Integrative analysis of the mouse embryonic transcriptome

Abstract

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.

Integrated transcriptomic response to cardiac chronic hypoxia: translation regulators and response to stress in cell survival

“…In addition, heart development after birth is the result of numerous genes changing expression level (e.g., Azfer et al 2006;Harrell et al 2007;Plageman and Yutzey 2006;Singh et al 2007). Therefore, we determined and compared the maturational profiles of each quantifiable gene in all three treatments, identifying the agedependent genes and the changes induced by the hypoxic stress.…”

Pathway modeling of microarray data: A case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP)

“…The KEGG database is widely used for studying mammalian gene pathways (Arum et al, 2010;Liu et al, 2010;Kitami and Nadeau, 2002;Bono and Okazaki, 2005;Guo et al, 2006;Kovacs et al, 2007;Singh et al, 2007;Zhou et al, 2007;Fardet et al, 2008) and the most comprehensively compiled web source for metabolic pathway study. Any pathway method is limited by currently available pathway knowledge and, as a result, numerous genes not linked to known pathways are not considered in pathway analyses.…”

Computational Toxicology

“…The Birth Defects Systems Manager (BDSM) Singh et al 2005Singh et al , 2007a serves as an example of a knowledgebase that is human readable and that is designed to facilitate discovery of interesting data associations across developmental stages, organ systems, and disease phenotypes. The supporting database also provides embryo-based, high-content gene expression data curated from GEO Singh et al 2005) and data from other sources in a searchable environment that allows for genomics analysis and the building and mining of data relationships.…”

“…BDSM is presently being modified to become a machine-readable knowledgebase that can supply data for computer models of a developing mammalian embryo. BDSM has many programming retrieval capabilities to facilitate hypothesis generation and testing; in particular, QueryBDSM allows specific queries across experiments to facilitate secondary analysis of developmental genomics data and the applications of comparative bioinformatics across technology platforms and study types (Singh et al 2007a).…”