生物复杂性中的简单性

Natasa Przulj, Noel Malod-Dognin
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摘要

异构、互联、系统级的分子数据越来越多,成为精准医疗的关键。我们需要利用这些数据更好地对患者进行风险分层,发现新的生物标记物和靶点,重新利用已知药物并发现新药,从而实现个性化医疗。现有方法存在局限性,需要进行范式转变,以实现定量和定性的突破。在这篇视角论文中,我们对文献进行了调查,并主张开发一个全面、通用的框架,用于嵌入多尺度分子网络数据,使其在精准医疗中的线性时间内得到可解释的利用。网络嵌入方法将节点映射到低维空间中的点,从而使学习空间中的邻近度反映网络的拓扑-函数关系。然而,迄今为止的研究仅限于这些问题和数据的特殊变体,其性能取决于底层拓扑-功能网络生物学假设、生物医学应用和评估指标。多原子数据的可用性、现代图嵌入范式和计算能力要求创建和训练高效、可解释和可控制的模型,这些模型没有潜在危险和意外行为,能带来质的突破。我们建议为多原子网络数据开发一个通用、全面的嵌入框架,从模型到高效、可扩展的软件实现,并将其应用于生物医学信息学。这将导致计算和生物医学对数据和疾病的理解发生范式转变,为解决精准医学和其他领域的一些主要瓶颈开辟道路。
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Simplicity within biological complexity
Heterogeneous, interconnected, systems-level, molecular data have become increasingly available and key in precision medicine. We need to utilize them to better stratify patients into risk groups, discover new biomarkers and targets, repurpose known and discover new drugs to personalize medical treatment. Existing methodologies are limited and a paradigm shift is needed to achieve quantitative and qualitative breakthroughs. In this perspective paper, we survey the literature and argue for the development of a comprehensive, general framework for embedding of multi-scale molecular network data that would enable their explainable exploitation in precision medicine in linear time. Network embedding methods map nodes to points in low-dimensional space, so that proximity in the learned space reflects the network's topology-function relationships. They have recently achieved unprecedented performance on hard problems of utilizing few omic data in various biomedical applications. However, research thus far has been limited to special variants of the problems and data, with the performance depending on the underlying topology-function network biology hypotheses, the biomedical applications and evaluation metrics. The availability of multi-omic data, modern graph embedding paradigms and compute power call for a creation and training of efficient, explainable and controllable models, having no potentially dangerous, unexpected behaviour, that make a qualitative breakthrough. We propose to develop a general, comprehensive embedding framework for multi-omic network data, from models to efficient and scalable software implementation, and to apply it to biomedical informatics. It will lead to a paradigm shift in computational and biomedical understanding of data and diseases that will open up ways to solving some of the major bottlenecks in precision medicine and other domains.
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