Identification of new biomarker candidates for glucocorticoid induced insulin resistance using literature mining

Abstract

BackgroundGlucocorticoids are potent anti-inflammatory agents used for the treatment of diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and psoriasis. Unfortunately, usage is limited because of metabolic side-effects, e.g. insulin resistance, glucose intolerance and diabetes. To gain more insight into the mechanisms behind glucocorticoid induced insulin resistance, it is important to understand which genes play a role in the development of insulin resistance and which genes are affected by glucocorticoids.Medline abstracts contain many studies about insulin resistance and the molecular effects of glucocorticoids and thus are a good resource to study these effects.ResultsWe developed CoPubGene a method to automatically identify gene-disease associations in Medline abstracts. We used this method to create a literature network of genes related to insulin resistance and to evaluate the importance of the genes in this network for glucocorticoid induced metabolic side effects and anti-inflammatory processes.With this approach we found several genes that already are considered markers of GC induced IR, such as phosphoenolpyruvate carboxykinase (PCK) and glucose-6-phosphatase, catalytic subunit (G6PC). In addition, we found genes involved in steroid synthesis that have not yet been recognized as mediators of GC induced IR.ConclusionsWith this approach we are able to construct a robust informative literature network of insulin resistance related genes that gave new insights to better understand the mechanisms behind GC induced IR. The method has been set up in a generic way so it can be applied to a wide variety of disease networks.

Application of text mining in the biomedical domain

“…The most used IR system by researchers in the biomedical domain is PubMed [9] that gives access to open source full text articles and abstracts of the MED-LINE database. Besides scientific literature, other literature resources such as patents, medical records, FDAs Medwatch reports, EudraVigilance reports, biomedical related blogs and websites are relevant text resources for biomedical research [1,[49][50][51].…”

“…Relationships between keywords can be summarized in tables that can be sorted and filtered based on scoring schemas yielding ranked lists of genes, drugs or diseases which can be used for guiding follow up experiments [51,79,80]. It is important to link the keywords and concepts in these results back to the original text source where they can be highlighted in the text, providing the context in which they are mentioned [9,81].…”

Sociocultural Behavior Sensemaking: State of the Art in Understanding the Operational Environment

“…When the number of documents is small these cases often include a tree diagram (or "dendrogram"). For example, in Figure 21 Fleuren et al (2013) used the publicly available CoPub tool (Fleuren et al, 2011) to cluster abstracts from the Medline database that related to insulin resistance, together with the authors' additions of categories (large letters, "Blood," "Cancer," etc.). (We note that the graph is difficult to read even in the original, and that the numbers relate to part of the analysis that is not directly relevant here.)…”

Network analysis: a new approach to study endocrine disorders

“…Fleuren et al (2013) have recently reported on the use of gene networks to identify which genes may play a role in the development of insulin resistance induced by glucocorticoids and identified several candidates, including phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Treatment with r-hGH can present short-term complications including insulin sensitivity which we have studied in pre-pubertal children with GHD.…”