A Whirlwind Tour of A Whirlwind Tour of Biomedical InformaticsBiomedical Informatics

Kun-Mao Chao (趙坤茂 )

National Taiwan University

http://www.csie.ntu.edu.tw/~kmchao/

2

About this courseAbout this course

• Course: Introduction to Biomedical Informatics• Spring semester, 2013• 9:10 - 12:10 Monday, 101 CSIE Building.• 3 credits• Web site:

http://www.csie.ntu.edu.tw/~kmchao/bioinformatics13spr• Instructor: Kun-Mao Chao (趙坤茂 )• Teaching assistant:

– Chia-Jung Chang (張家榮 ) & Wu-Lung R. Yang (楊伍隆 )

3

TA: Chia-Jung Chang (TA: Chia-Jung Chang ( 張家榮張家榮 ) & ) & Wu-Lung R. Yang (Wu-Lung R. Yang ( 楊伍隆楊伍隆 ) )

Chia-JungChia-Jung Wu-LungWu-Lung

4

CourseworkCoursework

• Homework assignments and Class participation (10%)

• Two midterm exams (70%; 35% each): – Midterm #1: April 1, 2013 (tentative)– Midterm #2: May 13, 2013 (tentative)

• Oral presentation of selected papers/projects (20%)

5

The Best? The Cheapest?The Best? The Cheapest?

The Best Entrance The Cheapest

6

Bio-X? X-Informatics?Bio-X? X-Informatics?

Bio-X Bioinformatics X-Informatics

Source: NIH, Bioinformatics Journal, NPS

7

Interdisciplinary PioneersInterdisciplinary Pioneers

Leonardo da Vinci Isaac NewtonArchimedes of Syracuse

Source: Wikipedia

8

Amphibia, TriphibiaAmphibia, Triphibia

Source: Wikipedia, xplanes

9

Band AlignmentBand Alignment(Joint work with W. Pearson and W. Miller, 1992)(Joint work with W. Pearson and W. Miller, 1992)

Seq. 1

Seq

. 2

10

Alignment in an Arbitrary RegionAlignment in an Arbitrary Region(Joint work with R. C. Hardison and W. Miller, 1993)(Joint work with R. C. Hardison and W. Miller, 1993)

11

Aligning Very Similar SequencesAligning Very Similar Sequences (Joint work with J. Zhang, J. Ostell and Webb Miller, 1997)(Joint work with J. Zhang, J. Ostell and Webb Miller, 1997)

12

Generalized Global AlignmentGeneralized Global Alignment (Joint work with X. Huang, 2003)(Joint work with X. Huang, 2003)

13

Tag SNPs & Haplotype InferenceTag SNPs & Haplotype Inference (Joint work with Y.-T. Huang (Joint work with Y.-T. Huang et alet al., 2006)., 2006)

Yao-Ting Huang Ting ChenKui Zhang Chia-Jung Chang Kun-Mao Chao

14

Sequence Comparison: Theory and Methods (Joint work with L. Zhang, 2009) (Joint work with L. Zhang, 2009)

15

Bioinformatics for BiologistsBioinformatics for BiologistsEdited by Pavel Pevzner and Ron Shamir Edited by Pavel Pevzner and Ron Shamir

Cambridge University Press, 2011Cambridge University Press, 2011

16

Bioinformatics for BiologistsBioinformatics for BiologistsEdited by Pavel Pevzner and Ron Shamir Edited by Pavel Pevzner and Ron Shamir

17

Bioinformatics for BiologistsBioinformatics for BiologistsEdited by Pavel Pevzner and Ron Shamir Edited by Pavel Pevzner and Ron Shamir

18

Central Dogma of Molecular BiologyCentral Dogma of Molecular Biology

Source: http://www.ncbi.nlm.nih.gov

19

From Genes to ProteinsFrom Genes to Proteins

Source: http://www.ornl.gov

20

Double HelixDouble Helix

Source: http://www.nature.com

21

A Brief History of GeneticsA Brief History of Genetics

• 1859 Charles Darwin published “The Origin of Species.”

• 1865 Genes are particular factors. [Gregor Mendel]

• 1869 Discovery of nucleic acid [Friedrich Miescher]

• 1903 Chromosomes are hereditary units. [Walter Sutton]

• 1910 Genes lie on chromosomes. [Thomas Hunt Morgan]

• 1913 Chromosomes are linear arrays of genes. [Alfred Sturtevant]

• 1931 Recombination occurs by crossing over. [Harriet Creighton and

Barbara McClintock]

22

A Brief History of Genetics (cont’d)A Brief History of Genetics (cont’d)

• 1944 DNA is the genetic material. [Oswald Avery, Colin McLeod and Maclyn McCarty]

• 1953 DNA is a double helix. [James Watson and Francis Crick]

• 1961-1967 Genetic code is triplet. [Marshall Nirenberg, Har Gobind Khorana, Sydney Brenner & Francis Crick]

• 1977 DNA was sequenced for the first time. [Fred Sanger, Walter Gilbert, and Allan Maxam]

• 21th Century: Many genomes completely sequenced

MIT Open Courseware:Biology 7.012 Introduction to Biology

23

Multiple Nobel LaureatesMultiple Nobel Laureates

24

Milestones of BioinformaticsMilestones of Bioinformatics

• 1962 Pauling's theory of molecular evolution• 1965 Margaret Dayhoff's Atlas of Protein Sequences• 1970 Needleman-Wunsch algorithm• 1977 DNA sequencing and software to analyze it (

Staden)• 1981 Smith-Waterman algorithm developed• 1981 The concept of a sequence motif (Doolittle)• 1982 GenBank Release 3 made public• 1982 Phage lambda genome sequenced

25

Milestones of Bioinformatics (cont’d)Milestones of Bioinformatics (cont’d)

• 1983 Sequence database searching algorithm (Wilbur-Lipman)

• 1985 FASTP/FASTN: fast sequence similarity searching• 1988 National Center for Biotechnology Information

(NCBI) created at NIH/NLM• 1990 BLAST: fast sequence similarity searching• 1991 EST: expressed sequence tag sequencing• 1993 Sanger Centre, Hinxton, UK• 1994 EMBL European Bioinformatics Institute,

Hinxton, UK

26

Milestones of Bioinformatics (cont’d)Milestones of Bioinformatics (cont’d)

• 1995 First bacterial genomes completely sequenced• 1996 Yeast genome completely sequenced• 1997 PSI-BLAST• 1998

Worm (multicellular) genome completely sequenced • 1999 Fly genome completely sequenced

27

Milestones of Bioinformatics (cont’d)Milestones of Bioinformatics (cont’d)

• Human Genome Project (1990-2003)

• Mouse 2002

• Rat 2004

• Chimpanzee 2005

• Completed Genomes

28

Chimpanzee GenomeChimpanzee Genome

29

The Primate Family TreeThe Primate Family Tree

Source: Nature

30

orz’s Sequence Evolutionorz’s Sequence Evolution

orz (kid)OTZ (adult)Orz (big head)Crz (motorcycle driver)on_ (soldier)or2 (bottom up)oΩ (back high)STO (the other way around)Oroz (me)

the origin?

their evolutionary relationships?

their putative functional relationships?

31

TopicsTopics

• Sequencing and genotyping technologies • Molecular sequence analysis • Recognition of genes and regulatory elements • Comparative genomics• Gene expression • Molecular structural biology• Biological networks • Systems biology • Computational proteomics • Molecular evolution• Phylogenetic trees• Population genetics • Medical informatics

32

Bioinformatics CentersBioinformatics Centers

• National Center for Biotechnology Information (NCBI, NIH):– http://www.ncbi.nlm.nih.gov/

• European Bioinformatics Institute (EBI):– http://www.ebi.ac.uk/

• DNA Data Bank of Japan (DDBJ):– http://www.ddbj.nig.ac.jp/index-e.html

• UCSC Genome Browser Home• RCSB Protein Data Bank

33

Bioinformatics DepartmentsBioinformatics Departments

Computational Biology and Bioinformatics, USCBioinformatics and Systems Biology, UCSDThe Broad Institute of MIT and HarvardComputational and Genomic Biology, UC BerkeleyBiomedical Informatics Research, Stanford UniversityComparative Genomics and Bioinformatics, Penn StatePenn Center for BioinformaticsMax Planck Institute for Molecular GeneticsBioinformatics and Computational Biology, Iowa State

34

Bioinformatics JournalsBioinformatics Journals

BioinformaticsJournal of Computational BiologyGenome ResearchNatureNucleic Acid ResearchPLoS Computational BiologyScience

35

Nature & ScienceNature & Science

36

Bioinformatics ConferencesBioinformatics Conferences

The Annual International Conference on Research in Computational Molecular Biology (RECOMB)

The Symposium on Intelligent Systems for Molecular Biology (ISMB)

The European Conferences on Computational Biology (ECCB)

37

Bioinformatics BooksBioinformatics Books

38

Bioinformatics CommunityBioinformatics Community

• The International Society for Computational Biology (ISCB)

– Senior Scientist Accomplishment Award

39

10 Steps to Success in Bioinformatics10 Steps to Success in Bioinformaticsby Webb Millerby Webb Miller

1. Become a biologist.

2. Value your number of citations above your number of publications.

3. Collaborate, and do it with great collaborators.

4. Do not expect a warm welcome from everyone.

5. Be a good collaborator.

6. Distribute and maintain software and/or run web servers that you personally continue to use.

40

10 Steps to Success in Bioinformatics10 Steps to Success in Bioinformaticsby Webb Millerby Webb Miller

7. Alternate between working on specific datasets and writing general-purpose software.

8. Write some of your own software.

9. Don't give up.

10. Be excited about your work.