Spatial Organization of the Gene Regulatory Program: An Information Theoretical Approach to Breast Cancer Transcriptomics

Entropy (Basel). 2019 Feb 19;21(2):195. doi: 10.3390/e21020195.

Abstract

Gene regulation may be studied from an information-theoretic perspective. Gene regulatory programs are representations of the complete regulatory phenomenon associated to each biological state. In diseases such as cancer, these programs exhibit major alterations, which have been associated with the spatial organization of the genome into chromosomes. In this work, we analyze intrachromosomal, or cis-, and interchromosomal, or trans-gene regulatory programs in order to assess the differences that arise in the context of breast cancer. We find that using information theoretic approaches, it is possible to differentiate cis-and trans-regulatory programs in terms of the changes that they exhibit in the breast cancer context, indicating that in breast cancer there is a loss of trans-regulation. Finally, we use these programs to reconstruct a possible spatial relationship between chromosomes.

Keywords: cancer transcriptomics; gene regulatory program; markov random field; mutual information; spatial dependency structures.