Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Department of Biostatistics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
Genome Biol. 2023 Jul 26;24(1):174. doi: 10.1186/s13059-023-03014-8.
We propose a statistical framework ISLET to infer individual-specific and cell-type-specific transcriptome reference panels. ISLET models the repeatedly measured bulk gene expression data, to optimize the usage of shared information within each subject. ISLET is the first available method to achieve individual-specific reference estimation in repeated samples. Using simulation studies, we show outstanding performance of ISLET in the reference estimation and downstream cell-type-specific differentially expressed genes testing. We apply ISLET to longitudinal transcriptomes profiled from blood samples in a large observational study of young children and confirm the cell-type-specific gene signatures for pancreatic islet autoantibody. ISLET is available at https://bioconductor.org/packages/ISLET .
我们提出了一个统计框架 ISLET，用于推断个体特异性和细胞类型特异性转录组参考面板。ISLET 对重复测量的批量基因表达数据进行建模，以优化每个主体内共享信息的使用。ISLET 是在重复样本中实现个体特异性参考估计的第一种可用方法。通过模拟研究，我们展示了 ISLET 在参考估计和下游细胞类型特异性差异表达基因测试中的出色性能。我们将 ISLET 应用于从小儿大型观察性研究中血液样本中提取的纵向转录组，并确认了胰岛自身抗体的细胞类型特异性基因特征。ISLET 可在 https://bioconductor.org/packages/ISLET 获得。
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