From desk to bed: Computational simulations provide indication for rheumatoid arthritis clinical trials

BMC Systems Biology

Christine Nardini¹  Jennifer E Dent² 

[1] Group of Clinical Genomic Networks, Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China;Population Health Research Centre, Division of Population Health Sciences and Education, St. George’s University of London, Cranmer Terrace, London, UK

关键词: BioLayout express;    Simulation modelling;    Tyrosine kynase;    Rheumatoid arthritis;   

Others  :  1143217
DOI  :  10.1186/1752-0509-7-10

 received in 2012-07-15, accepted in 2013-01-18,  发布年份 2013

【 摘 要 】

Background

Rheumatoid arthritis (RA) is among the most common human systemic autoimmune diseases, affecting approximately 1% of the population worldwide. To date, there is no cure for the disease and current treatments show undesirable side effects. As the disease affects a growing number of individuals, and during their working age, the gathering of all information able to improve therapies -by understanding their and the disease mechanisms of action- represents an important area of research, benefiting not only patients but also societies. In this direction, network analysis methods have been used in previous work to further our understanding of this complex disease, leading to the identification of CRKL as a potential drug target for treatment of RA. Here, we use computational methods to expand on this work, testing the hypothesis in silico.

Results

Analysis of the CRKL network -available at http://www.picb.ac.cn/ClinicalGenomicNTW/software.html webcite- allows for investigation of the potential effect of perturbing genes of interest. Within the group of genes that are significantly affected by simulated perturbation of CRKL, we are lead to further investigate the importance of PXN. Our results allow us to (1) refine the hypothesis on CRKL as a novel drug target (2) indicate potential causes of side effects in on-going trials and (3) importantly, provide recommendations with impact on on-going clinical studies.

Conclusions

Based on a virtual network that collects and connects a large number of the molecules known to be involved in a disease, one can simulate the effects of controlling molecules, allowing for the observation of how this affects the rest of the network. This is important to mimic the effect of a drug, but also to be aware of -and possibly control- its side effects. Using this approach in RA research we have been able to contribute to the field by suggesting molecules to be targeted in new therapies and more importantly, to warrant efficacy, to hypothesise novel recommendations on existing drugs currently under test.

【 授权许可】

   
2013 Dent and Nardini; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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