Abstract
Recently, network controllability studies have proposed several frameworks for the control of large complex biological networks using a small number of life molecules. However, age-related changes in the brain have not been investigated from a controllability perspective. In this study, we compiled the gene expression profiles of four normal brain regions from individuals aged 20–99 years and generated dynamic probabilistic protein networks across their lifespan. We developed a new algorithm that efficiently identified critical proteins in probabilistic complex networks, in the context of a minimum dominating set controllability model. The results showed that the identified critical proteins were significantly enriched with well-known ageing genes collected from the GenAge database. In particular, the enrichment observed in replicative and premature senescence biological processes with critical proteins for male samples in the hippocampal region led to the identification of possible new ageing gene candidates.
Highlights
Extensive studies based on gene expression changes have been performed in order to demonstrate the cognitive deterioration of patients with Alzheimer’s disease (AD) [5], there are far fewer large-scale computational analyses and models of transcriptomic changes observed in several healthy brain regions across the lifespan
By following steps (1) and (3), we examined whether the critical probabilistic minimum dominating set (CPMDS) network-based model identified critical proteins that were associated with known ageing genes
While previous studies have focused on transcriptome changes in the normal brain, age-related changes in the brain have not been investigated from a network controllability perspective
Summary
Among these, ageing is responsible for modifications in brain cognitive abilities, such as memory and reasoning, as well as changes in executive functions, including planning and abstract thinking. Most of these functions are orchestrated in the hippocampus (HC), which is located in the temporal lobe of the brain [3,4]. Extensive studies based on gene expression changes have been performed in order to demonstrate the cognitive deterioration of patients with Alzheimer’s disease (AD) [5], there are far fewer large-scale computational analyses and models of transcriptomic changes observed in several healthy brain regions across the lifespan
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