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Introduction to Bioinformatics
Zhiping Weng, 翁志萍
Program in Bioinformatics and Integrative Biology University of Massachusetts Medical School
同济⼤大学 ⽣生命科学与技术学院 ⽣生物信息学系
Outline
• Personal perspective of the history of bioinformatics
• Examples in chronological order
Outline
• Personal perspective of the history of bioinformatics
• Examples in chronological order
What is Bioinformatics?
• Informatics was coined in the early 1990s
• Informatics = Information Science + Technology
• Bioinformatics = Biology + Informatics (circa 1992)
1996
Boston University������
U Mass Medical School
“Bioinformatics” dates back to the 1960s
• Molecules as documents of evolutionary history���Journal of Theoretical Biology (1965) 8:357-66 ���Emile Zuckerkandl and Linus Pauling
• Computer analysis of protein evolution���Scientific American (1969) 221:86-95 ���Margaret Dayhoff
Genbank was established in 1982
Human genome was sequenced
1015
(1011)
In 1983 “bioinformatics” shook the world
• Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. ���Nature (1983) 304:35-9���Waterfield MD et al.
• Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor���Science 1983 221:275-7 ���Doolittle RF et al.
50 years from DNA to genomes • 1953 Watson & Crick discovered the double helix
• 1970s Recombinant DNA technology
• 1987 “Genomics” coined by T. Roderick: ���Gene + Chromosome + “ics” = Genomics
• 1990 Human Genome Project launched
• 1998 Human Genome Project accelerated by Celera Genomics Inc.
• 2001 Human Genome published twice
• 2003 “Finished” Human Genome sequence
• 2005, 2007, 2010, Human variation, Hapmap, 1000 genomes
• 2010 6216 Sequenced genomes (2313 eukaryotes)
• 2013 personal genomes, epigenomes, proteomes, etc.
Repaid development of sequencing technologies
Illumina HiSeq ABI SOLiD 454 Sequencer
Capable of resequencing a human genome in 1 week and under $5,000
Capillary
Automated capillary
454
Solexa/Illumina GA
HiSeq
GA2 GA2x
Technological improvements
Plummeting cost of DNA sequencing
Next generation sequencing applications
Gogol-Döring A, Chen W. Methods Mol Biol. 2012;802:249-57.
Outline
• Personal perspective of the history of bioinformatics
• Examples in chronological order
1
Two genomes enable detection of Segmental duplications (SD)
Creatine transporter (SLC6A8) and adrenoleukodystrophy (ABCD1) segmental duplication
2
Having a more ancient genome can tell history
• Whole genome duplication can supply raw materials for new functions.
• Polyploidy causes genome instability.
• Whole genome duplication is accompanied by massive gene loss.
• There are 8% genes in baker’s yeast Saccharomyces cerevisiae that are duplicated.
• Did the yeast undergo whole genome duplication?
A distance relative K. Waltii reveals synteny
Kellis, ..., Lander Nature (2004) 428: 617-624
3
Assaying expression of all genes in a genome
Prediction of central nervous system embryonal tumor outcome based on gene expression Pomeroy, ..., Golub, T. Nature (2002) 415, 436-442
4
Look beyond genes in the human genome
Where are the regulatory regions?
Genome-wide detection of regulatory regions
The ENCODE (ENCyclopedia Of DNA Elements) Project"Science (2004) 306:636-640."
DNase hypersensitive sites
What are ubiquitous hypersensitive sites?
Xi, ... , Weng, Crawford, PLoS Genetics (2007) 8:8-20
5
Sequence cancer genomes
Campbell,...Stratton, Futreal. Nature Genetics (2008) 40:6-13
6
Genome rearrangement creates a fused gene
Campbell,...Stratton, Futreal. Nature Genetics (2008) 40:6-13
7
Epigenome
Bernstein, ... Lander, Cell (2007) 128:669-681
H3K4me3 in human prefrontal cortex neurons
Cheung, Shulha, ..., Weng, Akbarian, PNAS (2010)
What kind of genes are on only in neurons?
• alkali metal ion binding
• transmembrane transporter activity
• voltage-gated potassium channel activity
• synaptic transmission
• transmission of nerve impulse
• Cell-cell communication
• These genes can be targets for drug development
8
Personalized medicine
Ng, ... Venter. Nature (2009) 461:724-726
A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase
inhibitors in cancer
Ng et al., Nature Medicine, 2012
9
Network analysis���Integrating all types of data at a system level
http://www.cell.com/issue?pii=S0092-8674%2811%29X0006-5
Networks in Cellular Systems Vidal et al., Cell, Volume 144, Issue 6, 986-998, 18 March 2011
10
Integrative inference of transcriptional networks
D. Marbach et al., Genome Res. 2012 July; 22(7): 1334–1349.
11
Evolution of gene regulatory networks
IS Peter and EH Davidson, Cell, Volume 144, Issue 6, 18 March 2011, Pages 970–985
12
Developing network models in
cancer ���
Dana Pe'er and Nir Hacohen. Cell ,Volume 144, Issue 6, 18 March
2011, Pages 864-873
