Novel Application of Text Mining Methods to Identify Transcriptional Targets

Scientists from FDA's NCTR and NIH’s National Center for Advancing Translational Sciences (NCATS) applied a text mining method (author topic modeling) to integrate two different types of assay data (small molecule bioassays from Tox21 and in vitrohuman gene expression profiles from the Japanese Toxicogenomics Project) to discover transcriptional targets regulated by nuclear receptors. This novel application of text mining methods resulted in effective identification of associated/affected nuclear receptors and their target genes and provided biologically meaningful hypotheses embedded in their relationships. The study demonstrated that text mining methodologies can be an effective systems biology approach for integration of diverse sources of data from different technologies for an enhanced understanding of underlying mechanisms of disease and toxicity. A manuscript detailing the study is available online atToxicological Sciences.

For additional information, please contact Weida Tong, Ph.D, Director, Division of Bioinformatics and Biostatistics, NCTR.

Visitors to NCTR

Thomas W. Jones, Ph.D., Chief Scientific Officer, Toxicology and Pathology, Eli Lilly and Company

Seminar: “Is It Safe? Understanding the Performance of Nonclinical Safety Assessment Models in Predicting Human Outcomes”

Dr. Jones' career at Eli Lilly has included a variety of technical and administrative roles. Currently, as Chief Scientific Officer for the Toxicology and Pathology organization, Dr. Jones has administrative responsibility for the nonclinical safety support of the Lilly Research Laboratories portfolio. Through his accumulated experiences in academia, his career, and his involvement in the Society of Toxicology for over 25 years, Dr. Jones has developed valuable insights into the challenges and opportunities associated with the application of nonclinical safety data in human risk management.

Yasushi Yamazoe, Ph.D, Professor Emeritus, University of Tohoku and Food Safety Commission of Japan

Dr. Yasushi Yamazoe, an Emeritus Professor at Tohoku University in Sendai, Japan and Commissioner, Food Safety Commission, Cabinet Office, for the Government of Japan received the Asia Pacific Scientific Achievement Award. He is a past president of the Japanese Society for the Study of Xenobiotics and has served on the boards of many other scientific organizations. Dr. Yamazoe has enjoyed a long scientific career in drug metabolism and has made significant contributions to the study of the toxicity of drugs and chemicals.

Gareth Morgan, M.D., FRCP, FRCPath, Ph.D._UAMS

Gareth Morgan, M.D., FRCP, FRCPath, Ph.D., Director of the Myeloma Institute for Research and Therapy/University of Arkansas for Medical Sciences (UAMS)

Seminar: "Genetics of Myeloma"

Dr. Gareth Morgan is an internationally recognized scientist and clinician in the field of molecular genetics in blood cell cancers — in particular, multiple myeloma. He does influential work in characterizing the myeloma genome, defining specific subsets of the disease that have prognostic importance, and developing personalized therapeutic strategies targeted to each subtype. He is also engaged in advanced research in molecular diagnostics, drug development and clinical trials. Within the United Kingdom, he has been instrumental in the implementation of a national cancer policy in terms of governmental initiatives to address myeloma.

Dr. Jufeng Wang, Director, National Center for Safety Evaluation of Drugs/ National Institute for Food and Drug Control (NIFDC) Chinese FDA

Seminar: Current Research Projects in National Center for Safety Evaluation of Drugs

PBPK Model for Assessment of Human Exposure to Bisphenol A

Collaborators at NCTR and Pacific Northwest National Laboratory modified and recalibrated a nonhuman primate, physiologically based pharmacokinetic (PBPK) model for Bisphenol A (BPA) by incorporating human data to reduce uncertainties associated with the model simulations. The new model incorporated experimental data (serum concentration and urinary excretion profiles) from human volunteers who consumed deuterated BPA added in cookies and soup; along with in vitrostudies on BPA metabolism in the liver and the small intestine. This model improves human-exposure assessments and reduces uncertainties incurred during extrapolation across doses and species. A manuscript describing the model is available online atToxicology and Applied Pharmacology.

For additional information, please contact Jeffrey Fisher, Ph.D. or Xiaoxia Yang, Staff Fellow, Division of Biochemical Toxicology, NCTR.