Protein networks as a scaffold for structuring other data
Lars Juhl Jensen
EMBL Heidelberg
cell cycle regulation
interaction networks
what is an interaction?
functional interactions
physical interactions
complex pull-down
degree distribution
network robustness
self-activating baits
highly expressed proteins
can we trust this data?
the human interactome
1936
13
4
4
1385
65
18465
Stelzl et al. Rual et al.
Small-scale studies
32
0
3
4
18
4
23
Stelzl et al. Rual et al.
Small-scale studies
62 8 39
Small-scale studies
Stelzl et al. Rual et al.
852
17
473
432
69
260
3.5% and 21% sensitivity
the yeast interactome
1150
117
117
72
4053
118
4469
Uetz et al. Ito et al.
Small-scale studies
162
53
34
72
180
29
338
Uetz et al. Ito et al.
Small-scale studies
511 189 616
Small-scale studies
Uetz et al. Ito et al.
439
178
759
897
190
1347
19% and 12% sensitivity
complex pull-down
14186
784
1178
287
19492
230
3475
Gavin et al. Ho et al.
Small-scale studies
2341
125
656
287
2725
42
149
Gavin et al. Ho et al.
Small-scale studies
4431 1465 5041
Small-scale studies
Gavin et al. Ho et al.
14913
1071
632
8047
517
746
63% and 41% sensitivity
what about accuracy?
30–50% specificity
what can we do about it?
topology-based scoring
complex pull-down
log[(N12·N)/((N1+1)·(N2+1))]
-log((N1+1)·(N2+1))
calibrate against KEGG
subcellular localization
synchronized cell culture
microarray time series
periodically expressed genes
Ahdesmäki et al.
Willbrand et al.
Andersson et al.
protein interactions
temporal network
very low error rate
30+ uncharacterized proteins
detailed function prediction
global statements
dynamic and static
CDK–cyclin complexes
consistent timing
pre-replication complex
just-in-time assembly
how can we test this?
evolutionary conservation
more expression data
microarray time series
periodically expressed genes
Whitfield et al.
cross-species comparison
orthology assignment
individual genes
just-in-time assembly
protein complexes
pre-replication complex
chromatid cohesion
reproduces what is known
known differences
timing has changed
identity has changed
protein complexes
individual genes
broader perspective
protein networks
Acknowledgments
Ulrik de LichtenbergThomas Skøt JensenChristian von Mering
Søren BrunakPeer Bork