Stalin Muñoz

The combination of the functionalities of feedback circuits is determinant for the attractors’ number and size in pathway-like Boolean networks

Molecular regulation was initially assumed to follow both a unidirectional and a hierarchical organization forming pathways. Regulatory processes, however, form highly interlinked networks with non-hierarchical and non-unidirectional structures that contain statistically overrepresented circuits or motifs. Here, we analyze the behavior of pathways containing non-unidirectional (i.e. bidirectional) and non-hierarchical interactions that create motifs. In comparison with unidirectional and hierarchical pathways, our pathways have a high diversity of behaviors, characterized by the size and number of attractors. Motifs have been studied individually showing that feedback circuit motifs regulate the number and size of attractors. It is less clear what happens in molecular networks that usually contain multiple feedbacks. Here, we find that the way feedback circuits couple to each other (i.e., the combination of the functionalities of feedback circuits) regulate both the number and size of the attractors. We show that the different expected results of epistasis analysis (a method to infer regulatory interactions) are produced by many non-hierarchical and non-unidirectional structures. Thus, these structures cannot be correctly inferred by epistasis analysis. Finally, we show that the combinations of functionalities, combined with other network properties, allow for a better characterization of regulatory structures.

Inference of Boolean Networks from Gene Interaction Graphs Using a SAT Solver

Boolean networks are important models of gene regulatory networks. Such models are sometimes built from: (1) a gene interaction graph and (2) a set of biological constraints. A gene interaction graph is a directed graph representing positive and negative gene regulations. Depending on the biological problem being solved, the set of biological constraints can vary, and may include, for example, a desired set of stationary states. We present a symbolic, SAT-based, method for inferring synchronous Boolean networks from interaction graphs augmented with constraints. Our method first constructs Boolean formulas in such a way that each truth assignment satisfying these formulas corresponds to a Boolean network modeling the given information. Next, we employ a SAT solver to obtain desired Boolean networks. Through a prototype, we show results illustrating the use of our method in the analysis of Boolean gene regulatory networks of the Arabidopsis thaliana root stem cell niche.

A model of the regulatory network involved in the control of the cell cycle and cell differentiation in the Caenorhabditis elegans vulva

BackgroundThere are recent experimental reports on the cross-regulation between molecules involved in the control of the cell cycle and the differentiation of the vulval precursor cells (VPCs) of Caenorhabditis elegans. Such discoveries provide novel clues on how the molecular mechanisms involved in the cell cycle and cell differentiation processes are coordinated during vulval development. Dynamic computational models are helpful to understand the integrated regulatory mechanisms affecting these cellular processes.ResultsHere we propose a simplified model of the regulatory network that includes sufficient molecules involved in the control of both the cell cycle and cell differentiation in the C. elegans vulva to recover their dynamic behavior. We first infer both the topology and the update rules of the cell cycle module from an expected time series. Next, we use a symbolic algorithmic approach to find which interactions must be included in the regulatory network. Finally, we use a continuous-time version of the update rules for the cell cycle module to validate the cyclic behavior of the network, as well as to rule out the presence of potential artifacts due to the synchronous updating of the discrete model. We analyze the dynamical behavior of the model for the wild type and several mutants, finding that most of the results are consistent with published experimental results.ConclusionsOur model shows that the regulation of Notch signaling by the cell cycle preserves the potential of the VPCs and the three vulval fates to differentiate and de-differentiate, allowing them to remain completely responsive to the concentration of LIN-3 and lateral signal in the extracellular microenvironment.

Obstacle Avoidance Behaviors for Mobile Robots Using Genetic Algorithms and Recurrent Neural Networks

Abstract This paper discusses how to generate mobile robots’ behaviors using genetic algorithms (GA). The behaviors are built using state machines implemented in recurrent neural networks (RNN), controlling the movements of a humanoid mobile robot. The weights of the RNN are found using a GA, these are evaluated according to a fitness function that grades their performance. Basically, this function evaluates the robots performance when it goes from an origin to a destination, and the grading of the robot evaluates also that the robots behavior using RNN is similar to the behavior generated by a potential fields approach for navigation. Our objective was to prove that GA is a good option as a method for finding behaviors for mobile robots’ navigation and also that these behaviors can be implemented using RNN.

The combination of the functionalities of feedback circuits is determinant for the number and size of attractors of molecular networks

Molecular regulation was initially assumed to follow both a unidirectional and a hierarchical organization forming pathways. Regulatory processes, however, form highly interlinked networks with non-hierarchical and non-unidirectional structures that contain statistically overrepresented circuits (motifs). Here, we analyze the behavior of pathways containing non-hierarchical and non-unidirectional interactions that create motifs. In comparison with unidirectional and hierarchical pathways, our pathways have a high diversity of behaviors, characterized by the size and number of attractors. Motifs have been studied individually showing that feedback circuit motifs regulate the number and size of attractors. It is less clear what happens in molecular networks that usually contain multiple feedbacks. Here, we find that the way feedback circuits couple to each other (i.e., the combination of the functionalities of feedback circuits) regulate both the precise number and size of the attractors. We show that the different sets of expected results of epistasis analysis (a method to infer regulatory interactions) are produced by many non-hierarchical and non-unidirectional structures. Thus, these structures cannot be correctly inferred by epistasis analysis. Finally, we show that the structures producing the epistasis results have remarkably similar sets of combinations of functionalities, that combined with other network properties could greatly improve epistasis analysis.

Lagrangian model, simulation and control of a spherical robot

The derivation of the Lagrangian for different configurations of spherical robots is explored through the use of the Euler Lagrange equations and additional constrains for the generalized velocities. The degrees of freedom are specified with rotation matrices and linear displacement vectors, allowing to determine the necessary elements for all the models in a procedural way, and to obtain the dynamics of the system. One of the thus obtained models is used for simple velocity control tests with two approaches, using the torque and velocity of the rotatory actuators as control inputs, with successful results for a simplified system with one degree of freedom, and satisfactory results for the general system.

Griffin: A Tool for Symbolic Inference of Synchronous Boolean Molecular Networks

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 Griffin, a computer tool enhancing this method. Griffin incorporates a number of well-established algorithms, such as Dubrova and Teslenkos algorithm for finding attractors in synchronous Boolean networks. In addition, a formal definition of regulation allows Griffin 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 exact 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 Griffins 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 Griffin with three case studies drawn from the Arabidopsis thaliana literature. Griffin is available at: http://turing.iimas.unam.mx/griffin.