PMID- 19293828
OWN - NLM
STAT- MEDLINE
DCOM- 20090720
LR  - 20220408
IS  - 1744-4292 (Electronic)
IS  - 1744-4292 (Linking)
VI  - 5
DP  - 2009
TI  - Toward accurate reconstruction of functional protein networks.
PG  - 248
LID - 10.1038/msb.2009.3 [doi]
AB  - Genome-scale screening studies are gradually accumulating a wealth of data on the 
      putative involvement of hundreds of genes/proteins in various cellular responses 
      or functions. A fundamental challenge is to chart out the protein pathways that 
      underlie these systems. Previous approaches to the problem have either employed a 
      local optimization criterion, aiming to infer each pathway independently, or a 
      global criterion, searching for the overall most parsimonious subnetwork. Here, 
      we study the trade-off between the two approaches and present a new intermediary 
      scheme that provides explicit control over it. We demonstrate its utility in the 
      analysis of the apoptosis network in humans, and the telomere length maintenance 
      (TLM) system in yeast. Our results show that in the majority of real-life cases, 
      the intermediary approach provides the most plausible solutions. We use a new set 
      of perturbation experiments measuring the role of essential genes in telomere 
      length regulation to further study the TLM network. Surprisingly, we find that 
      the proteasome plays an important role in telomere length regulation through its 
      associations with transcription and DNA repair circuits.
FAU - Yosef, Nir
AU  - Yosef N
AD  - The Blavatnik School of Computer Science, Tel-Aviv University, Tel-Aviv, Israel. 
      niryosef@post.tau.ac.il
FAU - Ungar, Lior
AU  - Ungar L
FAU - Zalckvar, Einat
AU  - Zalckvar E
FAU - Kimchi, Adi
AU  - Kimchi A
FAU - Kupiec, Martin
AU  - Kupiec M
FAU - Ruppin, Eytan
AU  - Ruppin E
FAU - Sharan, Roded
AU  - Sharan R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090317
PL  - Germany
TA  - Mol Syst Biol
JT  - Molecular systems biology
JID - 101235389
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Algorithms
MH  - Apoptosis
MH  - Databases, Protein
MH  - Humans
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Binding
MH  - Saccharomyces cerevisiae/cytology/*metabolism
MH  - Saccharomyces cerevisiae Proteins/*metabolism
MH  - Telomere/metabolism
PMC - PMC2671920
COIS- The authors declare that they have no conflict of interest.
EDAT- 2009/03/19 09:00
MHDA- 2009/07/21 09:00
PMCR- 2009/03/17
CRDT- 2009/03/19 09:00
PHST- 2008/10/06 00:00 [received]
PHST- 2009/01/07 00:00 [accepted]
PHST- 2009/03/19 09:00 [entrez]
PHST- 2009/03/19 09:00 [pubmed]
PHST- 2009/07/21 09:00 [medline]
PHST- 2009/03/17 00:00 [pmc-release]
AID - msb20093 [pii]
AID - 10.1038/msb.2009.3 [doi]
PST - ppublish
SO  - Mol Syst Biol. 2009;5:248. doi: 10.1038/msb.2009.3. Epub 2009 Mar 17.