Computational Methods in Evolutionary Biology, WS 2016/2017
Language: English
Instructor: Prof. Dr. Dirk Metzler
Time:
Lecture: Each Wednesday and Friday from 8:45 to 10:15
in room C00.013
Exercises: Each Wednesday from 10:15 to 11:00 and each Friday from 10:15 to
12:00 in the computer room C00.005
Additional exercises and lecture for block courses Phylogenetics I/II and
Comp. Pop. Gen. I/II: Tuesday 9:00 to 12:00 and Wednesday from 11:00 to 12:00.
Make-up exam for computational population genetics II: 24. March 2017 from
2:00 p.m. to 3:00 p.m. in seminar room C00.013. Note: to take this make-up exam it is necessary to register before 20. March by e-mail to Prof. Dr. Dirk Metzler.
Make-up exam for computational methods in evolutionary biology (for bioinformaticians): 24. March 2017 from
2:00 p.m. to 4:00 p.m. in seminar room C00.013. Note: to take this make-up exam it is necessary to register before 20. March by e-mail to Prof. Dr. Dirk Metzler.
Please note that you can bring an A4 formula sheet and a pocket
calculator. Then A4 formula sheet must only contain your original
handwriting! It can be two-sided. This holds for both exams.
Target group / Zielgruppe:
Master's and PhD students in EES/MEME, Bioinformatics, Biostatistics, Biology, Mathematics, Statistics,...
Students in block-structured programms like EES, MEME and the
Master's program in Biology can participate block-wise:
Phylogenetics I (Block I, Oct 17 - Nov 4)
Phylogenetics II (Block II, Nov 7 - Nov 25)
Computational
Methods in Population Genetics I
(Block III, Nov 28 - Dec 23)
Computational
Methods in Population Genetics II
(Block IV, Jan 9 - Feb 10)
Contents
Data sets of DNA, RNA or protein sequences contain a lot of hidden informations
about the history of evolution, about evolutionary processes and about the roles of
particular genes in evolutionary adaptation. It is a challenge to develop
methods to uncover these informations. Methods that are based on explicit
models for evolutionary processes and on the application of statistical principles
(like likelihood-maximization or Bayesian inferrence) are most promising. Some of these methods,
however, can be very demanding - computationally and intellectually. A
thorough understanding of the models and methods is crucial, not only for those
who aim to contribute to the further development of such methods but also for those who
want to apply these methods to their datasets and have to decide which method
to choose, how to set their optional parameters and how to interprete the outcome.
In the first half of the semester we will focus on computational methods in phylogenetics In the second
half of the semester we will turn to population genetics.
Bayesian and likelihood-based Phylogenetics
We discuss methods from computational statistics and their applications in
phylogenetic tree reconstruction. First we compare maximum-likelihood (ML)
methods to parsimonious and distance-based methods. Then we turn to Bayesian
methods that are based on Markov-Chain Monte-Carlo (MCMC) approaches like the
Metropolis-Hastings algorithm and Gibbs sampling. Such methods allow to sample
phylogenies (approximately) according to their posterior probability,
i.e. conditioned on the given sequence data. Thus, it is also possible to
assess the uncertainty of the estimation. Among the special applications that
we discuss are phylogeny estimation with time-calibration (e.g. according to
the fossil record) and methods for the reconcilement of gene trees and species trees.
Statistical methods are always based on probabilistic models for the origin of
the data. Therefore, we discuss evolution models for biological sequences
(Jukes-Cantor, PAM, F81, HKY, F84, GTR, Gamma-distributed rates,....) and the
fundamentals about Markov processes that are necessary to understand these
models. Furthermore, we will discuss relaxed molecular-clock models and
Brownian-motion models for the evolution of quantitative traits along
phylogenetic trees. Another topic are statical sequence-alignment methods that
are based on explicit sequence evolution models with insertions and deletions
(TKF91, TKF92,...).
Software:
PHYLIP,
Seq-Gen,
R
with the ape package,
RAxML,
MrBayes,
BEAST,
Bali-Phy,
....
Computational methods in population genetics
Given population genetic data, how can we infer evolutionary and
ecological features like population substructure, change of population
size, recent speciation, natural selection and adaptation? Many
computational methods for this purpose have been proposed and most of
them are freely available in software packages. In this course we will
discuss the theoretical and practical aspects of these methods. The
theoretical aspects are the underlying models, statistical principles
and computational strategies. In the practical part we will analyze these
methods. We will also try out
various software packages and explore under which circumstances they
are appropriate. Among the models that we discuss are the coalescent
process and its variants with structure and demography, the ancestral
selection graph, and the ancestral recombination graph. Among the
parameter estimation strategies are full-likelihood and full-Bayesian
methods, methods based on summary statistics, and Approximate-Bayesian
Computation. These methods use computational strategies like
importance sampling and variants of MCMC. Software:
LAMARC,
GENETREE,
Hudson's MS,
IM/IMa,
MIMAR,
STRUCTURE,
etc...
Handouts
The following handouts contain only a summary of the contents of the slides shown in
the lecture. More detailed explanations are given on the whiteboard during the
lectures. The handouts will be updated during the
semester.
Handout on Phylogenetics: PhyloHandout.pdf,
handout on Computational Population
Genetics: CMPG_handout.pdf
Exercises on Phylogenetics
phylo01.pdf
phylo02.pdf
phylo03.pdf
phylo04.pdf
, PAM_rate_matrix.txt, pfold_rate_matrix.txt
phylo05.pdf, pruning.R
phylo06.pdf, QuantTraitsA.csv, QuantTraitsB.csv, QuantTraitsC.csv, QuantTraits_Tree.txt
Phylogenetics example files
primates.nex, primates.phylip, primates.R, NJvsMPvsML.zip
Exercises on Computational Population Genetics
sheet01.pdf
sheet02.pdf
sheet03.pdf
sheet04.pdf
sheet05.pdf
sheet06.pdf, cheater.txt, cpg_islands.txt.zip
Comp PopGen software example files
Tajimas_D.R, abc.R
SortSequences.R (Example R file to convert ms/seq-gen output to Migrate input file, which can be read by Lamarac
input file converter)
Linux
In the practical part of the cours(es) we will use Linux. If you are new to
Linux/Unix, you may be interested in some online tutorials such as
http://www.ee.surrey.ac.uk/Teaching/Unix/.
Announcement for bioinformaticians in official LMU course overview
web page last updated: Dirk Metzler, 13. March 2017