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arXiv 2602.22239stat.APcs.LGq-bio.GN
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VAE-MS:一种用于突变特征提取的非对称变分自编码器

VAE-MS: An Asymmetric Variational Autoencoder for Mutational Signature Extraction

Center for Clinical Data Science(临床数据科学中心);Aalborg University(奥胡斯大学);Aalborg University Hospital(奥胡斯大学医院);Nuffield Department of Surgical Sciences(外科科学努尔菲尔德部门);University of Oxford(牛津大学);Nuffield Department of Women’s and Reproductive Health(妇女和生殖健康努尔菲尔德部门)

Ida Egendal, Rasmus Froberg Brøndum, Dan J Woodcock, Christopher Yau, Martin Bøgsted

AI总结:

VAE-MS通过结合非对称架构和概率方法,提升了突变特征提取的准确性和泛化能力。

摘要:

突变特征分析已成为揭示驱动癌症发展的潜在生物学过程的强大方法。然而,通常使用非负矩阵分解(NMF)进行的特征提取过程往往缺乏可靠性和临床应用性。为了解决这些限制,已经引入了多种解决方案,包括使用神经网络以获得更准确的估计以及使用概率方法以更好地捕捉数据中的自然变化。在本工作中,我们介绍了用于突变特征提取的变分自编码器(VAE-MS),这是一种新颖的模型,利用非对称架构和概率方法进行突变特征提取。VAE-MS与三种最先进的突变特征提取模型进行了比较:SigProfilerExtractor,基于NMF的黄金标准;MUSE-XAE,一种使用非对称设计但没有概率组件的自编码器;以及SigneR,一种贝叶斯NMF模型,以展示在非线性提取与概率模型结合方面的优势。在数据重构能力和泛化到未见数据的能力方面,具有概率组件的模型(VAE-MS、SigneR)明显优于没有概率组件的模型(SigProfilerExtractor、MUSE-XAE)。基于NMF的模型(SigneR、SigProfilerExtractor)在模拟数据中具有最准确的重构,而VAE-MS在真实癌症数据中重构更准确。在评估提取特征的一致性能力时,没有模型显示出明显的优势。VAE-MS的软件可在https://github.com/CLINDA-AAU/VAE-MS上获得。

英文摘要:

Mutational signature analysis has emerged as a powerful method for uncovering the underlying biological processes driving cancer development. However, the signature extraction process, typically performed using non-negative matrix factorization (NMF), often lacks reliability and clinical applicability. To address these limitations, several solutions have been introduced, including the use of neural networks to achieve more accurate estimates and probabilistic methods to better capture natural variation in the data. In this work, we introduce a Variational Autoencoder for Mutational Signatures (VAE-MS), a novel model that leverages both an asymmetric architecture and probabilistic methods for the extraction of mutational signatures. VAE-MS is compared to with three state-of-the-art models for mutational signature extraction: SigProfilerExtractor, the NMF-based gold standard; MUSE-XAE, an autoencoder that employs an asymmetric design without probabilistic components; and SigneR, a Bayesian NMF model, to illustrate the strength in combining a nonlinear extraction with a probabilistic model. In the ability to reconstruct input data and generalize to unseen data, models with probabilistic components (VAE-MS, SigneR) dramatically outperformed models without (SigProfilerExtractor, MUSE-XAE). The NMF-baed models (SigneR, SigProfilerExtractor) had the most accurate reconstructions in simulated data, while VAE-MS reconstructed more accurately on real cancer data. Upon evaluating the ability to extract signatures consistently, no model exhibited a clear advantage over the others. Software for VAE-MS is available at https://github.com/CLINDA-AAU/VAE-MS.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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