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Record W4405178333 · doi:10.1021/jacsau.4c00890

Quantitative Characterization of Partitioning Stringency in SELEX

2024· article· en· W4405178333 on OpenAlex
An T. H. Le, Eden Teclemichael, Svetlana M. Krylova, Sergey N. Krylov

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueJACS Au · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAdvanced biosensing and bioanalysis techniques
Canadian institutionsYork University
FundersNatural Sciences and Engineering Research Council of CanadaYork University
KeywordsSystematic evolution of ligands by exponential enrichmentAptamerSelection (genetic algorithm)BiologyComputer scienceGeneticsArtificial intelligenceRNA

Abstract

fetched live from OpenAlex

Maintaining stringent conditions in SELEX (Systematic Evolution of Ligands by EXponential enrichment) is crucial for obtaining high-affinity aptamers. However, excessive stringency greatly increases the risk of SELEX failure. Controlling stringency has remained a technical challenge, largely dependent on intuition, due to the absence of a clear, quantitative measure of stringency. This study was motivated by our insight that, while stringency is influenced by multiple factors, it can be quantified by its effect: increasing stringency reduces the quantity of binders normalized to that of nonbinders after partitioning. Based on this insight, we propose measuring stringency using the binder-to-nonbinder ratio (BNR), where a lower BNR indicates higher stringency. We derive an experimental method for determining BNR via quantitative PCR. Our theoretical analysis and SELEX experiments using two distinct proteins as selection targets underscore the importance of maintaining a BNR significantly greater than zero to avoid failure, a principle we call the SELEX nonfailure criterion. By employing inverse BNR to quantify stringency and applying this criterion, researchers can more rationally control SELEX progress. The quantitative stringency measure and nonfailure criterion can also be applied to other artificial evolution methods, provided that selected binders are quantifiable.

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.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.191

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 head0.014
GPT teacher head0.302
Teacher spread0.288 · 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