Structural Bioinformatics Syllabus
Spring 2009

Instructor: Dr. Steve Sontum,

Professor, Middlebury College Dept. of Chemistry&Biochemistry

Schedule

Lectures: Tuesdays and Thursdays, Feb 10-May 7, 9:30-10:45 AM,
McCardell Bicentennial Hall room 117
Computer Lab: Tuesday 1:30-4:15 PM,
 McCardell Bicentennial Hall room 546

Textbooks:

Genomics, Proteomics, & Bioinformatics by Campbell and Heyer
Developing Bioinformatics Computer Skills by Gibas and Jambeck
This is a practical "hands-on" course in Bioinformatics that will emphasize how to use computers and the web, as tools to analyze and represent large collections of biological sequence and structure data. Prerequisites include a basic understanding of the stucture of biological molecules, and some mathematics and statistics, but no prior knowledge of computer programming or computer hardware is necessary. You will gain practical experience with Perl, a programming language widely used in bioinformatics, web programming, and text processing.

Contents


Tues, Feb. 10
Lecture 1. Introduction to the course and Bioinformatics

Slides:
Lecture 1 PowerPoint slides
Reading:
What is Bioinformatics
Course Syllabus
Laboratory:
Questions Chapter 1: Lab 1: Using OMIM
Outline:
  • Course structure, project and policies
  • Overview of Bioinformatics
  • Genomics and Proteomics data bases
  • OMICS and the Molecular Biology OMES
  • Topics in Bioinformatics
  • Applications

Thurs, Feb. 12
Lecture 2. Continuation Lecture 1: Applications of Bioinformatics.

Slides:
Lecture 2 PowerPoint slides
Reading:
Chapter 1: "Whats Wrong with my Child" Campbell and Heyer
Project Consultation
 
Outline:
  • Designing New Drugs: Homology Modeling
  • Finding Homologs
  • Genome Characterization
  • Pharmacogenomics
  • Quiz

Tues, Feb. 17
Lecture 3. Whats Wrong with my Child: Medical Bioinformatics

Slides:
Lecture 3 PowerPoint slides
Reading:
Searching PubMed
Laboratory:
Finish Chapter 1 begin Chapter 2: (1-34): Lab 2: Using NCBI
Outline:
  • Introduction to NCBI
  • OMIM medical genetics data base
  • PDB protein structure data base
  • BLASTp on GenBank
  • CDD Conserved Domain Data Base
  • Entrez: Cross referenced data base
  • Searching PubMed
  • Discussion Ch 10 discovery questions

Thurs, Feb. 19
Lecture 4: Genome Sequence Acquisition and Analysis

Slides:
Lecture 4 PowerPoint slides
Reading:
Chapter 1: "Genome Sequence Acquisition and Analysis" Campbell and Heyer
NCBI: Accession Numbers
HGP Genomics Primer
Outline:
  • Nucleic Acid Sequencing
  • Human Genome Project
  • BLASTn, BLASTp, PSI-BLAST
  • Genbank SNPs, GOG, STSs, and ESTs data bases
  • Weizmann Institute GeneCard
  • HGP Genome Browser
  • EMBL Ensemble gene cross reference data base

Tues, Feb. 24
Lecture 5: Continuation of Lecture 4, Data Mining

Slides:
Lecture 5 PowerPoint slides
Reading:
Chapter 1: "Genome Sequence Acquisition and Analysis" Campbell and Heyer
NCBI: Blast Programs
DOE HGP: Gene Gateway to investigate genes
Laboratory:
Finish Discovery questions Chapter 2: (1-34)
Start Editing protein pdb files using Vim and VMD: Lab 3: Using VMD and VIM
Outline:
  • Genomic Data Mining
  • NCBI data bases: ESTs, UniGene, ORFs, and GOGs
  • Tools: MIT GenScan, Weizmann GeneCard, HGP Genome Browser, EMBL Ensemble
  • Proteomic Data Mining: Parametric Sequence Analysis
  • Tools: Expasy/Protscale and EBI/SignalP
  • UniProt cross referenced protein data base
  • Psi-Blast to find distantly related proteins
  • Discussion Ch 1 discovery questions

Tues, Mar. 3
Lecture 6: Visualizing Protein Structures and Computing Structural Properties

Slides:
Lecture 6 PowerPoint slides on protein structure
Reading:
Chapter 9: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
VMD Protein Visualization assignment
VMD Protein Visualization tutorial
Outline:
  • The basic building blocks: amino acids
  • Secondary structure
  • Forces that drive folding
  • Motifs or super-secondary structure
  • Domains
  • Finding out more about structures
  • How to visualize molecules with VMD
  • How to edit Protein Data Bank files

Thurs, Mar. 5
Lecture 7: Proteomics: Visualizing Protein Structures and Discussion of CH 2 Lab

Slides:
Lecture 7 PowerPoint slides on Proteomics
Reading:
Chapter 9: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Basic VMD graphics commands
Basic Vi editor commands
Assignment:
VMD graphics tutorial and questions
Outline:
  • Discussion of Discovery question CH 2
  • EST data bases

Tues, Mar. 10
Lecture 7: Proteomics: Protein Structure and Discussion of CH 2 Lab

Slides:
Lecture 7 PowerPoint slides on Proteomics
Reading:
Chapter 9: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Chapter 8: "Proteomics" Campbell and Heyer
Basic VMD graphics commands
VMD second homework set
VMD tutorial on tRNA synthetase
Protein Data Base
Assignment:
VMD AARS tutorial and questions
Discovery questions CH 6: (28-34)
Outline:
  • Discussion of Discovery question CH 2
  • EST data bases

Thurs, Mar. 12
Lecture 7: Proteomics: Searching 3D data bases

Slides:
Lecture 7 PowerPoint slides on Proteomics
Reading:
Chapter 9: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Chapter 8: "Proteomics" Campbell and Heyer
Basic VMD graphics commands
VMD second homework set
VMD tutorial on tRNA synthetase
Protein Data Base
Assignment:
VMD AARS tutorial and questions
Discovery questions CH 6: (28-34)
Outline:
  • How 3D structures of Proteins are Determined
  • What a RMS deviation and Least Squares means
  • What a distance matrix is
  • How Protein Structures are Superimposed
  • Multiple Structural Alignments of the AARS family

Tues, Mar. 17
Lecture 8: Proteomics: Summary of Bioinformatic methods

Slides:
Lecture 8 PowerPoint slides Summary of Proteomics
Reading:
Chapter 9: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Chapter 8: "Proteomics" Campbell and Heyer
VMD tutorial on tRNA synthetase
Laboratory:
VMD AARS tutorial and questions
Outline:
  • Review protein classification
  • Review structural proteomic methods
  • Enumerate the steps for protein identification
  • Parts list searches: Motif, Domain, CCD and COGs
  • Using Psi-Blast
  • Discussion: VMD first homework set

Tues, Mar. 31
Lecture 9: Building a Website

Slides:
Lecture 9 PowerPoint slides WebSites
Reading:
Chapter 12: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Basic Web page commands
Assignment:
Generate an index.html for your first web page
Prepare your web talk for Thursday after break
Outline:
  • History of the Web
  • LINUX file structure
  • Simple HTML tags
  • Writing HTML with Word, Power Point, Dream Weaver, and Nvu
  • Publishing your web page: Dream Weaver, Nvu, and FTP

Thurs, Mar. 19
Lecture 10: Continuation of Lecture 9: Publishing a Website

Slides:
Lecture 9 PowerPoint slides WebSites
Reading:
Chapter 12: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
How to use Dream weaver
Discussion:
Homology modeling: Rhodes Tutorial
Outline:
  • Selecting Your Template
  • Aligning two templates with VMD Stamp
  • Aligning two templates with SwissPDB
  • Evaluating your Homology Model

Tues, Mar. 31
Lecture 11: Sequence Analysis, Pairwise Alignment, and Database Searching

Slides:
Lecture 11 PowerPoint slides Pairwise sequence Alignment
Reading:
Chapter 7: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Needleman paper on global alignment
Waterman paper on local alignment
Current BLAST reference
NCBI Field Guide Exercises
Laboratory:
Prepare and Publish your Web talk or Work on your Exam
Outline:
  • Protein evolution, similarity, and homology
  • Methods for Pairwise alignment
    - Hand alignment
    - Dot Plots
    - Heuristic FastA and BLAST
    - Dynamic Programming
  • Parameters of Sequence Alignment
    - Gap penalties
    - Protein scoring matrices

Thurs, Apr. 2
Lecture 12: Continuation of Lecture 11 Pairwise Alignment

Slides:
Lecture 11 PowerPoint slides Pairwise sequence Alignment
Reading:
On Ramp to BLAST
On Ramp to Multisequence alignment
On Ramp to protein similarity searches
On Ramp to similarity searching
Pearson's tutorial on protein evolution -Fasta
Discussion:
First Project presentations and webpage demonstrations
Outline:
  • Methods for Pairwise alignment
    - Heuristic FastA and BLAST
    - Dynamic Programming
  • Parameters of Sequence Alignment
    - Gap penalties
    - Protein scoring matrices

Thurs, Mar. 12
Lecture 13: Predicting Protein Structure and Function from Sequence

Slides:
Lecture 14 PowerPoint slides Homology Models
Reading:
Chapter 10: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Structural Genomics
Homology Modeling
Basic Swiss PDB viewer commands
Assignment:
Swiss PDB viewer tutorial DeepView Tutorial
Outline:
  • Promise of Structural Bioinformatics
  • Anfinsen’s Thermodynamic Hypothesis
  • CASP and EVA assessment
  • Homology Modeling
    1) Template Selection
    2) Sequence alignment
    3) Threading Model
    4) Evaluating Model

Tues, Apr. 7
Lecture 14: Continuation of Lecture 13: Homology Modeling

Slides:
Lecture 14 PowerPoint slides Homology Modeling
Reading:
Chapter 10: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Laboratory:
- Project Proposal Presentations
- Work on Midterm Exam
Outline:
  • Homology Modeling
    2) Sequence alignment
    3) Threading Model
    4) Evaluating Model

Thurs, Apr. 9
Lecture 15: Homology Modeling

Slides:
Lecture 14 PowerPoint slides Homology Modeling
Reading:
Chapter 10: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Rhodes Homology Tutorial one
Assignment:
- Swiss PDB viewer tutorial DeepView Tutorial
- Rhodes tutorial Rhodes Tutorial Homework
- Your Final Project
Outline:
  • Homology Modeling
    3) Threading Model
    4) Evaluating Model
  • Web based homology modeling servers
  • Protein docking servers

Tues, Apr. 14
Lecture 16: Continuation of Lecture 15: Homology Modeling

Slides:
Lecture 14 PowerPoint slides Homology Modeling
Reading:
Chapter 10: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Rhodes Homology Tutorial one
Laboratory:
- Swiss PDB viewer tutorial DeepView Tutorial
- Rhodes tutorial Rhodes Tutorial
- Your Final Project
Outline:
  • Homology Modeling
  • Web based homology modeling servers
  • Protein docking servers

Thurs, Apr. 16
Lecture 17: Automating Bioinformatics with Perl

Slides:
Lecture 17 PowerPoint slides Perl Programing
Reading:
Chapter 12: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Sample Perl programs 1
How Perl Saved the Human Genome Project
Homework:
Perl homework 1
Midterm Exam:
Take home midterm exam
Outline:
  • Introduction to Perl
    A. Running Perl
    B. Scalar variables
    C. Binding operator =~
    D. String substitution and translation
    E. Reading a file

Tues, Apr 21
Lecture 18: Continuation Lecture 17: Automating Bioinformatics with Perl

Slides:
Lecture 17 PowerPoint slides Perl Subroutines
Reading:
Chapter 12: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Sample Perl programs 2
Homework:
Perl homework 2
Outline:
  • Introduction to Perl
    A. Writing Files
    B. Conditional Statements
    C. Pattern Matching
    D. Subroutines
    E. BioPerl

Thurs, Apr. 23
Lecture 19: Continuation Lecture 17: Automating Bioinformatics with Perl

Slides:
Lecture 19 PowerPoint slides Perl Subroutines
Reading:
Chapter 12: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Sample Perl programs 2
Outline:
  • Introduction to Perl
    B. Conditional Statements
    C. Pattern Matching (Regular Expressions)
    D. Subroutines
    E. BioPerl

Tues, Apr. 28
Lecture 20: Continuation Lecture 19: Automating Bioinformatics with Perl

Slides:
Lecture 19 PowerPoint slides Perl Subroutines
Reading:
Chapter 12: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
Sample Perl programs 2
Laboratory:
Final Project preparation
Outline:
  • Introduction to Perl
    D. Subroutines
    E. BioPerl

Thurs, Apr. 30
Lecture 21: Introduction to Microarrays

Slides:
Lecture 21 PowerPoint slides Microarray Introduction
Reading:
Chapter 4: "Basic Research with DNA Microarrays" Campbell and Heyer
Sample Microarray paper
Outline:
  • Understand the principles of the microarray technique.
  • Appreciate the limitations of microarrays and problems associated with the technique.
  • Know what types of output are generated from different microarray analysis packages and what they mean.
  • Understand and be able to evaluate research papers about microarrays.

Tues, May 5
Lecture 22: Cancer and Genomic Microarrays

Slides:
Lecture 22 PowerPoint slides Microarrays and Cancer
Reading:
Chapter 4: "Basic Research with DNA Microarrays" Campbell and Heyer
Sample Microarray paper
Laboratory:
Final Project preparation
Outline:
  • Goals of a Microarray experiment.
  • Myeloid leukamia (AML) vs. acute lymphoblastic leukemia (ALL)
  • Normalization of Miroarray data.
  • Detecting differential gene expression.
  • Principle component analysis.
  • Clustering analysis.

Thurs,  May 7
Lecture 23: Continuation Lecture 22: Cancer and Genomic Microarrays

Slides:
Lecture 22 PowerPoint slides Microarrays and Cancer
Reading:
Chapter 4: "Basic Research with DNA Microarrays" Campbell and Heyer
Sample Microarray paper
Laboratory:
Final Project preparation
Outline:
  • Detecting differential gene expression.
  • Principle component analysis.
  • Clustering analysis.
  • Course overview