HST.508 | Fall 2005 | Graduate

Quantitative Genomics

Lecture Notes

SES # TOPICS
L0 Introduction - Prof. Leonid Mirny (PDF - 1.8 MB)
Module 1: Evolutionary and Population Genetics - Lectures by Prof. Robert Berwick
L1 The Basic Forces of Evolution: Mutation, Recombination and Mating, Migration, Neutral Evolution and Drift, Effective Population Size (PDF)
L2 Selection, Fitness, Probability of Fixation, Coalescent Theory (PDF - 3.3 MB)

Parameter Estimation

R1 The Basic Forces of Evolution: Mutation, Recombination and Mating, Migration, Neutral Evolution and Drift, Effective Population Size

Selection, Fitness, Probability of Fixation, Coalescent Theory

Parameter Estimation

L3 Selection, Fitness, and Diffusion Models (PDF - 3.4 MB)

Molecular Evolution, Jukes-Cantor Model, Kimura Model

L4 Human/Mouse/Rat Examples

Measuring Selection: From ‘Classical’ Methods to Maximum Likelihood (With Applications to Disease Evolution, HIV and Influenza)

McDonald-Kreitman Test

R2 Discussion of Problem Set 1
L5 Medical Lecture: Genetic Diversity and Evolution of Hepatitis C Virus - Prof. Isaac Kohane
L6 Guest Lecture - Prof. Richard Lewontin
Module 2: Comparative Genomics - Lectures by Prof. Shamil Sunyaev
L7 Domain Structure of Proteins, Sequence-Structure-Function Relationships

Orthologs, Paralogs, In/Out-Paralogs

_Pairwise Sequence Comparison
_- Substitution Matrices (PAM, BLOSUM, Gonnet)
- Alignment Methods
- Alignment Statistics

L8 Structure of the Genome

Genome Comparison and Genome Evolution: Duplication, Recombination, Insertions, Repeats

Finding Genome Elements: Genes, Regulatory Regions

Motif Searching

Conserved Non-coding

R3 Infinite Site Model: Nucleotide Diversity, Allele Frequency
L9 Multiple Alignments, Profiles and PSSM, HMMs, Domain Databases

Prediction of Gene Function Using: Homology, Context, Structure

L10 SNPs: Microevolution, Inference of Population History

LD, Haplotypes, Medical Applications

Effect of SNPs on Function

R4 Recitation: SNPs
L11 Medical Lecture: Human Variations Genes, Genotypes and Generations - Dr. Marco Ramoni (PDF) (Courtesy of Dr. Marco Ramoni. Used with permission.)
Module 3: Structural Genomics and Proteomics - Lectures by Prof. Leonid Mirny
L12 Overview of Protein Structures, Domain Architecture (PDF - 1.2 MB)

Sequence-structure Mapping, Protein Folding, Forces and Interactions

L13 Structure-based Substitution Matrices (PDF - 1.1 MB)

Protein Structure Prediction

Threading

Protein Function: Binding and Kinetics, Michaelis-Menthen Kinetics, Inhibition

Protein-DNA Recognition: Models and Algorithms

L14 Proteomics: Networks of Protein-protein Interactions, Complexes, Modules

Power-law Distributions, Clustering Coefficient

L15 Proteomics: Evolution of Protein and Regulatory Networks, Function and Misfunction of Genes in Networks
R5 Recitation
L16 Medical Lecture: Hemoglobin and the Anemias - Prof. Isaac Kohane
L17 Guest Lecture
Module 4: Functional Genomics and Networks - Lectures by Prof. Alvin Kho
L18 Gene Regulation and Function, Conservation, Detecting Regulatory Elements (PDF - 2.0 MB)
L19 RNA Expression: Clustering and Classification (PDF - 5.0 MB)
L20 RNA Expression: Classification, 2-way Clustering, Regulatory Modules (PDF)

Integration of Expression and Proteomic Data

R6 Recitation
L21 Dynamics of Biological Networks Metabolic, Regulatory

FBA, Signaling, Regulation of Gene Expression

L22 Medical Lectures - Prof. Isaac Kohane
Two Examples: Phenylketonuria (monogenic) and Diabetes Type 2 (multigenic+)

“Disease” Genes vs. “Susceptibility” Genes

“Environmental” vs. “Developmental” Regulation of Gene Expression

L23 Guest Lecture
L24 Final Presentations