Version history

{
  "description": "Investigate mechanisms of epigenetic reprogramming in aging neurons, including DNA methylation changes, histone modification dynamics, chromatin remodeling, and partial reprogramming approaches (e.g., Yamanaka factors) to reverse age-related epigenetic alterations in post-mitotic neurons.",
  "domain": "neurodegeneration",
  "status": "partially_addressed",
  "priority_score": 0.85,
  "importance_score": 0.88,
  "tractability_score": 0.72,
  "novelty_score": 0.82,
  "composite_score": 0.7059,
  "source": "orchestra_task",
  "evidence_summary": "{\"hypothesis_matches\": [{\"id\": \"h-9d22b570\", \"title\": \"Programmable Neuronal Circuit Repair via Epigenetic CRISPR\", \"target_gene\": \"NURR1, PITX3, neuronal identity transcription factors\", \"target_pathway\": \"CRISPRa epigenetic activation of dopaminergic transcription factor network\", \"match_score\": 0.37, \"composite_score\": 0.4470493886505538, \"status\": \"proposed\"}, {\"id\": \"h-1a34778f\", \"title\": \"Senescent Cell Mitochondrial DNA Release\", \"target_gene\": \"CGAS/STING1/DNASE2\", \"target_pathway\": \"Mitochondrial dynamics / bioenergetics\", \"match_score\": 0.3, \"composite_score\": 0.5427562421654517, \"status\": \"proposed\"}, {\"id\": \"h-baba5269\", \"title\": \"Partial Neuronal Reprogramming via Modified Yamanaka Cocktail\", \"target_gene\": \"OCT4\", \"target_pathway\": \"Epigenetic regulation\", \"match_score\": 0.3, \"composite_score\": 0.41395985477374386, \"status\": \"proposed\"}, {\"id\": \"h-19003961\", \"title\": \"Arginine Methylation Enhancement Therapy\", \"target_gene\": \"PRMT1\", \"target_pathway\": \"Arginine methylation / epigenetic regulation\", \"match_score\": 0.27, \"composite_score\": 0.46290667837852434, \"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\": 0.24, \"composite_score\": 0.49103059326293774, \"status\": \"proposed\"}, {\"id\": \"h-637a53c9\", \"title\": \"Chaperone-Mediated APOE4 Refolding Enhancement\", \"target_gene\": \"HSPA1A, HSP90AA1, DNAJB1, FKBP5\", \"target_pathway\": \"Heat shock protein / proteostasis\", \"match_score\": 0.2, \"composite_score\": 0.47806149316774604, \"status\": \"proposed\"}, {\"id\": \"h-7c3c0f40\", \"title\": \"Epigenetic Memory Reprogramming via CRISPRa-Mediated Chromatin Remodeling\", \"target_gene\": \"SIRT1, FOXO3, NRF2, TFAM\", \"target_pathway\": null, \"match_score\": 0.2, \"composite_score\": 0.43814309484239156, \"status\": \"proposed\"}, {\"id\": \"h-c9486869\", \"title\": \"HSP70 Co-chaperone DNAJB6 Universal Cross-Seeding Inhibitor\", \"target_gene\": \"DNAJB6\", \"target_pathway\": \"HSP70-HSP40 (DNAJB6) chaperone-mediated amyloid inhibition\", \"match_score\": 0.2, \"composite_score\": 0.4181516118115807, \"status\": \"proposed\"}], \"total_matching_hypotheses\": 8, \"gap_tokens_sample\": [\"DNA\", \"aging\", \"alterations\", \"changes\", \"chromatin\", \"dynamics\", \"epigenetic\", \"factors\", \"histone\", \"including\", \"investigate\", \"methylation\", \"mitotic\", \"modification\", \"neurons\"], \"updated_at\": \"2026-04-06T08:21:05.867616+00:00\"}",
  "market_price": 0.5
}