In the last two decades the study of changes in the genome function that are not induced by changes in DNA has consolidated a strong research field called ”epigenetics”. Chromatin state changes play an essential role in the regulation of transcription of many genes, thus controlling cell differentiation. A large part of these changes is due to histone modifications that alter the accessibility of the DNA.

Current state of the art visualization methods for the analysis of epigenetic data sets are not suited to represent the relationship between the combinatorial pattern of histone modifications and their regulatory effects. A recent strategy to generate a global overview of these interactions is the use of scatterplots. One of the biggest weaknesses of scatterplots is the overplotting. This can be solved using a 2D tiled-binned representation strategy, where dividing scatterplot into bins consisting of tiles for each modification pattern is possible. However, this 2D strategy does not allow to represent the interaction of more than two histone modifications.

Here, TiBi-3D, a tool that can visualize the combinatorics of histone modifications with tiled-binned 3D scatterplots, is presented. Two important features of TiBi-3D are that tiles are represented with spheres in the scatterplot, and that their position and color encodes the histone modification pattern they represent. TiBi-3D also includes a transparency value assigned to each of that spheres to depict the amount of data points in each bin. In addition, to reduce the occlusion in the scatterplot each transparency value is initially filtered by an outlier detection, transformed to log scale, and then normalized. TiBi-3D provides features for exploration and interaction with the scatterplot and the data, thus enabling to examine the data set thoroughly. It is also possible to export the results as figures or in bed file format for further processing. By using TiBi-3D, for example, it was possible to observe new relations between the CpG-density and histone modifications in different cell types. In conclusion, TiBi-3D is an excellent tool for the analysis of global patterns in epigenetic data.

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