Gene4PD: a comprehensive genetic database of Parkinson's disease

Abstract

BackgroundParkinson's disease (PD) is a complex neurodegenerative disorder with a strong genetic component. A growing number of variants and genes have been reported to be associated with PD; however, there is no database that integrate different type of genetic data, and support analyzing of PD-associated genes (PAGs).MethodsBy systematic review and curation of multiple lines of public studies, we integrate multiple layers of genetic data (rare variants and copy-number variants identified from patients with PD, associated variants identified from genome-wide association studies, differential expression genes, and differential DNA methylation genes) and clinical data in PD. A weighted scoring system was employed to prioritize PAGs. Permutation test and protein-protein interaction network was used to evaluate the interconnectivity and functional correlation among the PAGs. The relationship between AAO and PAGs was further analyzed. A PHP-based web framework was used to construct a database. ResultWe integrated five layers of genetic data with different levels of evidences from more than 3,000 studies and prioritized 124 PAGs with strong or suggestive evidences. These PAGs were identified to be significantly interacted with each other and formed an interconnected functional network enriched in several functional pathways involved in PD, suggesting these genes may contribute to the pathogenesis of PD, which also highlighting the reliability of these genetic data for PD. Furthermore, we identified 10 genes were associated with a juvenile-onset (age ≤ 30 years), 11 genes were associated with an early-onset (age of 30–50 years), whereas another 10 genes were associated with a late-onset (age > 50 years). Notably, the AAOs of patients with loss of function variants in five genes (GCH1, PINK1, PRKN, FBXO7, ATP13A2) were significantly lower than that of patients with deleterious missense variants, while patients with VPS13C (P = 0.01) was opposite. Finally, we developed an online database named Gene4PD (http://genemed.tech/gene4pd) which integrated published genetic data in PD, the PAGs, and 63 popular genomic data sources, as well as an online pipeline for prioritize risk variants in PD.ConclusionGene4PD provides researchers and clinicians comprehensive genetic knowledge and analytic platform for PD, and would also improve the understanding of pathogenesis in PD.Availability and Implementation: Gene4PD can be freely accessed at http://genemed.tech/gene4pd.

Single Cell transcriptional analysis ofex vivomodels of cortical and hippocampal development identifies unique longitudinal trends

“…Next we curated and investigated the gene expression patterns and cell specificity of 94 genes associated with genetic epilepsy (compiled and curated from [59, 60]), 227 Autism Spectrum Disorder (ASD) genes (SFARI Category 1 and SPARK genes[61, 62, 86, 87]), 32 schizophrenia genes [63, 88], 16 dystonia genes [64, 65], 84 genes associated with Alzheimer’s Disease [66], 55 Parkinson’s disease genes from the Gene4PD database [67], 57 Obesity genes [89], and 87 Coronary Artery Disease (CAD) genes [90, 91] (Table S9).…”

“…The extent and specifics of the dynamic temporal gene expression in these postnatal cultures over network development is not well characterized, and is crucial for experimental design when using these cultures, or deciding which model to use. This is of increased importance when looking at genes that are known to be causal for, or associated with, neurological disorders [59][60][61][62][63][64][65][66][67].…”

The Combination of Tradition and Future: Data-Driven Natural-Product-Based Treatments for Parkinson’s Disease

“…e wellstructured databases can not only store and manage existing data but also can be utilized for data sharing and integrated analysis. Good examples for such databases in PD research include NDDVD [19], Gene4PD [20], and PDmethDB [21]. Natural products have a broad range of compounds, and a large number of diseases can be treated by them.…”