Shared Gene-network Signatures Between the Human Heavy Metal Proteome and Neurological Disorders and Cancer Types

In this work, for the first time, the human heavy metal proteome was predicted. According to the results, aluminum, cadmium, mercury and lead metalloproteomes might constitute up to 8.9%, 18.4%, 15% and 4% of the entire human proteome, respectively. The abundance of the predicted heavy metal-binding proteins in various organ-specific proteomes was retrieved from the Human Protein Atlas database showing higher expression profiles for Cd- and Hg-binding proteins in all studied organs (especially in the prostate, heart and pancreas) compared with the other heavy metals. Possible perturbations in cellular trafficking and homeostasis of essential metals by heavy metal proteomes were highlighted. Furthermore, this study showed that molecular linkages between heavy metal proteomes and major neurological disorders or various types of cancer were more significant for Cd followed by Hg, Al and Pb. Interestingly, integrated gene network analysis revealed that Cd and Hg proteomes share so far unknown gene circuits with these two types of disorder.