BSC3402, section 3 — Experimental Biology Lab: Comparative Genomics. Fall Semester 2004. Lectures — Tuesdays from 11:15 to 12:15 AM, in Dirac 152; Laboratory — Tuesdays from 1:00 to 3:00 PM, also in Dirac 152. Credit hours: two. Instructors: Fredrik Ronquist and Steve Thompson of FSU's School of Computational Science and Information Technology and FSU's Biology Department; and Teaching Assistant Calin Marian of FSU's Biology Department. Course Statement The computer analysis of genetic information is increasingly vital for biological research and in applications ranging from drug development to nature conservation. This course aims to provide first-hand experience in this area. It begins with lectures introducing the genomics databases, the molecular biology behind the data, and the computational techniques used to analyze it. Concurrently, the computer lab provides a hands-on learning experience on searching the databases, analyzing the data, and using scientific literature. Each student finishes the semester by independently designing and executing an original research project, after which they submit a written paper and give a talk presenting their results. What is comparative genomics? to compare . . . within and across species . . . genomes — the complete genetic (DNA) complement of an organism. What types of genomics databases are available? sequence — protein (e.g. SwissProt) and/or DNA (e.g. GenBank), mapping — linkage associations, literature — e.g. PubMed references. And how are they accessed? often through a browser, e.g: NCBI Genomes, the Online Mendelian Inheritance in Man, the Human Genome Database, the Stanford Genomic Resource, Indiana University's FlyBase, The Institute for Genomic Research; but dedicated software too: the GCG Wisconsin Package. What is the molecular biology behind the analyses? the Central Dogma: DNA —> RNA—> protein, complications: alternative splicing, RNA editing, prions, etc. Homology: related by decent! What types of analyses are available and why do we care? Again, there's dedicated software, such as: the GCG Wisconsin Package; and stuff on the World Wide Web for finding similar sequences: Blast at NCBI, FastA at the University of Virginia; and for aligning and analyzing them — both small, e.g: ClustalW, and big: TIGR software, PipMaker and MultiPipMaker, Comparative Genomics Center at Lawrence Livermore National Laboratory, Southwest Biotechnology and Informatics Center. Phylogenetics: inferring the patterns and processes of molecular evolution. Phylogenomics! correlating sequence to function with trees. 2 The Course Syllabus. Session Date Lecture Laboratory 1 August 24 Introduction Library Research Instruction session 2 August 31 Molecular Biology Web molecular biology resources 3 September 7 Genomics Web genome browsers 4 September 14 Genome Databases I Web genome analyses 5 September 21 Genome Databases II Using GCG 6 September 28 Similarity Searches Group Project 7 October 5 Alignment Group Project 8 October 12 Phylogenetics I Group Project 9 October 19 Phylogenetics II Group Project 10 October 26 Research writing How to write a proposal 11 November 2 Proposal due / counselling Counselling 12 November 9 Individual Project Individual Project 13 November 16 Individual Project Individual Project 14 November 23 Individual Project Individual Project 15 November 30 Project Reports Due No lab 16 December 7 Oral Presentations Oral Presentations (continued) In more detail: 1A. Lecture: Introduction (Fredrik Ronquist) Introduction to the course: schedule, what is required, grades, computational and other resources needed for the project, practical arrangements etc. What is the "Scientific Method," experiment, hypothesis, theory? What is comparative genomics? 1B. Lab: Library (Presented by Michael Luesebrink, Dirac Science Librarian.) Library Research Instruction session — Web resources in the FSU library system. 2A. Lecture: Introduction to Molecular Biology (Fredrik Ronquist) DNA, RNA, and proteins, packing of DNA, the central dogma — the translation of genetic material to proteins, the genetic code, gene expression and regulation, RNA splicing and alternative products, and metabolic pathways. 3 2B. Lab: Molecular Biology resources on the Web (Steve Thompson) Functions and relations of proteins in WIT, KEGG and similar resources on the Web. Instructional tools for molecular biology on the Web. 3A. Lecture: Introduction to genomics (Fredrik Ronquist) DNA copying and mutation; DNA sequencing, fragment assembly, restriction mapping, and PCR techniques; Size and structure of genomes in different organisms; Recognizing coding regions and annotating genes; Proteomics and microarrays. 3B. Lab: Genomics (Steve Thompson) Finding and browsing genome maps on the web, e.g Ensemble and FlyBase. Get started on Group Project by finding relevant Web genome data. 4A. Lecture: Genomics databases I (Steve Thompson) What Web databases and resources are available for genomic research? Specifically — how do I get scientific literature references, medical implications, and gene mapping information? 4B. Lab: Genomics databases I (Steve Thompson) Using Web interfaces to genomics analyses, including genomic comparisons and gene finding. 5A. Lecture: Genomics databases II (Steve Thompson) Accessing Web genomics databases, continued Specifically — What sequence and structure data is available on the Web? 5B. Lab: Genomics databases II (Steve Thompson) Introduction to GCG and access to its data. 6A. Lecture: Similarity searches and pairwise alignment (Steve Thompson) How do you discover sequence similarity and what is dynamic programming? 6B. Lab: Similarity searches (Steve Thompson) Find sequence data set for Group Project. 7A. Lecture: Multiple sequence alignment (Steve Thompson) 4 How do we align more than just two sequences at the same time? 7B. Lab: Alignment Align sequences for Group Project. 8A. Lecture: Phylogenetics I (Fredrik Ronquist) Distance measures Neighbor joining and parsimony 8B. Lab: Phylogenetics I (Fredrik Ronquist) Do NJ and parsimony analyses of sequences for Group Project. 9A. Lecture: Phylogenetics II (Fredrik Ronquist) Statistical inference principles Maximum likelihood inference Bayesian inference 9B. Lab: Phylogenetics II (Fredrik Ronquist) Do ML and Bayesian analyses of sequences for Group Project. 10A. Lecture: Summary (Fredrik Ronquist) Summarize project. How to write a paper based on the Group Project. How to write a proposal for the Individual Project. 10B. Lab: Project proposal Choose an Individual Project, Start writing a proposal. 11. Project proposal due (maximum of two pages). Worth 25% of grade. One-to-one counseling on the project proposal. 12-14. Work on individual project. 15. Written report on individual project due (between ten and twenty pages). Worth 50% of grade. 16. Oral Final presentations (eight minutes per student). 5 Worth 25% of grade. Your project and what we expect from you for your grade: Grading Requirements Grades will be based on: Points are translated to grades as follows: 1. Project Proposal (25 points) 2. Project Report (50 points) 3. Oral Presentation (25 points) 90 – 100 A 80 – 89 B 70 – 79 C 60 – 69 D 0 – 59 F The following criteria should be met to obtain the full score for each item: 1. Project Proposal (25 pt) The proposal should be handed in on time (5 points deduction if late). The proposal should be machine printed (not hand-written), legible and well organized (all margins should be 1 inch; pages should be paginated). It should be stapled together. The proposal should not be more than two pages long (excluding References) and it should be printed using 12 pt serif font and single line spacing. The language should be such that a fellow student would be able to read the proposal and understand its content. The proposal should contain the following sections or items: Series Title, Title, Author, Background, Aim, Methods, and References. The Series Title should be given at the top of the first page (12 pt font, italics, centered) and should read: Project Proposal, Comparative Genomics, Fall -04. The Title of the proposal should be short and descriptive (bold 14 pt sans serif font, centered). The Author should be given (name, email address) (centered). The Background section should explain why the question being asked is of interest. The Aim section should clearly state the scientific question being asked. It should also derive testable predictions relevant to the proposed project. The Methods section should describe how these predictions are to be tested. The References section should list all the cited references in a consistent format. The references should be correctly and consistently cited in the proposal text. Each one of the headings Background, Aim, Methods, and References should be on a separate line (14 pt font, bold, left-aligned). 2. Project Report (50 pt) The proposal should be handed in on time (5 points deduction if late). The proposal should be machine printed (not hand-written), legible and well organized (all margins should be 1 inch; pages should be paginated). It should be stapled together. 6 The manuscript should be between 10 and 20 pages long (double line spacing, 12 pt font unless stated otherwise) (excluding figure legends, tables, and figures). The length should be appropriate considering the scope of the content. The language should be such that a fellow student would be able to read the report and understand its content. The proposal should contain the following sections or items: Series Title, Title, Author, Background, Aim, Methods, and References. The Series Title should be given at the top of the first page (12 pt font, italics, centered) and should read: Project Report, Comparative Genomics, Fall -04. The Title of the proposal should be short and descriptive (bold 16 pt sans serif font, centered). The Author should be given (name, email address) (centered). The Introduction section should clearly state the question in focus and why it is of general interest. It should also briefly describe how it was addressed in the project. The introduction should summarize background information from at least two major scientific papers that are directly relevant to the topic of the report. The Data and Methods section should briefly describe the data and how it was obtained. It should also describe the methods used to analyze it. The Results and Discussion section should give the main results of the analyses, preferably in the form of figures and tables (appended to the end of the report). It should also discuss how these results relate to the question being asked. It might well turn out that the results did not answer the question being addressed in the project, typically for reasons that were impossible or difficult to anticipate when the project was designed. This is OK and will not result in points being lost. However, the results still need to be summarized and there must be a discussion on why the results did not answer the question being asked and some suggestions for how the project could be modified to address the question. The References section should list all the cited references in a consistent format. The references should be correctly and consistently cited in the main text of the report. Each one of the headings Introduction, Data and Methods, Results and Discussion, and References should be on a separate line (14 pt font, bold, left-aligned). 3. Oral Presentation (25 pt) The presentation should be 8 minutes long (10 pt will be deduced if the presentation is longer). It should be possible for fellow students to understand the presentation. The presentation should state the question being asked and briefly describe the method used to address it. The main result(s) should be presented in the form of a simple diagram or table that is easy to understand. ADA Statement: Florida State University provides high-quality services to students with disabilities, and we encourage you to take advantage of them. Students with disabilities needing academic accommodations should: (a) register with, and provide documentation to, the Student Disability Resource Center (SDRC) in room 108 in the Student Services Building (644-9566); and 7 (b) bring me a letter from SDRC indicating your needed academic accommodations. Please do this during the first week of class. For more information on this see the Resource Center's web site. Academic Honor code: Students are expected to uphold the Academic Honor Code published in The Florida State University Bulletin and in the Student Handbook. The first paragraph says: The Academic Honor System of Florida State University is based on the premise that each student has the responsibility to uphold the highest standards of academic integrity in the student's own work. 8