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Max-Planck-Institut für molekulare Genetik EBSV06 Martin Vingron Max-Planck-Institut für molekulare Genetik Reporting on work mainly by Tobias Müller,

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Presentation on theme: "Max-Planck-Institut für molekulare Genetik EBSV06 Martin Vingron Max-Planck-Institut für molekulare Genetik Reporting on work mainly by Tobias Müller,"— Presentation transcript:

1 Max-Planck-Institut für molekulare Genetik EBSV06 Martin Vingron Max-Planck-Institut für molekulare Genetik Reporting on work mainly by Tobias Müller, Antje Krause, Hannes Luz Family Specific Rates of Protein Evolution or, more general Markov models in protein evolution: Resolvent method, Systers, FSR

2 Max-Planck-Institut für molekulare Genetik EBSV06 Amino Acid Replacement

3 Max-Planck-Institut für molekulare Genetik EBSV06 Degree of Divergence

4 Max-Planck-Institut für molekulare Genetik EBSV06 Markov Assumption

5 Max-Planck-Institut für molekulare Genetik EBSV06 Exponential function p(t) = exp(qt) P(t) = exp(Qt) The same works with matrices: Infinitesimal generator, Rate matrix Transition probabilites A C R K F L

6 Max-Planck-Institut für molekulare Genetik EBSV06 The Model Variables

7 Max-Planck-Institut für molekulare Genetik EBSV06 The Problem

8 Max-Planck-Institut für molekulare Genetik EBSV06 Dayhoffs Estimation Procedure

9 Max-Planck-Institut für molekulare Genetik EBSV06 Linear Approximation

10 Max-Planck-Institut für molekulare Genetik EBSV06 Shortcomings

11 Max-Planck-Institut für molekulare Genetik EBSV06 The Problem (revisited) Homologous Sequences Evolutionary Distance Input DataRates

12 Max-Planck-Institut für molekulare Genetik EBSV06 An alternative Representation The întergral is called Resolvent of the transition probabilities.

13 Max-Planck-Institut für molekulare Genetik EBSV06 Resolvent Estimation Procedure

14 Max-Planck-Institut für molekulare Genetik EBSV06 ML Estimation of alignment distance

15 Max-Planck-Institut für molekulare Genetik EBSV06 Resolvent function theoretical estimated theoretical estimated ij

16 Max-Planck-Institut für molekulare Genetik EBSV06 Amino Acid Score Matrix

17 Max-Planck-Institut für molekulare Genetik EBSV06 Here we are… VT160

18 Max-Planck-Institut für molekulare Genetik EBSV06 Proportion of true relations found The proof of the pudding…. … is in the eating! Number of false positive matches Proportion of true relations found Many false positives, few true homologs Few false positives, many true homologs References: [1] Gavin A. Price, Gavin E. Crooks, Richard E. Green, and Steven E. Brenner Statistical evaluation of pairwise proteinsequence comparison with the Bayesian bootstrap.Bioinformatics, 21: [2] Gavin E. Crooks, and Steven E. Brenner An alternative model of amino acid replacement, 7,21,


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