Skip to content

OpenScientist deep-research batch: 10 open hypotheses (2026-07-06)

Provenance note for a batch of OpenScientist deep-research runs launched against ten genuinely open mechanistic hypotheses in the knowledge base. Outputs land under kb/hypotheses/<Disease>/<hypothesis_group_id>/openscientist.md (plus the .citations.md sidecar), produced by:

uv run python scripts/hypothesis_deep_research.py run openscientist <Disease> <hypothesis_group_id>

Selection method

The candidate pool was the 103 disease-level mechanistic_hypotheses that carried no existing OpenScientist run, enumerated with:

uv run python scripts/hypothesis_deep_research.py list --missing-provider openscientist

From that pool the batch deliberately favours hypotheses where the mechanism is still contested — ALTERNATIVE and EMERGING status entries, and competing origin models — because an adversarial multi-source synthesis adds the most value where the literature has not converged. Canonical, well-settled mechanisms were deprioritised. The ten span neurodegeneration, pulmonary fibrosis, post-viral illness, dysautonomia, psychiatry, reproductive endocrinology, immunology, and oncology so the batch is not concentrated in one subsystem.

The ten selected hypotheses

# Disease Hypothesis group Status Why it is worth investigating
1 Parkinson's Disease body_first_enteric_alpha_synuclein_model ALTERNATIVE The "body-first" (gut/vagal) vs "brain-first" origin debate is a live, high-stakes question in PD pathogenesis.
2 Parkinson's Disease brain_first_central_alpha_synuclein_model ALTERNATIVE Paired counterpart to #1; running both sides lets OpenScientist adjudicate the competing origin models.
3 Idiopathic Pulmonary Fibrosis senescence_first_model ALTERNATIVE Senescence-first vs injury-centric origin of fibrosis is unresolved and therapeutically consequential (senolytics).
4 Long COVID herpesvirus_reactivation_model EMERGING EBV/herpesvirus reactivation as a driver of post-acute sequelae is topical and genuinely open.
5 Postural Orthostatic Tachycardia Syndrome neuropathic_denervation_model ALTERNATIVE POTS has multiple competing subtype mechanisms; the neuropathic/autoimmune-denervation arm needs a rigorous evidence audit.
6 Schizophrenia complement_synaptic_pruning_hypothesis EMERGING C4/complement-mediated excess synaptic pruning is a major emerging hypothesis with mixed human evidence.
7 Alzheimer's Disease ev_mediated_tau_propagation_model EMERGING Extracellular-vesicle-mediated tau spread is an emerging propagation mechanism distinct from canonical trans-synaptic seeding.
8 Polycystic Ovary Syndrome neuroendocrine_lh_first_model ALTERNATIVE The neuroendocrine (GnRH/LH-first) vs insulin-first origin debate is central to PCOS pathophysiology.
9 IgG4-Related Disease innate_first_bystander_model ALTERNATIVE Whether IgG4-RD is innate-driven with IgG4 as a bystander, or antibody-driven, remains an open immunopathogenesis question.
10 Gorlin Syndrome gli_bypass_resistance_model EMERGING SMO-independent GLI activation as a Hedgehog-inhibitor resistance mechanism is an emerging precision-oncology question.

Verification discipline

OpenScientist is a deep-research provider and its outputs are leads, not ground truth (see the DR-verification and NEC sections of CLAUDE.md). Before any snippet, PMID, or ontology term from these reports is promoted into a kb/disorders/ or kb/modules/ entry, it must pass the standard anti-hallucination workflow: just fetch-reference for each PMID, snippet-substring verification against the cached abstract, and just validate-terms-file. This batch only generates the research; promotion into curated YAML is a separate, verified step.