Network-based inference from complex proteomic mixtures using SNIPE.
BACKGROUND
Proteomics presents the opportunity to provide novel insights about the global biochemical state of a tissue. However, a significant problem with current methods is that shotgun proteomics has limited success at detecting many low abundance proteins, such as transcription factors from complex mixtures of cells and tissues. The ability to assay for these proteins in the context of the entire proteome would be useful in many areas of experimental biology.


RESULTS
We used network-based inference in an approach named SNIPE (Software for Network Inference of Proteomics Experiments) that selectively highlights proteins that are more likely to be active but are otherwise undetectable in a shotgun proteomic sample. SNIPE integrates spectral counts from paired case-control samples over a network neighbourhood and assesses the statistical likelihood of enrichment by a permutation test. As an initial application, SNIPE was able to select several proteins required for early murine tooth development. Multiple lines of additional experimental evidence confirm that SNIPE can uncover previously unreported transcription factors in this system. We conclude that SNIPE can enhance the utility of shotgun proteomics data to facilitate the study of poorly detected proteins in complex mixtures.


METHODS
An implementation for the R statistical computing environment named snipeR has been made freely available at http://genetics.bwh.harvard.edu/snipe/.


BACKGROUND
ssunyaev@rics.bwh.harvard.edu


BACKGROUND
Supplementary data are available at Bioinformatics online.
Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
David P
DP
Nusinow
Adam
A
Kiezun
Daniel J
DJ
O'Connell
Joel M
JM
Chick
Yingzi
Y
Yue
Richard L
RL
Maas
Steven P
SP
Gygi
Shamil R
SR
Sunyaev
D000465:Algorithms; D000818:Animals; D019295:Computational Biology / Q000379:methods; D051379:Mice; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D012984:Software; D014070:Tooth / Q000378:metabolism
D020543:Proteome