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Optimizacija rabe kodonov sintetičnih genov za izražanje v E. coli s strojnim učenjem
ID Špendl, Martin (Author), ID Gunčar, Gregor (Mentor) More about this mentor... This link opens in a new window

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Abstract
Diplomsko delo je usmerjeno v razvoj algoritma za načrtovanje nukleotidnega zaporedja genov za izražanje v E. coli. Dosedanja metoda za optimizacijo rabe kodonov temelji na rabi posameznih kodonov skozi celoten genom. Ta način optimizacije ne upošteva časa translacije in njegove povezave z zvijanjem proteina ter zanemari pogostost transkriptov v celici. Avtorji smo ustvarili algoritem za načrtovanje optimiziranega zaporedja kodonov proteina iz aminokislinskega zaporedja. Algoritem temelji na povezavi med zaporedjem kodonov in časom translacije, ki ga napoveduje nevronska mreža z dolgim kratkoročnim spominom. Čas translacije proteina je izračunan kot lokalno povprečje časov translacije posameznih kodonov. Pretvorba časa translacije proteina v zaporedje kodonov poteka s prileganjem časa translacije različnih kombinacij kodonov. Napoved algoritma je primerljiva z dosedanjo metodo optimizacije kodonov. Primerjava časov translacije je pokazala odstopanja, ki predstavljajo predvsem odseke proteinov s povišanim časom translacije. Optimizacija kodonov na teh odsekih je pomembna za izkoristek pri sintezi sintetičnih proteinov, saj čas translacije vpliva na zvijanje proteinov.

Language:Slovenian
Keywords:optimizacija rabe kodonov, čas translacije, strojno učenje, nevronska mreža, LSTM
Work type:Bachelor thesis/paper
Typology:2.11 - Undergraduate Thesis
Organization:FKKT - Faculty of Chemistry and Chemical Technology
Year:2020
PID:20.500.12556/RUL-119536 This link opens in a new window
COBISS.SI-ID:28322819 This link opens in a new window
Publication date in RUL:09.09.2020
Views:1786
Downloads:195
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Secondary language

Language:English
Title:Machine learning codon usage optimisation of synthetic genes for E. coli expression
Abstract:
Bachelor's thesis is aiming at developing an algorithm for designing nucleotide sequences of genes for expression in E. coli. The current method for codon usage optimization is based on codon usage of each codon throughout the whole genome. However, this optimization procedure does not account for translation time and it's relation to protein folding while disregarding the frequency of transcripts in a single cell. The authors built an algorithm for designing an optimized codon sequence of a protein from an amino acid sequence. The algorithm is based on the connection between codon sequence and translation time, which is predicted by a long short-term memory neural network. The translation time of a protein is calculated as a local average of translation times of individual codons. Translation time is converted into a codon sequence as the best fit of the translation time of different combinations of codons. The model prediction is comparable to the current method of codon optimization. The comparison of translation times indicates there are sections of proteins with higher translation time. Codon optimization in those sections is important for yield in the synthesis of proteins because translation time affects protein folding.

Keywords:ccodon usage optimization, translation time, machine learning, artificial neural network, LSTM

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