Finite Models of Splicing and Their Complexity

Durante las dos últimas décadas ha surgido una colaboración estrecha entre informáticos, bioquímicos y biólogos moleculares, que ha dado lugar a la investigación en un área conocida como la computación biomolecular. El trabajo en esta tesis pertenece a este área, y estudia un modelo de cómputo llamado sistema de empalme (splicing system). El empalme es el modelo formal del corte y de la recombinación de las moléculas de ADN bajo la influencia de las enzimas de la restricción.Esta tesis presenta el trabajo original en el campo de los sistemas de empalme, que, como ya indica el título, se puede dividir en dos partes. La primera parte introduce y estudia nuevos modelos finitos de empalme. La segunda investiga aspectos de complejidad (tanto computacional como descripcional) de los sistema de empalme. La principal contribución de la primera parte es que pone en duda la asunción general que una definición finita, más realista de sistemas de empalme es necesariamente débil desde un punto de vista computacional. Estudiamos varios modelos alternativos y demostramos que en muchos casos tienen más poder computacional. La segunda parte de la tesis explora otro territorio. El modelo de empalme se ha estudiado mucho respecto a su poder computacional, pero las consideraciones de complejidad no se han tratado apenas. Introducimos una noción de la complejidad temporal y espacial para los sistemas de empalme. Estas definiciones son utilizadas para definir y para caracterizar las clases de complejidad para los sistemas de empalme. Entre otros resultados, presentamos unas caracterizaciones exactas de las clases de empalme en términos de clases de máquina de Turing conocidas. Después, usando una nueva variante de sistemas de empalme, que acepta lenguajes en lugar de generarlos, demostramos que los sistemas de empalme se pueden usar para resolver problemas. Por último, definimos medidas de complejidad descriptional para los sistemas de empalme. Demostramos que en este respecto los sistemas de empalme finitos tienen buenas propiedades comparadosOver the last two decades, a tight collaboration has emerged between computer scientists, biochemists and molecular biologists, which has spurred research into an area known as DNAComputing (also biomolecular computing). The work in this thesis belongs to this field, and studies a computational model called splicing system. Splicing is the formal model of the cutting and recombination of DNA molecules under the influence of restriction enzymes.This thesis presents original work in the field of splicing systems, which, as the title already indicates, can be roughly divided into two parts: 'Finite models of splicing' on the onehand and 'their complexity' on the other. The main contribution of the first part is that it challenges the general assumption that a finite, more realistic definition of splicing is necessarily weal from a computational point of view. We propose and study various alternative models and show that in most cases they have more computational power, often reaching computational completeness. The second part explores other territory. Splicing research has been mainly focused on computational power, but complexity considerations have hardly been addressed. Here we introduce notions of time and space complexity for splicing systems. These definitions are used to characterize splicing complexity classes in terms of well known Turing machine classes. Then, using a new accepting variant of splicing systems, we show that they can also be used as problem solvers. Finally, we study descriptional complexity. We define measures of descriptional complexity for splicing systems and show that for representing regular languages they have good properties with respect to finite automata, especially in the accepting variant

Splicing Systems from Past to Future: Old and New Challenges

A splicing system is a formal model of a recombinant behaviour of sets of double stranded DNA molecules when acted on by restriction enzymes and ligase. In this survey we will concentrate on a specific behaviour of a type of splicing systems, introduced by P\u{a}un and subsequently developed by many researchers in both linear and circular case of splicing definition. In particular, we will present recent results on this topic and how they stimulate new challenging investigations.Comment: Appeared in: Discrete Mathematics and Computer Science. Papers in Memoriam Alexandru Mateescu (1952-2005). The Publishing House of the Romanian Academy, 2014. arXiv admin note: text overlap with arXiv:1112.4897 by other author

Computational Complexity Theory in Membrane Computing: Seventeen Years After

In this work we revisit the basic concepts, definitions of computational complexity theory in membrane computing. The paper also discusses a novel methodology to tackle the P versus NP problem in the context of the aforementioned theory. The methodology is illustrated with a collection of frontiers of tractability for several classes of P systems.Ministerio de Economía, Industria y Competitividad TIN2017-89842-

Complexity and modeling power of insertion-deletion systems

SISTEMAS DE INSERCIÓN Y BORRADO: COMPLEJIDAD Y CAPACIDAD DE MODELADO El objetivo central de la tesis es el estudio de los sistemas de inserción y borrado y su capacidad computacional. Más concretamente, estudiamos algunos modelos de generación de lenguaje que usan operaciones de reescritura de dos cadenas. También consideramos una variante distribuida de los sistemas de inserción y borrado en el sentido de que las reglas se separan entre un número finito de nodos de un grafo. Estos sistemas se denominan sistemas controlados mediante grafo, y aparecen en muchas áreas de la Informática, jugando un papel muy importante en los lenguajes formales, la lingüística y la bio-informática. Estudiamos la decidibilidad/ universalidad de nuestros modelos mediante la variación de los parámetros de tamaño del vector. Concretamente, damos respuesta a la cuestión más importante concerniente a la expresividad de la capacidad computacional: si nuestro modelo es equivalente a una máquina de Turing o no. Abordamos sistemáticamente las cuestiones sobre los tamaños mínimos de los sistemas con y sin control de grafo.COMPLEXITY AND MODELING POWER OF INSERTION-DELETION SYSTEMS The central object of the thesis are insertion-deletion systems and their computational power. More specifically, we study language generating models that use two string rewriting operations: contextual insertion and contextual deletion, and their extensions. We also consider a distributed variant of insertion-deletion systems in the sense that rules are separated among a finite number of nodes of a graph. Such systems are refereed as graph-controlled systems. These systems appear in many areas of Computer Science and they play an important role in formal languages, linguistics, and bio-informatics. We vary the parameters of the vector of size of insertion-deletion systems and we study decidability/universality of obtained models. More precisely, we answer the most important questions regarding the expressiveness of the computational model: whether our model is Turing equivalent or not. We systematically approach the questions about the minimal sizes of the insertiondeletion systems with and without the graph-control

Communication in membrana Systems with symbol Objects.

Esta tesis está dedicada a los sistemas de membranas con objetos-símbolo como marco teórico de los sistemas paralelos y distribuidos de procesamiento de multiconjuntos.Una computación de parada puede aceptar, generar o procesar un número, un vector o una palabra; por tanto el sistema define globalmente (a través de los resultados de todas sus computaciones) un conjunto de números, de vectores, de palabras (es decir, un lenguaje), o bien una función. En esta tesis estudiamos la capacidad de estos sistemas para resolver problemas particulares, así como su potencia computacional. Por ejemplo, las familias de lenguajes definidas por diversas clases de estos sistemas se comparan con las familias clásicas, esto es, lenguajes regulares, independientes del contexto, generados por sistemas 0L tabulados extendidos, generados por gramáticas matriciales sin chequeo de apariciones, recursivamente enumerables, etc. Se prestará especial atención a la comunicación de objetos entre regiones y a las distintas formas de cooperación entre ellos.Se pretende (Sección 3.4) realizar una formalización los sistemas de membranas y construir una herramienta tipo software para la variante que usa cooperación no distribuida, el navegador de configuraciones, es decir, un simulador, en el cual el usuario selecciona la siguiente configuración entre todas las posibles, estando permitido volver hacia atrás. Se considerarán diversos modelos distribuidos. En el modelo de evolución y comunicación (Capítulo 4) separamos las reglas tipo-reescritura y las reglas de transporte (llamadas symport y antiport). Los sistemas de bombeo de protones (proton pumping, Secciones 4.8, 4.9) constituyen una variante de los sistemas de evolución y comunicación con un modo restrictivo de cooperación. Un modelo especial de computación con membranas es el modelo puramente comunicativo, en el cual los objetos traspasan juntos una membrana. Estudiamos la potencia computacional de las sistemas de membranas con symport/antiport de 2 o 3 objetos (Capítulo 5) y la potencia computacional de las sistemas de membranas con alfabeto limitado (Capítulo 6).El determinismo (Secciones 4.7, 5.5, etc.) es una característica especial (restrictiva) de los sistemas computacionales. Se pondrá especial énfasis en analizar si esta restricción reduce o no la potencia computacional de los mismos. Los resultados obtenidos para sistemas de bombeo del protones están transferidos (Sección 7.3) a sistemas con catalizadores bistabiles. Unos ejemplos de aplicación concreta de los sistemas de membranas (Secciones 7.1, 7.2) son la resolución de problemas NP-completos en tiempo polinomial y la resolución de problemas de ordenación.This thesis deals with membrane systems with symbol objects as a theoretical framework of distributed parallel multiset processing systems.A halting computation can accept, generate or process a number, a vector or a word, so the system globally defines (by the results of all its computations) a set of numbers or a set of vectors or a set of words, (i.e., a language), or a function. The ability of these systems to solve particular problems is investigated, as well as their computational power, e.g., the language families defined by different classes of these systems are compared to the classical ones, i.e., regular, context-free, languages generated by extended tabled 0L systems, languages generated by matrix grammars without appearance checking, recursively enumerable languages, etc. Special attention is paid to communication of objects between the regions and to the ways of cooperation between the objects.An attempt to formalize the membrane systems is made (Section 3.4), and a software tool is constructed for the non-distributed cooperative variant, the configuration browser, i.e., a simulator, where the user chooses the next configuration among the possible ones and can go back. Different distributed models are considered. In the evolution-communication model (Chapter 4) rewriting-like rules are separated from transport rules. Proton pumping systems (Sections 4.8, 4.9) are a variant of the evolution-communication systems with a restricted way of cooperation. A special membrane computing model is a purely communicative one: the objects are moved together through a membrane. We study the computational power of membrane systems with symport/antiport of 2 or 3 objects (Chapter 5) and the computational power of membrane systems with a limited alphabet (Chapter 6).Determinism (Sections 4.7, 5.5, etc.) is a special property of computational systems; the question of whether this restriction reduces the computational power is addressed. The results on proton pumping systems can be carried over (Section 7.3) to the systems with bi-stable catalysts. Some particular examples of membrane systems applications are solving NP-complete problems in polynomial time, and solving the sorting problem

Formal models of the extension activity of DNA polymerase enzymes

The study of formal language operations inspired by enzymatic actions on DNA is part of ongoing efforts to provide a formal framework and rigorous treatment of DNA-based information and DNA-based computation. Other studies along these lines include theoretical explorations of splicing systems, insertion-deletion systems, substitution, hairpin extension, hairpin reduction, superposition, overlapping concatenation, conditional concatenation, contextual intra- and intermolecular recombinations, as well as template-guided recombination. First, a formal language operation is proposed and investigated, inspired by the naturally occurring phenomenon of DNA primer extension by a DNA-template-directed DNA polymerase enzyme. Given two DNA strings u and v, where the shorter string v (called the primer) is Watson-Crick complementary and can thus bind to a substring of the longer string u (called the template) the result of the primer extension is a DNA string that is complementary to a suffix of the template which starts at the binding position of the primer. The operation of DNA primer extension can be abstracted as a binary operation on two formal languages: a template language L1 and a primer language L2. This language operation is called L1-directed extension of L2 and the closure properties of various language classes, including the classes in the Chomsky hierarchy, are studied under directed extension. Furthermore, the question of finding necessary and sufficient conditions for a given language of target strings to be generated from a given template language when the primer language is unknown is answered. The canonic inverse of directed extension is used in order to obtain the optimal solution (the minimal primer language) to this question. The second research project investigates properties of the binary string and language operation overlap assembly as defined by Csuhaj-Varju, Petre and Vaszil as a formal model of the linear self-assembly of DNA strands: The overlap assembly of two strings, xy and yz, which share an overlap y, results in the string xyz. In this context, we investigate overlap assembly and its properties: closure properties of various language families under this operation, and related decision problems. A theoretical analysis of the possible use of iterated overlap assembly to generate combinatorial DNA libraries is also given. The third research project continues the exploration of the properties of the overlap assembly operation by investigating closure properties of various language classes under iterated overlap assembly, and the decidability of the completeness of a language. The problem of deciding whether a given string is terminal with respect to a language, and the problem of deciding if a given language can be generated by an overlap assembly operation of two other given languages are also investigated

DNA Computing: Modelling in Formal Languages and Combinatorics on Words, and Complexity Estimation

DNA computing, an essential area of unconventional computing research, encodes problems using DNA molecules and solves them using biological processes. This thesis contributes to the theoretical research in DNA computing by modelling biological processes as computations and by studying formal language and combinatorics on words concepts motivated by DNA processes. It also contributes to the experimental research in DNA computing by a scaling comparison between DNA computing and other models of computation. First, for theoretical DNA computing research, we propose a new word operation inspired by a DNA wet lab protocol called cross-pairing polymerase chain reaction (XPCR). We define and study a word operation called word blending that models and generalizes an unexpected outcome of XPCR. The input words are uwx and ywv that share a non-empty overlap w, and the output is the word uwv. Closure properties of the Chomsky families of languages under this operation and its iterated version, the existence of a solution to equations involving this operation, and its state complexity are studied. To follow the XPCR experimental requirement closely, a new word operation called conjugate word blending is defined, where the subwords x and y are required to be identical. Closure properties of the Chomsky families of languages under this operation and the XPCR experiments that motivate and implement it are presented. Second, we generalize the sequence of Fibonacci words inspired by biological concepts on DNA. The sequence of Fibonacci words is an infinite sequence of words obtained from two initial letters f(1) = a and f(2)= b, by the recursive definition f(n+2) = f(n+1)*f(n), for all positive integers n, where * denotes word concatenation. After we propose a unified terminology for different types of Fibonacci words and corresponding results in the extensive literature on the topic, we define and explore involutive Fibonacci words motivated by ideas stemming from theoretical studies of DNA computing. The relationship between different involutive Fibonacci words and their borderedness and primitivity are studied. Third, we analyze the practicability of DNA computing experiments since DNA computing and other unconventional computing methods that solve computationally challenging problems often have the limitation that the space of potential solutions grows exponentially with their sizes. For such problems, DNA computing algorithms may achieve a linear time complexity with an exponential space complexity as a trade-off. Using the subset sum problem as the benchmark problem, we present a scaling comparison of the DNA computing (DNA-C) approach with the network biocomputing (NB-C) and the electronic computing (E-C) approaches, where the volume, computing time, and energy required, relative to the input size, are compared. Our analysis shows that E-C uses a tiny volume compared to that required by DNA-C and NB-C, at the cost of the E-C computing time being outperformed first by DNA-C and then by NB-C. In addition, NB-C appears to be more energy efficient than DNA-C for some input sets, and E-C is always an order of magnitude less energy efficient than DNA-C

In Memoriam, Solomon Marcus

This book commemorates Solomon Marcus’s fifth death anniversary with a selection of articles in mathematics, theoretical computer science, and physics written by authors who work in Marcus’s research fields, some of whom have been influenced by his results and/or have collaborated with him