The iPlant Collaborative Vision Enable life science researchers and educators to use and extend cyberinfrastructure

1986 DOE announces Human Genome Initiative-- $5.3 million to develop technology DOE & NIH present their HGP plan to Congress Escherichia coli genome published 1997 Yeast genome published 2000 Fruit fly (Drosophila) genome published Working draft of the human genome announced Thale cress (Arabidopsis) genome published (2x) Rice genome published (2x) Human genome published First tree genome published in Science First metagenomics study published Important Dates in Genomics

Just as computer software is rendered in long strings of 0s and 1s, the GENOME or “software” of life is represented by a string of the four nucleotides, A, G, C, and T. To understand the software of either - a computer or a living organism - we must know the order, or sequence, of these informative bits. What is sequencing? Slide: JGI, 2009

A GENOME is all of a living thing’s genetic material. The genetic material is DNA (DeoxyriboNucleic Acid) DNA, a double helical molecule, is made up of four nucleotide “letters”: A-- G-- T-- C-- What is a genome? Slide: JGI, 2009

Exciting? >mouse_ear_cress_1080 GAAATAATCAATGGAATATGTAGAGGTCTCCTGTACCTTCACAGAGATTCTAGGCTGAGAGCAGTGCATATAGATATCTTT CGTACTCATCTGCTTTTTCTGGTCTCCATCACAAAAGCCAACTAGGTAATCATATCAATCTCTCTTTACCGTTTACTCGAC CTTTTCCAATCAGGTGCT TCTGGTGTGTCTACTACTATCAGTTTTAGGTCTTTGTATACCTGATCTTATCTGCTACTG AGGCTTGTAAAAGTGATTAAAACTGTGACATTTACTCTAAGAGAAGTAACCTGTTTGATGCATTTCCCTAATATACCGGTG TGGAAAAGTGTAGGTATCTGTACTCAGCTGAAATGGTGGACGATTTTGAAGAAGATGAACTCTCATTGACTGAAAGCGGGT TGAAGAGTGAAGATGGCGTTATTATCGAGATGAATGTCTCCTGGATGCTTTTATTATCATGTTTGGGAATTTACCAAGGGA GAGGTATCAGAATCTATCTTAGAAGGTTACATTTAGCTCAAGCTTGCATCAACATCTTTACTTAGAGCTCTACGGGTTTTA GTGTGTTTGAAGTTTCTTAACTCCTAGTATAATTAGAATCTTCTGCAGCAGACTTTAGAGTTTTGGGATGTAGAGCTAACC AGAGTCGGTTTGTTTAAACTAGAATCTTTTTATGTAGCAGACTTGTTCAGTACCTGAATACCAGTTTTAAATTACCGTCAG ATGTTGATCTTGTTGGTAATAATGGAGAAACGGAAGAATAATTAGACGAAACAAACTCTTTAAGAACGTATCTTTCAGTTT TCCATCACAAATTTTCTTACAAGCTACAAAAATCGAACTATATATAACTGAACCGAATTTAAACCGGAGGGAGGGTTTGAC TTTGGTCAATCACATTTCCAATGATACCGTCGTTTGGTTTGGGGAAGCCTCGTCGTACAAATACGACGTCGTTTAAGGAAA GCCCTCCTTAACCCCAGTTATAAGCTCAAAGTTGTACTTGACCTTTTTAAAGAAGCACGAAACGAAAAACCCTAAAATTCC CAAGCAGAGAAAGAGAGACAGAGCAAGTACAGATTTCAACTAGCTCAAGATGATCATCCCTGTTCGTTGCTTTACTTGTGG AAAGGTTGATATTTTCCCCTTCGCTTTGGTCTTATTTAGGGTTTTACTCCGTCTTTATAGGGTTTTAGTTACTCCAAATTT GGCTAAGAAGAGATCTTTACTCTCTGTATTTGACACGAATGTTTTTAATCGGTTGGATACATGTTGGGTCGATTAGAGAAA TAAAGTATTGAGCTTTACTAAGCTTTCACCTTGTGATTGGTTTAGGTGATTGGAAACAAATGGGATCAGTATCTTGATCTT CTCCAGCTCGACTACACTGAAGGGTAAGCTTACAATGATTCTCACTTCTTGCTGCTCTAATCATCATACTTTGTGTCAAAA AGAGAGTAATTGCTTTGCGTTTTAGAGAAATTAGCCCAGATTTCGTATTGGGTCTGTGAAGTTTCATATTAGCTAACACAC TTCTCTAATTGATAACAGAAGCTATAAAATAGATTTGCTGATGAAGGAGTTAGCTTTTTATAATCTTCTGTGTTTGTGTTT TACTGTCTGTGTCATTGGAAGAGACTATGTCCTGCCTATATAATCTCTATGTGCCTATCTAGATTTTCTATACAATTGATA TTTGATAGAAGTAGAAAGTAAGACTTAAGGTCTTTTGATTAGACTTGTGCCCATCTACATGATTCTTATTGGACTAATCAT TCTTTGTGTGAAAATAGAATACTTTGTCTGAACATGAGAGAATGGTTCATAATACGTGTGAAGTATGGGATTAGTTCAACA ATTTCGCTATTGGAGAAGCAAACCAAGGGTTAATCGTTTATAGGGTTAAGCTAATGCTCTGCTCTTTATATGTTATTGGAA CAGACTATTGTTGTGCCTATCTTGTTTAGTTGTAGATTCTATCTCGACTGTTATAAGTATGACTGAAGGCTTGATGACTTA TGATTCTCTTTACACCTGTAGAAGGATTTAAGCTTGGTGTCTAGATATTCAATCTGTGTTGGTTTTGTCTTTCTTTTGGCT CTTAGTGTTGTTCAATCTCCTCAATAGGTATGAAGTTACAATATCCTTATTATTTTGCAGGGACGCACTTGATGCACTCCA GCTAGTCAGATACTGCTGCAGGCGTATGCTAATGACCTTGCATCAACATCTTTACTTAGAGCTCTACGGGTTTTAGTGTGT

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Find Gene Families Generate mathematical evidence Analyze large data amounts Browse in context Build gene models Gather biological evidence Annotation workflow Get DNA sequence

Walk or…

DNA Subway 2014

Coming into the Genome Age For the first time in the history of science students can work with the same data and tools that are used by researchers. Learning by asking and answering question. Students generate new knowledge.

Workshop Objectives Illustrate evolving concepts (e.g. “gene”) Conceptualize a “big picture” of complex, dynamic genomes. Guide students to address real problems through modern genome science. Use educational and research interfaces for bioinformatics. Work with “real” genome sequences gathered by students – in the lab or online.

Molecular biology and bioinformatics concepts RepeatMasker Eukaryotic genomes contain large amounts of repetitive DNA. Transposons can be located anywhere; they can mutate like any other DNA. FGenesH Gene Predictor Protein-coding information begins with start, followed by codons, ends in stop. Codons in mRNA (AUG, UAA,…) have sequence equivalents in DNA (ATG, TAA,…). Most eukaryotic introns have “canonical splice sites,” GT---AG (mRNA: GU---AG). Gene prediction programs search for patterns to predict genes and their structure. Different gene prediction programs may predict different genes and/or structures. Multiple Gene Predictors The protein coding sequence of a mRNA is flanked by untranslated regions (UTRs). UTRs hold regulatory information. BLAST Searches Gene or protein homologs share similarities due to common ancestry. Biological evidence is needed to curate gene models predicted by computers. mRNA transcripts and protein sequence data provide “hard” evidence for genes.

What is a gene? Can we define a gene? Has the definition of a gene changed? How can we find genes?

The Changing Concept of “Gene” Genes are independent hereditary units; Mendel (1866) Genes are located on chromosomes; Morgan (1915) One gene encodes one enzyme; Beadle & Tatum (1941) DNA is the molecule of heredity; Avery (1944) DNA > RNA > Protein; Crick, Watson, Wilkins (1953) Some genes move; McClintock (1940s) RNA > DNA; Temin & Baltimore (1970) Some genes are split; Roberts & Sharp (1977) RNA interference; Fire and Mello (1998) Pseudogenes have functions; Poliseno (2011)

Sequence & course material repository Don’t open items, save them to your computer!! Annotation (sequences & evidence) Manuals (DNA, Subway, Apollo, JalView) Presentations (.ppt files) Prospecting (sequences) Readings (Bioinformatics tools, splicing, etc.) Worksheets (Word docs, handouts, etc.) BCR-ABL (temporary; not course-related)