Drug targets and lipid biomarkers of hyperlipidemia associated diseases
Notice bibliographique
Résumé
Hyperlipidemia (HL) is characterized by elevated level of plasma lipids affecting regular functioning of lipid-protein interactions leading to disease. The traditional lipid biomarkers utilized for detection of individuals with HL and Cardiovascular Diseases (CVD) risk, sometimes fail to predict future CVD events therefore, establishing need of novel lipid biomarkers for CVD detection. It was attempted to predict the lipid biomarkers using systems biology and by a meta-analysis of lipidomics studies. A lipid-protein-protein interaction network (LPPIN) was built by incorporating differentially expressed genes in fatty liver of obese subjects obtained from Gene Expression Omnibus, with the interacting lipids obtained from STITCH database. The protein interactions were derived using PathwayLinker and lipid interactions were acquired from STITCH 4.0. For identification of novel lipid biomarkers comparative analysis of normolipidemic, hyperlipidemic and CVD lipid profile was conducted. Cholesterol, diacylglycerol, phosphatidylinositol-bis-phosphate and inositol-triphosphate were central to LPPIN, therefore had the largest systemic effect. The choke point analysis identified proteins having maximum interactions with network lipids, malfunctioning of which could lead to HL associated diseases. Cluster analysis recognized CVD, cancer, Alzheimer's disease and type-2-diabetes to be linked with HL. Lipids associated with the disease clusters consisted of triacylglycerol, cholesterol, oleic acid, linoleic acid, arachidonic acid, palmitate, inositol triphosphate, inositol-1,4-bisphosphate and phosphatidinositol-4-phosphate. Approved HL drug targets like Proprotein Convertase Subtilisin Kexin Type 9 and Niemann-Pick C1-Like 1 may be repurposed for treatment of hyperlipidemia associated diseases. Using a combination of gene prioritization and bridging centrality, Coactosin-like binding protein 1, Vasodilator stimulated phosphoprotein and Hedgehog acyltransferase were identified as a potential drug target for CVD, cancer and Alzheimer's, respectively. A comparative lipidomics analysis revealed that palmitoyl-lysophosphatidylcholine level was decreased while plasma level of free fatty acids and ceramides were elevated in HL and CVD. Both HL and CVD were associated with changes in lipid composition. HL was associated with increased level of saturated diacylglycerol, triacylglycerol and phospholipids while CVD was associated with increase in small chain fatty acids with low double bond content in triacylglycerol, cholesteryl ester and sphingomyelin. Our work highlights new drug targets and biomarkers for hyperlipidemia.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».