首页> 美国卫生研究院文献>PLoS Computational Biology >A numerical approach for a discrete Markov model for progressing drug resistance of cancer
【2h】

A numerical approach for a discrete Markov model for progressing drug resistance of cancer

机译:离散马尔可夫模型用于提高癌症耐药性的数值方法

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

The presence of treatment-resistant cells is an important factor that limits the efficacy of cancer therapy, and the prospect of resistance is considered the major cause of the treatment strategy. Several recent studies have employed mathematical models to elucidate the dynamics of generating resistant cancer cells and attempted to predict the probability of emerging resistant cells. The purpose of this paper is to present numerical approach to compute the number of resistant cells and the emerging probability of resistance. Stochastic model was designed and developed a method to approximately but efficiently compute the number of resistant cells and the probability of resistance. To model the progression of cancer, a discrete-state, two-dimensional Markov process whose states are the total number of cells and the number of resistant cells was employed. Then exact analysis and approximate aggregation approaches were proposed to calculate the number of resistant cells and the probability of resistance when the cell population reaches detection size. To confirm the accuracy of computed results of approximation, relative errors between exact analysis and approximation were computed. The numerical values of our approximation method were very close to those of exact analysis calculated in the range of small detection size M = 500, 100, and 1500. Then computer simulation was performed to confirm the accuracy of computed results of approximation when the detection size was M = 10000,30000,50000,100000 and 1000000. All the numerical results of approximation fell between the upper level and the lower level of 95% confidential intervals and our method took less time to compute over a broad range of cell size. The effects of parameter change on emerging probabilities of resistance were also investigated by computed values using approximation method. The results showed that the number of divisions until the cell population reached the detection size is important for emerging the probability of resistance. The next step of numerical approach is to compute the emerging probabilities of resistance under drug administration and with multiple mutation. Another effective approximation would be necessary for the analysis of the latter case.
机译:耐药细胞的存在是限制癌症治疗功效的重要因素,耐药前景被认为是治疗策略的主要原因。最近的几项研究采用数学模型来阐明产生抗性癌细胞的动力学,并试图预测产生抗性细胞的可能性。本文的目的是提出一种数值方法来计算耐药细胞的数量和出现耐药的可能性。设计并开发了随机模型,该方法可以近似但有效地计算耐药细胞的数量和耐药概率。为了模拟癌症的进展,采用了离散状态的二维马尔可夫过程,其状态为细胞总数和耐药细胞数。然后提出了精确的分析和近似的聚集方法来计算抗性细胞的数量和当细胞数量达到检测大小时抗性的概率。为了确认近似计算结果的准确性,计算了精确分析和近似之间的相对误差。我们的近似方法的数值非常接近在小检测尺寸M = 500、100和1500的范围内计算出的精确分析的数值。然后进行计算机仿真,以确认检测尺寸时近似计算结果的准确性。分别为M = 10000,30000,50000,100000和1000000。所有近似值的数值结果都落在95%机密区间的上层和下层之间,并且我们的方法花费较少的时间来计算较宽的像元大小。还使用近似方法通过计算值研究了参数变化对电阻出现概率的影响。结果表明,直到细胞数量达到检测大小为止的分裂数对于产生抗药性的概率很重要。数值方法的下一步是计算在药物管理和多重突变的情况下出现耐药的可能性。对于后一种情况的分析,需要另一个有效的近似值。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号