Abstract
BackgroundIn cell differentiation, a cell of a less specialized type becomes one of a more specialized type, even though all cells have the same genome. Transcription factors and epigenetic marks like histone modifications can play a significant role in the differentiation process.ResultsIn this paper, we present a simple analysis of cell types and differentiation paths using phylogenetic inference based on ChIP-Seq histone modification data. We precisely defined the notion of cell-type trees and provided a procedure of building such trees. We propose new data representation techniques and distance measures for ChIP-Seq data and use these together with standard phylogenetic inference methods to build biologically meaningful cell-type trees that indicate how diverse types of cells are related. We demonstrate our approach on various kinds of histone modifications for various cell types, also using the datasets to explore various issues surrounding replicate data, variability between cells of the same type, and robustness. We use the results to get some interesting biological findings like important patterns of histone modification changes during cell differentiation process.ConclusionsWe introduced and studied the novel problem of inferring cell type trees from histone modification data. The promising results we obtain point the way to a new approach to the study of cell differentiation. We also discuss how cell-type trees can be used to study the evolution of cell types.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2105-15-269) contains supplementary material, which is available to authorized users.
Highlights
In cell differentiation, a cell of a less specialized type becomes one of a more specialized type, even though all cells have the same genome
Since all cells in one individual organism have the same genome, epigenetic factors and transcriptional factors play an important role in cell differentiation [1,2,3]
We show that preprocessing the data is very important: are ChIP-Seq data fairly noisy, but the ENCODE data are based on several individuals and this adds an independent source of noise
Summary
A cell of a less specialized type becomes one of a more specialized type, even though all cells have the same genome. Transcription factors and epigenetic marks like histone modifications can play a significant role in the differentiation process. Since all cells in one individual organism have the same genome, epigenetic factors and transcriptional factors play an important role in cell differentiation [1,2,3]. Cell-lineage trees, reconstructed from genomic variability caused by somatic mutations, represent the history of cell division in one individual organism from the very first cell, the zygote [9]. It is possible that in the cell differentiation process, a complex interplay between histone modifications, DNA methylation, transcription factors etc. Plays an important role in how cells of various cell-types in one organism behave differently the genome is almost same. In this study we attempt to build cell-type trees by looking at histone modification data. In [10] unsupervised hierarchical clustering of whole genome expression data was done for some cell-types
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