The evolutionary scope and neurological disease linkage of yeast-prion-like proteins in humans
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Notice bibliographique
Résumé
BACKGROUND: Prions are proteinaceous particles that propagate alternative protein conformations/states to further copies of the same proteins, and are transmitted from cell-to-cell, and organism-to-organism. Prions are usually made of the beta-sheet rich assemblies termed amyloid. The original prion protein PrP causes devastating neurodegenerative disorders in humans and other mammals. In the yeast Saccharomyces cerevisiae, many prion-forming proteins have been observed; a prominent feature of these proteins is an intrinsically disordered domain rich in glutamine (Q) and asparagine (N) residues. Several human proteins that are yeast-prion-like, in particular those with poly-glutamine (poly-Q) expansions, have been experimentally implicated in human neurodegenerative diseases. RESULTS: Here, we have constructed a comprehensive list of human yeast-prion-like proteins that are linked to human neurological disease. Surprisingly, different methods to annotate yeast-prion-like proteins in humans have limited intersection. However, independent of annotation method, we find that human yeast-prion-like proteins as a group have a statistically significant genetic linkage to neurological disease, that is caused specifically by linkage to neurodegenerative diseases. This is despite: (i) no especially high expression of yeast-prion-like proteins in the central nervous system, or (ii) no general enrichment of intrinsically disordered proteins in neurological/neurodegenerative diseases. Cytoskeletal proteins are significantly overrepresented in the set of human yeast-prion-like neurological proteins. Whether involved in neurological pathomechanisms or not, yeast-prion-like proteins in humans have very limited conservation outside of Deuterostomia (< ~10 %) with only a handful having prion-like character in both human and S. cerevisiae. The only such protein with a disease linkage is PUB1/TIA1, which functions as a stress granule component. Thus, the yeast-prion-like character of proteins linked to neurodegenerative diseases has not been conserved over the deep evolutionary time since the last common ancestor of yeasts and humans. CONCLUSION: Our results provide a comprehensive picture of yeast-prion-like proteins in humans and contribute to the strategic basis for experimental investigation of the link between yeast-prion-like protein character and neurological disease. REVIEWERS: Reviewed by Istvan Simon and Alexander Schleiffer. For the full reviews, please go to the Reviewers' comments section.
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
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