Supervised Theses

Abstract:

After years of research there are still many open questions on the topic of genetic code evolution. It is unclear how the code could evolve in the first place and how it could evolve as fast as it has, how its universality and ambiguity evolved and why it is not perfect in more than one aspect. Current research focuses on various aspects of genetic code evolution as for example coevolution, tRNA driven evolution, the first coding codons and coded amino acids and many more but the influence of aaRSs (aminoacyl-tRNA-synthetases) is none of the focal points.

It can be assumed that the first genetic code didn’t have the high structure of today’s code but a more random structure. A random structure means that today’s stable aaRS feedback loop hasn’t been stable in early evolution. The given aaRSs didn’t support their own reproduction but the production of other kinds of aaRSs. This behaviour is founded in an ambiguous genetic code and it is unclear how ambiguity and therefore a stable feedback cycle evolved. In this thesis it is assumed that the aaRS feedback loop was an important driver of genetic code evolution.

This thesis provides an analysis of the aaRS feedback cycle. It is applied on randomly generated genetic codes and the influence of various start conditions is observed. The process is defined mathematically and simulated with a computer simulation. The results of the simulation are analysed with the classification algorithm J48 and with sta- tistical tests to form new hypotheses that can be further explored.

Abstract:
In a collaboration with the Medical Faculty Mannheim of the University of Heidelberg and the KIT we work on image analysis as a means to control the quality of stored red blood cells. Recent result is a Master Thesis by Clemens Böcker, Hochschule Mannheim (2018): Flow Cytomorphometry for assessment of Red Blood Cells. In an ongoing collaboration with several internal and external partners, we work on image analysis of production process relevant animal cells (see e.g. www.imz.hs-mannheim.de/institute/research/prof-wiedemann.html). Momentarily, we focus on NS0 cells.

Abstract:
The Standard Genetic Code (SGC) is of immense importance. It enables the translation of DNA and thus genetic information. The DNA consists of a strand of bases. Three of them form a triplet. The SGC assigns exactly one amino acid to such a triplet. Chained together, amino acids form then proteins. In total, there are 20 different amino acids and 64 triplets. Theoretically, other assignments would also be possible. From the point of view of evolution, the SGC should be the best option. So he should also be particularly robust against point mutations. From this point of view, this work examines the development or emergence of the genetic code. For this purpose, a corresponding model was developed and implemented in the form of a simulator.

Abstract:
So-called maximal self-complementary circular codes are a set of 20 trinucleotides that can recognize frameshifts in DNA. There are 216 of these maximal self-complementary circular codes. Out of these 216 is one circular code X0 that  has been found to be overrepresented in healthy tissues with many analyses in the past. In this work, this code usage is considered under the weighting with gene expressions and coding sequence lengths of genes in normal tissues and  additionally in carcinogenic tissues to find out how often in tissues the coding sequences with X0 are used and how large the parts of the coding sequences are that make them. It turns out that the code usage of X0 in normal sequences remains high despite the weighting, whereas in carcinogenic sequences it is partly low and partly high. The error-correcting property of X0 is confirmed with these results, nevertheless they also raise new questions.

Abstract:

A variety of algorithms is used to compress sequenced DNA. New findings in the patterns of how the building blocks of DNA are distributed, might provide a chance to improve long used compression algorithms. The comparison of four widely used compression methods and an analysis on their implemented algorithms, leads to the conclusion that improvements are feasible. The closing discussion provides insights, to possible optimization approaches and which challenges they  might involve.

Abstract:
The search for an explanation of the origin of life is one of the oldest and most popular topics in molecular biology. However, there is still no accepted theory on the evolutionary beginnings. One possible approach to study the early evolutionary genetic code is the closer study of RNA, which plays a role in basic cellular mechanisms. The most successful structures are small, circular RNA rings. The main goal of the work is to calculate minimal RNA rings from an evolutionary subset of the 20 known amino acids. From the available theories, the sets of Jiménez-Montaño (1999) and Di Giulio (2008) were selected for consideration in this work. For both sets, minimal rings could be successfully calculated. The circularity of the minimal rings was on average 96.17% and the ring lengths were 10 and 11 nucleotides. The set of amino acids according to the theory of Jiménez-Montaño was the more successful, regardless of the translation table used (standard code and mitochondrial, vertebrate code). The calculation of a larger number of random sets of the same ring sizes and the extension of the sets from other theories is recommended for future considerations.

Abstract:
Circular codes had been discovered in a biological setting by a statistical investigation on the distribution of codons from the genetic code in large data of coding sequences. They are assumed to play an important role in maintaining the correct reading frame during the translational process in the ribosome. A stronger version - the so-called comma-free codes - had been intensively studied before over finite alphabets as part of coding theory. In this thesis we aim to construct circular codes over finite alphabets by generalizing a recently devoped algorithmic approach for the genetic code setting. The algorithm is based on so-called shape sets that yield circular codes when combined in the correct way.

Abstract:
Circular Codes offer a possible solution to explain the high error tolerance of the genetic code. By using circular codes a frame shift can be detected within two to three codons. Therefore a continuous sequence of circular code codons, a so called motif, is essential. The ancient genetic code is believed to consist only of codons from circular codes. To test this theory, a selection of coding sequences was mutated based on 216 self-complementary C 3 codes. The aim was to restore the ancient sequence, considering conditions for a biologically realistic substitution. Sequences with a code usage of up to 84.32 % could be generated. In two sequences the average length of the motifs could be increased by a total of 25.32% compared to the expected value. However, the best results were achieved outside of the original reading frame. Therefore a further tracking of shifted sequences is suggested.

Abstract:
Splicing is a topic that more and more people are paying attention to. The issue is particularly important because  advances in the understanding of the splicing process can lead to a breakthrough in some medical areas such as cancer research. The aim of this Bachelor thesis is to investigate whether a suitable computer model for RNA splicing can be found.  In particular, the following question is addressed: What factors influence RNA splicing and which splicing errors are caused by it?

Abstract:
The genetic code has many facettes and one of the most ineteresting is its assignment between codons and amino acids that shows a unique redundancy. In this thesis the Fibonacci numbers will be studied and how they can be used in non-power models to describe such redunancy of ancient genetic codes and variants of the present code.

Abstract:

Proximity queries and penetration depth calculation of non-convex meshes is still a computationally expensive task. However this is required for real-time surgical simulations. In this thesis is selected an algorithm for calculating proximity queries as well as penetration depth for convex meshes and extended to non-convex meshes. This algorithm was implemented, integrated in a commercial collision-detection library, and examined in its real-time capability. The algorithm is based on the assumption that there exists a specific decomposition for all non-convex meshes into convex meshes at runtime. The specific requirements for this decomposition that guarantee a successful application of the algorithm are discussed and shown both intuitive and practical. This opens the possibility to construct the decomposition with moderate effort. To achieve the objective the Gilbert-Johnson-Keerthi-Algorithm for proximity queries and the Expanding-Polytope-Algorithm for penetration depths were implemented and modified accordingly. A speed analysis shows the real-time capability of the developed algorithm.

Abstract:

DNA contains genetic information that is passed on in every living being. It consists of a sequence of 4 bases: adenine (A), cytosine (C), guanine (G) and thymine (T). Chargaffs parity rules state that the amount of A is roughly equal to the amount of T and the amount of G is roughly equal to the amount of C even in a single DNA strand. This rule was analyzed by Mascher et al. in so called mononucleotide skews. The skew gives a concrete value for how precise Chargaffs second rule is applied in a single sequence. Petoukhov observed
further symmetries in he named tetra group symmetries.

A DNA sequence (for example, TAACCCTAACG...) can be represented in the following forms: as a text of 1-letter words (T-A-A-C-C-C-T-A-A-C-...); as a text of 2-letter words (TA-AC-CC-TA-AC-...);

The analysis of Petoukhov showed that the frequencies of every base in a 1-letter word is the same frequency as the base in each position of 2-letter words and 3-letter word, up to 5-letter words. For this thesis, five different species were analyzed, observing the skews and tetra group symmetries in those species. Another question was, whether these symmetries could be observed when comparing different parts of the DNA. To verify the significance, random models were analyzed and used as a comparative measure. Petoukhovs methods were additionally tested and applied to larger tuple sizes. The symmetries stated by Petoukhov could be confirmed for tuple sizes up to 50. When analyzing random sequences in the same manner as the chromosomes, a similar behavior was observed. These results, however, require  further biological analyses.