Ciliate Gene Unscrambling with Fewer Templates

One of the theoretical models proposed for the mechanism of gene unscrambling in some species of ciliates is the template-guided recombination (TGR) system by Prescott, Ehrenfeucht and Rozenberg which has been generalized by Daley and McQuillan from a formal language theory perspective. In this paper, we propose a refinement of this model that generates regular languages using the iterated TGR system with a finite initial language and a finite set of templates, using fewer templates and a smaller alphabet compared to that of the Daley-McQuillan model. To achieve Turing completeness using only finite components, i.e., a finite initial language and a finite set of templates, we also propose an extension of the contextual template-guided recombination system (CTGR system) by Daley and McQuillan, by adding an extra control called permitting contexts on the usage of templates.Comment: In Proceedings DCFS 2010, arXiv:1008.127

Synthetic Biology: A Bridge between Artificial and Natural Cells.

Artificial cells are simple cell-like entities that possess certain properties of natural cells. In general, artificial cells are constructed using three parts: (1) biological membranes that serve as protective barriers, while allowing communication between the cells and the environment; (2) transcription and translation machinery that synthesize proteins based on genetic sequences; and (3) genetic modules that control the dynamics of the whole cell. Artificial cells are minimal and well-defined systems that can be more easily engineered and controlled when compared to natural cells. Artificial cells can be used as biomimetic systems to study and understand natural dynamics of cells with minimal interference from cellular complexity. However, there remain significant gaps between artificial and natural cells. How much information can we encode into artificial cells? What is the minimal number of factors that are necessary to achieve robust functioning of artificial cells? Can artificial cells communicate with their environments efficiently? Can artificial cells replicate, divide or even evolve? Here, we review synthetic biological methods that could shrink the gaps between artificial and natural cells. The closure of these gaps will lead to advancement in synthetic biology, cellular biology and biomedical applications

Query-Time Data Integration

Today, data is collected in ever increasing scale and variety, opening up enormous potential for new insights and data-centric products. However, in many cases the volume and heterogeneity of new data sources precludes up-front integration using traditional ETL processes and data warehouses. In some cases, it is even unclear if and in what context the collected data will be utilized. Therefore, there is a need for agile methods that defer the effort of integration until the usage context is established. This thesis introduces Query-Time Data Integration as an alternative concept to traditional up-front integration. It aims at enabling users to issue ad-hoc queries on their own data as if all potential other data sources were already integrated, without declaring specific sources and mappings to use. Automated data search and integration methods are then coupled directly with query processing on the available data. The ambiguity and uncertainty introduced through fully automated retrieval and mapping methods is compensated by answering those queries with ranked lists of alternative results. Each result is then based on different data sources or query interpretations, allowing users to pick the result most suitable to their information need. To this end, this thesis makes three main contributions. Firstly, we introduce a novel method for Top-k Entity Augmentation, which is able to construct a top-k list of consistent integration results from a large corpus of heterogeneous data sources. It improves on the state-of-the-art by producing a set of individually consistent, but mutually diverse, set of alternative solutions, while minimizing the number of data sources used. Secondly, based on this novel augmentation method, we introduce the DrillBeyond system, which is able to process Open World SQL queries, i.e., queries referencing arbitrary attributes not defined in the queried database. The original database is then augmented at query time with Web data sources providing those attributes. Its hybrid augmentation/relational query processing enables the use of ad-hoc data search and integration in data analysis queries, and improves both performance and quality when compared to using separate systems for the two tasks. Finally, we studied the management of large-scale dataset corpora such as data lakes or Open Data platforms, which are used as data sources for our augmentation methods. We introduce Publish-time Data Integration as a new technique for data curation systems managing such corpora, which aims at improving the individual reusability of datasets without requiring up-front global integration. This is achieved by automatically generating metadata and format recommendations, allowing publishers to enhance their datasets with minimal effort. Collectively, these three contributions are the foundation of a Query-time Data Integration architecture, that enables ad-hoc data search and integration queries over large heterogeneous dataset collections

Bottom-up construction of complex biomolecular systems with cell-free synthetic biology

Cell-free systems offer a promising approach to engineer biology since their open nature allows for well-controlled and characterized reaction conditions. In this review, we discuss the history and recent developments in engineering recombinant and crude extract systems, as well as breakthroughs in enabling technologies, that have facilitated increased throughput, compartmentalization, and spatial control of cell-free protein synthesis reactions. Combined with a deeper understanding of the cell-free systems themselves, these advances improve our ability to address a range of scientific questions. By mastering control of the cell-free platform, we will be in a position to construct increasingly complex biomolecular systems, and approach natural biological complexity in a bottom-up manner

Word Blending and Other Formal Models of Bio-operations

As part of ongoing efforts to view biological processes as computations, several formal models of DNA-based processes have been proposed and studied in the formal language literature. In this thesis, we survey some classical formal language word and language operations, as well as several bio-operations, and we propose a new operation inspired by a DNA recombination lab protocol known as Cross-pairing Polymerase Chain Reaction, or XPCR. More precisely, we define and study a word operation called word blending which models a special case of XPCR, where two words x w p and q w y sharing a non-empty overlap part w generate the word x w y. Properties of word blending that we study include closure properties of the Chomsky families of languages under this operation and its iterated version, existence of solution to equations involving this operation, and its state complexity

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

Model Organisms in Plant Genetics

Model plants are required for research when targeted plant species are difficult to study or when research material is unavailable. Importantly, knowledge gained from model plants can be generally translated to other related plant species because many key cellular and molecular processes are conserved and regulated by ‘blueprint’ genes inherited from a common ancestor. Model Organisms in Plant Genetics addresses characteristics of model plants such as Arabidopsis, moss, soybean, maize, and cotton, highlighting their advantages and limitations as well as their importance in studies of plant development, plant genome polyploidization, adaptive selection, evolution, and domestication, as well as their importance in crop improvement