Computational systems analysis of developmental toxicity: design, development and implementation of a Birth Defects Systems Manager (BDSM)

Singh, Amar V.; Knudsen, Kenneth B.; Knudsen, Thomas B.

doi:10.1016/j.reprotox.2004.11.008

Cited by 24 publications

(16 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The meta-analytical approaches implemented in this study also uncovered additional functions not discussed by Singh et al (2005). In particular, genes with transferase activity and signal transducer activity were identified by the meta-analytical approaches.…”

Section: Representation Of Pathway Themesmentioning

confidence: 75%

“…Singh et al (2005) compiled multiple microarray experiments including the studies considered in the present meta-analysis and others from multiple species and platforms and reported many of the differentially expressed GO categories and pathways identified in this study. As expected, many of the results in this study are consistent with the results reported by Singh et al (2005); however, additional biological processes (i.e., cellular development) were also uncovered. Wang et al (2007) reported on the effect of ethanol on the alcohol metabolic pathway in the Japanese Medaka embryogenesis.…”

Section: Representation Of Pathway Themesmentioning

confidence: 99%

“…Many of the genes in the glycolysis pathway can be associated with mitochondrial-related processes. Soleman et al (2003) described the activation of the mitochondrial apoptotic pathway in mouse embryos by the teratogenic agents and Singh et al (2005) noted the critical role of mitochondria in embryo development. Green et al (2007) reported significant representation of genes associated with protein degradation and translocation, glycolysis, chaperone proteins, and proteasome subunits on the embryos treated with ethanol.…”

Section: Representation Of Pathway Themesmentioning

confidence: 99%

“…The GEO series are GSE 1068, GSE 1069, GSE 1070, GSE 1072, GSE 1074, GSE 1075, GSE 1076, GSE 1077, and GSE 1079 used the same two-dye cDNA platform and fluorescence intensities were available for 2382 sequence-verified human gene elements that effectively hybridize to mouse, human, and rat target mRNA. Detailed description of the treatment doses and timing, sampling time, mouse strains, platform, RNA isolation, labeling, and hybridization is available in the GEO database and are also provided by Nemeth et al (2005), Singh et al (2005) and Green et al (2007). These microarray experiments were conducted to assess the expression profile of mouse embryos exposed to teratogenic agents that can potentially interfere with normal embryo development and cause birth defects.…”

Section: Datamentioning

confidence: 99%

See 3 more Smart Citations

Advancing the understanding of the embryo transcriptome co-regulation using meta-, functional, and gene network analysis tools

Rodriguez-Zas¹,

Ko²,

Adams³

et al. 2008

Reproduction

View full text Add to dashboard Cite

Embryo development is a complex process orchestrated by hundreds of genes and influenced by multiple environmental factors. We demonstrate the application of simple and effective meta-study and gene network analyses strategies to characterize the co-regulation of the embryo transcriptome in a systems biology framework. A meta-analysis of nine microarray experiments aimed at characterizing the effect of agents potentially harmful to mouse embryos improved the ability to accurately characterize gene co-expression patterns compared with traditional within-study approaches. Simple overlap of significant gene lists may result in under-identification of genes differentially expressed. Sample-level meta-analysis techniques are recommended when common treatment levels or samples are present in more than one study. Otherwise, study-level meta-analysis of standardized estimates provided information on the significance and direction of the differential expression. Cell communication pathways were highly represented among the genes differentially expressed across studies. Mixture and dependence Bayesian network approaches were able to reconstruct embryo-specific interactions among genes in the adherens junction, axon guidance, and actin cytoskeleton pathways. Gene networks inferred by both approaches were mostly consistent with minor differences due to the complementary nature of the methodologies. The top-down approach used to characterize gene networks can offer insights into the mechanisms by which the conditions studied influence gene expression. Our work illustrates that further examination of gene expression information from microarray studies including meta-and gene network analyses can help characterize transcript co-regulation and identify biomarkers for the reproductive and embryonic processes under a wide range of conditions. Reproduction (2008) 135 213-224

show abstract

Section: Representation Of Pathway Themesmentioning

confidence: 75%

Section: Representation Of Pathway Themesmentioning

confidence: 99%

Section: Representation Of Pathway Themesmentioning

confidence: 99%

Section: Datamentioning

confidence: 99%

See 2 more Smart Citations

Advancing the understanding of the embryo transcriptome co-regulation using meta-, functional, and gene network analysis tools

Rodriguez-Zas¹,

Ko²,

Adams³

et al. 2008

Reproduction

View full text Add to dashboard Cite

show abstract

“…Among the genes detected by the meta-analysis approaches there was extensive representation of genes pertaining to glycolysis, cell communication, and proteasome pathways previously reported by Singh et al (2005). Additional biological processes including cellular development were also uncovered.…”

Section: Meta-analysesmentioning

confidence: 87%

Biological interpretations of transcriptomic profiles in mammalian oocytes and embryos

2008

View full text Add to dashboard Cite

The characterization of gene-expression profiles in oocytes and embryos is critical to understand the influence of genetic and environmental factors on preimplantation and fetal development. Numerous gene-expression microarray studies using different platforms and species are offering insights into the biological processes extensively represented among the genes exhibiting differential expression. Major advances on understanding the direct relationship between gene expression and developmental competence are being reported. Integration of information across studies using meta-analysis techniques can increase the precision and accuracy to identify expression profiles associated with embryo development. Gene network and pathway analyses are offering insights into gene interactions and expression profiles of embryos. All these advances are cementing the way toward a comparative and systems approach to understanding the complex processes underlying vertebrate development.

show abstract

Systems Modeling in Developmental Toxicity

Knudsen

DeWoskin

2009

General, Applied and Systems Toxicology

View full text Add to dashboard Cite

High‐throughput or high‐content studies are now providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential in vivo toxicity. EPA's ToxCast™ project, and the broader Tox21 consortium, as well as other projects worldwide, are providing high‐throughput and high‐content screening data (HTS‐HCS) focusing on the in vitro targets and cellular bioactivity profiles for thousands of chemical compounds in commerce or entering the environment. A goal of chemical profiling is to rapidly identify and efficiently classify signatures of biological activity that are potentially diagnostic of in vivo toxicities using automated technologies. Predictive modeling of developmental toxicity faces several challenges: correlating in vitro concentration–response with internal dose–response kinetics; understanding how in vitro bioactivity profiles extrapolate from one cell‐type or technology platform to another; and linking individual targets of in vitro bioactivity to complex signatures associated with pathways of in vivo toxicity. Toxicity in the intact organism is an expression of complex and interwoven events that follow from cellular perturbations. As such, multicellular computer models known as ‘virtual tissues’ that recapitulate developmental events can provide a technology platform to simulate non‐linear behaviors of dynamical systems and to model perturbations. A virtual embryo, for example, might be envisaged as a toolbox of computational ( in silico ) models that execute morphogenetic programs to simulate developmental toxicity.

show abstract

Computational systems analysis of developmental toxicity: design, development and implementation of a Birth Defects Systems Manager (BDSM)

Cited by 24 publications

References 30 publications

Advancing the understanding of the embryo transcriptome co-regulation using meta-, functional, and gene network analysis tools

Advancing the understanding of the embryo transcriptome co-regulation using meta-, functional, and gene network analysis tools

Biological interpretations of transcriptomic profiles in mammalian oocytes and embryos

Systems Modeling in Developmental Toxicity

Contact Info

Product

Resources

About