A wiring of the human nucleolus.
Recent proteomic efforts have created an extensive inventory of the human nucleolar proteome. However, approximately 30% of the identified proteins lack functional annotation. We present an approach of assigning function to uncharacterized nucleolar proteins by data integration coupled to a machine-learning method. By assembling protein complexes, we present a first draft of the human ribosome biogenesis pathway encompassing 74 proteins and hereby assign function to 49 previously uncharacterized proteins. Moreover, the functional diversity of the nucleolus is underlined by the identification of a number of protein complexes with functions beyond ribosome biogenesis. Finally, we were able to obtain experimental evidence of nucleolar localization of 11 proteins, which were predicted by our platform to be associates of nucleolar complexes. We believe other biological organelles or systems could be "wired" in a similar fashion, integrating different types of data with high-throughput proteomics, followed by a detailed biological analysis and experimental validation.
Hinsby
Anders M
AM
Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, DK-2800 Lyngby.
Kiemer
Lars
L
Karlberg
E Olof
EO
Lage
Kasper
K
Fausbøll
Anders
A
Juncker
Agnieszka S
AS
Andersen
Jens S
JS
Mann
Matthias
M
Brunak
Søren
S
D001185:Artificial Intelligence; D002466:Cell Nucleolus / Q000737:chemistry* / Q000378:metabolism*; D016208:Databases, Factual; D014644:Genetic Variation; D006801:Humans; D008954:Models, Biological; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012270:Ribosomes / Q000378:metabolism*; D012985:Software Design
D020543:Proteome