AutDB: a platform to decode the genetic architecture of autism

Abstract

AutDB is a deeply annotated resource for exploring the impact of genetic variations associated with autism spectrum disorders (ASD). First released in 2007, AutDB has evolved into a multi-modular resource of diverse types of genetic and functional evidence related to ASD. Current modules include: Human Gene, which annotates all ASD-linked genes and their variants; Animal Model, which catalogs behavioral, anatomical and physiological data from rodent models of ASD; Protein Interaction (PIN), which builds interactomes from direct relationships of protein products of ASD genes; and Copy Number Variant (CNV), which catalogs deletions and duplications of chromosomal loci identified in ASD. A multilevel data-integration strategy is utilized to connect the ASD genes to the components of the other modules. All information in this resource is manually curated by expert scientists from primary scientific publications and is referenced to source articles. AutDB is actively maintained with a rigorous quarterly data release schedule. As of June 2017, AutDB contains detailed annotations for 910 genes, 2197 CNV loci, 1060 rodent models and 38 296 PINs. With its widespread use by the research community, AutDB serves as a reference resource for analysis of large datasets, accelerating ASD research and potentially leading to targeted drug treatments. AutDB is available at http://autism.mindspec.org/autdb/Welcome.do.

Figure 1.

Modular architecture of AutDB. The Human Gene module is the central component of AutDB collecting genetic risk factors for ASD including rare and common variants identified from high- as well as low-throughput studies. The CNV module includes a comprehensive collection of deletions and duplications of chromosomal loci identified in ASD individuals. To comprehend the functional significance of genetic risk factors, two additional sources of data are included: animal models and protein interactomes of ASD-associated genes. Notably, the diverse structures of genetic and functional data are captured and integrated using annotation models that preserve the biological meaning of the entities. Module-specific front pages provide easy ways for navigation across the other modules in AutDB.

Figure 2.

Growth of Human Gene module of AutDB (March 2012–June 2017). The number of genes associated with ASD increased from 328 to 910 with concomitant increase of rare and common variants from 1282 to 8938 and 549 to 1203, respectively. Rare variants are defined as those with a population frequency <1%; common variants are defined as those found in the general population at a frequency of ≥1%.