Higher-order co-mutation interactions in mitochondrial genomes

Pair-wise co-mutation networks of the mitochondrial genome have already provided ample evidences about the roles of genetic interactions in the manifestation of phenotype under altered environmental conditions. Here, we present a method to construct and analyze higher-order interactions, namely, 3-uniform hypergraphs of the mitochondrial genome for different altitude populations to decipher the role of co-mutating variable sites beyond pair-wise interactions. While the weights distribution of such gene hyperedges manifested power-law for all the altitudes, we identified altitude-specific genes based on gene hyperedge weight. This framework of hypergraphs serves a promising avenue for future investigation of nuclear genomes in context of phenotypic association and genetic disorders.