Gibbs sampling Morten Nielsen CBS Bio Sys DTU

Gibbs sampling Morten Nielsen, CBS, Bio. Sys, 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/Easy. Gibbs 100 10 mer peptides 2100~1030 combinations Monte Carlo simulations can do it

Gibbs sampler. Monte Carlo simulations RFFGGDRGAPKRG YLDPLIRGLLARPAKLQV KPGQPPRLLIYDASNRATGIPA GSLFVYNITTNKYKAFLDKQ SALLSSDITASVNCAK GFKGEQGPKGEP DVFKELKVHHANENI SRYWAIRTRSGGI TYSTNEIDLQLSQEDGQTIE E 1 = 5. 4 RFFGGDRGAPKRG YLDPLIRGLLARPAKLQV KPGQPPRLLIYDASNRATGIPA GSLFVYNITTNKYKAFLDKQ SALLSSDITASVNCAK GFKGEQGPKGEP DVFKELKVHHANENI SRYWAIRTRSGGI TYSTNEIDLQLSQEDGQTIE E 2 = 5. 7 Paccept =1 E 2 = 5. 2 0 < Paccept < 1

Monte Carlo Temperature • What is the Monte Carlo temperature? • Say d. E=-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

Use of Gibbs sampling • More than 1, 000 papers in Pub. Med 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