Download A Database of Peak Annotations of Empirically Derived Mass Spectra

A Database of Peak Annotations of Empirically Derived
Mass Spectra
Dennis Harman[1], Patrick Smyth[2], and David Sigfredo Angulo[3]
DePaul University, CTI. [email protected]
[2] DePaul University, CTI. [email protected]
[1]
Abstract
[3]
DePaul University, [email protected]
(to whom correspondence is to be addressed)
IBG-MSP Database and the Data Loaded
Mass spectrometry has generated vast amounts of data and is the central technology in proteomics research.
Presently, several databases containing empirically derived tandem mass spectrum (MS/MS) data are publicly
available. These can be used singly or in a concatenated fashion; together they contain the sequences of more than
12 million proteins. We have imported these into the Illinois Bio-Grid Mass Spectrometry Proteomics Database
(IBG-MSP) along with annotations. The aim is to consolidate these now scattered public databases into a central
resource and to allow this database to be utilized for protein identification.
Database searching is the most popular approach used to identify unknown proteins. Spectra of unknown proteins
are matched against theoretical spectra derived from genomic or proteomic sequence databases. We have developed
software to utilize our empirical database to match against these unknown protein spectra which allows for more
accurate protein identification, especially in cases of post-translational modifications.
Our IBG-MSP contains a plethora of metadata including the amino acid sequence and details on the experimental
techniques utilized in collecting the samples. The overall format for the metadata closely follows mzXML, an
industry standard supported by HUPO. The IBG-MSP also supports MS/MS annotations, where peaks may be
annotated using terminology conventionally used in describing MS/MS fragment ion series. This is accomplished
through the implementation of algorithms based on the fragmentation rules of Collisionally Induced Dissociation
(CID) of protonated peptide ions. An annotated theoretical spectrum is generated from each amino acid sequence,
and the masses in each theoretical spectrum are matched to those in each experimental spectrum. Those annotations
are then stored in the database. As a centralized, computational solution for mass spectrometry-based proteomic
analyses, the IBG-MSP will not only be utilized to identification of proteins, but to provide training data for
development of new proteomic analysis tools.
The ER diagram shown displays the principal
tables and their associated relations contained
within the IBG-MSP database. The meta data from
xml file sources (Accession id, machine type,
precursor mass, etc..) is contained within the
database. Researchers can perform searches on
any data items.
Annotations such as a, b, or c and x, y, or z ions,
neutral loss or gain, immonium ion, or internal
cleavage ion can be found in the following tables:
ionSeriesDetail, neutrallosscharge, and
internalclevageion.
The Batch Import Module is a Java program, which is hosted on a 20 node cluster and is used to download data
from various publicly currated databases. The Module takes, as input, mass spectra, which are stored in mzXML
files, and the peptide sequences (stored in xml or csv files) associated with the spectra. A Fragmentation Modeling
Tool is utilized to annotate the spectra, as the data are imported into the database. The Module utilizes Java Beans,
Java JAXB technology, and the ProteomeCommons IO Framework [5].
Sources of Imported Data
Peptide Atlas [6]
http://www.peptideatlas.org/repository
Tranche @ ProteomeCommons.org [5]
http://www.proteomecommons.org/data.jsp
Fragmentation Modeling Tool
Peptide ions do not fragment at
random, but instead they always
fragment with a certain order, which is
well understood. A Fragmentation
Modeling Software Tool was
implemented that can be used to predict
the potential ions that could
theoretically be produced given a
specific amino acid sequence. The
Tool implements the rules of the
peptide fragmentation process and uses
data structures that we had previously
developed [2], [3]. Based on the amino
acid sequence associated with the
spectrum being imported, the Tool
computes the theoretical peaks of ions
containing the N terminus and the C
terminus (see figure to the right). These
theoretical peaks are then compared
with the peaks in the imported
spectrum using a linear time matching
algorithm. Where a match is found, the
annotation of the theoretical peak is
used to annotate the actual peak in the
imported spectrum.
References
[1] M. Kinter and N.E. Sherman, Protein Sequencing and Identification Using Tandem Mass Spectrometry, 2000; John
Wiley & Sons, Inc, New York, NY.
[2] Harman, D. and D. S. Angulo. Annotation of Mass Spectrum Data (Poster). Proceedings of the DePaul CTI Research
Symposium. Chicago, IL. May 5, 2997
[3] Harman, D.; Angulo, D.; Drew, K; Schilling, A. A Data Model for Annotating the Peaks of Mass Spectrum Data
(Poster). Proceedings of the Midwest Software Engineering Conference/DePaul CTI Research Symposium. Chicago,
IL. April 29, 2006.
[4] http://www.illinoisbiogrid.org/MSDB
[5] http://www.proteomecommons.org/
[6] http://www.peptideatlas.org/repository
Peptide Structure and Fragmentation
Fragmentation of peptides typically occurs along
the peptide backbone. The terminology
conventionally used in describing MS ions
encapsulates information about the
fragmentation processes that took place to
produce the ions. Each residue in the peptide
chain successively fragments off, both in the Nto-C and C-to-N directions. The location in the
backbone where the fragmentation occurs and
the terminus retaining the ionization charge
result in the formation of various ion types, a, b,
or c and x, y, or z ions. Doubly charged tryptic
peptides mainly yield singly charged y- and bions. A loss of a CO group resulting in a mass
difference of 27.9949 Da relative to the b-ion
can also occur and form a-ions. Other ions due
to losses of neutral H2O and NH3 are possible.