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Scientific Software Support and Bioinformatics Core Facility

Jonathan Epstein, MS
  • Jonathan Epstein, MS, Head, Unit on Biologic Computation

We provide end-user scientific software support for laboratories within NICHD’s Division of Intramural Research. Operating as a core facility, we perform most of our work in conjunction with or on behalf of these laboratories.

Mass spectrometry

We continue to collaborate with the Mass Spectrometry Core Facility. Our previous development of software for the de novo identification of peptides included a large data set (LIPCUT) that exhaustively enumerates all possible amino acid combinations falling into a given mass range. We recently developed software to enumerate the elemental composition of peptides in an analogous fashion and were able to leverage favorable combinatorics to perform such enumeration for higher mass peptides (4,500 daltons versus 1,750 daltons for LIPCUT). We are seeking to combine these resources with a newly developed isotopic clustering algorithm to improve existing peptide fragmentation database searches by submitting refined versions of the original spectrum to the search engine.

The current work also uses a database of known human proteins as a guide as to whether a given isotope cluster is likely to have been derived from an unmodified peptide or a peptide subjected to one or more common post-translational modifications.

In an effort to identify previously unannotated human gene products and alternative splicing, we are beginning to analyze high-throughput sequencing for RNA (RNA-Seq) by running previously acquired human mass spectra against the 6-frame translation of this voluminous RNA-Seq resource.

Short-read genome assembly and analysis

We are actively involved in a joint project with the Program in Genomics of Differentiation’s Section on Molecular and Cell Biology. Thus far, we have aligned Solexa reads of S. pombe to its reference genome and have remediated a set of S. pombe third-party genome corrections. We are working with three strains of S. pombe, one of which is a parent of the other two strains. We hope to identify differences between the parent strain and the canonical reference strain and, more importantly, to identify differences between the parent strain and its two mutants.

We have successfully identified a few known laboratory-induced mutations using these computational techniques, where the location of the mutations was intentionally withheld from us by our collaborators.

We have identified a single mutation that would appear to account for the primary mutation of interest between a parent strain and a mutant strain, but unfortunately this mutation corresponds to a synonymous mutation in the only known reading frame in the associated gene. Laboratory analysis by our collaborators will be necessary to resolve this mystery, possibly confirming that this mutation affects phenotype in an as yet unexplained manner.

Radiation hybrid mapping

Despite the availability of a draft zebrafish genome, we see demand for radiation hybrid mapping in zebrafish. We recently dismantled the LN54 radiation hybrid panel mapping web site (for technical reasons) and now receive requests to perform radiation hybrid mapping on a semimanual basis.

Microarrays

We continue to serve as a core facility for microarray analysis for NICHD laboratories. On behalf of the Program in Genomics of Differentiation's Section on Molecular Regulation, we performed analysis of Affymetrix® microarrays, including the selection of gene up/down regulation and the associated gene functions as guided by the Gene Ontology database.

General bioinformatics

We provided ongoing consultation on DNA and protein sequence analysis and on general bioinformatics issues to the Program in Genomics of Differentiation and have consulted with regard to evolving high-throughput DNA sequencing technology.

Publications

  • Toyama R, Chen X, Jhawar N, Aamar E, Epstein J, Reany N, Alon S, Gothilf Y, Klein DC, Dawid IB. Transcriptome analysis of the zebrafish pineal gland. Dev Dyn 2009 238:1813-1826.

Collaborators

  • Peter Backlund, PhD, Mass Spectrometry Core Facility, NICHD, Bethesda, MD
  • Igor Dawid, PhD, Program in Genomics of Differentiation, NICHD, Bethesda, MD
  • Bruce Howard, MD, Program in Genomics of Differentiation, NICHD, Bethesda, MD
  • James Iben, PhD, Program in Genomics of Differentiation, NICHD, Bethesda, MD
  • Richard Maraia, MD, Program in Genomics of Differentiation, NICHD, Bethesda, MD
  • Matthew Olson, MD, The Johns Hopkins University, Baltimore, MD
  • Dan Sackett, PhD, Program in Physical Biology, NICHD, Bethesda, MD
  • Steven Salzberg, PhD, University of Maryland, College Park, MD
  • Reiko Toyama, PhD, Program in Genomics of Differentiation, NICHD, Bethesda, MD
  • Alfred Yergey, PhD, Mass Spectrometry Core Facility, NICHD, Bethesda, MD

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