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Codon optimization: a mathematical programing approach

2020· article· en· W3016851473 on OpenAlexaff
Alper Şen, Kamyar Kargar, Esma Akgün, Mustafa Ç. Pı̆nar

Bibliographic record

VenueBioinformatics · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA and protein synthesis mechanisms
Canadian institutionsUniversity of Waterloo
Fundersnot available
KeywordsCodon usage biasHeuristicsComputer scienceGenetic codeSolverMathematical optimizationComputational biologyMathematicsBiologyGeneticsAmino acidProgramming languageGeneGenome

Abstract

fetched live from OpenAlex

MOTIVATION: Synthesizing proteins in heterologous hosts is an important tool in biotechnology. However, the genetic code is degenerate and the codon usage is biased in many organisms. Synonymous codon changes that are customized for each host organism may have a significant effect on the level of protein expression. This effect can be measured by using metrics, such as codon adaptation index, codon pair bias, relative codon bias and relative codon pair bias. Codon optimization is designing codons that improve one or more of these objectives. Currently available algorithms and software solutions either rely on heuristics without providing optimality guarantees or are very rigid in modeling different objective functions and restrictions. RESULTS: We develop an effective mixed integer linear programing (MILP) formulation, which considers multiple objectives. Our numerical study shows that this formulation can be effectively used to generate (Pareto) optimal codon designs even for very long amino acid sequences using a standard commercial solver. We also show that one can obtain designs in the efficient frontier in reasonable solution times and incorporate other complex objectives, such as mRNA secondary structures in codon design using MILP formulations. AVAILABILITY AND IMPLEMENTATION: http://alpersen.bilkent.edu.tr/codonoptimization/CodonOptimization.zip.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.711
Threshold uncertainty score0.417

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.022
GPT teacher head0.230
Teacher spread0.208 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreMethods

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations76
Published2020
Admission routes1
Has abstractyes

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