Inhibiting angiopoietin-like protein 3: clear skies or clouds on the horizon?
Bibliographic record
Abstract
Angiopoietin-like protein 3 (ANGPTL3) is encoded by the ANGPTL3 gene which lies within an intron of the much larger DOCK7 gene on the short arm of chromosome (Chr) 1. Expression in highest in the liver, where the 7 exons of the gene are transcribed into messenger ribonucleic acid (mRNA) transcripts, yielding a mature protein of 460 amino acids that circulates in plasma. Several pharmaceutical agents inhibit ANGPTL3 production or block its activity at various stages, including genome editing with VERVE-201, RNA interference by the allele specific oligonucleotide (ASO) vupanorsen and small interfering RNA (siRNA) zodasiran, and binding to protein epitopes in plasma by the monoclonal antibody evinacumab. These drugs have been variably given to a non-human primate (NHP) model of familial hypercholesterolemia (FH), and to patients with combined hyperlipidemia (HLP), homozygous familial hypercholesterolemia (HoFH), familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS). Impact of these treatments on plasma concentrations of ANGPTL3, low-density lipoprotein cholesterol (LDL-C) and triglycerides are shown. ND means not determined in the clinical trial
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.017 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.005 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.008 | 0.011 |
| Insufficient payload (model declined to judge) | 0.015 | 0.010 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".