Muñoz Stalin, Carrillo Miguel, Azpeitia Eugenio, Rosenblueth David A
Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Facultad de Ingeniería, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Front Genet. 2018 Mar 6;9:39. doi: 10.3389/fgene.2018.00039. eCollection 2018.
Boolean networks are important models of biochemical systems, located at the high end of the abstraction spectrum. A number of Boolean gene networks have been inferred following essentially the same method. Such a method first considers experimental data for a typically underdetermined "regulation" graph. Next, Boolean networks are inferred by using biological constraints to narrow the search space, such as a desired set of (fixed-point or cyclic) attractors. We describe , a computer tool enhancing this method. incorporates a number of well-established algorithms, such as Dubrova and Teslenko's algorithm for finding attractors in synchronous Boolean networks. In addition, a formal definition of regulation allows to employ "symbolic" techniques, able to represent both large sets of network states and Boolean constraints. We observe that when the set of attractors is required to be an set, prohibiting additional attractors, a naive Boolean coding of this constraint may be unfeasible. Such cases may be intractable even with symbolic methods, as the number of Boolean constraints may be astronomically large. To overcome this problem, we employ an Artificial Intelligence technique known as "clause learning" considerably increasing 's scalability. Without clause learning only toy examples prohibiting additional attractors are solvable: only one out of seven queries reported here is answered. With clause learning, by contrast, all seven queries are answered. We illustrate with three case studies drawn from the literature. is available at: http://turing.iimas.unam.mx/griffin.
布尔网络是生化系统的重要模型,位于抽象频谱的高端。许多布尔基因网络都是按照基本相同的方法推断出来的。这种方法首先考虑一个典型的欠定“调控”图的实验数据。接下来,通过使用生物学约束来缩小搜索空间来推断布尔网络,例如一组期望的(定点或循环)吸引子。我们描述了一种增强这种方法的计算机工具。它整合了许多成熟的算法,比如杜布罗娃和特斯连科在同步布尔网络中寻找吸引子的算法。此外,调控的形式定义允许使用“符号”技术,能够表示大量的网络状态集和布尔约束。我们观察到,当要求吸引子集合为一个集合,禁止额外的吸引子时,对这个约束进行简单的布尔编码可能不可行。即使使用符号方法,这种情况也可能难以处理,因为布尔约束的数量可能大得惊人。为了克服这个问题,我们采用一种称为“子句学习”的人工智能技术,大大提高了该工具的可扩展性。没有子句学习时,只有禁止额外吸引子的简单示例才能解决:这里报告的七个查询中只有一个得到回答。相比之下,有了子句学习,所有七个查询都得到了回答。我们用从文献中选取的三个案例研究来说明该工具。该工具可在以下网址获取:http://turing.iimas.unam.mx/griffin。