1. Morten Nielsen, CBS, BioSys, DTU
Gibbs sampling
Morten Nielsen,
CBS, BioSys,
DTU

2. Class II MHC binding
MHC class II binds peptides in the class II antigen presentation pathway
Binds peptides of length 9-18 (even whole proteins can bind!)
Binding cleft is open
Binding core is 9 aa

3. Gibbs sampler www.cbs.dtu.dk/biotools/EasyGibbs
100 10mer peptides
2100~1030 combinations
Monte Carlo simulations can do it

4. Gibbs sampler. Monte Carlo simulations
RFFGGDRGAPKRG
YLDPLIRGLLARPAKLQV
KPGQPPRLLIYDASNRATGIPA
GSLFVYNITTNKYKAFLDKQ
SALLSSDITASVNCAK
GFKGEQGPKGEP
DVFKELKVHHANENI
SRYWAIRTRSGGI
TYSTNEIDLQLSQEDGQTIE
RFFGGDRGAPKRG
YLDPLIRGLLARPAKLQV
KPGQPPRLLIYDASNRATGIPA
GSLFVYNITTNKYKAFLDKQ
SALLSSDITASVNCAK
GFKGEQGPKGEP
DVFKELKVHHANENI
SRYWAIRTRSGGI
TYSTNEIDLQLSQEDGQTIE
E1 = 5.4
E2 = 5.7
Paccept =1
E2 = 5.2
0 < Paccept < 1

5. Monte Carlo Temperature
What is the Monte Carlo temperature, T?
Say dE=-0.2, T=1
T=0.001

6. Gibbs sampler. Monte Carlo simulations
Getting stucked in local minima
Shift alignment window

7. It works
High Temperature
Low Temperature

8. Gibbs sampler. Prediction accuracy

9. More than 1,000 papers in PubMed using Gibbs sampling methods
Use of Gibbs sampling
More than 1,000 papers in PubMed using Gibbs sampling methods
Transcription start-sites
Receptor binding sites
Acceptor:Donor sites
...

10. Summary
Weight matrices can accurately describe a sequence motif like MHC class I
Use sequence weighting to remove data redundancy
Use pseudo count to compensate for few data points
Gibbs sampling can detect MHC class II binding motif (and other gap-free motif with weak sequence signal)