Abstract
BackgroundLiterature derived knowledge assemblies have been used as an effective way of representing biological phenomenon and understanding disease etiology in systems biology. These include canonical pathway databases such as KEGG, Reactome and WikiPathways and disease specific network inventories such as causal biological networks database, PD map and NeuroMMSig. The represented knowledge in these resources delineates qualitative information focusing mainly on the causal relationships between biological entities. Genes, the major constituents of knowledge representations, tend to express differentially in different conditions such as cell types, brain regions and disease stages. A classical approach of interpreting a knowledge assembly is to explore gene expression patterns of the individual genes. However, an approach that enables quantification of the overall impact of differentially expressed genes in the corresponding network is still lacking.ResultsUsing the concept of heat diffusion, we have devised an algorithm that is able to calculate the magnitude of regulation of a biological network using expression datasets. We have demonstrated that molecular mechanisms specific to Alzheimer (AD) and Parkinson Disease (PD) regulate with different intensities across spatial and temporal resolutions. Our approach depicts that the mitochondrial dysfunction in PD is severe in cortex and advanced stages of PD patients. Similarly, we have shown that the intensity of aggregation of neurofibrillary tangles (NFTs) in AD increases as the disease progresses. This finding is in concordance with previous studies that explain the burden of NFTs in stages of AD.ConclusionsThis study is one of the first attempts that enable quantification of mechanisms represented as biological networks. We have been able to quantify the magnitude of regulation of a biological network and illustrate that the magnitudes are different across spatial and temporal resolution.
Highlights
Literature derived knowledge assemblies have been used as an effective way of representing biological phenomenon and understanding disease etiology in systems biology
Mitochondrial dysfunction in Parkinson’s disease (PD) The candidate mechanism perturbation amplitude (CMPA) analysis of mitochondrial dysfunction in different age-groups of PD patients depicts that the mechanism is perturbed the most in age-group 40–50 when compared to other age-groups (Fig. 1a)
As the NeuroMMSig server embeds numerous molecular signatures implicated in Alzheimer’s Disease (AD) and PD, it provides us the opportunity to extend the CMPA analysis beyond the two mechanisms we have undertaken in this study
Summary
Literature derived knowledge assemblies have been used as an effective way of representing biological phenomenon and understanding disease etiology in systems biology. Warren et al (2015) reconfirmed essential differences between these two species at the molecular level by showing that mouse models mimicked only 12% of the genes dysregulated in human conditions [16]. These studies clearly suggest that entities involved in pathways can be specific to species, tissue, cell types, and especially diseases
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
