Jonathan Epstein, MS, Head, Unit on Biologic Computation
Xiongfong Chen, PhD, Guest Researcher
We provide end-user scientific software support for laboratories within the NICHD Division of Intramural Research. As a core facility, the Unit performs most of its work in conjunction with or on behalf of these laboratories.
Mass spectrometry
Epstein, Chen; in collaboration with Yergey
We have carried out much of our recent work in collaboration with the Laboratory of Cellular and Molecular Biophysics’s (LCMB) Section on Mass Spectrometry and Metabolism (SMSM); during the past year, we focused on the development of software and original algorithms for the de novo identification of peptides from mass spectra. Thus, we generate a database of all possible amino acid compositions up to 2000 daltons, indexed by mass and sequence length. We then query selected portions of this database based upon an input mass spectrum and the inherent mass accuracy of the instrument used to acquire the mass spectrum. Our software is written in Perl but some low-level optimizations are performed using C. We also obtain further performance improvements by using parallel computation. We have submitted one manuscript, and an additional manuscript focusing primarily algorithms we developed and formal computational analysis is in preparation.
We have also developed software to export raw mass spectral data from the ABI 4700 mass spectrometer into one of the evolving XML standards for proteomics data, mzXML. We developed a rudimentary Web-based laboratory management system for SMSM’s mass spectral data. We are testing Genologics® laboratory management software on behalf of LCMB/SMSM and expect that the Unit will function as a testbed for several other NIH institutes as well.
Microarrays
Chen, Epstein; in collaboration with Adler-Wailes, Baron, Harrington, Loh, Toyama, Zhao
We continue to act as a core facility for microarray analysis for several NICHD laboratories. On behalf of the Laboratory of Gene Regulation and Development, we have performed extensive analysis of Affymetrix microarrays, providing information derived from the Gene Ontologyä Consortium for selected upregulated and downregulated genes and undertaking considerable statistical analysis and the development of Web-based software tools. We also performed microarray analysis for the Section on Women’s Health Research and the Section on Growth and Development in the Developmental Endocrinology Branch. We completed additional work on behalf of the Section on Cellular Neurobiology. We are seeking to employ a variant of Principal Components Analysis derived from mass spectrometry analysis in order to apply the same techniques in microarray experiments that contain several independent factors or treatments.
Yang X, Dondeti V, Dezube R, Maynard DM, Geer LY, Epstein J, Chen X, Markey SP, Kowalak JA. DBPAerser: web-based software for shotgun proteomic data analysis. J Proteome Res 2004;3:1002-1008.
Two-dimension gel electrophoresis
Epstein; in collaboration with Garland, Giulian
With assistance from collaborators at NIMH and NEI, we developed a data representation for 2D-PAGE. The data representation includes a knowledge base stored in the industry-standard Protégé-2000 database. The ultimate goal is to tie the knowledge base into an expert system that will permit technicians or researchers who are not 2D-PAGE experts to select an appropriate laboratory protocol for running their gel. We have begun the process of top-down analysis of the procedure to complement our older bottom-up approach.
Clinical genomics
Epstein; in collaboration with Sastry
We have consulted with the Unit on Computer Support Services of the Office of the Scientific Director with respect to the design of its clinical trials database and the possible interface of its system with the National Center for Biotechnology Information’s single-nucleotide polymorphism database (dbSNP).
Three-dimensional protein structure
Chen, Epstein; in collaboration with Aguilera
We guided members of the Developmental Endocrinology Branch through the process of identifying structures and candidate binding sites of a family of G-coupled receptors.
Promoter analysis
Chen; in collaboration with Owens
We performed promoter identification, analysis, and annotation for the UGT gene family on behalf of the Heritable Disorders Branch.
Collaborators
Diane Adler-Wailes, MS, Developmental Endocrinology Branch, NICHD, Bethesda, MD
Greti Aguilera, MD, Developmental Endocrinology Branch, NICHD, Bethesda, MD
Jeffrey Baron, MD, PhD, Developmental Endocrinology Branch, NICHD, Bethesda, MD
Donita Garland, PhD, Laboratory of Mechanisms of Ocular Diseases, NEI, Bethesda, MD
Gary Giulian, MD, NIST, Gaithersburg, MD
Peter de B. Harrington, PhD, Ohio University, Athens, OH
Peng Loh, PhD, Section on Cellular Neurobiology, NICHD, Bethesda, MD
Matthew Olson, BS, Laboratory of Cellular and Molecular Biophysics, NICHD, Bethesda, MD
Ida Owens, PhD, Heritable Disorders Branch, NICHD, Bethesda, MD
Chandan Sastry, PhD, Office of the Scientific Director, NICHD, Bethesda, MD
Reiko Toyama, PhD, Laboratory of Molecular Genetics, NICHD, Bethesda, MD
Alfred Yergey, PhD, Laboratory Cellular and Molecular Biophysics, NICHD, Bethesda, MD
Hui Zhao, PhD, Laboratory of Molecular Genetics, NICHD, Bethesda, MD
For further information, contact jonathan_epstein@nih.gov.
