just-in-time assembly - co-evolution of transcriptional and post-translational cell-cycle regulation...

Just-in-time assemblyCo-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.

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 this before

Ota et al.

Rustici et al.

Dyczkowski and Vingron

technical issues

orthology definitions

no reanalysis

different analysis methods

no error estimates

no biological explanation

turn back time …

temporal network

S. cerevisiae cell cycle

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

DNA polymerases

dynamic subunits

time of peak expression

time of action

just-in-time assembly

CDK substrates

Übersax et al.

Loog et al.

Phospho.ELM

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

Acknowledgments

Thomas Skøt JensenUlrik de Lichtenberg

Søren BrunakPeer Bork

Thank you!

Questions?