Mapping a role for SNPs in drug development.
Explore the source record for details and available documents.
Algorithms↗
Biomedical subjects
B E Rothberg
Publications and source records attributed to B E Rothberg.
The use of animal models in expression pharmacogenomic analyses.
Expression pharmacogenomics applies genome/proteome scale differential expression technologies to both in vivo and in vitro models of drug response to identify candidate markers correlative with and predictive of drug toxicity and efficacy. It is anticipated to streamline drug development by triaging towards lead compounds and clinical candidates that maximize efficacy while minimizing safety risks. As the majority of expression pharmacogenomics will be performed on preclinical therapeutic candidates, compatibility with favored preclinical animal model systems will be essential. This review will address expression pharmacogenomics in the context of those animal model systems commonly used for pharmacokinetic, pharmacodynamic and toxicologic analyses. Specific discussions will cover: (A) relative robustness of genomic and proteomic technology platforms used to generate drug response data in critical model systems; (B) animal handling, treatment and other experimental design optimizations; (C) data analysis strategies for extracting and validating candidate pharmacogenomic markers; and (D) overarching limitations in applying expression pharmacogenomics to animal model systems.
Animals↗
Gene expression analysis by transcript profiling coupled to a gene database query.
We describe an mRNA profiling technique for determining differential gene expression that utilizes, but does not require, prior knowledge of gene sequences. This method permits high-throughput reproducible detection of most expressed sequences with a sensitivity of greater than 1 part in 100,000. Gene identification by database query of a restriction endonuclease fingerprint, confirmed by competitive PCR using gene-specific oligonucleotides, facilitates gene discovery by minimizing isolation procedures. This process, called GeneCalling, was validated by analysis of the gene expression profiles of normal and hypertrophic rat hearts following in vivo pressure overload.
Animals↗
Implications of oncogenomics for cancer research and clinical oncology.
The explosion of information generated by large-scale functional genomics technologies has resulted in an exponential increase in the number of potential genes and proteins available for pharmaceutical and diagnostic research development. In order to tap this potential, the primary challenge is to develop a strategy to effectively integrate and extract meaning from the human genomic sequence information that has been generated since the start of the Human Genome Project. This article deals with the strategies being applied by academics and by the biotechnology sector to sort and triage this information with the ultimate goal of identifying future therapeutic targets for cancer and other diseases.
Animals↗