Whole-organism phenotypic screening methods used in early-phase anthelmintic drug discovery
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.
Bibliographic record
Abstract
Diseases caused by parasitic helminths (worms) represent a major global health burden in both humans and animals. As vaccines against helminths have yet to achieve a prominent role in worm control, anthelmintics are the primary tool to limit production losses and disease due to helminth infections in both human and veterinary medicine. However, the excessive and often uncontrolled use of these drugs has led to widespread anthelmintic resistance in these worms - particularly of animals - to almost all commercially available anthelmintics, severely compromising control. Thus, there is a major demand for the discovery and development of new classes of anthelmintics. A key component of the discovery process is screening libraries of compounds for anthelmintic activity. Given the need for, and major interest by the pharmaceutical industry in, novel anthelmintics, we considered it both timely and appropriate to re-examine screening methods used for anthelmintic discovery. Thus, we reviewed current literature (1977–2021) on whole-worm phenotypic screening assays developed and used in academic laboratories, with a particular focus on those employed to discover nematocides. This review reveals that at least 50 distinct phenotypic assays with low-, medium- or high-throughput capacity were developed over this period, with more recently developed methods being quantitative, semi-automated and higher throughput. The main features assessed or measured in these assays include worm motility, growth/development, morphological changes, viability/lethality, pharyngeal pumping, egg hatching, larval migration, CO2- or ATP-production and/or enzyme activity. Recent progress in assay development has led to the routine application of practical, cost-effective, medium- to high-throughput whole-worm screening assays in academic or public-private partnership (PPP) contexts, and major potential for novel high-content, high-throughput platforms in the near future. Complementing this progress are major advances in the molecular data sciences, computational biology and informatics, which are likely to further enable and accelerate anthelmintic drug discovery and development.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it