Observ-OM and Observ-TAB: Universal syntax solutions for the integration, search, and exchange of phenotype and genotype information

Abstract

Genetic and epidemiological research increasingly employs large collections of phenotypic and molecular observation data from high quality human and model organism samples. Standardization efforts have produced a few simple formats for exchange of these various data, but a lightweight and convenient data representation scheme for all data modalities does not exist, hindering successful data integration, such as assignment of mouse models to orphan diseases and phenotypic clustering for pathways. We report a unified system to integrate and compare observation data across experimental projects, disease databases, and clinical biobanks. The core object model (Observ-OM) comprises only four basic concepts to represent any kind of observation: Targets, Features, Protocols (and their Applications), and Values. An easy-to-use file format (Observ-TAB) employs Excel to represent individual and aggregate data in straightforward spreadsheets. The systems have been tested successfully on human biobank, genome-wide association studies, quantitative trait loci, model organism, and patient registry data using the MOL-GENIS platform to quickly setup custom data portals. Our system will dramatically lower the barrier for future data sharing and facilitate integrated search across panels Additional Supporting Information may be found in the online version of this article.

Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19

“…These programs are all integrated in our MOLGENIS Compute analysis pipeline developed by the Genomics Coordination Center, Department of Genetics, University of Groningen (http:// wiki.gcc.rug.nl/wiki/GccStart). 18 Pathogenicity predictions for variants were obtained from PolyPhen 2.0, SIFT, and Align GVD. [19][20][21][22][23] Variations were validated by direct Sanger sequencing and analyzed using DNA Variant Analysis Software Mutation Surveyor.…”

MEFVmutations affecting pyrin amino acid 577 cause autosomal dominant autoinflammatory disease

“…Using snpEff (http://snpeff.sourceforge.net), variants were annotated with information from dbSNP132, 1000 Genomes Project (phase 1, 2 and 3) and Ensembl build 37.64, which are all integrated into the pipeline MOLGENIS Compute developed by the Genomics Coordination Center of the Department of Genetics, University of Groningen, Groningen, The Netherlands (http://wiki.gcc.rug.nl/wiki/GccStart).8 Variant pathogeneity predictions were obtained with PolyPhen V.2.0, SIFT and Align GVD 9–12…”

VarioML framework for comprehensive variation data representation and exchange

“…We began by incorporating previous work on data requirements [6,8,14] and data modelling activities, such as PaGE-OM [15] and its generalization Observ-OM [16], in the design of VarioML LSDBs specification.…”

“…This highlighted the need for a new harmonized model for describing scientific observations in general, providing a common language usable across all domains. For this purpose, a new object model, Observ-OM [16], was developed.…”