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ADAPTS:用于组织特异性细胞的轮廓自动解卷积增强。

ADAPTS: Automated deconvolution augmentation of profiles for tissue specific cells.

机构信息

Celgene Corporation, Seattle, Washington, United States of America.

Institute for Systems Biology, Seattle, Washington, United States of America.

出版信息

PLoS One. 2019 Nov 19;14(11):e0224693. doi: 10.1371/journal.pone.0224693. eCollection 2019.

Abstract

Immune cell infiltration of tumors and the tumor microenvironment can be an important component for determining patient outcomes. For example, immune and stromal cell presence inferred by deconvolving patient gene expression data may help identify high risk patients or suggest a course of treatment. One particularly powerful family of deconvolution techniques uses signature matrices of genes that uniquely identify each cell type as determined from single cell type purified gene expression data. Many methods from this family have been recently published, often including new signature matrices appropriate for a single purpose, such as investigating a specific type of tumor. The package ADAPTS helps users make the most of this expanding knowledge base by introducing a framework for cell type deconvolution. ADAPTS implements modular tools for customizing signature matrices for new tissue types by adding custom cell types or building new matrices de novo, including from single cell RNAseq data. It includes a common interface to several popular deconvolution algorithms that use a signature matrix to estimate the proportion of cell types present in heterogenous samples. ADAPTS also implements a novel method for clustering cell types into groups that are difficult to distinguish by deconvolution and then re-splitting those clusters using hierarchical deconvolution. We demonstrate that the techniques implemented in ADAPTS improve the ability to reconstruct the cell types present in a single cell RNAseq data set in a blind predictive analysis. ADAPTS is currently available for use in R on CRAN and GitHub.

摘要

肿瘤的免疫细胞浸润和肿瘤微环境可能是决定患者预后的重要因素。例如,通过对患者基因表达数据进行去卷积推断出的免疫和基质细胞的存在,可能有助于识别高风险患者或提示治疗方案。一类特别强大的去卷积技术使用基因特征矩阵来唯一识别每种细胞类型,这些特征矩阵是根据单细胞类型纯化的基因表达数据确定的。该家族的许多方法最近已经发表,通常包括新的适用于特定目的的特征矩阵,例如研究特定类型的肿瘤。ADAPTS 包通过引入细胞类型去卷积框架,帮助用户充分利用这个不断扩展的知识库。ADAPTS 通过添加自定义细胞类型或从头构建新的矩阵(包括从单细胞 RNAseq 数据构建),为新的组织类型定制特征矩阵提供了模块化工具。它包括一个通用接口,可用于几种流行的使用特征矩阵来估计异质样本中存在的细胞类型比例的去卷积算法。ADAPTS 还实现了一种新的方法,将难以通过去卷积区分的细胞类型聚类成组,然后使用层次去卷积重新拆分这些聚类。我们证明,ADAPTS 中实现的技术可以提高在盲预测分析中重建单细胞 RNAseq 数据集中文本细胞类型的能力。ADAPTS 目前可在 CRAN 和 GitHub 上的 R 中使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ce/6863530/982443db41b4/pone.0224693.g001.jpg

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