title: A wiring of the human nucleolus.
abstract: 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.
authors.affiliation: Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, DK-2800 Lyngby.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Hinsby
authors.forename: Lars
authors.initials: L
authors.lastname: Kiemer
authors.forename: E Olof
authors.initials: EO
authors.lastname: Karlberg
authors.forename: Kasper
authors.initials: K
authors.lastname: Lage
authors.forename: Anders
authors.initials: A
authors.lastname: Fausbøll
authors.forename: Agnieszka S
authors.initials: AS
authors.lastname: Juncker
authors.forename: Jens S
authors.initials: JS
authors.lastname: Andersen
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Søren
authors.initials: S
authors.lastname: Brunak
mesh_terms: 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
chemical_list: D020543:Proteome