AutismKB

AutismKB aggregates and scores genetic and genomic evidence to compile an evidence-based knowledgebase of genes, single nucleotide polymorphisms (SNPs), variable number tandem repeats (VNTRs), copy number variations (CNVs), and linkage regions implicated in autism spectrum disorder (ASD).

Key Features:

• Curated genetic associations: Manually curated associations include 2,193 genes, 2,806 SNPs or VNTRs, 4,544 CNVs, and 158 linkage regions reported in ASD studies.
• Evidence sources: Associations were collected from studies including genome-wide association studies (GWAS), genome-wide CNV analyses, linkage analyses, low-scale genetic association studies, expression profiling, and other experimental approaches.
• Scoring and ranking system: A robustness score evaluates each study using clinical and demographic features, experimental design, and statistical significance to prioritize evidence.
• High-confidence gene set: A core dataset of 434 high-confidence ASD genes was established based on the scoring system.
• Pathway annotation: Implicated genes are annotated to pathways such as neuroactive ligand-receptor interaction, synapse transmission, and axon guidance.
• Database integration: Integration from over 30 external databases provides gene expression patterns, protein interactions, animal model data, and pharmacogenetic information.
• Data storage: The knowledgebase is implemented on a MySQL-based platform.

Scientific Applications:

• Gene prioritization: Rank and prioritize ASD candidate genes for follow-up genetic and functional studies using the evidence scores.
• Variant interpretation: Contextualize SNPs, VNTRs, and CNVs implicated in ASD with supporting study-level evidence and annotations.
• Pathway and network analysis: Investigate enrichment and interactions among ASD-associated genes in pathways such as synaptic transmission and axon guidance.
• Functional follow-up: Leverage integrated animal model and expression data to support experimental validation of ASD-associated genes.
• Pharmacogenetic investigation: Use integrated pharmacogenetic information to explore therapeutic and translational implications of ASD-associated genes.

Methodology:

Manual literature review and curation of reported associations from GWAS, genome-wide CNV analyses, linkage analyses, low-scale genetic association studies, expression profiling, and other experimental approaches; application of a scoring and ranking system assessing clinical/demographic features, experimental design, and statistical significance; integration of data from over 30 databases; storage on a MySQL platform.