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A super quick introduction to molecular biology and genomics

Héctor Corrada Bravo

• Dept. of Computer Science

Center for Bioinformatics and Computational Biology University of Maryland University of Maryland, Spring 2012

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TCAGTTGGAGCTGCTCCCCCACGGCCTCTCCTCACATTCCACGTCCTGTAGCTCTATGACCTCCACCTTTGAGTCCCTCCTCTCACACCTGAC ATGAAAAGGCACATGAGGATCCTCAAATACCCCGTGATCAGTCTCAGGGTAGCTCTCATAGCCTGGACAGGGCCCCCCTCGGGGGTTGCGCCC AGGTCCAGGCGGGGGATGCACAGCAACAGTCACCGAAGCAGAAGCCGTCACAGTGGTGATGGGCTGGCAGTAGCTGGGCACAGAGCTGCCCAT GGCGGTGGACGTTGGGTTCCGAGGGTTGTGAGAACGGGCCCCACGGGGCCCTGAGCGGTCCCTATTGCTAGGGCCAGAATGCCCTTCAGTAGA AATTTCAAAAGCGTCTCTGCGCGGTCTGTAGGGGGGTGGCCGCAAGCCTTCTCTAGGGGGATCCCTTCGAGGCTGCTGGCCTTGCCGTCCAGG GGACAAGGAGCCAGAGTCCAGGTGGGGCTGTTGCCGAGGGGTCAAGGGAGGCTGATGTCTGGAGTCCGGATGGACCACCTGCAGAGGAGAGAC ATAGGTCAACACAGGGAGGTAGGATGGTGGTGATGTTCCACCCACAAAAGAAAACCTATTCCTTTAGAAACCTCCAGGATGTGAATCCTGCCT GCACCTGCACAGCTGGCTGGAGGCATATAGCCACTGCCCATAGATCTCAACTTACCCTCACAACCAACTGCCCCCAGGCCTAAGTTCTCTGCC TCAAAACTGCCAAGGCCTGGATAGCCAAGAGCCTGGGTGTCTTGGAAATATGCAACCATAAATAGTAGCTTTTAGAAGTATAAGGCTCCTGTT TCTGGGTCATATTAGTGTTGTTTTCACCTGTCCCCAGCCCTAAGCCAGGTGTGGCCAGAAGCAAATGTACTGTAAGAGCAGAGCAAAAACTTC CACACAGATAGTTCTGTTAGGCAATACATCTCTGCCTGACTATTAGGAATCTGGTTTCTGGGTCCTCTGTACAAAGCTCGGAGCAACACAGTG GCCACATCAATCAAAAGGACCGTGACCAACTTCAAAGTCGGTGAGCTTGTACCTATTTTTAGGCTCCTGCTGAACAGAACCAGATTCACACTA CAGCTCAGCAGGGCATCGTCACGGGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTTGGGGGGGGGGGGTGGACAGAGGACGGGGAC ACAATTCACTGGCCAGCCCTTCTCTCCTTCAAGGAAGGCTGCTCTAGCCTGGGACTGGAATACACATTTCCTGTAAACATGGTGGGGGCCTCA GGCAAGCCAGAGTTTTGGAGCCTTCCTTAACTCTTCAAGGTGAGCATCTTGACTTGGAGGGTGGGGGTGCGGGTAAGGAAGGAACCTGTGGAC TCCTCCCTACAAGACAGAAAAGGAATAAGCCACGAAGACAATAACGATTTTTGTATCAAGCGTCCTCTCCCATTTCAGCTTACCTGACAATGA AATCAAATTCGGACCCTGCAAGCATCAGTACACCCAGCAGAGTGGACACAGCACCGTCCAGAACGGGAGCAAACATGTGCTCCAGAGCGAGCA TAGCCCTGTGGTTCTTGTCCCCAATGGCTGTCAGAAAGGCCTGAACAAAGGAGAAAATTGACACGGTCACATTCTGGGTGTGGTAAAGTGCTC AGCTGTGTCTATACTTGGGTTTTGTAT…

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The genetic code

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http://www.uniprot.org/uniprot/P09238

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RNA-seq differential expression

GATCACAGGTCTATCACCCTATTAACCACTCACGGGAGCTCTCCATGCATTTGGTATTTTCGTCTGGGGGGTATGCACGCGATAGCATTGCGAGACGCTGGAGCCGGAGCACCCTATGTCGCAGTATCTGTCTTTGATTCCTGCCTCATCCTATTATTTATCGCACCTACGTTCAATATT GTCGCAGTATCTGTCT GTCGCAGTATCTGTCT GTCGCAGTATCTGTCT GTCGCAGTATCTGTCT GTCGCAGTATCTGTCT TGTCGCAGTATCTGTC TATGTCGCAGTATCTG TATATCGCAGTATCTG TATATCGCAGTATCTG TATATCGCAGTATCTG CCCTATATCGCAGTAT AGCACCCTATGTCGCA AGCACCCTATATCGCA AGCACCCTATGTCGCA GAGCACCCTATGTCGC CCGGAGCACCCTATAT CCGGAGCACCCTATAT GCCGGAGCACCCTATG GTCGCAGTANCTGTCT ||||||||| |||||| GTCGCAGTATCTGTCT GGATCTGCGATATACC |||||| ||||||||| GGATCT-CGATATACC AATCTGATCTTATTTT |||||||||||||||| AATCTGATCTTATTTT ATATATATATATATAT |||||||||||||||| ATATATATATATATAT TCTCTCCCANNAGAGC ||||||||| ||||| TCTCTCCCAGGAGAGC

Gene 1 differentially expressed?: YES p-value: 0.0012

TGTCGCAGTATCTGTC AGCACCCTATGTCGCA GCCGGAGCACCCTATG GTCGCAGTANCTGTCT ||||||||| |||||| GTCGCAGTATCTGTCT GGATCTGCGATATACC |||||| ||||||||| GGATCT-CGATATACC AATCTGATCTTATTTT |||||||||||||||| AATCTGATCTTATTTT ATATATATATATATAT |||||||||||||||| ATATATATATATATAT TCTCTCCCANNAGAGC ||||||||| |||||

Gene 1

Sample A Sample B

Slide courtesy B. Langmead

31 Monday, January 30, 2012

article

MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia

Scott A. Armstrong1–4, Jane E. Staunton5, Lewis B. Silverman1,3,4, Rob Pieters6, Monique L. den Boer6, Mark

• D. Minden7, Stephen E. Sallan1,3,4, Eric S. Lander5, Todd R. Golub1,3,4,5* & Stanley J. Korsmeyer2,4,8*

*These authors contributed equally to this work. Published online: 3 December 2001, DOI: 10.1038/ng765

32 Monday, January 30, 2012

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[Corrada Bravo, et al. Gene expression anti-profiles. Submitted.]

33 Monday, January 30, 2012

gene regulation

34 Monday, January 30, 2012

gene regulation

http://string-db.org/version_9_0/newstring_cgi/show_network_section.pl?identifier=9606.ENSP00000279441&all_channels_on=1&network_flavor=evidence&targetmode=proteins

35 Monday, January 30, 2012

[Ji, et al. Nature Biotechnology, 2008.]

ChIP-seq

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Measurement

42 Monday, January 30, 2012

Sec-gen Sequencing for SNPs

GATCACAGGTCTATCACCCTATTAACCACTCACGGGAGCTCTCCATGCATTTGGTATTTTCGTCTGGGGGGTATGCACGCGATAGCATTGCGAGACGCTGGAGCCGGAGCACCCTATGTCGCAGTATCTGTCTTTGATTCCTGCCTCATCCTATTATTTATCGCACCTACGTTCAATATT

GTCGCAGTANCTGTCT ||||||||| |||||| GTCGCAGTATCTGTCT GGATCTGCGATATACC |||||| ||||||||| GGATCT-CGATATACC AATCTGATCTTATTTT |||||||||||||||| AATCTGATCTTATTTT ATATATATATATATAT |||||||||||||||| ATATATATATATATAT TCTCTCCCANNAGAGC ||||||||| ||||| TCTCTCCCAGGAGAGC

Align Reference

Call: HET A, G

GTCGCAGTATCTGTCT GTCGCAGTATCTGTNN TGTCGCAGTATCTGTC TATGTCGCAGTATCTG TATATCGCAGTATCTT TATATCGCAGTATCTG NATATCGCAGTATNTG CCCTATATCGCAGTAT ACACCCTATGTCGCA ACACCCTATCTCGCA ACACCCTATGTCGCA GA-CACCCTATGTCGC CCGGA-CACCCTATAT CCGGA-CACCCTATAT GCCGGA-CACCCTATG “Coverage” “Pileup” or “Coverage plot” “Depth of coverage” = 14

(slide courtesy of Ben Langmead)

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DNA Methylation in cancer

56 Monday, January 30, 2012

[Hansen et al. Nature Genetics 2011]

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