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Record W4214486663 · doi:10.1021/acssynbio.1c00600

Design of Synthetic Mammalian Promoters Using Highly Palindromic Subsequences

2022· article· en· W4214486663 on OpenAlexafffund
Polina Govorkova, Chee Ka Candice Lam, Kevin Truong

Bibliographic record

VenueACS Synthetic Biology · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Interference and Gene Delivery
Canadian institutionsUniversity of Toronto
FundersInstitute of AgingNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsPromoterPalindromePalindromic sequenceEnhancerBiologyGeneGeneticsCRISPRComputational biologyGene expression

Abstract

fetched live from OpenAlex

To express transgenes in specific cell types and states, promoters for endogenous genes are commonly created by truncating the sequence upstream of the transcriptional start site until the promoter is no longer functional. In this paper, we developed a method to design shorter synthetic mammalian promoters for endogenous genes by concatenating only its highly palindromic subsequences with a minimal core promoter. After developing metrics for palindromic density, analysis across all the human and mouse promoters showed higher palindromic density than expected by random. As experimental demonstrations, we applied the method to the CMV promoter (reduced to 432 nucleotides) and the mouse synapsin-1 promoter (383 nucleotides) to express fluorescent protein as reporters. Remarkably, the highly palindromic subsequences of these synthetic promoters contained sites important for strong constitutive expression and neuron-specific expression. As a resource to the community, we created enhancer sequences for all the human and mouse promoters.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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: none
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
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 science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

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 head0.031
GPT teacher head0.263
Teacher spread0.231 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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

Citations1
Published2022
Admission routes2
Has abstractyes

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