Open Access Methodology article

Study of cell differentiation by phylogenetic analysis using histone modification data

Nishanth Ulhas Nair15, Yu Lin2, Ana Manasovska1, Jelena Antic1, Paulina Grnarova1, Avinash Das Sahu3, Philipp Bucher45* and Bernard ME Moret15*

Author Affiliations

1 School of Computer and Communication Sciences, École Polytechnique Fédérale de Lausanne (EPFL), EPFL IC IIF LCBB, INJ 211 (Batiment INJ), Station 14, CH-1015 Lausanne, Switzerland

2 Department of Computer Science and Engineering, University of California, San Diego, San Diego, USA

3 Department of Computer Science, University of Maryland, College Park, Maryland, USA

4 School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

5 Swiss Institute of Bioinformatics, Lausanne, Switzerland

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BMC Bioinformatics 2014, 15:269  doi:10.1186/1471-2105-15-269

Published: 8 August 2014



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. Transcription factors and epigenetic marks like histone modifications can play a significant role in the differentiation process.


In 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.


We 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.

Cell differentiation; Development; Cell-type trees; Epigenomics; Histone modifications; Phylogenetics; Evolution of cell types