4.0 Article

Comparing Alzheimer's and Parkinson's diseases networks using graph communities structure

期刊

BMC SYSTEMS BIOLOGY
卷 10, 期 -, 页码 -

出版社

BMC
DOI: 10.1186/s12918-016-0270-7

关键词

Systems biology; Network analysis; Graphs; Alzheimer's diseases; Parkinson's disease; Communities; Clustering; Network comparison

资金

  1. FLAGSHIP InterOmics [PB.P05]
  2. Italian Minister of University and Research (MIUR) (PRIN)
  3. Italian Minister of University and Research (MIUR) (SYSBIONET-Italian ROADMAP ESFRI Infrastructures)
  4. Italian Minister of University and Research (MIUR) (IVASCOMAR-Cluster Nazionale)
  5. Blueprint Pharma srl fellowship
  6. PRIMM srl fellowship
  7. Associazione Levi-Montalcini fellowship

向作者/读者索取更多资源

Background: Recent advances in large datasets analysis offer new insights to modern biology allowing system-level investigation of pathologies. Here we describe a novel computational method that exploits the ever-growing amount of omics data to shed light on Alzheimer's and Parkinson's diseases. Neurological disorders exhibit a huge number of molecular alterations due to a complex interplay between genetic and environmental factors. Classical reductionist approaches are focused on a few elements, providing a narrow overview of the etiopathogenic complexity of multifactorial diseases. On the other hand, high-throughput technologies allow the evaluation of many components of biological systems and their behaviors. Analysis of Parkinson's Disease (PD) and Alzheimer's Disease (AD) from a network perspective can highlight proteins or pathways common but differently represented that can be discriminating between the two pathological conditions, thus highlight similarities and differences. Results: In this work we propose a strategy that exploits network community structure identified with a state-of-the-art network community discovery algorithm called InfoMap, which takes advantage of information theory principles. We used two similarity measurements to quantify functional and topological similarities between the two pathologies. We built a Similarity Matrix to highlight similar communities and we analyzed statistically significant GO terms found in clustered areas of the matrix and in network communities. Our strategy allowed us to identify common known and unknown processes including DNA repair, RNA metabolism and glucose metabolism not detected with simple GO enrichment analysis. In particular, we were able to capture the connection between mitochondrial dysfunction and metabolism (glucose and glutamate/glutamine). Conclusions: This approach allows the identification of communities present in both pathologies which highlight common biological processes. Conversely, the identification of communities without any counterpart can be used to investigate processes that are characteristic of only one of the two pathologies. In general, the same strategy can be applied to compare any pair of biological networks.

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