基于混合模型的沿一维轨迹的细胞状态丰度的去卷积(MeDuSA)。

Mixed model-based deconvolution of cell-state abundances (MeDuSA) along a one-dimensional trajectory.

机构信息

College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.

School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.

出版信息

Nat Comput Sci. 2023 Jul;3(7):630-643. doi: 10.1038/s43588-023-00487-2. Epub 2023 Jul 13.

Abstract

Deconvoluting cell-state abundances from bulk RNA-sequencing data can add considerable value to existing data, but achieving fine-resolution and high-accuracy deconvolution remains a challenge. Here we introduce MeDuSA, a mixed model-based method that leverages single-cell RNA-sequencing data as a reference to estimate cell-state abundances along a one-dimensional trajectory in bulk RNA-sequencing data. The advantage of MeDuSA lies primarily in estimating cell abundance in each state while fitting the remaining cells of the same type individually as random effects. Extensive simulations and real-data benchmark analyses demonstrate that MeDuSA greatly improves the estimation accuracy over existing methods for one-dimensional trajectories. Applying MeDuSA to cohort-level RNA-sequencing datasets reveals associations of cell-state abundances with disease or treatment conditions and cell-state-dependent genetic control of transcription. Our study provides a high-accuracy and fine-resolution method for cell-state deconvolution along a one-dimensional trajectory and demonstrates its utility in characterizing the dynamics of cell states in various biological processes.

摘要

从批量 RNA 测序数据中推断细胞状态丰度可以为现有数据增加相当大的价值,但实现精细分辨率和高精度的推断仍然是一个挑战。在这里,我们介绍了 MeDuSA,这是一种基于混合模型的方法,利用单细胞 RNA 测序数据作为参考,估计批量 RNA 测序数据中沿一维轨迹的细胞状态丰度。MeDuSA 的优势主要在于估计每个状态的细胞丰度,同时将相同类型的其余细胞分别拟合为随机效应。广泛的模拟和真实数据基准分析表明,MeDuSA 大大提高了一维轨迹的现有方法的估计准确性。将 MeDuSA 应用于队列水平的 RNA 测序数据集揭示了细胞状态丰度与疾病或治疗条件的关联,以及转录的细胞状态依赖性遗传控制。我们的研究提供了一种高精度和精细分辨率的方法,用于沿一维轨迹进行细胞状态推断,并展示了其在各种生物学过程中描述细胞状态动态的实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1348/10766563/0505ff414e70/43588_2023_487_Fig1_HTML.jpg

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