rcCAE: a convolutional autoencoder method for detecting intra-tumor heterogeneity and single-cell copy number alterations
Intra-tumor heterogeneity (ITH) is one of the major confounding factors that result in cancer relapse, and deciphering ITH is essential for personalized therapy. Single-cell DNA sequencing (scDNA-seq) now enables profiling of single-cell copy number alterations (CNAs) and thus aids in high-resolution inference of ITH. Here, we introduce an integrated framework called rcCAE to accurately infer cell subpopulations and single-cell CNAs from scDNA-seq data. A convolutional autoencoder (CAE) is employed in rcCAE to learn latent representation of the cells as well as distill copy number information from noisy read counts data. This unsupervised representation learning via the CAE model makes it convenient to accurately cluster cells over the low-dimensional latent space, and detect single-cell CNAs from enhanced read counts data. Extensive performance evaluations on simulated datasets show that rcCAE outperforms the existing CNA calling methods, and is highly effective in inferring clonal architecture. Furthermore, evaluations of rcCAE on two real datasets demonstrate that it is able to provide a more refined clonal structure, of which some details are lost in clonal inference based on integer copy numbers. Keywords: Autoencoder; Copy number alteration; Hidden Markov model; Single-cell sequencing.
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数据分析:流式数据分析、组化数据分析、多因子数据分析
基因水平:PCR Array、RT-PCR、PCR、单细胞测序
蛋白水平:MSD、Luminex、CBA、Elispot、Antibody Array、ELISA、Sengenics
细胞水平:细胞染色、细胞分选、细胞培养、细胞功能
组织水平:空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析:流式数据分析、组化数据分析、多因子数据分析
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