Autophagy, Lysosome, and Endolysosomal Trafficking Consensus

Consensus Summary

Autophagic flux, lysosomal acidification, endosomal sorting, vesicle recycling, and proteolipid stress determine whether toxic cargo is cleared.

This consensus cluster currently contains 103 active SciDEX hypotheses with average composite score 0.5959. Disease coverage: cross_neurodegeneration: 74, proteomics: 14, protein folding: 4, protein biochemistry: 3, unspecified: 3, AD: 2, lipidomics: 1, multi: 1.

Cross-Disease Signal

Shared disease buckets represented here: AD, cross_neurodegeneration. Clusters with AD/PD/ALS/FTD co-coverage are priority targets for transfer hypotheses, debate scheduling, and Forge validation tasks.

Top Hypotheses

• APOE-Dependent Autophagy Restoration (h-51e7234f): neurodegeneration, score 0.894887

• Autophagy-Lysosomal Pathway Dysfunction as a Unifying Proteostasis Failure (h-b007ca967f): neurodegeneration, score 0.82

• G2019S primarily raises baseline LRRK2 kinase activity rather than amplifying lysosomal swelling gain (h-d4ac0303f6): neurodegeneration, score 0.79

Category Definition

Mechanism terms used for deterministic assignment: autophagy, lysosom, endosom, endolysosom, tfeb, gcase, gba, lrrk2, vps, rab, cathepsin, p62, sqstm1, ubiquitin, proteasome, clearance, exosome.

Provenance

Generated by scripts/atlas_mechanism_consensus_map.py for Atlas task be26e8ca-f0cf-4a8d-b2ed-31a8e19e8c71 from the live PostgreSQL hypotheses table. Hypotheses are linked to the cluster node through knowledge_edges.relation='belongs_to_pathway_cluster'.