Biomedical Technology Resources
Collaboration Through Dissemination
Visit Website Back

Proteomics Research Resource for Integrative Biology

Richard D. Smith, Ph.D.
P41RR018522
Active

Center Overview

The Proteomics Research Resource for Integrative Biology at Pacific Northwest National Laboratory (PNNL) was established to provide new proteomic technologies for use in the biomedical research community.

The possible roles and importance of proteomics are rapidly growing across essentially all areas of biological research. The precise and comprehensive measurement of levels of expressed proteins and their modified forms can provide new insights into the molecular nature of cell-signaling pathways and networks, the cell cycle, cellular differentiation, and other processes relevant to understanding human health and the progression of various disease states.

However, the most advanced proteomic technologies and capabilities, mostly developmental by nature, have been largely unavailable to the biomedical research community. This P41 Center has been established to bridge that gap, by developing and integrating new proteomic technologies for collaborative and service studies, disseminating the new technologies, and training scientists in their use.

Impact on Human Health

Researchers in the Center are pursuing biomedically relevant collaborative subprojects that involve proteomics studies of medically important areas of microbial pathogenicity, medical trauma research, diabetes, cellular migration, chronic virulent infections, kidney transplantation, neuroproteomics, mammary oncology, radiation response, human biofluid characterization, and the characterization of phosphoproteomes and other post translational modifications to understand the regulation of cellular signal transduction.

The Center has an ongoing collaboration with the CTSA located at the Oregon Health & Science University (OHSU), Portland, which focuses on a large population study. This study was designed to analyze serum samples already collected from a large, well-characterized human population to initially demonstrate and evaluate large-scale population proteomics, and potentially identify protein predictors of common and important outcomes of aging such as the development of sarcopenia. The outcome of these efforts will provide the first proof-of-principle for population proteomics, and drive the development of informatics and statistical tools needed to understand and interpret population level proteomics data.

Additionally, the Center has recently embarked on several new areas of research that further contribute to human health. These new areas include:

  1. an advanced technological platform that can be readily disseminated to the benefit of important biomedically related projects at other laboratories;
  2. advances in understanding of the human biological variability associated with the normal proteome and how this knowledge applies to interpreting proteomics results obtained in studies of highly complex mammalian systems (e.g., the mouse blood plasma proteome by measuring a diverse set of ~100 strains of mice and the human blood plasma proteome by measuring samples from 20 monozygotic twins); and
  3. the application of the modified, advanced proteomics platform to reveal new, highly credentialed biomarkers from cerebrospinal fluid (CSF) for the diagnosis of chronic fatigue syndrome in human patients.

These CSF studies will build upon recent Center efforts that have defined the CSF proteome for neurologically normal individuals (Schutzer et al., Establishing the Proteome of Normal Human Cerebrospinal Fluid, PLoS ONE 2010, 5:e10980), and also shown that the CSF proteome distinguishes chronic fatigue from post-treatment Lyme syndrome (Schutzer et al., Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome, PLoS ONE 2011, 6:e17287). Application of the modified platform for highly effective proteomic characterization of a large CSF sample cohort has significant potential not only for revealing confident biomarker candidates relevant for diagnosis of chronic fatigue syndrome, but also for gaining insights into disease pathogenesis.

Resources

ResourceDescriptionSupported PlatformsSupported FormatsData TypeData Size (compressed)
DanteR
Proteomics Research Resource for Integrative Biology
NIGMS

Used to perform various downstream data analysis, data reduction, and data comparison steps including normalization, hypothesis testing and clustering.

Linux, Mac OSX, Windows Excel, Text (.txt) N/A N/A
Decon2LS
Proteomics Research Resource for Integrative Biology
NIGMS

Used to de-isotope MS spectra and to detect features from MS data using isotopic signatures of expected components.

Windows Agilent Wiff, Bruker, Micromass,...(more) N/A N/A
DeconMSn
Proteomics Research Resource for Integrative Biology
NIGMS

Used to create .Dta files or .MGF files from tandem MS/MS data (Thermo Finnigan or mzXML format) with accurate parent monoisotopic mass and charge determined using the isotopic signatures of the parent ions.

Windows mzXML, Thermo Raw N/A N/A
DtaRefinery
Proteomics Research Resource for Integrative Biology
NIGMS

Improves mass measurement errors for parent ions of tandem MS/MS data by modeling systematic errors based on putative peptide identifications. This information is used to subtract out errors from parent ion protonated masses.

Windows Concatenated DTA.txt, DTA N/A N/A
ICR-2LS
Proteomics Research Resource for Integrative Biology
NIGMS

Finds peaks in raw mass spectra. Capable of full waveform generation, automated mass spectra interpretation and databas searching integration of FASTA or GenBank files.

Windows Agilent Wiff, Bruker, Micromass,...(more) N/A N/A
MASIC
Proteomics Research Resource for Integrative Biology
NIGMS

Generates selected ion chromatograms (SICs) for all of the parent ions chosen for fragmentation in an LC-MS/MS analysis.

Windows mzXML, Thermo Raw N/A N/A
Molecular Weight Calculator
Proteomics Research Resource for Integrative Biology
NIGMS

Calculates the molecular weight and percent composition of chemical formulas and amino acids.

Windows N/A N/A
MS File Info Scanner
Proteomics Research Resource for Integrative Biology
NIGMS

Scans a series of MS data files (or data folders) and extracts the acquisition start and end times, number of spectra, and the total size of the data, saving the values in the file DatasetTimeFile.txt.

Windows Agilent .D, Agilent Wiff,...(more) N/A N/A
MultiAlign
Proteomics Research Resource for Integrative Biology
NIGMS

Aligns multiple LC-MS datasets to one another, afterwhich LC-MS features can be matched to a database of peptides (e.g. an AMT tag database).

Windows Decon2LS .CSV files, ICR2LS...(more) N/A N/A
Normalized Elution Time Prediction Utility
Proteomics Research Resource for Integrative Biology
NIGMS

Used to compute the predicted normalized elution time (NET) value for a list of peptide sequences.

Windows Text (.txt) N/A N/A
Peptide Hit Results Processor
Proteomics Research Resource for Integrative Biology
NIGMS

Converts an X!Tandem results file (XML format) or a SEQUEST Synopsis/First Hits file to a series of tab-delimited text files summarizing the results.

Windows Text (.txt), X!Tandem XML N/A N/A
Protein Digestion Simulator
Proteomics Research Resource for Integrative Biology
NIGMS

Used to read a text file containing protein or peptide sequences (Fasta format or delimited text) and output the data to a tab-delimited file.

Windows FASTA, Text (.txt) N/A N/A
SpectrumLook
Proteomics Research Resource for Integrative Biology
NIGMS

Allows users to visually browse the MS/MS spectra that led to the peptide identifications, including viewing annotations for the identified b and y ions, plus neutral loss ions where appropriate.

Windows mzXML, Text (.txt) N/A N/A
Venn Diagram Plotter
Proteomics Research Resource for Integrative Biology
NIGMS

Draws correctly proportioned and positioned two and three circle Venn diagrams whose colors can be customized and the diagrams copied to the clipboard or saved to disk.

Windows mzXML, Text (.txt) N/A N/A
VIPER
Proteomics Research Resource for Integrative Biology
NIGMS

Used to visualize and characterize the features detected during LC-MS analyses.

Decon2LS .CSV files, ICR2LS...(more) N/A N/A