Correlation-associated peptide networks of human cerebrospinal fluid.
Profiling of peptides and small proteins from either human body fluids or tissues by chromatography and subsequent mass spectrometry reveals several thousand individual peptide signals per sample. Any peptide is an intermediate in the course of biosynthesis, post-translational modification (PTM), proteolytic processing and degradation. Changes in the concentration of one peptide often affects the concentration of the other, hence a challenge consists in the development of suitable tools to turn this large amount of data into biologically relevant information. Comprehensive statistical analysis of the peptide profiling data allows associating peptides, which are closely related in terms of peptide biochemistry. Here, the bioinformatic concept of peptide networks, correlation-associated peptide networks (CANs), is introduced. Peptides with statistical similarity of their concentrations are grouped in form of networks, and these networks are interpreted in terms of peptide biochemistry. The spectrum of functional relationships found in cerebrospinal fluid CAN covers PTM and proteolytic degradation of peptides, clearance processing in the complement cascade, common secretion of peptides by neuroendocrine cells as well as ubiquitin-mediated degradation. Our results indicate that CAN is a powerful bioinformatic tool for the systematic analysis and interpretation of large peptidomics and proteomics data and helps to discover novel bioactive and diagnostic peptides.
Lamerz
Jens
J
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology ETH, Zürich, Switzerland. j.lamerz@biovision-discovery.de
Selle
Hartmut
H
Scapozza
Leonardo
L
Crameri
Reto
R
Schulz-Knappe
Peter
P
Mohring
Thomas
T
Kellmann
Markus
M
Khamenia
Valeri
V
Zucht
Hans-Dieter
HD
D005591:Chemical Fractionation; D002853:Chromatography, Liquid; D020650:Combinatorial Chemistry Techniques; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D030562:Databases, Protein; D006801:Humans; D018716:Molecular Mimicry; D010449:Peptide Mapping / Q000379:methods*; D010455:Peptides / Q000134:cerebrospinal fluid*; D040081:Protein Array Analysis; D011499:Protein Processing, Post-Translational; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D010455:Peptides