AI reveals insights into link between CD33 and cognitive impairment in Alzheimer's Disease.
PLoS Comput Biol
; 19(2): e1009894, 2023 02.
Article
en En
| MEDLINE
| ID: mdl-36780558
ABSTRACT
Modeling biological mechanisms is a key for disease understanding and drug-target identification. However, formulating quantitative models in the field of Alzheimer's Disease is challenged by a lack of detailed knowledge of relevant biochemical processes. Additionally, fitting differential equation systems usually requires time resolved data and the possibility to perform intervention experiments, which is difficult in neurological disorders. This work addresses these challenges by employing the recently published Variational Autoencoder Modular Bayesian Networks (VAMBN) method, which we here trained on combined clinical and patient level gene expression data while incorporating a disease focused knowledge graph. Our approach, called iVAMBN, resulted in a quantitative model that allowed us to simulate a down-expression of the putative drug target CD33, including potential impact on cognitive impairment and brain pathophysiology. Experimental validation demonstrated a high overlap of molecular mechanism predicted to be altered by CD33 perturbation with cell line data. Altogether, our modeling approach may help to select promising drug targets.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Alzheimer
/
Disfunción Cognitiva
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
PLoS Comput Biol
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania