In a recent study published in The American Journal of Pathology researchers found a novel gene, ADAMTS18 that impacts body fat percentage and fat cell size. Mice that are lacking the gene also showed early metabolic syndrome including hyperlipidemia, blood glucose metabolic disorder, and hypertension.
As the article concludes, the details of the specific molecular mechanism is yet unknown. Using the Euretos AI platform a detailed ‘in silico’ target validation can be done to explore the underlying molecular mechanism.
Euretos Search confirms that currently no literature exists linking ADAMTS18 to Metabolic Syndrome X. Also the suggested search using synonyms yields no results. The novelty of the gene in Metabolic Syndrome X therefore seems confirmed.
Figure 1: Search confirming ADAMTS18 novelty (source: Euretos AI Platform)
A next step in assessing the involvement of ADAMTS18 is analysing its gene interactome. Using the Euretos Analytics application, the following interactions are found:
Figure 2: Gene interactome of ADAMTS18 (source: Euretos AI Platform)
Especially interesting in the interactome is the relation with the ACAN gene where ADAMTS18 controls the post translational modification of the gene. This warrants further analyses whether the ACAN gene may play a role in Metabolic Syndrome X.
Using the Gene-Disease function, the role of the ACAN gene can be assessed in great detail, taking into account biological 10 aspects of target-disease interaction. For each of these aspects the interactome of the ACAN is assessed only for those interactors that are already associated with Metabolic Syndrome X:
Figure 3: Aspects of gene - disease interaction provided by the Euretos AI Platform
Based on this analysis, the ACAN gene seems likely involved in Metabolic Syndrome X as it has multiple interactions with relevant genes playing a role in relevant phenotypes. This includes, for instance, the key metabolic process of hyperglycemia. The ACAN gene shows interactions with 9 genes, in this phenotypes, including 2 genes from the ADAMTS gene family:
Figure 4: Involvement of ACAN in genes associated with Metabolic Syndrome X and Hyperglycemia (source: Euretos AI Platform)
There are many literature references supporting these various interactions providing many possibilities to validate each specific interaction:
Figure 5: Literature supporting ACAN interactome involvement Metabolic Syndrome X and Hyperglycemia (source: Euretos AI Platform)
Of course further research will be required to fully understand the specific mechanism driving the ADAMST18/ACAN - Metabolic Syndrome X interactions. This initial analysis shows that there are many promising angles that can be investigated.
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About this series - The purpose of the Euretos Research Note series is to provide a data analytics perspective on recent life sciences publications. The series focuses on two types of questions: (1) Did the available data already point in the direction of a discovery? (2) What further research angles does the available data suggest?