Department of Physics, University of Regensburg, 93040, Regensburg, Germany.
Institute for Geometry and Applied Mathematics, RWTH Aachen University, 52062, Aachen, Germany.
J Math Biol. 2022 Dec 2;86(1):7. doi: 10.1007/s00285-022-01846-9.
Cancer progression can be described by continuous-time Markov chains whose state space grows exponentially in the number of somatic mutations. The age of a tumor at diagnosis is typically unknown. Therefore, the quantity of interest is the time-marginal distribution over all possible genotypes of tumors, defined as the transient distribution integrated over an exponentially distributed observation time. It can be obtained as the solution of a large linear system. However, the sheer size of this system renders classical solvers infeasible. We consider Markov chains whose transition rates are separable functions, allowing for an efficient low-rank tensor representation of the linear system's operator. Thus we can reduce the computational complexity from exponential to linear. We derive a convergent iterative method using low-rank formats whose result satisfies the normalization constraint of a distribution. We also perform numerical experiments illustrating that the marginal distribution is well approximated with low rank.
癌症的进展可以用连续时间马尔可夫链来描述,其状态空间随体细胞突变数量呈指数增长。肿瘤的诊断年龄通常是未知的。因此,感兴趣的数量是所有可能肿瘤基因型的时间边缘分布,定义为通过指数分布的观测时间积分的瞬态分布。它可以作为一个大型线性系统的解来获得。然而,这个系统的巨大规模使得经典的求解器不可行。我们考虑转移率是可分离函数的马尔可夫链,这允许对线性系统算子进行高效的低秩张量表示。因此,我们可以将计算复杂度从指数级降低到线性级。我们使用低秩格式推导出一种收敛迭代方法,其结果满足分布的归一化约束。我们还进行了数值实验,表明低秩可以很好地逼近边缘分布。