Cho Youna, Kim Erin, Kim Minyoung, Rho Mina
Department of Computer Science, Hanyang University, 222 Wangsimni-ro, Seoul 04763, Republic of Korea.
Department of Artificial Intelligence, Hanyang University, 222 Wangsimni-ro, Seoul 04763, Republic of Korea.
Brief Bioinform. 2025 Sep 6;26(5). doi: 10.1093/bib/bbaf450.
Mobile genetic elements (MGEs) play an important role in facilitating the acquisition of antibiotic resistance genes (ARGs) within microbial communities, significantly impacting the evolution of antibiotic resistance. Understanding the mechanism and trajectory of ARG acquisition requires a comprehensive analysis of the ARG-carrying mobilome-a collective set of MGEs carrying ARGs. However, identifying the mobilome within complex microbiomes poses considerable challenges. Existing MGE prediction methods, designed primarily for single genomes, exhibit substantial limitations when applied to metagenomic data, often producing high false positive rates in identifying target MGEs from metagenome sequencing data.
To address these challenges, we developed DeepMobilome, a novel approach for accurately identifying target MGEs within the microbiome. DeepMobilome leverages a convolutional neural network trained on read alignment data derived from sequence alignment map (SAM) files, providing superior accuracy in detecting MGEs. Trained on 364 647 cases, DeepMobilome achieved a high validation accuracy of 0.99. DeepMobilome consistently outperformed existing methods in discerning the presence of target MGE sequences across diverse test sets. In single-genome test scenarios, DeepMobilome showed an F1-score of 0.935, compared to 0.755 and 0.670 for MGEfinder and ISMapper, respectively, demonstrating its substantial improvements in prediction accuracy. Extensive evaluations across simulated microbiomes further validated the robustness and reliability of DeepMobilome in practical applications. In real microbiome data, DeepMobilome successfully identified six ARG-carrying MGEs across diverse populations. By addressing the limitations of current methods, DeepMobilome offers a powerful tool for advancing our understanding of ARG dissemination and supports targeted interventions in combating antibiotic resistance.
移动遗传元件(MGEs)在促进微生物群落中抗生素抗性基因(ARGs)的获得方面发挥着重要作用,对抗生素抗性的演变产生重大影响。了解ARGs获得的机制和轨迹需要对携带ARGs的移动基因组进行全面分析,即携带ARGs的MGEs的集合。然而,在复杂的微生物群落中识别移动基因组面临着巨大挑战。现有的MGE预测方法主要是为单个基因组设计的,应用于宏基因组数据时存在很大局限性,在从宏基因组测序数据中识别目标MGEs时往往产生较高的假阳性率。
为应对这些挑战,我们开发了DeepMobilome,这是一种在微生物群落中准确识别目标MGEs的新方法。DeepMobilome利用基于从序列比对图(SAM)文件导出的读段比对数据训练的卷积神经网络,在检测MGEs方面具有更高的准确性。在364647个案例上进行训练后,DeepMobilome实现了0.99的高验证准确率。在识别不同测试集中目标MGE序列的存在方面,DeepMobilome始终优于现有方法。在单基因组测试场景中,DeepMobilome的F1分数为0.935,而MGEfinder和ISMapper的F1分数分别为0.755和0.670,表明其在预测准确性上有显著提高。对模拟微生物群落的广泛评估进一步验证了DeepMobilome在实际应用中的稳健性和可靠性。在真实的微生物组数据中,DeepMobilome成功地在不同人群中识别出六个携带ARGs的MGEs。通过克服当前方法的局限性,DeepMobilome为增进我们对ARGs传播的理解提供了一个强大工具,并支持在对抗抗生素抗性方面的针对性干预。