Integrative Genomics: In Silico Coupling of Rat Physiology and Complex Traits With Mouse and Human Data

Twigger, Simon; Nie, Jeff; Ruotti, Victor; Yu, J.; Chen, Dan; Li, Dawei; Mathis, Jed; Narayanasamy, Vijay; Gopinath, Gopal; Pasko, Dean; Shimoyama, Mary; Cruz, Norberto de la; Bromberg, Susan K.; Kwitek, Anne E.; Jacob, Howard J.; Tonellato, Peter J.

doi:10.1101/gr.1974504

Cited by 19 publications

(10 citation statements)

References 65 publications

(58 reference statements)

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“…It is therefore essential to properly evaluate a new animal model prior to employing such a biological system in elaborate large-scale studies for testing new drugs or biomedical treatments. The biological integration of genomic, proteomic and physiological data sets from both human and animal model analyses will be an important aspect towards unravelling the fundamental differences between species [31,32]. Taking into account the above outlined potential problems with biomedical data generated from animal experiments, a good animal model should exhibit the following characteristics.…”

Section: Biomedical Importance and Pathobiochemical Limitations Of Anmentioning

confidence: 99%

Proteomic profiling of animal models mimicking skeletal muscle disorders

Doran

Gannon

O’Connell

et al. 2007

Proteomics Clinical Apps

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Over the last few decades of biomedical research, animal models of neuromuscular diseases have been widely used for determining pathological mechanisms and for testing new therapeutic strategies. With the emergence of high-throughput proteomics technology, the identification of novel protein factors involved in disease processes has been decisively improved. This review outlines the usefulness of the proteomic profiling of animal disease models for the discovery of new reliable biomarkers, for the optimization of diagnostic procedures and the development of new treatment options for skeletal muscle disorders. Since inbred animal strains show genetically much less interindividual differences as compared to human patients, considerably lower experimental repeats are capable of producing meaningful proteomic data. Thus, animal model proteomics can be conveniently employed for both studying basic mechanisms of molecular pathogenesis and the effects of drugs, genetic modifications or cell-based therapies on disease progression. Based on the results from comparative animal proteomics, a more informed decision on the design of clinical proteomics studies could be reached. Since no one animal model represents a perfect pathobiochemical replica of all of the symptoms seen in complex human disorders, the proteomic screening of novel animal models can also be employed for swift and enhanced protein biochemical phenotyping.

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Section: Biomedical Importance and Pathobiochemical Limitations Of Anmentioning

confidence: 99%

Proteomic profiling of animal models mimicking skeletal muscle disorders

Doran

Gannon

O’Connell

et al. 2007

Proteomics Clinical Apps

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“…Having multiple maps, such as genetic, RH, and genome maps allows for these consistency checks, given that they are generated essentially independently of one another. To visualize the consistency of the RH maps with other available maps, the new VCMapView tool (http:// rgd.mcw.edu/VCMAP/mapview.shtml; see Twigger et al 2004) was used to align the RH map with two reference genetic maps (SHRSP ‫ן‬ BN and FHH ‫ן‬ ACI), the RH map generated by Watanabe et al (1999), and the genome assembly (R3.1; Fig. 2).…”

Section: Error Checking and Validation Of Rh Mapsmentioning

confidence: 99%

“…These efforts have resulted in highdensity RH maps with extensive curation, which can be used for multiple applications in the discovery and understanding of complex disease pathology. Perhaps most importantly, this new RH map provides "sequence hooks" at nearly 10 STSs per Mb of genomic DNA, providing many integration points between various Rat maps as well as interspecies alignments, as illustrated in the VCMapView tool described in the companion paper within this issue (Twigger et al 2004).…”

mentioning

confidence: 99%

“…One such genomic resource, radiation hybrid (RH) maps, are a powerful tool for annotating the rat genome with systems biology information; they have been used to integrate genetic maps from different rat crosses used in QTL mapping, physical and draft genomic maps, and the genomes of different species via comparative mapping (Gosele et al 2000;Bihoreau et al 2001;Kwitek et al 2001;Dobbins et al 2002;Moujahidine et al 2002;Chowdhary et al 2003;Larkin et al 2003). The VCMap (Kwitek et al 2001) at the Rat Genome Database (RGD) has chosen the RH maps as the backbone platform for integrating available genomic data as well as for annotating disease QTLs for complex traits and diseases, using the new VCMapView tool (see Twigger et al 2004). Finally, the maps offer many direct links to the draft genomic sequence and help to validate the assembly of the rat genome sequence.…”

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confidence: 99%

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High-Density Rat Radiation Hybrid Maps Containing Over 24,000 SSLPs, Genes, and ESTs Provide a Direct Link to the Rat Genome Sequence

Kwitek¹,

Gullings-Handley²,

Yu³

et al. 2004

Genome Res.

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The laboratory rat is a major model organism for systems biology. To complement the cornucopia of physiological and pharmacological data generated in the rat, a large genomic toolset has been developed, culminating in the release of the rat draft genome sequence. The rat draft sequence used a variety of assembly packages, as well as data from the Radiation Hybrid (RH) map of the rat as part of their validation. As part of the Rat Genome Project, we have been building a high-density RH map to facilitate data integration from multiple maps and now to help validate the genome assembly. By incorporating vectors from our lab and several other labs, we have doubled the number of simple sequence length polymorphisms (SSLPs), genes, expressed sequence tags (ESTs), and sequence-tagged sites (STSs) compared to any other genome-wide rat map, a total of 24,437 elements. During the process, we also identified a novel approach for integrating the RH placement results from multiple maps. This new integrated RH map contains approximately 10 RH-mapped elements per Mb on the genome assembly, enabling the RH maps to serve as a scaffold for a variety of data visualization tools.

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“…43,44 Data concerning genomic synteny and comparable QTL localization across species may also be of use when available. 45 …”

Section: Treating Mrna Expression Levels As Quantitative Traitsmentioning

confidence: 97%

Integrating Genetic and Gene Expression Data to Study the Metabolic Syndrome and Diabetes in Mice

Drake

Schadt²,

Davis³

et al. 2005

American Journal of Therapeutics

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Increasingly, the mouse is becoming the standard model for mammalian physiology and disease. It can be genetically analyzed and manipulated with relative ease. Moreover, the endogenous genetic variation that exists among inbred mouse strains can be exploited to identify genetic control of complex physiologic processes involved in diabetes and the metabolic syndrome, among other conditions relevant to human disease. Recent advances in genetics and gene expression technology have greatly increased the knowledge to be derived from this approach when applied to traditional genetic studies.

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Integrative Genomics: In Silico Coupling of Rat Physiology and Complex Traits With Mouse and Human Data

Cited by 19 publications

References 65 publications

Proteomic profiling of animal models mimicking skeletal muscle disorders

Proteomic profiling of animal models mimicking skeletal muscle disorders

High-Density Rat Radiation Hybrid Maps Containing Over 24,000 SSLPs, Genes, and ESTs Provide a Direct Link to the Rat Genome Sequence

Integrating Genetic and Gene Expression Data to Study the Metabolic Syndrome and Diabetes in Mice

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