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鉴定细胞分化过程中的转录调控模式。

Identification of transcript regulatory patterns in cell differentiation.

机构信息

Department of Statistics, University of Leeds, Leeds LS2 9JT, UK.

出版信息

Bioinformatics. 2017 Oct 15;33(20):3235-3242. doi: 10.1093/bioinformatics/btx406.

Abstract

MOTIVATION

Studying transcript regulatory patterns in cell differentiation is critical in understanding its complex nature of the formation and function of different cell types. This is done usually by measuring gene expression at different stages of the cell differentiation. However, if the gene expression data available are only from the mature cells, we have some challenges in identifying transcript regulatory patterns that govern the cell differentiation.

RESULTS

We propose to exploit the information of the lineage of cell differentiation in terms of correlation structure between cell types. We assume that two different cell types that are close in the lineage will exhibit many common genes that are co-expressed relative to those that are far in the lineage. Current analysis methods tend to ignore this correlation by testing for differential expression assuming some sort of independence between cell types. We employ a Bayesian approach to estimate the posterior distribution of the mean of expression in each cell type, by taking into account the cell formation path in the lineage. This enables us to infer genes that are specific in each cell type, indicating the genes are involved in directing the cell differentiation to that particular cell type. We illustrate the method using gene expression data from a study of haematopoiesis.

AVAILABILITY AND IMPLEMENTATION

R codes to perform the analysis are available in http://www1.maths.leeds.ac.uk/∼arief/R/CellDiff/.

CONTACT

a.gusnanto@leeds.ac.uk.

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

摘要

动机

研究细胞分化过程中的转录调控模式对于理解不同细胞类型的形成和功能的复杂性质至关重要。这通常是通过测量细胞分化不同阶段的基因表达来实现的。然而,如果可用的基因表达数据仅来自成熟细胞,则在识别控制细胞分化的转录调控模式方面存在一些挑战。

结果

我们建议利用细胞分化谱系的信息,即细胞类型之间的相关结构。我们假设,在谱系中接近的两种不同的细胞类型将表现出许多共同的基因,这些基因相对于谱系中较远的基因表现出共表达。当前的分析方法倾向于忽略这种相关性,通过测试细胞类型之间的差异表达来假设某种独立性。我们采用贝叶斯方法来估计每个细胞类型中表达平均值的后验分布,同时考虑到谱系中的细胞形成路径。这使我们能够推断出每个细胞类型特有的基因,表明这些基因参与指导细胞分化为特定的细胞类型。我们使用造血研究中的基因表达数据来说明该方法。

可用性和实现

可在 http://www1.maths.leeds.ac.uk/∼arief/R/CellDiff/ 上获得执行分析的 R 代码。

联系人

a.gusnanto@leeds.ac.uk

补充信息

补充数据可在生物信息学在线获得。

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