Calcium signaling system in multiple species : structural and functional analyses of protein interaction networks

Abstract

Calcium is an important second messenger to have a key role in many processes occurring in the cell. Understanding the mechanisms of calcium signaling in multiple species i.e. yeast and worm may help to untangle calcium signaling pathways in human and suggest some drug targets to cure calcium related diseases. For these aims, the calcium signaling pathways in the aforementioned species using an algorithm that counts for physical interaction cascades based on gene ontology annotations. The resultant interaction networks are investigated in macroscopic and microscopic details to find out the important pivotal elements of these networks. By ontology enrichment study, it is found that all three networks are a part of transcription, and in more general, cell proliferation and growth. Using graph theoretical approaches, the networks are compared according to their topological characteristics, revealing that yeast and human calcium signaling networks are alike having almost the same degree and average path lengths. Calcium signaling in human brain shows more robust behaviour than the whole human brain interactome and the calcium signaling in human body in opposite of yeast and worm; implying that it has a distinct behaviour and duty to start and control brain and body functions. Worm, having a more imcomplete interactome compared to other two, shows unique topological properties. Modular segregation of the networks gives opportunity to functional annotation to those with unknown function. By a combination of neighborhood counting and module search methods, 17 yeast proteins are annotated with functional terms. Human and worm modules fail to qualify for such annotation. Finally, the search for diseases like Alzheimer‟s disease and Huntington disease caused by dysregulation of calcium signaling in human brain reveals the incompleteness of tissue specific protein interactome data, since the envisaged pathways for these diseases in literature and information gathered from various data sets fails to coincide.