three phenotypes had significant difference (pairwise comparison p < 0.05). Hazard ratio of all-cause mortality between patients in phenotype 1 (n = 91; high risk) and phenotype 3 (n = 329; intermediate risk) was 2.08 (95%CI 1.29–3.37, p = 0.003), and 0.26 (95%CI 0.11–0.61, p = 0.002) between phenotype 2 (n = 142; low risk) and phenotype 3. For phenotypes classification by random forest, AUCs of phenotypes 1, 2, and 3 were 0.736 ± 0.038, 0.815 ± 0.035, and 0.721 ± 0.03, respectively, slightly better than the decision tree. Then, the classifier effectively identified the phenotypes for new patients in the validation dataset with significant difference on survival curves and hazard ratios. Finally, age and creatinine clearance rate were identified as the top two most important predictors. ML could effectively identify patient prognostic phenotypes, facilitating reasonable management and treatment considering prognostic condition. MDPI 2022-05-24 /pmc/articles/PMC9224610/ /pubmed/35743806 http://dx.doi.org/10.3390/life12060776 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhou, Xue
Nakamura, Keijiro
Sahara, Naohiko
Asami, Masako
Toyoda, Yasutake
Enomoto, Yoshinari
Hara, Hidehiko
Noro, Mahito
Sugi, Kaoru
Moroi, Masao
Nakamura, Masato
Huang, Ming
Zhu, Xin
Exploring and Identifying Prognostic Phenotypes of Patients with Heart Failure Guided by Explainable Machine Learning
title Exploring and Identifying Prognostic Phenotypes of Patients with Heart Failure Guided by Explainable Machine Learning
title_full Exploring and Identifying Prognostic Phenotypes of Patients with Heart Failure Guided by Explainable Machine Learning
title_fullStr Exploring and Identifying Prognostic Phenotypes of Patients with Heart Failure Guided by Explainable Machine Learning
title_full_unstemmed Exploring and Identifying Prognostic Phenotypes of Patients with Heart Failure Guided by Explainable Machine Learning
title_short Exploring and Identifying Prognostic Phenotypes of Patients with Heart Failure Guided by Explainable Machine Learning
title_sort exploring and identifying prognostic phenotypes of patients with heart failure guided by explainable machine learning
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224610/
https://www.ncbi.nlm.nih.gov/pubmed/35743806
http://dx.doi.org/10.3390/life12060776
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