Graph-Based Integration of Histone Modification Profiles

Abstract

In this work, we introduce a similarity-network-based approach to explore the role of interacting single-cell histone modification signals in haematopoiesis—the process of differentiation of blood cells. Histones are proteins that provide structural support to chromosomes. They are subject to chemical modifications—acetylation or methylation—that affect the degree of accessibility of genes and, in turn, the formation of different phenotypes. The concentration of histone modifications can be modelled as a continuous signal, which can be used to build single-cell profiles. In the present work, the profiles of cell types involved in haematopoiesis are built based on all the major histone modifications (i.e., H3K27ac, H3K27me3, H3K36me3, H3K4me1, H3K4me3, H3K9me3) by counting the number of peaks in the modification signals; then, the profiles are used to compute modification-specific similarity networks among the considered phenotypes. As histone modifications come as interacting signals, we applied a similarity network fusion technique to integrate these networks in a unique graph, with the aim of studying the simultaneous effect of all the modifications for the determination of different phenotypes. The networks permit defining of a graph-cut-based separation score for evaluating the homogeneity of subgroups of cell types corresponding to the myeloid and lymphoid phenotypes in the classical representation of the haematopoietic tree. Resulting scores show that separation into myeloid and lymphoid phenotypes reflects the actual process of haematopoiesis.