Jianlin Cheng, PhD Informatics Institute, Computer Science Department University of Missouri, Columbia Fall, 2011Objectives • Walk students through the complete process of sequencing, assembling and annotating a genome. During the process, students lean key bioinformatics techniques for analyzing a genome and its components (i.e. gene, RNA, protein, and pathway). • By working on a comprehensive genome annotation project, students develop practical skills to apply bioinformatics methods to solve major problems in genome assembly and annotation.Instructors • Jianlin Cheng, PhD (coordinator) • Dmitry Korkin, PhD • Chi-Ren Shyu, PhD • Dong Xu, PhDTopics • Introduction to the course and a project (Jianlin Cheng) • Genome sequencing and assembly (Dong Xu) • Gene prediction (Dong Xu) • Protein structure prediction (Jianlin Cheng) • Protein function prediction (Jianlin Cheng) • Protein interaction prediction (Dmitry Korkin) • Biological pathways and networks (Chi-Ren Shyu)Course Format • Theory phase (one month): lecturing, literature review, mid-term presentation • Practice phase (two and a half months): discussion, planning (group), presentation, programming (group), results (group), assessment (group), and report (group) • Teamwork & leadership (two groups) • See syllabus for detailsAssignments • Literature review, topic plan (in presentation style), implementations of genome assembly and annotations (programs and results), topic report, and final report and presentation. • All the assignments should be posted to the project web site or emailed to me by deadlines. ([email protected])Evaluation and Grading • literature reviews (individual, 10%), mid-term presentation (individual, 10%), class discussion (individual, 15%), topic presentations (group, 15%), topic plans and reports (i.e. progress and assessment) (group, 15%), topic implementation (group, 20%), a final presentation and report (group, 15%) • Group components may be graded by both instructors and group peersCourse Web & Class Schedule • Course web (demo): http://www.cs.missouri.edu/~chengji/infoinst8010/ • Class schedule and assignments: http://www.cs.missouri.edu/~chengji/infoinst8010/8010_schedule.htmIntroduction •Grow •Sustain •Adapt •Reproduce •Genome & Components •Environment http://www.scq.ubc.ca/wp-content/uploads/2006/08/molecular-machine.gifApplications of Genome KnowledgeGenome Sequencing – Cracking the Code • Virus & Bacteria genomes (small) • Human genomeHuman Genome ProjectFunGenome Sequencing RoutineMU Genome Sequencing • Soybean genome: Gary Stacey, Dong Xu, Jay Thelen, Jianlin Cheng, Henry Nguyen, etc (Nature, 2010) • Chris Pires – plant genomesSequencing processGenome Sequencing MachineTopic 1: Genome AssemblyTopic 2. Gene Prediction Pattern Recognition ProblemGene Product - ProteinProtein Sequence, Structure, Function AGCWY…… CellProtein Structure SpaceProtein Data BankTopic 3: Protein structure prediction • Epstein & Anfinsen, 1961: sequence uniquely determines structure • INPUT: sequence 3D structure and function • OUTPUT: B. Rost, 2005Topic 4: Protein Function PredictionGene OntologyTopic 5: Protein-Protein Interaction Prediction ATP SynthaseProtein Interaction NetworkTopic 6: Reconstruction of Biological Pathway and Networks •Metabolic pathway •Signal transduction pathway •Gene regulatory pathwayMetabolic Pathway (KEGG)Signal Transduction PathwayGene Regulatory PathwayGene Regulatory Network Gene Regulatory Network of TF family p53 in humanA lot of techniques and challenges, how can we get it done in one semester? Novel learning technique: doing one genome assembly and annotation project in six stepsGroup Project Input: Short-gun sequences of a bacteria genome Genome Assembly Gene Prediction Protein Structure Prediction Protein Function Prediction Protein Interaction Prediction Construction of Biological Pathways Solutions Programs Results EvaluationReading Assignment J.C. Venter et al.. The sequence of the Huan Genome. Science. 291:1304, 2001 Read: Introduction and first three sections: http://www.sciencemag.org/cgi/reprint/291/5507/1304.pdf Write a review (one page) to summarize the main problems, methods and