Gibbs sampling

Morten Nielsen,CBS, BioSys,

DTU

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

Gibbs samplerwww.cbs.dtu.dk/biotools/EasyGibbs

100 10mer peptides2100~1030 combinations

Monte Carlo simulations can do

it

Gibbs sampler. Monte Carlo simulations

RFFGGDRGAPKRGYLDPLIRGLLARPAKLQVKPGQPPRLLIYDASNRATGIPA GSLFVYNITTNKYKAFLDKQ SALLSSDITASVNCAK GFKGEQGPKGEPDVFKELKVHHANENI SRYWAIRTRSGGITYSTNEIDLQLSQEDGQTIE

RFFGGDRGAPKRGYLDPLIRGLLARPAKLQVKPGQPPRLLIYDASNRATGIPAGSLFVYNITTNKYKAFLDKQ SALLSSDITASVNCAK GFKGEQGPKGEPDVFKELKVHHANENI SRYWAIRTRSGGITYSTNEIDLQLSQEDGQTIE

E1 = 5.4 E2 = 5.7

E2 = 5.2

Paccept =1

0 < Paccept < 1

Monte Carlo Temperature

• What is the Monte Carlo temperature?

• Say dE=-0.2, T=1

• T=0.001

Shift alignment window

Gibbs sampler. Monte Carlo simulations

Getting stucked in local minima

It works

High Temperature Low Temperature

Gibbs sampler. Prediction accuracy

Use of Gibbs sampling

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

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