Morten Nielsen, CBS, BioSys, DTU 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 sampler www.cbs.dtu.dk/biotools/EasyGibbs 100 10mer peptides 2100~1030 combinations Monte Carlo simulations can do it

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

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

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

It works High Temperature Low Temperature

Gibbs sampler. Prediction accuracy

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 ...

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)