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Just-in-time assembly Co-evolution of transcriptional and post-translational cell-cycle regulation of protein complexes Lars Juhl Jensen EMBL Heidelberg
the cell cycle
grow and divide
one cell
two cells
four phases
G 1  phase
growth
S phase
DNA replication
G 2  phase
growth
M phase
cell division
 
regulation
gene expression
phosphorylation
targeted degradation
protein interactions
molecular biology
one gene
one postdoc
many types of data
a single gene
high-throughput biology
one lab
one technology
all the relevant genes
a single type of data
systems biology
many types of data
all the relevant genes
data integration
expression data
cell cultures
 
synchronization
microarrays
 
time courses
 
expression profiles
 
list of genes
periodically expressed
S. cerevisiae
expression data
Cho et al.
Spellman et al.
computational methods
Zhao et al.
Langmead et al.
Johansson et al.
Wichert et al.
Luan and Li
Lu et al.
Ahdesm äki et al.
Willbrand et al.
Chen
Qiu et al.
Ahnert et al.
Glynn et al.
Andersson et al.
Lu et al.
Xu et al.
Liew et al.
no benchmarking
reanalysis
benchmarking
 
no progress
no benchmarking
S. pombe
H. sapiens
A. thaliana
reanalysis
benchmarking
list of genes
periodically expressed
four organisms
orthologous groups
sequence similarity
 
not conserved
others had seen the same
Ota et al.
Rustici et al.
Dyczkowski and Vingron
no explanation
a long time ago in a journal far, far away …
(Science, 2005)
temporal network
 
dynamic and static subunits
just-in-time assembly
 
evolutionary flexibility
different organisms
different dynamic subunits
manual curation
protein complexes
 
 
 
different time scales
time warping
same color = same phase
deoxynucleotide synthesis
 
dynamic subunits
time of peak expression
time of action
just-in-time assembly
 
CDK substrates
Phospho.ELM
Übersax et al.
Loog et al.
NetPhosK
correlation
 
Fisher’s exact test
 
cell cycle vs. non-cell cycle
correlated changes
 
Fisher’s exact test
 
co-evolution
transcriptional regulation
phosphorylation
targeted degradation
just-in-time assembly
 
summary
reanalysis
benchmarking
integration
high-throughput data
reproduce what is know
biological discoveries
testable hypotheses
protein complex regulation
evolution
Acknowledgments ,[object Object],[object Object],[object Object],[object Object]
Thank you!
Questions?

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Just-in-time assembly - Co-evolution of transcriptional and post-translational cell-cycle regulation of protein complexes