Browsing by Author "Mladen A. Vouk, Committee Co-Chair"

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    Analysis of Genetic Translation using Signal Processing
    (2008-02-15) Ponnala, Lalit; Donald L. Bitzer, Committee Co-Chair; Winser E. Alexander, Committee Member; Mladen A. Vouk, Committee Co-Chair; Anne-Marie Stomp, Committee Co-Chair; Tiffany M. Barnes, Committee Member; Jeffrey L. Thorne, Committee Member
    A series of free energy estimates can be calculated from the ribosome's progressive interaction with mRNA sequences during the process of translation elongation in eubacteria. A sinusoidal pattern of roughly constant phase has been detected in these free energy signals. Frameshifts of the +1 type occur when the ribosome skips an mRNA base in the 5'-3' direction, and can be associated with local phase-shifts in the free energy signal. We propose a mathematical model that captures the mechanism of frameshift based on the information content of the signal parameters and the relative abundance of tRNA in the bacterial cell. The model shows how translational speed can modulate translational accuracy to accomplish programmed +1 frameshifts and could have implications for the regulation of translational efficiency. Results are presented using experimentally verified frameshift genes across eubacteria.
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    The Role of Free Energy Synchronization Signal in Translation of Prokaryotes
    (2004-05-19) Mishra, Madhup; Donald L. Bitzer, Committee Chair; Mladen A. Vouk, Committee Co-Chair; Steffen Heber, Committee Member
    Sequences upstream of the coding region in prokaryotes show a consensus sequence called the Shine Dalgarno sequence. This sequence is the Watson-Crick complement to the 3' tail of 16S ribosomal RNA. Rosnick analyzed the ensemble free energy scores between the 3' tail-end of the RNA and the underlying mRNA. He found that the affinity between the tail-end and the mRNA is not just restricted to the upstream Shine Dalgarno region (SD region), but also extends downstream throughout the length of the gene. He confirmed the SD region as the lock signal and found an ensemble periodic free energy signal called the synchronization signal in the downstream region with a harmonic that peaks every third nucleotide with respect to the start codon. The periodic signal is hypothesized to either have a role in keeping the ribosome in frame with the mRNA being translated, or being a good predictive indicator of that state. The current work: •Studies the hypothesis that the lock and the periodic signal seen in the ensemble of the species coding regions extends beyond just E.coli. Specifically the work is concerned with analysis of sample of species across bacteria and archae kingdoms of the prokaryotes. The analysis shows that the periodic signal is present in the coding regions but not in the non-coding regions and that in some cases a lock signal is not present. This work proposes an Exponential Binding Index Locking Model to account for the genes with no upstream lock signal. •Proposes a novel methodology for analysis of the synchronization signal over individual genes. The approach leverages the ensemble periodicity information through sinusoidal wave interpolation with frequency of 1/3rd to approximate the synchronization signal and study its magnitude and phase characteristics. The synchronization signal is seen as a good indicator of the process of translation as suggested by our investigations. The starting phase of the signal is dependent on the frame in which the Shine Dalgarno lock, where present happens upstream of start. An application of individual synchronization signal is identification of frameshifts in general in genes.The +1 programmed frameshifting gene prfB of E.Coli K12 was used as a case study to demonstrate this application.
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    Verifying Commitment Based Business Protocols and their Compositions: Model Checking using Promela and Spin
    (2006-08-22) Cheng, Zhengang; Laurie Williams, Committee Member; Peter R. Wurman, Committee Member; Munindar P. Singh, Committee Co-Chair; Mladen A. Vouk, Committee Co-Chair
    A protocol-oriented approach of modeling and enacting business processes and workflows has been developed recently that offers advantages in terms of supporting the autonomy and heterogeneity of business partners and the reconfigurability of their process. Importantly, protocols are described using commitments, map to the individual computation of the participating roles, and can be composed to yield more complex protocols. However, verifying that the protocols, especially composed protocols, fully satisfy appropriate correctness properties remains an open problem. This dissertation presents a novel way to model business protocols in terms of commitments involved and the constraints for protocol composition. The correct composition of a business process can be expressed via individual protocol definitions and their composition constraints,thereby enabling the verification of large processes. Importantly, as part of the verification process, protocols are translated into the language Promela, which makes them amenable to analysis and verification using the model checker Spin. As a result many important properties of business protocols and their compositions into partial and full workflows can be verified, and improved protocols can be produced. The contribution of this dissertation is in providing a generalized mechanism for modeling commitments, formulating and verifying properties related to commitments. In fact, the results are applicable to a wide range of processes and related protocols, such as scientific discovery processes and workflows.