Version history

{
  "description": "Analyze circuit-level changes in neurodegeneration using Allen Institute Neural Dynamics data. Focus on: (1) hippocampal circuit disruption, (2) cortical dynamics alterations, (3) sensory processing changes. Identify circuit-based therapeutic targets connecting genes, proteins, and brain regions to neurodegeneration phenotypes.",
  "domain": "neuroscience",
  "status": "partially_addressed",
  "priority_score": 0.95,
  "importance_score": 0.88,
  "tractability_score": 0.75,
  "novelty_score": 0.7,
  "composite_score": 0.6951,
  "estimated_effort": "high",
  "source": "human_submitted",
  "evidence_summary": "{\"hypothesis_matches\": [{\"id\": \"h-a87702b6\", \"title\": \"Cholesterol-CRISPR Convergence Therapy for Neurodegeneration\", \"target_gene\": \"HMGCR, LDLR, APOE regulatory regions\", \"target_pathway\": \"Brain cholesterol homeostasis (HMGCR synthesis \\u2192 CYP46A1 elimination)\", \"match_score\": 0.37, \"composite_score\": 0.5150203412333288, \"status\": \"proposed\"}, {\"id\": \"h-63b7bacd\", \"title\": \"Context-Dependent CRISPR Activation in Specific Neuronal Subtypes\", \"target_gene\": \"Cell-type-specific essential genes\", \"target_pathway\": \"CRISPRa transcriptional activation of neuronal identity genes\", \"match_score\": 0.3, \"composite_score\": 0.5390100892037201, \"status\": \"proposed\"}, {\"id\": \"h-856feb98\", \"title\": \"Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservation\", \"target_gene\": \"BDNF\", \"target_pathway\": \"Hippocampal neurogenesis and synaptic plasticity\", \"match_score\": 0.24, \"composite_score\": 0.7031497659630912, \"status\": \"proposed\"}, {\"id\": \"h-29ef94d5\", \"title\": \"Epigenetic Memory Reprogramming for Alzheimer's Disease\", \"target_gene\": \"BDNF, CREB1, synaptic plasticity genes\", \"target_pathway\": \"CREB/BDNF epigenetic regulation of synaptic plasticity\", \"match_score\": 0.2, \"composite_score\": 0.49103059326293774, \"status\": \"proposed\"}, {\"id\": \"h-827a821b\", \"title\": \"Metabolic Reprogramming via Coordinated Multi-Gene CRISPR Circuits\", \"target_gene\": \"PGC1A, SIRT1, FOXO3, mitochondrial biogenesis genes\", \"target_pathway\": \"PGC1\\u03b1/SIRT1/FOXO3 mitochondrial biogenesis network\", \"match_score\": 0.2, \"composite_score\": 0.4750374279493436, \"status\": \"proposed\"}, {\"id\": \"h-03e31e80\", \"title\": \"DAMP-Scavenging Microglial Reset\", \"target_gene\": \"HMGB1, S100 proteins\", \"target_pathway\": null, \"match_score\": 0.2, \"composite_score\": 0.4622222222222222, \"status\": \"proposed\"}, {\"id\": \"h-e23f05fb\", \"title\": \"Multi-Modal CRISPR Platform for Simultaneous Editing and Monitoring\", \"target_gene\": \"Disease-causing mutations with integrated reporters\", \"target_pathway\": \"Multiplexed CRISPR editing with integrated fluorescent reporters\", \"match_score\": 0.2, \"composite_score\": 0.4470493886505538, \"status\": \"proposed\"}, {\"id\": \"h-495454ef\", \"title\": \"Synthetic Biology Approach: Designer Mitochondrial Export Systems\", \"target_gene\": \"Synthetic fusion proteins\", \"target_pathway\": \"Synthetic biology mitochondrial export / organelle transplantation\", \"match_score\": 0.2, \"composite_score\": 0.3561780962214035, \"status\": \"proposed\"}], \"total_matching_hypotheses\": 8, \"gap_tokens_sample\": [\"allen\", \"alterations\", \"analyze\", \"brain\", \"changes\", \"circuit\", \"circuit-based\", \"circuit-level\", \"connecting\", \"cortical\", \"disruption\", \"dynamics\", \"focus\", \"genes\", \"hippocampal\"], \"updated_at\": \"2026-04-06T08:21:05.795601+00:00\"}",
  "resolution_criteria": "Resolved when: a circuit-level analysis links hippocampal, cortical, or sensory-processing dynamics from Allen Institute Neural Dynamics data to specific neurodegeneration phenotypes, reports quantitative effect sizes or model-performance metrics, cites the dataset version, and adds KG edges connecting affected circuits, brain regions, genes/proteins, and therapeutic targets, followed by a SciDEX debate or scored hypothesis evaluating causal plausibility.",
  "market_price": 0.5
}