用于表征表型的更具可解释性的多组学调控网络。

MORE interpretable multi-omic regulatory networks to characterise phenotypes.

作者信息

Aguerralde-Martin Maider, Clemente-Císcar Mónica, Conesa Ana, Tarazona Sonia

机构信息

Department of Applied Statistics, Operational Research and Quality, Universitat Politècnica de València, Camí de Vera s/n, Valencia 46022, Spain.

Igenomix, Ronda Narciso Monturiol, Parque tecnológico Paterna, Paterna 46980, Spain.

出版信息

Brief Bioinform. 2025 May 1;26(3). doi: 10.1093/bib/bbaf270.

Abstract

Studying phenotype-specific regulatory mechanisms is crucial to understanding the molecular basis of diseases and other complex traits. However, existing approaches for constructing multi-omic regulatory networks MO-RN are scarce, and most cannot integrate diverse omics modalities, incorporate prior biological knowledge, or infer phenotype-specific networks. To address these challenges, we present MORE (Multi-Omics REgulation), a novel R package for inferring multi-modal regulatory networks. MORE is available at https://github.com/BiostatOmics/MORE and supports any number and type of omics layers while optionally incorporating prior regulatory knowledge. Leveraging advanced regression-based models and variable selection techniques, MORE identifies significant regulatory relationships. This tool also provides useful functionalities for the biological interpretation of MO-RN: network visualisations, differential regulatory networks, and functional enrichment analyses of key network features. We evaluated MORE on simulated multi-omic datasets and benchmarked it against state-of-the-art tools. Our tool consistently outperformed other methods regarding accuracy in identifying significant regulators, model goodness-of-fit, and computational efficiency. We further applied MORE to a multi-omic ovarian cancer dataset to uncover tumour subtype-specific regulatory mechanisms associated with distinct survival outcomes. This analysis revealed differential regulatory patterns to understand the molecular basis of each subtype. By addressing the limitations of methods for multi-omic network inference, MORE represents a valuable resource for studying regulatory systems. Its ability to construct phenotype-specific regulatory networks with high accuracy and interpretability positions it as a useful resource for researchers seeking to unravel the complexities of molecular interactions and regulatory mechanisms across diverse biological contexts.

摘要

研究特定表型的调控机制对于理解疾病和其他复杂性状的分子基础至关重要。然而,现有的构建多组学调控网络(MO-RN)的方法稀缺,并且大多数方法无法整合多种组学模式、纳入先验生物学知识或推断特定表型的网络。为应对这些挑战,我们提出了MORE(多组学调控),这是一个用于推断多模态调控网络的新型R包。MORE可在https://github.com/BiostatOmics/MORE获取,支持任意数量和类型的组学层,同时可选择纳入先验调控知识。利用先进的基于回归的模型和变量选择技术,MORE可识别显著的调控关系。该工具还为MO-RN的生物学解释提供了有用的功能:网络可视化、差异调控网络以及关键网络特征的功能富集分析。我们在模拟的多组学数据集上对MORE进行了评估,并与现有最先进的工具进行了基准测试。在识别显著调控因子的准确性、模型拟合优度和计算效率方面,我们的工具始终优于其他方法。我们进一步将MORE应用于一个多组学卵巢癌数据集,以揭示与不同生存结果相关的肿瘤亚型特异性调控机制。该分析揭示了差异调控模式,以了解每种亚型的分子基础。通过解决多组学网络推断方法的局限性,MORE是研究调控系统的宝贵资源。它能够高精度且可解释地构建特定表型的调控网络,使其成为寻求揭示不同生物学背景下分子相互作用和调控机制复杂性的研究人员的有用资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db55/12204684/198d565e34ed/bbaf270f1.jpg

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