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利用随机森林揭示肿瘤微环境中距离变化的细胞相互作用的预测能力。

Using random forests to uncover the predictive power of distance-varying cell interactions in tumor microenvironments.

机构信息

Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Canada.

Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.

出版信息

PLoS Comput Biol. 2024 Jun 14;20(6):e1011361. doi: 10.1371/journal.pcbi.1011361. eCollection 2024 Jun.

Abstract

Tumor microenvironments (TMEs) contain vast amounts of information on patient's cancer through their cellular composition and the spatial distribution of tumor cells and immune cell populations. Exploring variations in TMEs between patient groups, as well as determining the extent to which this information can predict outcomes such as patient survival or treatment success with emerging immunotherapies, is of great interest. Moreover, in the face of a large number of cell interactions to consider, we often wish to identify specific interactions that are useful in making such predictions. We present an approach to achieve these goals based on summarizing spatial relationships in the TME using spatial K functions, and then applying functional data analysis and random forest models to both predict outcomes of interest and identify important spatial relationships. This approach is shown to be effective in simulation experiments at both identifying important spatial interactions while also controlling the false discovery rate. We further used the proposed approach to interrogate two real data sets of Multiplexed Ion Beam Images of TMEs in triple negative breast cancer and lung cancer patients. The methods proposed are publicly available in a companion R package funkycells.

摘要

肿瘤微环境(TME)包含大量有关患者癌症的信息,包括细胞组成、肿瘤细胞和免疫细胞群体的空间分布。探索不同患者群体之间的 TME 变化,并确定这些信息在多大程度上可以预测患者生存或新兴免疫疗法治疗成功等结果,这是非常重要的。此外,面对大量需要考虑的细胞相互作用,我们通常希望确定在进行此类预测时有用的特定相互作用。我们提出了一种基于使用空间 K 函数总结 TME 中空间关系的方法,然后应用功能数据分析和随机森林模型来预测感兴趣的结果并识别重要的空间关系。在模拟实验中,该方法在识别重要的空间相互作用的同时控制假发现率,被证明是有效的。我们进一步使用所提出的方法来研究三阴性乳腺癌和肺癌患者的 TME 多重离子束图像的两个真实数据集。所提出的方法在一个名为 funkycells 的 R 包中公开提供。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4f4/11210873/9714b95e6f63/pcbi.1011361.g001.jpg

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