Browsing by Subject "Codon optimization"
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Item Open Access Codon optimization by 0-1 linear programming(Elsevier, 2020-02) Arbib, C.; Pınar, Mustafa Ç.; Rossi, F.; Tessitore, A.The problem of choosing an optimal codon sequence arises when synthetic protein-coding genes are added to cloning vectors for expression within a non-native host organism: to maximize yield, the chosen codons should have a high frequency in the host genome, but particular nucleotide bases sequences (called “motifs”) should be avoided or, instead, included. Dynamic programming (DP) has successfully been used in previous approaches to this problem. However, DP has a computational limit, especially when long motifs are forbidden, and does not allow control of motif positioning and combination. We reformulate the problem as an integer linear program (IP) and show that, with the same computational resources, one can easily solve problems with much more nucleotide bases and much longer forbidden/desired motifs than with DP. Moreover, IP (i) offers more flexibility than DP to treat constraints/objectives of different nature, and (ii) can efficiently deal with newly discovered critical motifs by dynamically re-optimizing additional variables and mathematical constraints.Item Open Access SOX2 in focus: association of SOX2 copy number variation with TP53 mutation in TCGA pancancer cohorts and codon optimized design for de novo SOX2 synthesis using novel shiny application(Bilkent University, 2024-01) Çelik, Siber GüneşRecombinant proteins are crucial for diverse research applications such as biosensors and cancer studies. Proteins are engineered through de novo gene synthesis methods. Numerous tools and databases have emerged to facilitate the design of recombinant proteins, starting from the design of the gene sequence. De novo DNA synthesis enables the synthesis of custom-designed sequences, allowing codon optimization to enhance expression yield in heterologous systems. In cancer research, recombinant expression of proteins involved in tumorigenesis-related signaling pathways is employed for functional studies, potentially revealing new therapeutic targets. A notable example is the pivotal role of SOX2 expression in the formation of cancer stem cells (CSCs) across various cancer types. Previous studies highlight SOX2 expression functionally overlaps with TP53 expression on the PI3K/AKT signaling pathway. This association may stem from the p53-MDM2 interaction. This thesis investigates the association between SOX2 copy number gain and TP53 mutations within TCGA PanCancer cohorts. Fisher’s exact test results reveal varying association, dependent on tissue type and specific driver mutations within each cancer type. The findings suggest the potential therapeutic relevance of SOX2 in cancer research. Furthermore, the thesis employs an in-silico approach to design de novo SOX2 synthesis, utilizing a novel shiny app that integrates codon optimization and primer design functionalities. The app enables simultaneous codon optimization for multiple expression systems and offers distance analysis through hierarchical clustering. Codon optimization feature provides control over the rate of replacement value for codon substitution which validated through a case study involving human insulin. Finally, app design set of overlapping primers with synchronized melting temperature to be used in PCR assembly for de novo SOX2 gene synthesis.