NeuroCNVscore: a tissue-specific framework to prioritise the pathogenicity of CNVs in neurodevelopmental disorders.
BMJ Paediatr Open
; 7(1)2023 07.
Article
en En
| MEDLINE
| ID: mdl-37407247
ABSTRACT
BACKGROUND:
Neurodevelopmental disorders (NDDs) are associated with altered development of the brain especially in childhood. Copy number variants (CNVs) play a crucial role in the genetic aetiology of NDDs by disturbing gene expression directly at linear sequence or remotely at three-dimensional genome level in a tissue-specific manner. Despite the substantial increase in NDD studies employing whole-genome sequencing, there is no specific tool for prioritising the pathogenicity of CNVs in the context of NDDs.METHODS:
Using an XGBoost classifier, we integrated 189 features that represent genomic sequences, gene information and functional/genomic segments for evaluating genome-wide CNVs in a neuro/brain-specific manner, to develop a new tool, neuroCNVscore. We used Human Phenotype Ontology to construct an independent NDD-related set.RESULTS:
Our neuroCNVscore framework (https//github.com/lxsbch/neuroCNVscore) achieved high predictive performance (precision recall=0.82; area under curve=0.85) and outperformed an existing reference method SVScore. Notably, the predicted pathogenic CNVs showed enrichment in known genes associated with autism.CONCLUSIONS:
NeuroCNVscore prioritises functional, deleterious and pathogenic CNVs in NDDs at whole genome-wide level, which is important for genetic studies and clinical genomic screening of NDDs as well as for providing novel biological insights into NDDs.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Trastorno Autístico
/
Trastornos del Neurodesarrollo
Idioma:
En
Revista:
BMJ Paediatr Open
Año:
2023
Tipo del documento:
Article