The Genomics Education Partnership, 2011 Charles Hauser 1, Wilson Leung 3, Chris Shaffer 3, David Lopatto 2, Sarah Elgin 3 and faculty and students of the GEP 1 St. Edward’s University, Austin TX, 2 Grinnell College, Grinnell, IA, 3 Washington University, St. Louis

Genomics Education Partnership (GEP) additional schools

Participating TX Institutions University of St. Thomas Donald Frohlich University of the Incarnate Word Christy MacKinnon, Russell Raymond Prairie View A&M Gloria Regisford Austin College Kelynne Reed Texas Wesleyan University Chitra Chandrasekaran St. Edward’s University Charles Hauser

Supporting undergraduate research in genomics Broad consensus: 1.We need to bring more genomics into our curriculum, and increase student familiarity with computer-based tools 2.Students need to know how new knowledge is created in their field 3.AAMC/HHMI Future Physicians Competencies: “Apply quantitative knowledge and reasoning—including integration of data, modeling, computation, and analysis—and informatics tools to diagnostic and therapeutic clinical decision making.” The Genomics Education Partnership uses a lab course centered on genomics research during the academic year to address these aims.

Individual projects, common tools, pooled results

The Drosophila melanogaster fourth chromosome exhibits an amalgam of heterochromatic and euchromatic properties C C HP 1 Phase James et al,1989 Heterochromatic properties: - Antibody staining of HP1, H3K9me2/3 - Lack of recombination - High repeat density Euchromatic properties: - Banded structure in polytene chromosomes - Gene density similar to other euchromatic domains (~80 genes in the distal 1.2Mb) - Transcriptionally active

Use comparative genomics to learn more about heterochromatic domains, analyzing the dot chromosomes and a control euchromatic region of Drosophila genomes GEP research goal: FlyBase: Reference Status Completed Annotation Sequence Improvement

St. Edward’s Research Explorations in Genomics Course Structure: Meet 6 hrs/week (MW 5-8pm) Max of 10 students, 1 TA Finishing Projects (~8 weeks) Annotation Projects (~7weeks) Finishing Select overlapping set of fosmids (scale: 7-10) Each student finishes a fosmid Class reassembles completed overlapping set at end Annotation Select overlapping set of contigs (scale: 7-10) Each student annotates a contig Class reassembles completed overlapping set at end

Finishing a fosmid (40 kb): Typical challenges with 6X coverage Design needed experiments (choice of primers, template for additional data); view result; redesign, repeat experiment as needed Advantage: concrete goal, clear endpoint Final verification- compare in silico restriction digests to actual restriction digest Report process to group, defend conclusions Satisfaction of solving challenging problems, making an original contribution Each project finished twice independently by GEP partner schools (75% congruence)

D. grimshawi DGB15A19 Initial project 1 st round 2nd round Finished fosmid

Annotation: Create gene models using sequence similarity and computational predictions Gene Predictions Sequence Homology Finished Sequence

Become familiar with tools available for finding genes, manage data Identify genes, create accurate models (start, exons, stop etc.) Analyze genome organization (synteny), repeats Use power of comparative genomics; reference D. melanogaster Address questions of evolution Experience presenting data, supporting conclusions based on available evidence Making an original contribution Each project done twice independently ~75% congruence (D. erecta), ~60% (D. mojavensis) Student Gene Predictors Benefits of the annotation process…

RNA-Seq modENCODE Adding second generation sequencing data to the genome browsers

Constraints, solutions…. to achieve institutionalization Need large time blocks Need appropriate lab: computers, internet access. Generating letter grades: graded training exercises; lab reports that argue results from data. Is it cost-effective, in dollars and personnel? –Yes, similar or significantly lower costs compared with individual mentored lab experience. –Student work is of high quality! Student ownership is essential! Problem - things change! New problems every year.

GEP assessment For most gains, a GEP course is as effective as a summer research experience. Understanding the research process Tackling real problems Lab techniques

Comments from GEP students The class was very intellectually challenging for me. It taught me to think in a way that I had never thought before. The thing that sparked me the most was the fact that I was able to perform the BLAST searches on my own and was able to explain to my instructor what I had done.

More comments from GEP students I learned to fight through the frustration and eventually figure out the problem. It would have been helpful if the instructor had attempted to be more helpful. I know if I could survive this class then I could survive just about anything.

Lessons Learned - Faculty Students need ownership Generating letter grades works Challenging - things change! Quality of the experimental work is very good.

Distributed projects, collaborative effort Use systems where - unfinished sequence data available on web - BACs/fosmids available from resource center Web-based system for training materials, - video of WU Genome Sequencing Center - data in/out Workshops for faculty and TAs Publication goals: - deposit sequencing results in Genbank - deposit annotation results with Flybase - scientific literature ( Genetics, 2010; Genome Biology,2006 ) - science education literature ( CBE Life Sci Educ, 2010; Science,2008 )

The format is flexible Can be initiated as part of an existing course, as part of a lab in molecular genetics, or as a new course Technology requirements: –for annotation, a computer lab with internet access; –for finishing, Macs or unix based system. Washington University staff provide tech support as needed Needed background: –an understanding of genetics –ability to type, use a Mac or PC, use the internet.

Resources & Support Faculty, TA workshops Curriculum resources Forum, wiki –Finishing guidance –Annotation questions Tools –UCSC browser –Gene model checker

Website Genomics Education Partnership WU Science Outreach References: Leung, W. et al. (2010). Evolution of a Distinct Genomic Domain in Drosophila: Comparative Analysis of the Dot Chromosome in Drosophila melanogaster and Drosophila virilis. Genetics, Vol. 185, Lopatto, D. et al (2008) “Genomics Education Partnership” Science Oct 31, Lopatto, D. (2004) “Survey of Undergraduate Research Experiences (SURE): First Findings” Cell Biology Education, vol. 3, pages , Winter 2004 (available on line at We are looking for interested faculty to join our Genomics Education Partnership Next workshop August 4-6, 2011 and January 8-13,2012 (TA)

Acknowledgements Sarah C.R. Elgin Chris Shaffer, Wilson Leung, GEP faculty Students!

Putative Polymorphisms Aligned Reads Window Trace Window Putative SNP

Contig 11 Contig 12 Contig 13 Contig 14 Contig 16 Contig 17 Contig 19 Contig 21 Contig 22 Annotation

Figure 8. Comparison of SURE follow up (N = 609) results with the current GEP results. Shaffer et. al., 2010 Increased Independence

Figure 10. Shaffer et. al., 2010 More Active Learner

GEP 2010 GEP 2009 Student evaluation of future plans Dave Lopatto, 2011

D. grimshawi DGB15A19

Students must evaluate the available evidence, create the best gene model and defend their conclusions