Network-Based Analysis of Cognitive Impairment and Memory Deficits from Transcriptome Data

Abstract

Aging is an inevitable process that negatively affects all living organisms and their vital functions. The brain is one of the most important organs in living beings and is primarily impacted by aging. The molecular mechanisms of learning, memory and cognition are altered over time, and the impairment in these mechanisms can lead to neurodegenerative diseases. Transcriptomics can be used to study these impairments to acquire more detailed information on the affected molecular mechanisms. Here we analyzed learning- and memory-related transcriptome data by mapping it on the organism-specific protein-protein interactome network. Subnetwork discovery algorithms were applied to discover highly dysregulated subnetworks, which were complemented with co-expression-based interactions. The functional analysis shows that the identified subnetworks are enriched with genes having roles in synaptic plasticity, gliogenesis, neurogenesis and cognition, which are reported to be related to memory and learning. With a detailed analysis, we show that the results from different subnetwork discovery algorithms or from different transcriptomic datasets can be successfully reconciled, leading to a memory-learning network that sheds light on the molecular mechanisms behind aging and memory-related impairments.