PSCAN: Spatial scan tests guided by protein structures improve complex disease gene discovery and signal variant detection.
Genome Biol
; 21(1): 217, 2020 08 26.
Article
en En
| MEDLINE
| ID: mdl-32847609
ABSTRACT
Germline disease-causing variants are generally more spatially clustered in protein 3-dimensional structures than benign variants. Motivated by this tendency, we develop a fast and powerful protein-structure-based scan (PSCAN) approach for evaluating gene-level associations with complex disease and detecting signal variants. We validate PSCAN's performance on synthetic data and two real data sets for lipid traits and Alzheimer's disease. Our results demonstrate that PSCAN performs competitively with existing gene-level tests while increasing power and identifying more specific signal variant sets. Furthermore, PSCAN enables generation of hypotheses about the molecular basis for the associations in the context of protein structures and functional domains.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas
/
Predisposición Genética a la Enfermedad
/
Estudios de Asociación Genética
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Genome Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos