From desk to bed: computational simulations provide indication for rheumatoid arthritis clinical trials.
From desk to bed: computational simulations provide indication for rheumatoid arthritis clinical trials.
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从办公桌到床上：计算模拟为类风湿关节炎临床试验提供指示
DOI：
10.1186/1752-0509-7-10
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发表时间：
2013-01-22
影响因子：
--
通讯作者：
Nardini C
中科院分区：
文献类型：
--
作者：
Dent JE;Nardini C
背景类风湿性关节炎 (RA) 是最常见的人类系统性自身免疫性疾病之一，影响全球约 1% 的人口。迄今为止，该疾病尚无治愈方法，并且当前的治疗方法显示出不良副作用。随着这种疾病影响越来越多的人，并且在他们的工作年龄，收集所有能够通过了解其和疾病的作用机制来改进治疗的信息代表了一个重要的研究领域，不仅使患者受益，而且使社会受益。在这个方向上，之前的工作中已使用网络分析方法来进一步了解这种复杂疾病，从而确定 CRKL 作为治疗 RA 的潜在药物靶点。在这里，我们使用计算方法来扩展这项工作，在计算机中测试假设。结果 CRKL 网络的分析 - 可在 http://www.picb.ac.cn/ClinicalGenomicNTW/software.html 上获得 - 允许研究扰动感兴趣基因的潜在影响。在受 CRKL 模拟扰动显着影响的一组基因中，我们进一步研究 PXN 的重要性。我们的结果使我们能够（1）完善 CRKL 作为新药物靶点的假设（2）指出正在进行的试验中副作用的潜在原因，以及（3）重要的是，提供对正在进行的临床研究产生影响的建议。结论基于收集和连接大量已知与疾病有关的分子的虚拟网络，可以模拟控制分子的效果，从而观察其如何影响网络的其余部分。这对于模仿药物的作用很重要，而且对于了解并可能控制其副作用也很重要。在 RA 研究中使用这种方法，我们能够为该领域做出贡献，建议新疗法中的靶向分子，更重要的是，为了保证疗效，对目前正在测试的现有药物提出新的建议。
BackgroundRheumatoid 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 hypothesisin silico.ResultsAnalysis of the CRKL network -available at http://www.picb.ac.cn/ClinicalGenomicNTW/software.html - 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.ConclusionsBased 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.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.9
作者：
Shahrara S;Castro-Rueda HP;Haines GK;Koch AE
通讯作者：
Koch AE
影响因子：
5.8
作者：
Hucka, M;Finney, A;Wang, J
通讯作者：
Wang, J
DOI：
10.1124/jpet.106.109058
发表时间：
2006-12-01
影响因子：
3.5
作者：
Braselmann, Sylvia;Taylor, Vanessa;Masuda, Esteban S.
通讯作者：
Masuda, Esteban S.
影响因子：
20.3
作者：
Oda, A;Ochs, HD;Ikeda, H
通讯作者：
Ikeda, H