just-in-time assembly - the evolution of transcriptional and post-translational cell-cycle...
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Just-in-time assemblyThe evolution of transcriptional and post-translational
cell-cycle regulation of protein complexes
Lars Juhl JensenEMBL Heidelberg
the cell cycle
grow and divide
one cell
two cells
four phases
G1 phase
growth
S phase
DNA replication
G2 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.
Ahdesmäki et al.
Willbrand et al.
Chen
Qiu et al.
Ahnert et al.
Andersson et al.
Lu et al.
no benchmarking
reanalysis
benchmarking
no progress
no benchmarking
protein interactions
S. cerevisiae
Uetz et al.
Ito et al.
Gavin et al.
Ho et al.
topology-based scoring
quality threshold
subcellular localization
expression data
temporal network
benchmarking
30–50% false positives
3–5% false positives
detailed function prediction
uncharacterized proteins
who
whom
when
global statements
consistent timing
dynamic and static
just-in-time assembly
partial protein complexes
last missing subunits
post-translational regulation
phosphorylation
Übersax et al.
27% of dynamic proteins
8% of static proteins
targeted degradation
PEST regions
44% of dynamic proteins
29% of static proteins
undescribed link
transcriptional regulation
post-translational regulation
how can we test this?
cross-species comparison
evolutionary conservation
expression data
S. pombe
Rustici et al.
Peng et al.
Oliva et al.
no benchmarking
no integration
reanalysis
integration
benchmarking
no progress
no benchmarking
no integration
H. sapiens
Whitfield et al.
reanalysis
benchmarking
A. thaliana
Menges et al.
reanalysis
benchmarking
four organisms
list of genes
periodically expressed
orthology detection
sequence similarity
not conserved
individual genes
just-in-time assembly
protein complexes
different time scales
time warping
same color = same phase
just-in-time assembly
DNA polymerases
deoxynucleotide synthesis
phosphorylation
Übersax et al.
Loog et al.
Phospho.ELM
NetPhosK
correlation
cell cycle vs. non-cell cycle
co-evolution
transcriptional regulation
post-translational regulation
co-evolution
just-in-time assembly
multi-layer regulation
evolutionary flexibility
protein complexes
summary
reanalysis
integration
high-throughput data
reproduce what is know
biological discoveries
testable hypotheses
evolutionary conservation
Acknowledgments
Thomas Skøt JensenUlrik de Lichtenberg
Søren BrunakPeer Bork
Questions?