Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing.
Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing.
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人骨关节炎滑膜中的单细胞转录组学和计算机解卷积批量 RNA 测序
DOI：
10.1016/j.joca.2021.12.007
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发表时间：
2022-03
影响因子：
7
通讯作者：
Zhou, Z. K.
中科院分区：
文献类型：
--
作者：
Huang, Z. Y.;Luo, Z. Y.;Cai, Y. R.;Chou, C-H;Yao, M. L.;Pei, F. X.;Kraus, V. B.;Zhou, Z. K.
以单细胞分辨率揭示骨关节炎（OA）滑膜组织不同细胞类型的异质性，并通过新方法确定批量RNA-seq数据是否可以解卷积以创建用于滑膜组织分析的计算机scRNA-seq数据。17名接受全膝关节置换术的患者提供了OA scRNA-seq数据（102，077个滑膜细胞）;使用9个具有匹配scRNA-seq和批量RNA-seq数据的组织来评价6种计算机基因去卷积工具。比较预测和观察到的细胞类型和比例，以确定最佳的滑膜去卷积工具。我们在OA滑膜组织中鉴定了七种不同的细胞类型。基因解卷积鉴定了三个（六个）平台适合于从批量RNA-seq数据外推细胞基因表达。使用配对的scRNA-seq和批量RNA-seq数据，创建并验证“关节炎”特异性特征矩阵，以具有比默认特征矩阵显著更好的滑膜细胞预测性能。使用机器学习工具，通过估计RNA转录物的相对子集x（CIBERSORTx）进行细胞类型鉴定，以分析类风湿性关节炎（RA）和OA批量RNA-seq数据，产生了分别与来自RA和OA scRNA-seq数据的金标准观察结果相似的T细胞和成纤维细胞的比例。这项新的研究揭示了OA滑膜细胞类型的异质性和滑膜组织基因去卷积的可行性。
To reveal the heterogeneity of different cell types of osteoarthritis (OA) synovial tissues at a single-cell resolution, and determine by novel methodology whether bulk-RNA-seq data could be deconvoluted to create in silico scRNA-seq data for synovial tissue analyses. OA scRNA-seq data (102,077 synoviocytes) were provided by 17 patients undergoing total knee arthroplasty; 9 tissues with matched scRNA-seq and bulk RNA-seq data were used to evaluate six in silico gene deconvolution tools. Predicted and observed cell types and proportions were compared to identify the best deconvolution tool for synovium. We identified seven distinct cell types in OA synovial tissues. Gene deconvolution identified three (of six) platforms as suitable for extrapolating cellular gene expression from bulk RNA-seq data. Using paired scRNA-seq and bulk RNA-seq data, an “arthritis” specific signature matrix was created and validated to have a significantly better predictive performance for synoviocytes than a default signature matrix. Use of the machine learning tool, Cell-type Identification By Estimating Relative Subsets of RNA Transcripts x (CIBERSORTx), to analyze rheumatoid arthritis (RA) and OA bulk RNA-seq data yielded proportions of T cells and fibroblasts that were similar to the gold standard observations from RA and OA scRNA-seq data, respectively. This novel study revealed heterogeneity of synovial cell types in OA and the feasibility of gene deconvolution for synovial tissue.
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DOI：
10.1002/art.41486
发表时间：
2021-01
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Hsueh MF;Zhang X;Wellman SS;Bolognesi MP;Kraus VB
通讯作者：
Kraus VB
DOI：
10.1183/13993003.02441-2018
发表时间：
2019-08
期刊：
The European respiratory journal
影响因子：
--
作者：
Morse C;Tabib T;Sembrat J;Buschur KL;Bittar HT;Valenzi E;Jiang Y;Kass DJ;Gibson K;Chen W;Mora A;Benos PV;Rojas M;Lafyatis R
通讯作者：
Lafyatis R
影响因子：
4.6
作者：
Chou, Ching-Heng;Jain, Vaibhav;Kraus, Virginia B.
通讯作者：
Kraus, Virginia B.
影响因子：
16.6
作者：
Wang, Xuran;Park, Jihwan;Li, Mingyao
通讯作者：
Li, Mingyao
影响因子：
5.6
作者：
Hsieh JL;Shiau AL;Lee CH;Yang SJ;Lee BO;Jou IM;Wu CL;Chen SH;Shen PC
通讯作者：
Shen PC