70 research outputs found
Reducibility of Gene Patterns in Ciliates using the Breakpoint Graph
Gene assembly in ciliates is one of the most involved DNA processings going
on in any organism. This process transforms one nucleus (the micronucleus) into
another functionally different nucleus (the macronucleus). We continue the
development of the theoretical models of gene assembly, and in particular we
demonstrate the use of the concept of the breakpoint graph, known from another
branch of DNA transformation research. More specifically: (1) we characterize
the intermediate gene patterns that can occur during the transformation of a
given micronuclear gene pattern to its macronuclear form; (2) we determine the
number of applications of the loop recombination operation (the most basic of
the three molecular operations that accomplish gene assembly) needed in this
transformation; (3) we generalize previous results (and give elegant
alternatives for some proofs) concerning characterizations of the micronuclear
gene patterns that can be assembled using a specific subset of the three
molecular operations.Comment: 30 pages, 13 figure
The Fibers and Range of Reduction Graphs in Ciliates
The biological process of gene assembly has been modeled based on three types
of string rewriting rules, called string pointer rules, defined on so-called
legal strings. It has been shown that reduction graphs, graphs that are based
on the notion of breakpoint graph in the theory of sorting by reversal, for
legal strings provide valuable insights into the gene assembly process. We
characterize which legal strings obtain the same reduction graph (up to
isomorphism), and moreover we characterize which graphs are (isomorphic to)
reduction graphs.Comment: 24 pages, 13 figure
Strategies of Loop Recombination in Ciliates
Gene assembly in ciliates is an extremely involved DNA transformation
process, which transforms a nucleus, the micronucleus, to another functionally
different nucleus, the macronucleus. In this paper we characterize which loop
recombination operations (one of the three types of molecular operations that
accomplish gene assembly) can possibly be applied in the transformation of a
given gene from its micronuclear form to its macronuclear form. We also
characterize in which order these loop recombination operations are applicable.
This is done in the abstract and more general setting of so-called legal
strings.Comment: 22 pages, 14 figure
The Matrix Sortability Problem
Sorting is such a fundamental component of achieving efficiency that a significant body of mathematics is dedicated to the investigation of sorting. Any modern textbook on algorithms contains chapters on sorting.
One approach to arranging a disorganized list of items into an organized list is to successively identify two blocks of contiguous items, and swap the two blocks. In a fundamental paper D.A. Christie showed that a special version of block swapping, in recent times called context directed swapping and abbreviated cds, is the most efficient among block swapping strategies to achieve an organized list of items. The cds sorting strategy is also the most robust among block swap based sorting methods.
It has been discovered that the context directed block swap operation on a list of objects generalizes to an operation on simple graphs. In turn it has been discovered that this operation on simple graphs corresponds with an operation on the adjacency matrix of a simple graph. The adjacency matrix is a symmetric square matrix with entries 0 and 1, and all diagonal entries 0. The corresponding operation is denoted Mcds, abbreviating matrix context directed swap. The operation on the adjacency matrix naturally employs the arithmetic of GF(2), the finite field of two elements. It has been speculated that the Mcds operation on these specific matrices over GF(2) corresponds with the more than a century old Schur complement operation on these matrices.
In this thesis, we confirm this prior speculation about the correspondence between Mcds and the Schur complement, in the context of GF(2). We generalize the Mcds operation to not necessarily square matrices over arbitrary fields and we prove that the generalized Mcds corresponds with the Schur complement also in the more general context of all fields
Doctor of Philosophy
dissertationGenotype Phenotype Association (GPA) is a means to identify candidate genes and genetic variants that may contribute to phenotypic variation. Technological advances in DNA sequencing continue to improve the efficiency and accuracy of GPA. Currently, High Throughput Sequencing (HTS) is the preferred method for GPA as it is fast and economical. HTS allows for population-level characterization of genetic variation, required for GPA studies. Despite the potential power of using HTS in GPA studies, there are technical hurdles that must be overcome. For instance, the excessive error rate in HTS data and the sheer size of population-level data can hinder GPA studies. To overcome these challenges, I have written two software programs for the purpose of HTS GPA. The first toolkit, GPAT++, is designed to detect GPA using small genetic variants. Unlike pervious software, GPAT++'s association test models the inherent errors in HTS, preventing many spurious GPA. The second toolkit, Whole Genome Alignment Metrics (WHAM), was designed for GPA using large genetic variants (structural variants). By integrating both structural variant identification and association testing, WHAM can identify shared structural variants associated with a phenotype. Both GPAT++ and WHAM have been successfully applied to real-world GPA studie
Models of natural computation : gene assembly and membrane systems
This thesis is concerned with two research areas in natural computing: the computational nature of gene assembly and membrane computing. Gene assembly is a process occurring in unicellular organisms called ciliates. During this process genes are transformed through cut-and-paste operations. We study this process from a theoretical point of view. More specifically, we relate the theory of gene assembly to sorting by reversal, which is another well-known theory of DNA transformation. In this way we obtain a novel graph-theoretical representation that provides new insights into the nature of gene assembly. Membrane computing is a computational model inspired by the functioning of membranes in cells. Membrane systems compute in a parallel fashion by moving objects, through membranes, between compartments. We study the computational power of various classes of membrane systems, and also relate them to other well-known models of computation.Netherlands Organisation for Scientific Research (NWO), Institute for Programming research and Algorithmics (IPA)UBL - phd migration 201
Sorting Permutations: Games, Genomes, and Cycles
Permutation sorting, one of the fundamental steps in pre-processing data for
the efficient application of other algorithms, has a long history in
mathematical research literature and has numerous applications. Two
special-purpose sorting operations are considered in this paper: context
directed swap, abbreviated cds, and context directed reversal, abbreviated cdr.
These are special cases of sorting operations that were studied in prior work
on permutation sorting. Moreover, cds and cdr have been postulated to model
molecular sorting events that occur in the genome maintenance program of
certain species of single-celled organisms called ciliates.
This paper investigates mathematical aspects of these two sorting operations.
The main result of this paper is a generalization of previously discovered
characterizations of cds-sortability of a permutation. The combinatorial
structure underlying this generalization suggests natural combinatorial
two-player games. These games are the main mathematical innovation of this
paper.Comment: to appear in Discrete Mathematics, Algorithms and Application
- …