Genomics, Proteomics, & Bioinformatics by Campbell and Heyer
Structural Bioinformatics Syllabus
Spring 2008Instructor: Dr. Steve Sontum,
Professor, Middlebury College Dept. of Chemistry&Biochemistry
Schedule
Lectures: Tuesdays and Thursdays, Feb 12-May 8, 9:30-10:45 AM,
McCardell Bicentennial Hall room 117
Computer Lab: Thursdays 1:30-4:15 PM,
McCardell Bicentennial Hall room 117Textbooks:
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 protein and nucleic acid structure, and some mathematics and statistics, but no prior knowledge of computer programming or computer hardware is necessary.
Tues, Feb. 12
Lecture 1. Introduction to the course and Bioinformatics
- Slides:
- Lecture 1 PowerPoint slides
- Reading:
- What is bioinformatics
- Course Syllabus
- Outline:
- Course structure, project and policies
- Overview of Bioinformatics
- Genomic and Proteomic data bases
- OMICS and the Molecualr Biololgy OMES
- Topics in Bioinformatics
- Applications
Thurs, Feb. 14
Lecture 2. Continuation Lecture 1: Applications of Bioinformatics.
- Slides:
- Lecture 2 PowerPoint slides
- Reading:
- Chapter 10: "Whats Wrong with my Child" Campbell and Heyer
- Project Consultation
- Labratory:
- All Discovery questions Chapter 10
- Outline:
- Designing New Drugs: Homology Modeling
- Finding Homologs
- Genome Characterization
- Pharmacogenomics
- Quiz
Tues, Feb. 19
Lecture 3. Whats Wrong with my Child: Medical Bioinformatis
- Slides:
- Lecture 3 PowerPoint slides
- Reading:
- Searching PubMed
- 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. 21
Lecture 4: Genome Sequence Acquisition and Analysis
- Slides:
- Lecture 4 PowerPoint slides
- Reading:
- Chapter 1: "Genome Sequence Acuisistion and Analysis" Campbell and Heyer
- NCBI: Accession Numbers
- HGP Genomics Primer
- Laboratory:
- Discovery questions Chapter 1: (1-34)
- 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. 26
Lecture 5: Continuation of Lecture 4, Data Mining
- Slides:
- Lecture 5 PowerPoint slides
- Reading:
- Chapter 1: "Genome Sequence Acuisistion and Analysis" Campbell and Heyer
- NCBI: Blast Programs
- DOE HGP: Gene Gateway to investigate genes
- Assignment:
- Discovery questions Chapter 1: (1-34)
- 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
Thurs, Feb. 28
Lecture 6: Visualizing Protein Structures and Computing Structural Properties
- Slides:
- Lect 6 PowerPoint slides on protein structure
- Reading:
- Chapter 9: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
- Basic Vi editor commands
- VMD Protein Visualization assignment
- VMD Protein Visualization tutorial
- Laboratory:
- Finish Discovery questions Chapter 1: (1-34)
- Start Editing protein pdb files using Vim
- Outline:
- The basic building blocks: amino acids
- Secondary structure
- Forces that drive folding
- Motifs or supersecondary structure
- Domains
- Finding out more about structures
- How to visualize molecules with VMD
- How to edit Protein Data Bank files
Tues, Mar. 4
Lecture 7: Proteomics: Protein Structure and Dicussion of CH 2 Lab
- Slides:
- Lect 7 PowerPoint slides on proteomics
- Reading:
- Chapter 9: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
- Chapter 6: "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:
- Discusion of Discovery question CH 2
- EST data bases
Thurs, Mar. 6
Lecture 7: Proteomics: Proteomics: Searching 3D data bases
- Slides:
- Lect 7 PowerPoint slides on proteomics
- Reading:
- Chapter 9: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
- Chapter 6: "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. 11
Lecture 8: Proteomics: Summary of Bioinformatic methods
- Slides:
- Lect 8 PowerPoint slides Summary of proteomics
- Reading:
- Chapter 9: "Developing Bioinformatics Computer Skills" Gibas and Jambeck
- Chapter 6: "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
Thurs, Mar. 13
Lecture 13: Predicting Protein Structure and Function from Sequence
- Slides:
- Lect 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 ModelTues, Mar. 18
Lecture 14: Continuation of Lecture 13: Homology Modeling
- Slides:
- Lect 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 ModelThurs, Mar. 20
Lecture 15: Homology Modeling
- Slides:
- Lect 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. 1
Lecture 16: Continuation of Lecture 15: Homology Modeling
- Slides:
- Lect 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. 4
Lecture 9: Building a Website
- Slides:
- Lect 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
Tues, Apr. 8
Lecture 10: Continuation of Lecture 9: Publishing a Website
- Slides:
- Lect 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
- Alinging two templates with SwissPDB
- Evaluating your Homology Model
Thr, Apr. 11
Lecture 11: Sequence Analysis, Pairwise Alignment, and Database Searching
- Slides:
- Lect 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 matricesTues, Apr. 15
Lecture 12: Continuation of Lecture 11 Pairwise Alignment
- Slides:
- Lect 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 matricesThrs, Apr. 17
Lecture 17: Automating Bioinformatics with Perl
- Slides:
- Lect 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 fileThrs, Apr. 20
Lecture 18: Continuation Lecture 17: Automating Bioinformatics with Perl
- Slides:
- Lect 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. BioPerlTues, Apr. 25
Lecture 19: Continuation Lecture 17: Automating Bioinformatics with Perl
- Slides:
- Lect 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. BioPerlThurs, Apr. 27
Lecture 20: Continuation Lecture 19: Automating Bioinformatics with Perl
- Slides:
- Lect 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. BioPerlTues, May. 2
Lecture 21: Introduction to Microarrays
- Slides:
- Lect 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.
Thurs, May 4
Lecture 22: Cancer and Genomic Microarrays
- Slides:
- Lect 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.
Tues, May 9
Lecture 23: Continuation Lecture 22: Cancer and Genomic Microarrays
- Slides:
- Lect 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