Uncovering Proximity of Chromosome Territories using Classical Algebraic Statistics

Abstract

Abstract. Exchange type chromosome aberrations (ETCAs) are rearrangements of the genome that occur when chromosomes break and the resulting fragments rejoin with fragments from other chromosomes or from other regions within the same chromosome. ETCAs are commonly observed in cancer cells and in cells exposed to radiation. The frequency of these chromosome rearrangements is correlated with their spatial proximity, therefore it can be used to infer the three dimensional organization of the genome. Extracting statistical significance of spatial proximity from cancer and radiation data has remained somewhat elusive because of the sparsity of the data. We here propose a new approach to study the three dimensional organization of the genome using algebraic statistics. We test our method on a published data set of irradiated human blood lymphocyte cells. We provide a rigorous method for testing the overall organization of the genome, and in agreement with previous results we find a random relative positioning of chromosomes with the exception of the chromosome pairs {1,22} and {13,14} that have a significantly larger number of ETCAs than the rest of the chromosome pairs suggesting their spatial proximity. We conclude that algebraic methods can successfully be used to analyze genetic data and have potential applications to larger and more complex data sets.