title: Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells.
abstract: BACKGROUND
  The mitotic spindle is a complex mechanical apparatus required for accurate segregation of sister chromosomes during mitosis. We designed a genetic screen using automated microscopy to discover factors essential for mitotic progression. Using a RNA interference library of 49,164 double-stranded RNAs targeting 23,835 human genes, we performed a loss of function screen to look for small interfering RNAs that arrest cells in metaphase.
  
  
  RESULTS
  Here we report the identification of genes that, when suppressed, result in structural defects in the mitotic spindle leading to bent, twisted, monopolar, or multipolar spindles, and cause cell cycle arrest. We further describe a novel analysis methodology for large-scale RNA interference datasets that relies on supervised clustering of these genes based on Gene Ontology, protein families, tissue expression, and protein-protein interactions.
  
  
  CONCLUSIONS
  This approach was utilized to classify functionally the identified genes in discrete mitotic processes. We confirmed the identity for a subset of these genes and examined more closely their mechanical role in spindle architecture.
authors.affiliation: Genomics Institute of Novartis Research Foundation, John Jay Hopkins Drive, San Diego, California 92121, USA. drines@gnf.org
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Rines
authors.forename: Maria Ana
authors.initials: MA
authors.lastname: Gomez-Ferreria
authors.forename: Yingyao
authors.initials: Y
authors.lastname: Zhou
authors.forename: Paul
authors.initials: P
authors.lastname: DeJesus
authors.forename: Seanna
authors.initials: S
authors.lastname: Grob
authors.forename: Serge
authors.initials: S
authors.lastname: Batalov
authors.forename: Marc
authors.initials: M
authors.lastname: Labow
authors.forename: Dieter
authors.initials: D
authors.lastname: Huesken
authors.forename: Craig
authors.initials: C
authors.lastname: Mickanin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hall
authors.forename: Mischa
authors.initials: M
authors.lastname: Reinhardt
authors.forename: Francois
authors.initials: F
authors.lastname: Natt
authors.forename: Joerg
authors.initials: J
authors.lastname: Lange
authors.forename: David J
authors.initials: DJ
authors.lastname: Sharp
authors.forename: Sumit K
authors.initials: SK
authors.lastname: Chanda
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Caldwell
mesh_terms: D015894:Genome, Human; D006801:Humans; D008938:Mitosis / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure*
chemical_list: D034741:RNA, Small Interfering