I hear and I forget. I see and I remember. I do and I understand. - Confucius PCAST recommendation #2: “Advocate and provide support for replacing standard laboratory courses with discovery-based research courses.” Bioinformatics (genomics) will help us meet this challenge. The Genomics Education Partnership Sarah Elgin

Use comparative genomics to learn more about chromatin domains in Drosophila genomes: - improve sequence, annotate, analyze -dot chromosomes (F; heterochromatic) -comparison region (D; euchromatic) Our GEP research goal: FlyBase: Reference Status Completed Annotation Sequence Improvement New Project (motif finding) D. biarmipes

Annotation challenge: Create gene models from evidence: sequence similarity, computational predictions, RNA-Seq, etc. (local UCSC Browser) Improved Sequence Sequence Homology Gene Predictions RNA-Seq, TopHat, Cufflinks Repeats Students learn to use a UCSC genome browser, BLAST, FlyBase, Clustal, other data bases and tools.

Curriculum Question y = ax b No box: Derive the math, refine the algorithm How can we help students understand the mathematics or algorithm that underlies a bioinformatics tool? Glass box: Analyze the math, Model the relationships y = ax b Black box: Hide the math Give enough math to demystify the algorithm & relate it to key biological concepts

Interactive Excel Tool for Exploring Hidden Markov Models: Exon to Intron Transition Adjust probabilities to model specific system Excel computes likelihood of indiv. splice site positions Based on Eddy 2004 (Nat Biotech 22:1315–6) Anton Weisstein, Truman State University MO

Becoming intelligent users of bioinformatics tools (understanding algorithms, key parameters; command line manipulation) Analysis and data mining in complex eukaryotic genomes: new questions, new tools Metagenomics: interesting questions, needed analytical tools Analyzing RNA samples, mapping to known genomes (developmental progressions, environmental responses) Regulatory networks, signaling, patterns of relationships [Training biology faculty to become bioinformatics faculty] A bioinformatics course for biologists?

Science efficacy survey results comparing ~10 hr course (blue) and ~45 hr course (red) with summer-in-the-lab (green). GEP school SURE 09 Bio

The Genomics Workflow Public “draft” genomes Divide into overlapping student projects(~40kb) Sequence and assembly improvement Collect projects, compare and verify final consensus sequence Evidence-based gene annotation Collect projects, compare and confirm annotations Reassemble into high quality annotated sequence Analyze and publish results Sequence Improvement Annotation Students learn to use a UCSC genome browser, BLAST, FlyBase,Clustal, others. Students present findings at local meetings; GEP publishes as group.

9 Integration of genomics into the undergraduate biology curriculum Integration of research thinking into the academic year curriculum Advantages of bioinformatics / genomics: –Low laboratory costs (computers, internet connection) –No lab safety issues; open access 24/7 –Large pool of publically accessible raw data –Lends itself to peer instruction Currently ~100 faculty partners from > 110 colleges & universities; last year ~1300 students enrolled in GEP-associated courses. Goals :

Selected student quotes ….. 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. It was a great team-building and learning experience. It was independent work, but you were going through the same things as the other students and built camaraderie. I seriously think this should be the model for all biology courses.

But…more comments from GEP students I learned to fight through the frustration and eventually figure out the problem. I guess we learned about genomics through doing the tasks…. it was sort of a self-teaching class…. Everything we gained from the class…was either found by desperately messing around on the various websites …or by talking with other students. I know if I could survive this class then I could survive just about anything.

Can it work with freshmen? Yes - Phage Hunters! Graham Hatfull, U Pittsburgh: bacteriophage discovery and genomics for novice scientists Small genomes (50 – 150 kb, ~100 genes), simpler – continuous ORF. Now in use at many institutions, start-up supported by SEA (HHMI). Bioinformatics being introduced into general freshman course at Wash U as an optional lab, 20 contact hrs plus homework.

Phage Bioinformatics students: Angelica group organizes their workflow… GBrowse DNA Master (Roger Hendrix) BLAST Clustal Phamerator (Steve Cresawn)