Evaluation of Cell Line Suitability for Disease Specific Perturbation Experiments

Biryukov, Maria; Antony, Paul; Krishna, Abhimanyu; Trefois, Christophe

doi:10.1007/978-3-662-44983-7_26

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“…In order to evaluate the suitability of SH-SY5Y as in vitro model we adopted a framework described in [ 44 ] that integrated genetic sequence information, and topology analysis of either disease or process-specific networks. We applied betweenness-centrality ratio (BC-ratio), a metric that allowed us to quantitatively assess the impact of genes mutated in the cell line on the disease or process network.…”

Section: Resultsmentioning

confidence: 99%

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Systems genomics evaluation of the SH-SY5Y neuroblastoma cell line as a model for Parkinson’s disease

et al. 2014

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BackgroundThe human neuroblastoma cell line, SH-SY5Y, is a commonly used cell line in studies related to neurotoxicity, oxidative stress, and neurodegenerative diseases. Although this cell line is often used as a cellular model for Parkinson’s disease, the relevance of this cellular model in the context of Parkinson’s disease (PD) and other neurodegenerative diseases has not yet been systematically evaluated.ResultsWe have used a systems genomics approach to characterize the SH-SY5Y cell line using whole-genome sequencing to determine the genetic content of the cell line and used transcriptomics and proteomics data to determine molecular correlations. Further, we integrated genomic variants using a network analysis approach to evaluate the suitability of the SH-SY5Y cell line for perturbation experiments in the context of neurodegenerative diseases, including PD.ConclusionsThe systems genomics approach showed consistency across different biological levels (DNA, RNA and protein concentrations). Most of the genes belonging to the major Parkinson’s disease pathways and modules were intact in the SH-SY5Y genome. Specifically, each analysed gene related to PD has at least one intact copy in SH-SY5Y. The disease-specific network analysis approach ranked the genetic integrity of SH-SY5Y as higher for PD than for Alzheimer’s disease but lower than for Huntington’s disease and Amyotrophic Lateral Sclerosis for loss of function perturbation experiments.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-1154) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

“…In the experiments described here we considered interactions of all types, provided their confidence score was > = 0.7, classified as “high” by the database authors. (See [ 44 ] for more details about interactions in STRING.) This reduced the network size to 14688 nodes and 170570 edges.…”

Section: Methodsmentioning

confidence: 99%