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多任务深度潜空间用于癌症生存和药物敏感性预测。

Multi-task deep latent spaces for cancer survival and drug sensitivity prediction.

机构信息

Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio 70210, Finland.

Department of Science and Technology, University of Sannio, Benevento 82100, Italy.

出版信息

Bioinformatics. 2024 Sep 1;40(Suppl 2):ii182-ii189. doi: 10.1093/bioinformatics/btae388.

Abstract

MOTIVATION

Cancer is a very heterogeneous disease that can be difficult to treat without addressing the specific mechanisms driving tumour progression in a given patient. High-throughput screening and sequencing data from cancer cell-lines has driven many developments in drug development, however, there are important aspects crucial to precision medicine that are often overlooked, namely the inherent differences between tumours in patients and the cell-lines used to model them in vitro. Recent developments in transfer learning methods for patient and cell-line data have shown progress in translating results from cell-lines to individual patients in silico. However, transfer learning can be forceful and there is a risk that clinically relevant patterns in the omics profiles of patients are lost in the process.

RESULTS

We present MODAE, a novel deep learning algorithm to integrate omics profiles from cell-lines and patients for the purposes of exploring precision medicine opportunities. MODAE implements patient survival prediction as an additional task in a drug-sensitivity transfer learning schema and aims to balance autoencoding, domain adaptation, drug-sensitivity prediction, and survival prediction objectives in order to better preserve the heterogeneity between patients that is relevant to survival. While burdened with these additional tasks, MODAE performed on par with baseline survival models, but struggled in the drug-sensitivity prediction task. Nevertheless, these preliminary results were promising and show that MODAE provides a novel AI-based method for prioritizing drug treatments for high-risk patients.

AVAILABILITY AND IMPLEMENTATION

https://github.com/UEFBiomedicalInformaticsLab/MODAE.

摘要

动机

癌症是一种非常异质的疾病,如果不针对特定患者肿瘤进展的具体机制进行治疗,可能很难治疗。来自癌细胞系的高通量筛选和测序数据推动了药物开发的许多进展,然而,对于精准医学来说,有一些非常重要但经常被忽视的方面,即患者肿瘤与体外模拟它们的细胞系之间的固有差异。最近在患者和细胞系数据的迁移学习方法方面的进展表明,在计算机模拟中将细胞系的结果转化为个体患者的方面取得了进展。然而,迁移学习可能是强制性的,存在将患者的组学特征中的临床相关模式在该过程中丢失的风险。

结果

我们提出了 MODAE,这是一种用于探索精准医学机会的新型深度学习算法,用于整合细胞系和患者的组学谱。MODAE 将患者生存预测作为药物敏感性迁移学习方案中的附加任务来实现,并旨在平衡自动编码、域自适应、药物敏感性预测和生存预测目标,以更好地保留与生存相关的患者之间的异质性。虽然受到这些额外任务的影响,但 MODAE 的表现与基线生存模型相当,但在药物敏感性预测任务中表现不佳。尽管如此,这些初步结果还是很有希望的,表明 MODAE 为高风险患者优先选择药物治疗提供了一种新的基于人工智能的方法。

可用性和实现

https://github.com/UEFBiomedicalInformaticsLab/MODAE。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff71/11520233/d05fd8d217b7/btae388f1.jpg

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