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This study delves into a comprehensive performance analysis of three pre-trained convolutional neural network (CNN) architectures: ResNet50, DenseNet121, and Inception-ResNet-v2. To ensure the broad applicability of our approach, we curated a large-scale dataset comprising a diverse collection of chest X-ray images, that included both positive and negative cases of COVID-19. The models\u2019 performance was evaluated using separate datasets for internal validation (from the same source as the training images) and external validation (from different sources). Our examination uncovered a significant drop in network efficacy, registering a 10.66% reduction for ResNet50, a 36.33% decline for DenseNet121, and a 19.55% decrease for Inception-ResNet-v2 in terms of accuracy. Best results were obtained with DenseNet121 achieving the highest accuracy at 96.71% in internal validation and Inception-ResNet-v2 attaining 76.70% accuracy in external validation. Furthermore, we introduced a model ensemble approach aimed at improving network performance when making inferences on images from diverse sources beyond their training data. The proposed method uses uncertainty-based weighting by calculating the entropy in order to assign appropriate weights to the outputs of each network. Our results showcase the effectiveness of the ensemble method in enhancing accuracy up to 97.38% for internal validation and 81.18% for external validation, while maintaining a balanced ability to detect both positive and negative cases.<\/jats:p>","DOI":"10.1038\/s41598-024-56171-6","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T08:01:49Z","timestamp":1710144109000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Generalizable disease detection using model ensemble on chest X-ray images"],"prefix":"10.1038","volume":"14","author":[{"given":"Maider","family":"Abad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Casas-Roma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Prados","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"56171_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2021.104665","volume":"136","author":"Y Bouchareb","year":"2021","unstructured":"Bouchareb, Y. et al. 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