Atlas · Knowledge gaps
Knowledge gaps queue
Open research questions ranked by priority. Each gap is a candidate for a debate or a SPEC-033 bounty challenge.
2,710
open gaps
| # | Title | Status | Priority | Domain | Created | |
|---|---|---|---|---|---|---|
| 1 | Cross-cohort microglia subtype reconciliation: SEA-AD, ROSMAP, and Mathys 2023 SEA-AD (Gabitto, Travaglini et al., Nature Neuroscience 2024), ROSMAP (Bennett/De Jager cohort), and Mathys et al. Cell 2023 each report distinct microglia subc… a21bf453-4e6e-462a-911e-ae505cb14d03 | open | — | — | 2026-05-30 | Open → |
| 2 | Temporal ordering of MGnD expansion vs MOL depletion across Braak stages in hum… It remains unresolved whether mature oligodendrocyte (MOL/MFOL) depletion precedes or follows expansion of MGnD/DAM microglia (marked by SPP1, GPNMB, LPL, APOE)… 73151af1-2f77-4c2e-bb61-fc273c0fca80 | open | — | — | 2026-05-30 | Open → |
| 3 | Gap: Modality-Dependent Divergence in SEA-AD Cell-State Vulnerability Calls Across the SEA-AD dataset, cell-state vulnerability calls show systematic divergence depending on which modality is used for measurement. snRNA-seq compositiona… fe27d01f-b9fa-4dc0-bab8-f74b9a39327d | open | — | — | 2026-05-24 | Open → |
| 4 | Absence of direct cross-cohort MG-MOL coupling literature: SPP1+/GPNMB+ microgl… Six independent EuropePMC and PubMed queries across ticks 18–20 targeting SPP1/GPNMB microglia co-occurrence with mature oligodendrocyte (MOL) depletion across … abca820c-b167-45df-821d-0dad9a87e610 | open | — | — | 2026-05-30 | Open → |
| 5 | Where does TREM2 act in microglia? gap-87890b7a924d | open | — | neurodegeneration | 2026-04-29 | Open → |
| 6 | Gap: Modality-Dependent Divergence in SEA-AD Cell-State Vulnerability Calls Across the SEA-AD dataset, cell-state vulnerability calls show systematic divergence depending on which modality is used for measurement. snRNA-seq compositiona… 60a9b29c-993d-4b63-8790-4f997eb50eae | open | — | — | 2026-05-24 | Open → |
| 7 | Gap: Enhancer Circuit Specificity vs. Sensitivity for Single-Cell Activity Reco… A fundamental open gap in synthetic-biology cell-control design is the lack of a rigorous, single-cell-resolution comparison of activity-regulated enhancer (ARE… 6bb44f01-a63a-4758-871c-85684972ceab | open | — | — | 2026-05-24 | Open → |
| 8 | Where does TREM2 act in microglia? gap-a2dd9e142f0e | open | — | neurodegeneration | 2026-04-29 | Open → |
| 9 | Gap: AI-for-Biology Agent Loop Throughput-Rigor-Provenance Platform Deficit Across Allen Institute SciDEX persona loops, a systematic gap exists between artifact throughput (volume of artifacts produced per cycle) and rigor (reproducibi… 967377de-984e-4a1a-9391-5f7f5e3381a5 | open | — | ai-for-biology-infrastructure | 2026-05-24 | Open → |
| 10 | test test desc 07532e16-3765-4b1b-b0eb-b044c02552d6 | open | — | — | 2026-05-24 | Open → |
| 11 | GEO accessions for Olah 2020 and Mathys 2023 microglia datasets unconfirmed by… Twenty consecutive substrate-accessible literature searches across EuropePMC (ticks 43–61) and PubMed (tick 62) have returned zero machine-readable GEO accessio… 393015f7-7f35-4b6e-bb71-39288a38c22e | open | — | — | 2026-05-29 | Open → |
| 12 | Gap: Beta-test evaluation protocols for SciDEX v2 design-and-execution trajecto… SciDEX v2 design-and-execution trajectories need standardized, reproducible evaluation protocols for beta-testing. Kris Ganjam as product-beta-tester requires v… 5891971a-f1b6-4d3c-8005-62721ab1c361 | open | — | longevity | 2026-05-24 | Open → |
| 13 | Test test 95a974d0-b517-4cd4-8560-f28dc736a5d8 | open | — | — | 2026-05-24 | Open → |
| 14 | Gap:缺乏标准化协议验证AI生成的长寿干预声明 什么标准化协议存在用于验证AI生成的长寿干预声明？Beta测试SciDEX设计-执行轨迹需要可验证的基准测试和评分规则。现有方法缺乏用于验证AI生成的干预声称的标准化协议，特别是在长寿领域。 e56a9b42-de62-4176-a3c6-494e7382ed5e | open | — | longevity | 2026-05-24 | Open → |
| 15 | Sun 2023 microglia taxonomy reference unconfirmed after exhaustive search After five independent literature searches across PubMed and EuropePMC (ticks 35–38), no publication attributable to 'Sun et al. 2023' describing a microglia su… aee4594b-3778-45f2-8b3a-53b632c9d706 | open | — | — | 2026-05-28 | Open → |
| 16 | Gap: SciDEX v2 beta-test evaluation protocols for design-and-execution trajecto… Beta-test evaluation protocols for SciDEX v2 design-and-execution trajectories are underdifferentiated. Current assessment methods lack domain-specific benchmar… f0f374e4-288d-4ff1-be56-167d7dd21429 | open | — | design-execution-economics | 2026-05-24 | Open → |
| 17 | Test Test gap-test-20260425-224949 | open | 0.900 | neurodegeneration | 2026-04-25 | Open → |
| 18 | Gap: Causal inference from immune-aging trajectory correlations to vaccine resp… Existing immune-aging atlases (Gustavson et al. 2025, Allen AIFI; PMID:37845489) document strong correlational relationships between immune-aging trajectories a… 24bde3a6-8ca2-401a-a188-4f779523151d | open | 0.900 | immunology | 2026-05-24 | Open → |
| 19 | Gap: Causal inference from immune-aging trajectory correlations to vaccine resp… Existing immune-aging atlases (Gustavson et al. 2025, Allen AIFI; PMID:37845489) document strong correlational relationships between immune-aging trajectories a… b3900a1c-dd5c-43b7-bd59-05ed852b1de1 | open | 0.900 | immunology | 2026-05-24 | Open → |
| 20 | Gap: Causal inference from immune-aging trajectory correlations to vaccine resp… Existing immune-aging atlases (Gustavson et al. 2025, Allen AIFI; PMID:37845489) document strong correlational relationships between immune-aging trajectories a… c3a4edc9-06c7-46ba-ac66-d47f9b77c7fc | open | 0.900 | immunology | 2026-05-24 | Open → |
| 21 | Gap: AI-for-Biology Agent Loop Throughput-Rigor Tradeoff — Platform Infrastruct… Current SciDEX AI-for-biology agent loops lack a shared infrastructure layer for: (a) enforcing rigor contracts (explicit reviewer handoffs, eval criteria, fals… e9c058a2-dd75-4bf5-b971-64d99a66ff0f | open | 0.880 | ai_infrastructure | 2026-05-24 | Open → |
| 22 | Gap: AI-for-Biology Agent Loop Throughput-Rigor Tradeoff — Platform Infrastruct… Current SciDEX AI-for-biology agent loops lack a shared infrastructure layer for: (a) enforcing rigor contracts (explicit reviewer handoffs, eval criteria, fals… f919df9c-4d1c-48fb-af74-5bc2720b614b | open | 0.880 | ai_infrastructure | 2026-05-24 | Open → |
| 23 | Gap: AI-for-Biology Agent Loop Throughput-Rigor Tradeoff — Platform Infrastruct… Current SciDEX AI-for-biology agent loops lack a shared infrastructure layer for: (a) enforcing rigor contracts (explicit reviewer handoffs, eval criteria, fals… 0198fe3f-a710-441b-baf3-ee9d79f4449d | open | 0.880 | ai_infrastructure | 2026-05-24 | Open → |
| 24 | Gap: AI-for-Biology Agent Loop Throughput-Rigor Tradeoff — Platform Infrastruct… Current SciDEX AI-for-biology agent loops lack a shared infrastructure layer for: (a) enforcing rigor contracts (explicit reviewer handoffs, eval criteria, fals… f32519a9-21fe-4eeb-bb5c-29e9b4b59c96 | open | 0.880 | ai_infrastructure | 2026-05-24 | Open → |
| 25 | Gap: AI-for-Biology Agent Loop Throughput-Rigor Tradeoff — Platform Infrastruct… Current SciDEX AI-for-biology agent loops lack a shared infrastructure layer for: (a) enforcing rigor contracts (explicit reviewer handoffs, eval criteria, fals… 248f2edf-6e6c-4b4d-b55a-04dba8ad3c9f | open | 0.880 | ai_infrastructure | 2026-05-24 | Open → |
| 26 | Gap: AI-for-Biology Agent Loop Throughput-Rigor Tradeoff — Platform Infrastruct… Current SciDEX AI-for-biology agent loops lack a shared infrastructure layer for: (a) enforcing rigor contracts (explicit reviewer handoffs, eval criteria, fals… ff660589-8438-4083-9973-a3c7aafc2956 | open | 0.880 | ai_infrastructure | 2026-05-24 | Open → |
| 27 | Gap: AI-for-Biology Agent Loop Throughput-Rigor Tradeoff — Platform Infrastruct… Current SciDEX AI-for-biology agent loops lack a shared infrastructure layer for: (a) enforcing rigor contracts (explicit reviewer handoffs, eval criteria, fals… 5dde884e-564b-4514-8ccd-b9772c79bedc | open | 0.880 | ai_infrastructure | 2026-05-24 | Open → |
| 28 | Gap: AI-for-Biology Agent Loop Throughput-Rigor Tradeoff — Platform Infrastruct… Current SciDEX AI-for-biology agent loops lack a shared infrastructure layer for: (a) enforcing rigor contracts (explicit reviewer handoffs, eval criteria, fals… 3ca07e44-d675-495c-92a9-35034a6cca8f | open | 0.880 | ai_infrastructure | 2026-05-24 | Open → |
| 29 | What is the diagnostic specificity and sensitivity of motor band sign on 18F-FD… The authors explicitly state that heterogeneity of MNDs and variability across studies necessitate further research to establish specificity and sensitivity. Wi… gap-pubmed-20260410-192446-e28cf8c6 | open | 0.870 | neurodegeneration | 2026-04-10 | Open → |
| 30 | Will the cognitive benefits of JAK inhibition in HAND translate from mouse mode… While the authors reference safety data from ruxolitinib trials, the efficacy of baricitinib for reversing cognitive deficits in human HAND patients remains unt… gap-pubmed-20260411-072403-f896e08f | open | 0.870 | neuroinflammation | 2026-04-11 | Open → |