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Record W3162881235 · doi:10.1093/protein/gzab012

High-efficacy, high-manufacturability human VH domain antibody therapeutics from transgenic sources

2021· review· en· W3162881235 on OpenAlex

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

VenueProtein Engineering Design and Selection · 2021
Typereview
Languageen
FieldMedicine
TopicMonoclonal and Polyclonal Antibodies Research
Canadian institutionsUniversity of OttawaNational Research Council Canada
FundersNational Research Council Canada
KeywordsImmunogenicityAntibodyComputational biologyPhage displayDrug discoveryChemistrySingle-domain antibodyHeavy chainRecombinant DNACombinatorial chemistryBiochemistryBiologyGeneticsGene

Abstract

fetched live from OpenAlex

Interest in single-domain antibodies (sdAbs) stems from their unique structural/pronounced, hence therapeutically desirable, features. From the outset-as therapeutic modalities-human antibody heavy chain variable domains (VHs) attracted a particular attention compared with 'naturally-occurring' camelid and shark heavy-chain-only antibody variable domains (VHHs and VNARs, respectively) due to their perceived lack of immunogenicity. However, they have not quite lived up to their initial promise as the VH hits, primarily mined from synthetic VH phage display libraries, have too often been plagued with aggregation tendencies, low solubility and low affinity. Largely unexplored, synthetic camelized human VH display libraries appeared to have remediated the aggregation problem, but the low affinity of the VH hits still persisted, requiring undertaking additional, laborious affinity maturation steps to render VHs therapeutically feasible. A wholesome resolution has recently emerged with the development of non-canonical transgenic rodent antibody discovery platforms that appear to facilely and profusely generate high affinity, high solubility and aggregation-resistant human VHs.

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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.970
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.055
GPT teacher head0.340
Teacher spread0.285 · 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