Identification and analysis of patterns in DNA sequences, the genetic code and transcriptional gene regulation

The present cumulative work consists of six articles linked by the topic ”Identification and Analysis of Patterns in DNA sequences, the Genetic Code and Transcriptional Gene Regulation”. We have applied a binary coding, to efficiently findpatterns within nucleotide sequences. In the first and second part of my work one single bit to encode all four nucleotides is used. The three possibilities of a one - bit coding are: keto (G,U) - amino (A,C) bases, strong (G,C) - weak (A,U) bases, and purines (G,A) - pyrimidines (C,U). We found out that the best pattern could be observed using the purine - pyrimidine coding. Applying this coding we have succeeded in finding a new representation of the genetic code which has been published under the title ”A New Classification Scheme of the Genetic Code” in ”Journal of Molecular Biology” and ”A Purine-Pyrimidine Classification Scheme of the Genetic Code” in ”BIOForum Europe”. This new representation enables to reduce the common table of the genetic code from 64 to 32 fields maintaining the same information content. It turned out that all known and even new patterns of the genetic code can easily be recognized in this new scheme. Furthermore, our new representation allows us for speculations about the origin and evolution of the translation machinery and the genetic code. Thus, we found a possible explanation for the contemporary codon - amino acid assignment and wide support for an early doublet code. Those explanations have been published in ”Journal of Bioinformatics and Computational Biology” under the title ”The New Classification Scheme of the Genetic Code, its Early Evolution, and tRNA Usage”. Assuming to find these purine - pyrimidine patterns at the DNA level itself, we examined DNA binding sites for the occurrence of binary patterns. A comprehensive statistic about the largest class of restriction enzymes (type II) has shown a very distinctive purine - pyrimidine pattern. Moreover, we have observed a higher G+C content for the protein binding sequences. For both observations we have provided and discussed several explanations published under the title ”Common Patterns in Type II Restriction Enzyme Binding Sites” in ”Nucleic Acid Research”. The identified patterns may help to understand how a protein finds its binding site. In the last part of my work two submitted articles about the analysis of Boolean functions are presented. Boolean functions are used for the description and analysis of complex dynamic processes and make it easier to find binary patterns within biochemical interaction networks. It is well known that not all functions are necessary to describe biologically relevant gene interaction networks. In the article entitled ”Boolean Networks with Biologically Relevant Rules Show Ordered Behavior”, submitted to ”BioSystems”, we have shown, that the class of required Boolean functions can strongly be restricted. Furthermore, we calculated the exact number of hierarchically canalizing functions which are known to be biologically relevant. In our work ”The Decomposition Tree for Analysis of Boolean Functions” submitted to ”Journal of Complexity”, we introduced an efficient data structure for the classification and analysis of Boolean functions. This permits the recognition of biologically relevant Boolean functions in polynomial time

DECIPHERING CELL SIGNALING REWIRING IN HUMAN DISORDERS

The knowledge of cell molecular mechanisms implicated in human diseases is expanding and should be converted into guidelines for deciphering pathological cell signaling and suggesting appropriate treatment. The basic assumption is that during a pathological transformation, the cell does not create new signaling mechanisms, but rather it hijacks the existing molecular programs. This affects not only intracellular functions, but also a crosstalk between different cell types resulting in a new, yet pathological status of the system. There is a certain combination of molecular characteristics dictating specific cell signaling states that sustains the pathological disease status. Identifying and manipulating the key molecular players controlling these cell signaling states, and shifting the pathological status toward the desired healthy phenotype, are the major challenge for molecular biology of human diseases

Design and Analysis of Optical Interconnection Networks for Parallel Computation.

In this doctoral research, we propose several novel protocols and topologies for the interconnection of massively parallel processors. These new technologies achieve considerable improvements in system performance and structure simplicity. Currently, synchronous protocols are used in optical TDM buses. The major disadvantage of a synchronous protocol is the waste of packet slots. To offset this inherent drawback of synchronous TDM, a pipelined asynchronous TDM optical bus is proposed. The simulation results show that the performance of the proposed bus is significantly better than that of known pipelined synchronous TDM optical buses. Practically, the computation power of the plain TDM protocol is limited. Various extensions must be added to the system. In this research, a new pipelined optical TDM bus for implementing a linear array parallel computer architecture is proposed. The switches on the receiving segment of the bus can be dynamically controlled, which make the system highly reconfigurable. To build large and scalable systems, we need new network architectures that are suitable for optical interconnections. A new kind of reconfigurable bus called segmented bus is introduced to achieve reduced structure simplicity and increased concurrency. We show that parallel architectures based on segmented buses are versatile by showing that it can simulate parallel communication patterns supported by a wide variety of networks with small slowdown factors. New kinds of interconnection networks, the hypernetworks, have been proposed recently. Compared with point-to-point networks, they allow for increased resource-sharing and communication bandwidth utilization, and they are especially suitable for optical interconnects. One way to derive a hypernetwork is by finding the dual of a point-to-point network. Hypercube Q\sb{n}, where n is the dimension, is a very popular point-to-point network. It is interesting to construct hypernetworks from the dual Q\sbsp{n}{*} of hypercube of Q\sb{n}. In this research, the properties of Q\sbsp{n}{*} are investigated and a set of fundamental data communication algorithms for Q\sbsp{n}{*} are presented. The results indicate that the Q\sbsp{n}{*} hypernetwork is a useful and promising interconnection structure for high-performance parallel and distributed computing systems