In Kirk et al. (Cell systems, 4 (3), 2017), the concept of cross-talk between chromosomes, namely the inter-connectivity of chromosomal information, has been studied via a graphical representation of the physical interactions between proteins. For each protein the reference chromosome is identified. Thus, the model analyzes the balance between the inter-connectivity of a chromosome, by taking into account protein interactions with the rest of the genome, and intra-connectivity. These studies have highlighted particular behaviors of the human genome that support the survival of patients affected by chromosome 21 trisomy. In fact, the human chromosome 21 shows a marked intra-connectivity with respect to its inter-chromosomal connections.
An extension of this model was obtained through the creation of a heterogeneous system that involves proteins as well as biological elements that are key for their regulation, microRNAs. These elements are particular RNA that are not part of the main process of translation into protein, on the contrary, given their small lengths, they interact in a physical way with the other macromolecules (coding RNA and proteins) regulating their expression levels. Through this model it is possible to study the main interactions at the protein level and to enrich the representation of the cellular system with the microRNA-protein regulatory connections. The study of such regulations between chromosomes showed interesting differences of the cellular regulatory siystem in healthy conditions with respect to tumor conditions.
Research activities will mainly focus on the design and implementation of methods for the analysis of such complex systems. Among the goals, there is the extension of the mathematical model for the analysis of inter-chromosomal connectivity. In particular, the model will be extended with two additional types of biological entities. The first type of entity is to be considered at the genomic level and includes the set of transcription factors for gene regulation, therefore both of genes encoding proteins and genes producing non-coding RNA. Instead, the second type of entity acts at the system level through direct interaction with other biological entities, and it is given by the family of RNA that is not coding for protein but with similar functions, i.e. the long non-coding RNA. Furthermore, the interactions between the four types of biological entities will be represented in the form of weighted arcs. The weights assigned to these arcs will be extracted from previously performed studies and will represent both the validity of physical interactions, and more abstract concepts such as the correlation of such elements in specific pathological conditions.