Abstract

Monitoring global gene expression provides insight into how genes and regulatory signals work together to guide embryo development. The fields of developmental biology and teratology are now confronted with the need for automated access to a reference library of gene-expression signatures that benchmark programmed (genetic) and adaptive (environmental) regulation of the embryonic transcriptome. Such a library must be constructed from highly-distributed microarray data. Birth Defects Systems Manager (BDSM), an open access knowledge management system, provides custom software to mine public microarray data focused on developmental health and disease. The present study describes tools for seamless data integration in the BDSM library (MetaSample, MetaChip, CIAeasy) using the QueryBDSM module. A field test of the prototype was run using published microarray data series derived from a variety of laboratories, experiments, microarray platforms, organ systems, and developmental stages. The datasets focused on several developing systems in the mouse embryo, including preimplantation stages, heart and nerve development, testis and ovary development, and craniofacial development. Using BDSM data integration tools, a gene-expression signature for 346 genes was resolved that accurately classified samples by organ system and developmental sequence. The module builds a potential for the BDSM approach to decipher a large number developmental processes through comparative bioinformatics analysis of embryological systems at-risk for specific defects, using multiple scenarios to define the range of probabilities leading from molecular phenotype to clinical phenotype. We conclude that an integrative analysis of global gene-expression of the developing embryo can form the foundation for constructing a reference library of signaling pathways and networks for normal and abnormal regulation of the embryonic transcriptome. These tools are available free of charge from the web-site http://systemsanalysis.louisville.edu requiring only a short registration process.

Highlights

  • Animal development is fashioned by conserved signaling pathways that orchestrate morphogenesis, pattern formation, and cell differentiation - complex processes operating jointly in different parts of an embryo and in stages associated with sequential gene activation

  • [3] Gene Expression Omnibus (GEO) is one of the main national repositories for high-information content transcript data from microarray analysis and serial analysis of gene expression (SAGE). [4] GEO has grown from 18,235 records in June 2004 to 115,415 records in December 2006, reflecting an average growth of over 100 new entries per day

  • Implementation of QueryBDSM: For proof of concept we examined samples from GEO data source GSE1391, a series describing global gene-expression profiles of the mouse embryo during preimplantation stages

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Summary

Background

Animal development is fashioned by conserved signaling pathways that orchestrate morphogenesis, pattern formation, and cell differentiation - complex processes operating jointly in different parts of an embryo and in stages associated with sequential gene activation. Dataset collections: Search of PubMed using keywords =1), QueryBDSM automatically runs MetaSample to create ‘embryo’ and ‘microarray’ returned 495 records of which 193 a merged-table having 'columns' of normalized expression data used the technology to study developing animal (samples) in 'rows' derived from the platform, with unique probe systems. The probe identifiers from each platform from the public domain and 3 series containing 43 samples are converted to UniGene ID and merged with which are private These data represent 15 developing organ associated expression data, for those genes common across the systems, 6 chemical exposures, and 5 drug interventions across datasets. Functional annotation used the NIH/NIAID Database for Annotation, Visualization and Integrated Discovery (DAVID). [19] The highest-ranking biological themes were stratified by Gene Ontology (GO) terms

Discussion
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