Session 4: PoT Mapping Software

Informatics Tools for Discovery of Pathways of Toxicity
Michael Rosenberg, Ph.D., Agilent Technologies, Inc.

Michael Rosenberg, Ph.D.

Michael V. Rosenberg, Ph.D. is a Program Manager, Bioinformatics at Agilent Technologies Inc. where his responsibilities include development of analyses and visualization tools for GeneSpring, Agilent premier bioinformatics software package, scientific collaborati-
ons and strategic planning. Prior to joining Agilent Dr. Rosenberg held several research and management positions in biotechnology and pharmaceutical industry. He served as Director of Professional Services at Rosetta Inpharmatics LLC, a wholly owned subsidiary of Merck and Co. Inc., Head of Bioinformatics at Biogen IDEC and Head of Sequencing Bioinformatics at Sanofi Aventis. Dr. Rosenberg earned his M.Sc. in physical chemistry and Ph.D. in biophysics of enzyme catalysis. He completed postdoctoral training in molecular and developmental genetics at Brandeis University, Whitehead Institute and Massachusetts General Hospital where he developed novel genome mapping technologies, participated in sequencing human Y chromosome as part of Human Genome project and cloned several disease-associated genes in humans and model organisms. Dr. Rosenberg authored a number of scientific publications and
patents, his interests are focused on developing novel computational biology tools enabling high-throughput omics research.



The Human Toxome Project is an ambitious effort aimed to create a framework of tools and methods to map and annotate human Pathways of Toxicity (PoT). Towards this goal a consortium of 6 academic, government and commercial organizations is using complimentary –omics approaches including transcriptomics, cytogenetics, metabolomics and proteomics to profile MCF7 cells induced with estrogen agonists and antagonists. Comprehensive bioinformatics analysis already allowed us to identify putative PoT candidates, additional discovery and validation efforts are currently in progress.

Developing software for visualization and integrated analysis of multidimensional datasets is one of the key goals of the toxome project. Agilent GeneSpring multi-omics software has been a workhorse of toxome data analysis since the outset of the project. Creating new bioinformatics tools for mapping human toxome is a focus of GeneSpring development efforts at Agilent.

To date, in close collaboration with members of the consortium, we developed several new features including metadata framework, a set of tools for identification of estrogen responders using correlation statistics and advanced pathway visualization and analytics for KEGG, WikiPathways and Biocyc. Development of new tools for integrated analysis of proteomics and cytogenomics datasets is currently underway.

Collaborative analysis of omics datasets at multiple locations represents a formidable logistical challenge. To that end, the Agilent team has designed and implemented Human Toxome Collaboratorium, a shared analyses workspace in Amazon cloud currently used by 10 consortium analysts.

Today the Collaboratorium consists of 45 applications deployed on 6 cloud servers and includes a repository of all consortium and relevant public datasets. Shared bioinformatics infrastructure is complemented by highly customized metadata store based on Agilent Electronic Lab Notebook software.

Success of Collaboratorium suggests a provocative new model for sharing the results of large data-intensive projects with the scientific community. In the future, not only data files, but the entire bioinformatics environment complete with working applications loaded with relevant data, metadata and analyses results could become available on-demand to interested scientists at a fraction of their initial development costs.