0 hypotheses
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4 open gaps
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0 live debates
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0 tokens funded
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2/7 hub

What we know

  • 0 active hypothesises in scope
  • 4 open frontiers with evidence gaps
  • 10 indexed papers in corpus
0 hypotheses in scope
3 open frontiers
0 in-flight debates
0 tokens funded

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What determines the threshold effects and cooperative binding dynamics that govern protein network compensation?

The skeptic correctly identified that binary interaction maps miss the non-linear, concentration-dependent nature of compensatory networks. This mechanistic gap prevents accurate prediction of which tissues can buffer genetic variants. Source: Debate session sess_SDA-2026-04-08-gap-pubmed-20260406-062222-b5f44522 (Analysis: SDA-2026-04-08-gap-pubmed-20260406-062222-b5f44522)

priority 80%
How do protein-protein interaction networks mediate the causal effects of distant pQTLs?

The authors reveal an extensive network of direct protein-protein interactions and identify second proteins/transcripts as causal mediators of distant pQTL effects. The mechanistic basis of how these interaction networks propagate genetic effects across the proteome is not elucidated, representing a critical gap for understanding disease susceptibility networks. Gap type: unexplained_observation Source paper: Defining the consequences of genetic variation on a proteome-wide scale. (2016, Nature, PMID:27309819)

priority 76%
Which cell-type vulnerability signatures from SEA-AD single-cell data represent causal mechanisms versus secondary consequences of neurodegeneration?

All participants agreed that transcriptomic vulnerability signatures don't establish causation. Distinguishing primary vulnerability mechanisms from downstream effects is essential for identifying valid therapeutic targets rather than pursuing correlational biomarkers. Source: Debate session sess_analysis_sea_ad_001 (Analysis: analysis_sea_ad_001)

priority 90%
How do protein-protein interaction networks differ between PSP and CBD to produce distinct tau aggregation patterns?

The computational analysis revealed extensive MAPT interactions, but which specific interaction partners drive tufted astrocytes versus astrocytic plaques is unknown. This knowledge gap limits precision medicine approaches. Source: Debate session sess_sda-2026-04-01-gap-005 (Analysis: sda-2026-04-01-gap-005)

priority 75%

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