Introduction to Bioinformatics

for Medical Research

Gideon Greenspan
[email protected]
TA: Oleg Rokhlenko

Lecture 1
Introduction to Bioinformatics
 Introduction to Bioinformatics
• What is Bioinformatics?
• Why do we need it?
• Development timeline
• Journals, books, websites
• How to access bioinformatics tools?
• Why is bioinformatics hard?
• PubMed and OMIM databases
2
 Bioinformatics: What?
• NCBI: “Research, development, or application of
computational tools and approaches for expanding the use
of biological, medical, behavioral or health data, including
those to acquire, store, organize, archive, analyze, or
visualize such data.”
• Lincoln Stein: “Biologists using computers, or the
other way around.”
• Martin Gerstel (Compugen): “Bioinformatics is
a name which will probably disappear with time.”

3
 Bioinformatics: Why?
• Storing large quantity of data
– Sequencing
– Crystallography
– DNA chips
• Enabling fast retrieval
– Database searching
• Data mining and analysis
– Integrate diverse sources
4
 Human Genome Project
• Initiated in 1988, declared ‘complete’ 2003
• Major goals
– Determine 3¥109 base pairs
– Identify ~30,000 genes
• Computational tasks
– Storage and indexing
– Building contigs
– Scanning for genes
5
 Human Genome Progress

Source: EMBL Genome Monitoring Table

6
 IBM’s Blue Gene
• Task: in-silico
protein folding
• Announced 1999
– Expanded in 2001
• 500,000 times faster
than Pentium IV
• Aim: Fold one protein per year

7
 Bioinformatics: When?
Watson and Crick Sanger sequences
1955
DNA model insulin protein
1960
N-W sequence ARPANET (early
alignment 1965 Internet)

1970
PDB (Protein Sanger dideoxy
Data Bank) 1975 DNA sequencing

GenBank 1980 PCR (Polymerase

database Chain Reaction)
1985 8
 SWISS-PROT
USA’s NCBI
database

FASTA 1990
Human Genome
algorithm Initiative

BLAST
Israel’s INN
algorithm
1995
WWW (World
Europe’s EBI
Wide Web)

2000 First human

Celera Genomics
genome draft
9
 GenBank Growth

Source:
NCBI
10
 PubMed Growth
14,000,000

12,000,000
Articles in Database

10,000,000

8,000,000

6,000,000

4,000,000

2,000,000

0
59
62
65
68
71
74
77

0
83
86
89
92
95
98
01
8
19
19
19
19
19
19
19
19
19
19
19
19
19
19
20
11
 Bioinformatics: Where?
• Journals

12
• Books
– David W. Mount, Bioinformatics: Sequence and
Genome Analysis
– Cynthia Gibas, Developing Bioinformatics Computer
Skills
– Bryan P. Bergeron, Bioinformatics Computing

13
• World Wide Web
– USA National Center for Biotechnology
Information: www.ncbi.nlm.nih.gov
– European Bioinformatics Institute:
www.ebi.ac.uk
– ExPASy Molecular Biology Server:
www.expasy.org
– Israeli National Node: inn.org.il
– Open source news: bioinformatics.org
– German directory: bioinformatik.de

14
 Bioinformatics: How?
• Pre-packaged tools
– Majority on World Wide Web
– Some require downloading
– Most are free to use
• Beginning development
– Mostly Unix environment
– Perl programming language

15
 The Trouble with Nature
• Hard to represent
• Understanding still incomplete
• Some problems insoluble?

16
 The Trouble with Man
• Confusing choice of tools
• Developed independently
• Written by and for nerds

17
Making it Simpler

18
 PubMed
• MEDLINE publication database
– Over 17,000 journals
– Some other citations
• Papers from 1960s
– Over 12,000,000 entries
• Alerting services
– http://www.pubcrawler.ie/
– http://www.biomail.org/
19
 A PubMed Entry
• Journal reference
– Volume, number, date, pages
– Title, authors, affiliation
– Abstract Cancer 2003 May 1;97(9):2248-53

• Links Pregnancy and early-stage melanoma.

Daryanani D, Plukker JT, De Hullu JA,
– Related articles Kuiper H, Nap RE, Hoekstra HJ.
Division of Surgical Oncology, University
– Full text (sometimes) Medical Center, Groningen, The Netherlands.
– Database entries BACKGROUND: Cutaneous melanomas are
aggressive tumors with an unpredictable…
20
 Searching PubMed
• Structureless searches
– Automatic term mapping
• Structured searches
– Field names, e.g. [au], [ta], [dp], [ti]
– Boolean operators, e.g. AND, OR, NOT, ()
• Additional features
– Subsets, limits
– Clipboard, history
21
 OMIM
• Online Mendelian Inheritance in Man
– Genes and genetic disorders
– Edited by team at Johns Hopkins
– Updated daily
• Entries
– 10670 single-loci phenotypes (*)
– 1294 multi-loci phenotypes (#)
– 2415 unclassified phenotypes
22
 An OMIM Entry
• Phenotype description
– Clinical features
– Diagnosis and treatment
– Molecular genetics CYSTIC FIBROSIS; CF
• Inheritance Model Alternative titles; symbols
MUCOVISCIDOSIS
– Mapping history
Gene map locus 7q31.2
– Genetic locus/loci DESCRIPTION
Manifestations relate not only to the disruption
• References of exocrine function of the pancreas…

23
 Searching OMIM
• Search Fields
– Disease name, e.g. hypertension
– Cytogenetic location, e.g. 1p31.6
– Inheritance, e.g. autosomal dominant
• Browsing Interfaces
– Alphabetical by disease
– Genetic map
• Additional features like PubMed
24