A Computational Method for the Rate Estimation of Evolutionary Transpositions

Genome rearrangements are evolutionary events that shuffle genomic architectures. Most frequent genome rearrangements are reversals, translocations, fusions, and fissions. While there are some more complex genome rearrangements such as transpositions, they are rarely observed and believed to constitute only a small fraction of genome rearrangements happening in the course of evolution. The analysis of transpositions is further obfuscated by intractability of the underlying computational problems. We propose a computational method for estimating the rate of transpositions in evolutionary scenarios between genomes. We applied our method to a set of mammalian genomes and estimated the transpositions rate in mammalian evolution to be around 0.26.Comment: Proceedings of the 3rd International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO), 2015. (to appear

Phylogénétique basée sur les cassures du génome

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Models and Algorithms for Sorting Permutations with Tandem Duplication and Random Loss

A central topic of evolutionary biology is the inference of phylogeny, i. e., the evolutionary history of species. A powerful tool for the inference of such phylogenetic relationships is the arrangement of the genes in mitochondrial genomes. The rationale is that these gene arrangements are subject to different types of mutations in the course of evolution. Hence, a high similarity in the gene arrangement between two species indicates a close evolutionary relation. Metazoan mitochondrial gene arrangements are particularly well suited for such phylogenetic studies as they are available for a wide range of species, their gene content is almost invariant, and usually free of duplicates. With these properties gene arrangements of mitochondrial genomes are modeled by permutations in which each element represents a gene, i. e., a specific genetic sequence. The mutations that shape the gene arrangement of genomes are then represented by operations that rearrange elements in permutations, so-called genome rearrangements, and thereby bridge the gap between evolutionary biology and optimization. Many problems of phylogeny inference can be formulated as challenging combinatorial optimization problems which makes this research area especially interesting for computer scientists. The most prominent examples of such optimization problems are the sorting problem and the distance problem. While the sorting problem requires a minimum length sequence of rearrangements that transforms one given permutation into another given permutation, i. e., it aims for a hypothetical scenario of gene order evolution, the distance problem intends to determine only the length of such a sequence. This minimum length is called distance and used as a (dis)similarity measure quantifying the evolutionary relatedness. Most evolutionary changes occurring in gene arrangements of mitochondrial genomes can be explained by the tandem duplication random loss (TDRL) genome rearrangement model. A TDRL consists of a duplication of a consecutive set of genes in tandem followed by a random loss of one copy of each duplicated gene. In spite of the importance of the TDRL genome rearrangement in mitochondrial evolution, its combinatorial properties have rarely been studied. In addition, models of genome rearrangements which include all types of rearrangement that are relevant for mitochondrial genomes, i. e., inversions, transpositions, inverse transpositions, and TDRLs, while admitting computational tractability are rare. Nevertheless, especially for metazoan gene arrangements the TDRL rearrangement should be considered for the reconstruction of phylogeny. Realizing that a better understanding of the TDRL model is indispensable for the study of mitochondrial gene arrangements, the central theme of this thesis is to broaden the horizon of TDRL genome rearrangements with respect to mitochondrial genome evolution. For this purpose, this thesis provides combinatorial properties of the TDRL model and its variants as well as efficient methods for a plausible reconstruction of rearrangement scenarios between gene arrangements. The methods that are proposed consider all types of genome rearrangements that predominately occur during mitochondrial evolution. More precisely, the main points contained in this thesis are as follows: The distance problem and the sorting problem for the TDRL model are further examined in respect to circular permutations, a formal concept that reflects the circular structure of mitochondrial genomes. As a result, a closed formula for the distance is provided. Recently, evidence for a variant of the TDRL rearrangement model in which the duplicated set of genes is additionally inverted have been found. Initiating the algorithmic study of this new rearrangement model on a certain type of permutations, a closed formula solving the distance problem is proposed as well as a quasilinear time algorithm that solves the corresponding sorting problem. The assumption that only one type of genome rearrangement has occurred during the evolution of certain gene arrangements is most likely unrealistic, e. g., at least three types of rearrangements on top of the TDRL rearrangement have to be considered for the evolution metazoan mitochondrial genomes. Therefore, three different biologically motivated constraints are taken into account in this thesis in order to produce plausible evolutionary rearrangement scenarios. The first constraint is extending the considered set of genome rearrangements to the model that covers all four common types of mitochondrial genome rearrangements. For this 4-type model a sharp lower bound and several close additive upper bounds on the distance are developed. As a byproduct, a polynomial-time approximation algorithm for the corresponding sorting problem is provided that guarantees the computation of pairwise rearrangement scenarios that deviate from a minimum length scenario by at most two rearrangement operations. The second biologically motivated constraint is the relative frequency of the different types of rearrangements occurring during the evolution. The frequency is modeled by employing a weighting scheme on the 4-type model in which every rearrangement is weighted with respect to its type. The resulting NP-hard sorting problem is then solved by means of a polynomial size integer linear program. The third biologically motivated constraint that has been taken into account is that certain subsets of genes are often found in close proximity in the gene arrangements of many different species. This observation is reflected by demanding rearrangement scenarios to preserve certain groups of genes which are modeled by common intervals of permutations. In order to solve the sorting problem that considers all three types of biologically motivated constraints, the exact dynamic programming algorithm CREx2 is proposed. CREx2 has a linear runtime for a large class of problem instances. Otherwise, two versions of the CREx2 are provided: The first version provides exact solutions but has an exponential runtime in the worst case and the second version provides approximated solutions efficiently. CREx2 is evaluated by an empirical study for simulated artificial and real biological mitochondrial gene arrangements

Close and Distant Reading Visualizations for the Comparative Analysis of Digital Humanities Data

Traditionally, humanities scholars carrying out research on a specific or on multiple literary work(s) are interested in the analysis of related texts or text passages. But the digital age has opened possibilities for scholars to enhance their traditional workflows. Enabled by digitization projects, humanities scholars can nowadays reach a large number of digitized texts through web portals such as Google Books or Internet Archive. Digital editions exist also for ancient texts; notable examples are PHI Latin Texts and the Perseus Digital Library. This shift from reading a single book “on paper” to the possibility of browsing many digital texts is one of the origins and principal pillars of the digital humanities domain, which helps developing solutions to handle vast amounts of cultural heritage data – text being the main data type. In contrast to the traditional methods, the digital humanities allow to pose new research questions on cultural heritage datasets. Some of these questions can be answered with existent algorithms and tools provided by the computer science domain, but for other humanities questions scholars need to formulate new methods in collaboration with computer scientists. Developed in the late 1980s, the digital humanities primarily focused on designing standards to represent cultural heritage data such as the Text Encoding Initiative (TEI) for texts, and to aggregate, digitize and deliver data. In the last years, visualization techniques have gained more and more importance when it comes to analyzing data. For example, Saito introduced her 2010 digital humanities conference paper with: “In recent years, people have tended to be overwhelmed by a vast amount of information in various contexts. Therefore, arguments about ’Information Visualization’ as a method to make information easy to comprehend are more than understandable.” A major impulse for this trend was given by Franco Moretti. In 2005, he published the book “Graphs, Maps, Trees”, in which he proposes so-called distant reading approaches for textual data that steer the traditional way of approaching literature towards a completely new direction. Instead of reading texts in the traditional way – so-called close reading –, he invites to count, to graph and to map them. In other words, to visualize them. This dissertation presents novel close and distant reading visualization techniques for hitherto unsolved problems. Appropriate visualization techniques have been applied to support basic tasks, e.g., visualizing geospatial metadata to analyze the geographical distribution of cultural heritage data items or using tag clouds to illustrate textual statistics of a historical corpus. In contrast, this dissertation focuses on developing information visualization and visual analytics methods that support investigating research questions that require the comparative analysis of various digital humanities datasets. We first take a look at the state-of-the-art of existing close and distant reading visualizations that have been developed to support humanities scholars working with literary texts. We thereby provide a taxonomy of visualization methods applied to show various aspects of the underlying digital humanities data. We point out open challenges and we present our visualizations designed to support humanities scholars in comparatively analyzing historical datasets. In short, we present (1) GeoTemCo for the comparative visualization of geospatial-temporal data, (2) the two tag cloud designs TagPies and TagSpheres that comparatively visualize faceted textual summaries, (3) TextReuseGrid and TextReuseBrowser to explore re-used text passages among the texts of a corpus, (4) TRAViz for the visualization of textual variation between multiple text editions, and (5) the visual analytics system MusikerProfiling to detect similar musicians to a given musician of interest. Finally, we summarize our and the collaboration experiences of other visualization researchers to emphasize the ingredients required for a successful project in the digital humanities, and we take a look at future challenges in that research field

Evolutionary genomics : statistical and computational methods

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

Evolutionary Genomics

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

Technologies for detecting heritable mutations in human beings

A report on heritable mutations, permanent changes in the genetic material that can be passed on to succeeding generations, are the cause of a large but currently unquantifiable share of embryonic and fetal loss, disease, disability, and early death in the United States today. The methods now available to study heritable mutations, however, offer relatively little information about the kinds of mutations that can occur, their frequency, or their causes

27th Fungal Genetics Conference

Program and abstracts from the 27th Fungal Genetics Conference Asilomar, March 12-17, 2013