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Statistical Models in Computational Biology

News

May 1

Our paper Reliable detection of subclonal
single-nucleotide variants in tumor cell populations
appeared in Nature Communications today (see also ETH Life). In this work, we present the deepSNV algorithm and demonstrate its capability to detect subclonal mutations present in only 1/10,000 cells.

Gerstung et al. (2012) Nat Commun 3:811. DOI: 10.1038/ncomms1814.

News

Abstract

The course offers an introduction to graphical models and their application to complex biological systems. Graphical models combine a statistical methodology with efficient algorithms for inference in settings of high dimension and uncertainty. The unifying graphical model framework is developed and used to examine several classical and topical computational biology methods.

Objectives

The goal of this course is to establish the common language of graphical models for applications in computational biology and to see this methodology at work for several real-world data sets.

Description

Graphical models are a marriage between probability theory and graph theory. They combine the notion of probabilities with efficient algorithms for inference among many random variables. Graphical models play an important role in computational biology, because they explicitly address two features that are inherent to biological systems: complexity and uncertainty. We will develop the basic theory and the common underlying formalism of graphical models and discuss several computational biology applications. Topics covered include conditional independence, Bayesian networks, Markov random fields, Gaussian graphical models, EM algorithm, junction tree algorithm, model selection, Dirichlet process mixture, causality, the pair hidden Markov model for sequence alignment, probabilistic phylogenetic models, phylo-HMMs, microarray experiments and gene regulatory networks, protein interaction networks, learning from perturbation experiments, time series data and dynamic Bayesian networks. Some of the biological applications will be explored in small data analysis problems as part of the exercises.

Literature

Course Details

Course number: 262-0002-00L

  Date, Time
Room
Lecture Thursday, 10am – 12pm CAB G 56
Tutorial Thursday, 12pm – 1:30pm CAB G 59

All lectures will be given in English and are accompanied by a 2h tutorial every second week. For each tutorial, there will be assignments that need to be handed in (schedule to be announced). The final grade is 1/3 weekly problem solving, 1/3 data analysis projects in R, and 1/3 the oral exam.

Schedule

# Date
Title
Slides
Exercises Additional material Tutorial
1 Feb 24
Bayesian networks and gene regulation Introduction
Lecture 1
Exercise 1

Project 1

RInformation

Intro.R

Spellman.R

Boettcher2003

 1
2 Mar 3
EM algorithm and motif finding Lecture 2
     
3 Mar 10
Markov chains and hidden Markov models Lecture 3 Exercise 2

Project2

ATPases
GTP_binding_proteins
profileHMM.R
 2
4 Mar 17 Hidden Markov models for sequence alignment
Lecture 4      
5 Mar 24
Exact inference in graphical models: sum-product algorithm Lecture 5 Exercise 3

Project 3

Unclassified_proteins
profileHMM2.r
HMMs.r
 3
6 Mar 31
Junction tree algorithm Lecture 6      
7 Apr 7
Statistical phylogenetics Lecture 7 Exercise 4
Project 4
Phylo.r
ParisC2C4.txt
ParisRT.txt
ApeManual.pdf
PhangornManual.pdf

 4
8 Apr 14
Sampling and variational inference Lecture 8      
9
Apr 21 Model selection Lecture 9 Exercise 5

Project 5

dBNSpellmann.R

Spellman_alpha795.txt

True_Network

G1DBN_2.0.tar.gz

G1DBN_Manual.pdf

Lebre2009.pdf

 5
    --- Easter break ---        
10
May 5
Dynamic Bayesian networks and gene expression time series
Lecture 10      
11
May 12 Nested effects models and RNA interference Lecture 11 Exercise 6
Project 6
Tresch2008.pdf
Boutros2002.pdf

Nems.R

 6
12 May 19
Conjunctive Bayesian networks and cancer progression Lecture 12      
13 May 26
Deep sequencing of a mixed sample Lecture 13    
  Jun 2
-- Ascension Day --
       
 

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