小柯机器人

生成式深度学习模型发现2型糖尿病的药物-组学联系
2023-01-06 14:04

近日,丹麦哥本哈根大学Søren Brunak等研究人员合作利用生成式深度学习模型发现2型糖尿病的药物-组学联系。2023年1月2日,《自然—生物技术》杂志在线发表了这项成果。

据研究人员介绍,在生物医学队列中应用多种全息技术有可能揭示病人层面的疾病特征和对治疗的个体化反应。然而,多模态数据的规模和异质性使得整合和推理成为一项不简单的任务。
 
研究人员开发了一个基于深度学习的框架,即多组学变异自动编码器(MOVE),用于整合此类数据,并将其应用于789名新诊断的2型糖尿病患者的队列中,该队列由DIRECT联盟提供深度多组学表型。通过利用计算扰动,研究人员在多模态数据集中确定了2型糖尿病患者服用的20种最普遍的药物的药物-组学关联,其灵敏度大大高于单变量统计测试。从中,研究人员发现了二甲双胍和肠道微生物群之间的新关联,以及两种他汀类药物辛伐他汀和阿托伐他汀的相反分子反应。研究人员利用这些关联来量化了药物与药物之间的相似性,评估了多药性的程度,并得出结论,即药物效应分布于多组学模式。
 
附:英文原文

Title: Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models

Author: Allese, Rosa Lundbye, Lundgaard, Agnete Troen, Hernndez Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B., De Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E. Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T., t Hart, Leen M., Pattou, Francois, Raverdy, Violeta, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Mourby, Miranda, Kaye, Jane, Hattersley, Andrew, McDonald, Timothy, Ridderstrle, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Hansen, Torben, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, McCarthy, Mark I.

Issue&Volume: 2023-01-02

Abstract: The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.

DOI: 10.1038/s41587-022-01520-x

Source: https://www.nature.com/articles/s41587-022-01520-x

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:68.164
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex


本期文章:《自然—生物技术》:Online/在线发表

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