Transcript 2001 - Lectures For UG-5

What is Bioinformatics?
What is Bioinformatics?
Conceptualizing biology in terms of molecules
and then applying “informatics” techniques from
math, computer science, and statistics to
understand and organize the information
associated with these molecules on a large scale
Focus
Profile of a bioinformatician
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(General) knowledge of biology and genome sciences
Translation biology <-> informatics
Knowledge of Unix-based operating systems
Programming skills (Java, Python, Shell/Perl scripting, R)
(Parallel) computing environments
Data storage and database technology
Statistics
Mathematics
Freely adapted from Richter et al (2009) PLoS computational biology
How do we use Bioinformatics?
• Store/retrieve biological information (databases)
• Retrieve/compare gene sequences
• Predict function of unknown genes/proteins
• Search for previously known functions of a gene
• Compare data with other researchers
• Compile/distribute data for other researchers
Other bioinformatics organisations
• European Bioinformatics Institute (EBI)
– http://www.ebi.ac.uk/
• National Center for Biotechnology
Information (NCBI)
– http://www.ncbi.nlm.nih.gov/
• EMBnet
– http://www.embnet.org/
• International Society for
Computational Biology (ISCB)
– http://www.iscb.org/
1965 Margaret Dayhoff's Atlas of Protein Sequences
1970 Needleman-Wunsch algorithm (global alignment)
1977 DNA sequencing and software to analyze it (Staden)
1981 Smith-Waterman algorithm developed (local sequence alignment)
1981 The concept of a sequence motif (Doolittle)
1982 GenBank made public
1983 Sequence database searching algorithm (Wilbur-Lipman)
1987 Perl (Practical Extraction Report Language) is released by Larry Wall.
1988 National Center for Biotechnology Information (NCBI) created at NIH/NLM
1988 EMBnet network for database distribution
1990 BLAST: fast sequence similarity searching
1990 The HTTP 1.0 specification is published. First HTML document.
1990 Grid computing as a metaphor for making computer power as easy to access
as an electric power grid.
1994 EMBL European Bioinformatics Institute (EBI), Hinxton, UK
1995 Microsoft version 1.0 of IE. Sun version 1.0 of Java. Version 1.0 of Apache.
1997 PSI-BLAST
1997 International Society for Computational Biology was founded
1998 Worm (multicellular) genome completely sequenced
1999 e-Science was introduced by John Taylor, the Director General of the
United Kingdom's Office of Science and Technology
2000 Gene Ontology (GO)
2001 The human genome (3 Giga base pairs) is published.
2001 Minimum information about a microarray experiment (MIAME; Brazma).
2001 Genetical Genomics (Ritsert Jansen)
2002 BioMoby. Web-service repository
2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).
2004 Bioconductor: open software development for computational biology and bioinformatics
2005 Reactome: knowledge base of biological pathways
History of bioinformatics
1965 Margaret Dayhoff's Atlas of Protein Sequences
1970 Needleman-Wunsch algorithm (global alignment)
1977 DNA sequencing and software to analyze it (Staden)
1981 Smith-Waterman algorithm developed (local sequence alignment)
1981 The concept of a sequence motif (Doolittle)
1982 GenBank made public
1983 Sequence database searching algorithm (Wilbur-Lipman)
1987 Perl (Practical Extraction Report Language) is released by Larry Wall.
1988 National Center for Biotechnology Information (NCBI) created at NIH/NLM
1988 EMBnet network for database distribution
1990 BLAST: fast sequence similarity searching
1990 The HTTP 1.0 specification is published. First HTML document.
1990 Grid computing as a metaphor for making computer power as easy to access
as an electric power grid.
1994 EMBL European Bioinformatics Institute (EBI), Hinxton, UK
1995 Microsoft version 1.0 of IE. Sun version 1.0 of Java. Version 1.0 of Apache.
1997 PSI-BLAST
1997 International Society for Computational Biology was founded
1998 Worm (multicellular) genome completely sequenced
1999 e-Science was introduced by John Taylor, the Director General of the
United Kingdom's Office of Science and Technology
2000 Gene Ontology (GO)
2001 The human genome (3 Giga base pairs) is published.
2001 Minimum information about a microarray experiment (MIAME; Brazma).
2001 Genetical Genomics (Ritsert Jansen)
2002 BioMoby. Web-service repository
2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).
2004 Bioconductor: open software development for computational biology and bioinformatics
2005 Reactome: knowledge base of biological pathways
1965 Margaret Dayhoff's Atlas of Protein Sequences
1970 Needleman-Wunsch algorithm (global alignment)
1977 DNA sequencing and software to analyze it (Staden)
1981 Smith-Waterman algorithm developed (local sequence alignment)
1981 The concept of a sequence motif (Doolittle)
1982 GenBank made public
1983 Sequence database searching algorithm (Wilbur-Lipman)
1987 Perl (Practical Extraction Report Language) is released by Larry Wall.
1988 National Center for Biotechnology Information (NCBI) created at NIH/NLM
1988 EMBnet network for database distribution
1990 BLAST: fast sequence similarity searching
1990 The HTTP 1.0 specification is published. First HTML document.
1990 Grid computing as a metaphor for making computer power as easy to access
as an electric power grid.
1994 EMBL European Bioinformatics Institute (EBI), Hinxton, UK
1995 Microsoft version 1.0 of IE. Sun version 1.0 of Java. Version 1.0 of Apache.
1997 PSI-BLAST
1997 International Society for Computational Biology was founded
1998 Worm (multicellular) genome completely sequenced
1999 e-Science was introduced by John Taylor, the Director General of the
United Kingdom's Office of Science and Technology
2000 Gene Ontology (GO)
2001 The human genome (3 Giga base pairs) is published.
2001 Minimum information about a microarray experiment (MIAME; Brazma).
2001 Genetical Genomics (Ritsert Jansen)
2002 BioMoby. Web-service repository
2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).
2004 Bioconductor: open software development for computational biology and bioinformatics
2005 Reactome: knowledge base of biological pathways
Global alignment (toy example)
CATGATGA
CTGAGAT
Can you “align” these two sequences
 introduce “gaps” in these two sequences such that you maximize the
number of matching nucleotides
Global alignment (toy example)
CATGATGA
CTGAGAT
CATGATGAC-TGA-GAT
Helps us to understand the function of
‘new’DNA
Dynamic programming gives optimal solution…
… but is slow. Often heuristic methods are used (BLAST, BLAT)
1978
Paulien Hogeweg (1943)
Dutch theoretical biologist and
complex systems researcher studying
biological systems as dynamic
information processing systems at
many interconnected levels.
Together with Ben Hesper she coined
the term Bioinformatics in 1978 as the
study of informatic processes in biotic
systems
Hogeweg, P. (1978). Simulating the growth of cellular forms. Simulation 31,
90-96;
Hogeweg, P. and Hesper, B. (1978) Interactive instruction on population
interactions. Comput Biol Med 8:319-27.
1965 Margaret Dayhoff's Atlas of Protein Sequences
1967 Scientific director of NBIC was born
1970 Needleman-Wunsch algorithm (global alignment)
1977 DNA sequencing and software to analyze it (Staden)
1981 Smith-Waterman algorithm developed (local
sequence alignment)
1981 The concept of a sequence motif (Doolittle)
1982 GenBank made public
1983 Sequence database searching algorithm (Wilbur-Lipman)
1987 Perl (Practical Extraction Report Language) is released by Larry Wall.
1988 National Center for Biotechnology Information (NCBI) created at NIH/NLM
1988 EMBnet network for database distribution
1990 BLAST: fast sequence similarity searching
1990 The HTTP 1.0 specification is published. First HTML document.
1990 Grid computing as a metaphor for making computer power as easy to access
as an electric power grid.
1994 EMBL European Bioinformatics Institute (EBI), Hinxton, UK
1995 Microsoft version 1.0 of IE. Sun version 1.0 of Java. Version 1.0 of Apache.
1997 PSI-BLAST
1997 International Society for Computational Biology was founded
1998 Worm (multicellular) genome completely sequenced
1999 e-Science was introduced by John Taylor, the Director General of the
United Kingdom's Office of Science and Technology
2000 Gene Ontology (GO)
2001 The human genome (3 Giga base pairs) is published.
2001 Minimum information about a microarray experiment (MIAME; Brazma).
2001 Genetical Genomics (Ritsert Jansen)
2002 BioMoby. Web-service repository
2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).
2004 Bioconductor: open software development for computational biology and bioinformatics
2005 Reactome: knowledge base of biological pathways
1965 Margaret Dayhoff's Atlas of Protein Sequences
1967 Scientific director of NBIC was born
1970 Needleman-Wunsch algorithm (global alignment)
1977 DNA sequencing and software to analyze it (Staden)
1981 Smith-Waterman algorithm developed (local sequence alignment)
1981 The concept of a sequence motif (Doolittle)
1982 GenBank made public
1983 Sequence database searching algorithm (Wilbur-Lipman)
1987 Perl (Practical Extraction Report Language) is released by Larry Wall.
1988 National Center for Biotechnology Information (NCBI) created at NIH/NLM
1988 EMBnet network for database distribution
1990 BLAST: fast sequence similarity searching
1990 The HTTP 1.0 specification is published. First HTML document.
1990 Grid computing as a metaphor for making computer power as easy to access
as an electric power grid.
1994 EMBL European Bioinformatics Institute (EBI), Hinxton, UK
1995 Microsoft version 1.0 of IE. Sun version 1.0 of Java. Version 1.0 of Apache.
1997 PSI-BLAST
1997 International Society for Computational Biology was founded
1998 Worm (multicellular) genome completely sequenced
1999 e-Science was introduced by John Taylor, the Director General of the
United Kingdom's Office of Science and Technology
2000 Gene Ontology (GO)
2001 The human genome (3 Giga base pairs) is published.
2001 Minimum information about a microarray experiment (MIAME; Brazma).
2001 Genetical Genomics (Ritsert Jansen)
2002 BioMoby. Web-service repository
2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).
2004 Bioconductor: open software development for computational biology and bioinformatics
2005 Reactome: knowledge base of biological pathways
1965 Margaret Dayhoff's Atlas of Protein Sequences
1967 Scientific director of NBIC was born
1970 Needleman-Wunsch algorithm (global alignment)
1977 DNA sequencing and software to analyze it (Staden)
1981 Smith-Waterman algorithm developed (local sequence alignment)
1981 The concept of a sequence motif (Doolittle)
1982 GenBank made public
1983 Sequence database searching algorithm (Wilbur-Lipman)
1987 Perl (Practical Extraction Report Language) is released by Larry Wall.
1988 National Center for Biotechnology Information (NCBI) created at NIH/NLM
1988 EMBnet network for database distribution
1990 BLAST: fast sequence similarity searching
1990 The HTTP 1.0 specification is published. First HTML document.
1990 Grid computing as a metaphor for making computer power as
easy to access as an electric power grid.
1994 EMBL European Bioinformatics Institute (EBI), Hinxton, UK
1995 Microsoft version 1.0 of IE. Sun version 1.0 of Java. Version 1.0
of Apache.
1997 PSI-BLAST
1997 International Society for Computational Biology was founded
1998 Worm (multicellular) genome completely sequenced
1999 e-Science was introduced by John Taylor, the Director General of the
United Kingdom's Office of Science and Technology
2000 Gene Ontology (GO)
2001 The human genome (3 Giga base pairs) is published.
2001 Minimum information about a microarray experiment (MIAME; Brazma).
2001 Genetical Genomics (Ritsert Jansen)
2002 BioMoby. Web-service repository
2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).
1965 Margaret Dayhoff's Atlas of Protein Sequences
1967 Scientific director of NBIC was born
1970 Needleman-Wunsch algorithm (global alignment)
1977 DNA sequencing and software to analyze it (Staden)
1981 Smith-Waterman algorithm developed (local sequence alignment)
1981 The concept of a sequence motif (Doolittle)
1982 GenBank made public
1983 Sequence database searching algorithm (Wilbur-Lipman)
1987 Perl (Practical Extraction Report Language) is released by Larry Wall.
1988 National Center for Biotechnology Information (NCBI) created at NIH/NLM
1988 EMBnet network for database distribution
1990 BLAST: fast sequence similarity searching
1990 The HTTP 1.0 specification is published. First HTML document.
1990 Grid computing as a metaphor for making computer power as easy to access
as an electric power grid.
1994 EMBL European Bioinformatics Institute (EBI), Hinxton, UK
1995 Microsoft version 1.0 of IE. Sun version 1.0 of Java. Version 1.0 of Apache.
1997 PSI-BLAST
1997 International Society for Computational Biology was founded
1998 Worm (multicellular) genome completely sequenced
1999 e-Science was introduced by John Taylor, the
Director General of the United Kingdom's Office of
Science and Technology
2000 Gene Ontology (GO)
2001 The human genome (3 Giga base pairs) is published.
2001 Minimum information about a microarray experiment (MIAME; Brazma).
2001 Genetical Genomics (Ritsert Jansen)
2002 BioMoby. Web-service repository
2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).
2004 Bioconductor: open software development for computational biology and bioinformatics
1965 Margaret Dayhoff's Atlas of Protein Sequences
1967 Scientific director of NBIC was born
1970 Needleman-Wunsch algorithm (global alignment)
1977 DNA sequencing and software to analyze it (Staden)
1981 Smith-Waterman algorithm developed (local sequence alignment)
1981 The concept of a sequence motif (Doolittle)
1982 GenBank made public
1983 Sequence database searching algorithm (Wilbur-Lipman)
1987 Perl (Practical Extraction Report Language) is released by Larry Wall.
1988 National Center for Biotechnology Information (NCBI) created at NIH/NLM
1988 EMBnet network for database distribution
1990 BLAST: fast sequence similarity searching
1990 The HTTP 1.0 specification is published. First HTML document.
1990 Grid computing as a metaphor for making computer power as easy to access
as an electric power grid.
1994 EMBL European Bioinformatics Institute (EBI), Hinxton, UK
1995 Microsoft version 1.0 of IE. Sun version 1.0 of Java. Version 1.0 of Apache.
1997 PSI-BLAST
1997 International Society for Computational Biology was founded
1998 Worm (multicellular) genome completely sequenced
1999 The term e-Science was created by John Taylor, the Director General of the
United Kingdom's Office of Science and Technology
2000 Gene Ontology (GO)
2001 The human genome (3 Giga base pairs) is published.
2001 Minimum information about a microarray experiment (MIAME; Brazma).
2001 Genetical Genomics (Ritsert Jansen, Jan Peter Nap)
2002 BioMoby. Web-service repository
2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).
2004 Bioconductor: open software development for computational biology and bioinformatics
2005 Reactome: knowledge base of biological pathways
Bioinformatics in the Netherlands
1976 Pauline Hogeweg (theoretical biology)
1979 Gert Vriend (proteins)
1985 Computer Assisted Organic Synthesis/Computer Assisted Molecular
Modelling Centre (CAOS/CAMM) was founded (Nijmegen, Jan
Noordik)
1989 Jack Leunissen (first Dutch researcher with PhD in Bioinformatics)
90 ‘s Driving forces: Herman Berendsen, Charles Buys, Jacob de Vlieg
1999 CAOS/CAMM was reorganized; Gert Vriend becomes director of CMBI.
1999 KNAW committee(chaired by Berendsen) wrote the report ‘Bioexact’
in which strong stimulation of bioinformatics was recommended.
2000 KNCV working group bioinformatics
2000 NWO-BMI (Biomolecular informatics); program committee chaired by
De Vlieg
2001 NWO/KNAW workshop ‘The future of bioinformatics in the
Netherlands’
2002 Position paper ‘De toekomst van de bioinformatica in Nederland’
representing the vision of the NWO/KNAW
2003 NBIC was founded
2003 First BioRange proposal (Vriend, Berendsen, Hertzberger, Tellegen)
2005 Start of BioRange (NBIC-I)
2008 ……………
Publication history
http://dan.corlan.net/medline-trend.html
Bioinformatics tools and databases
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Many different bioinformatic tools are freely available
– BLAST, EMBOSS, EnsEMBL, GenScan, BioConductor,........
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Many different biological databases are freely available
– GenBank, UniProtKB, KEGG,........
•
Many publications in open access journals
– BMC bioinformatics
– PLoS computational biology
•
Also many commercial software packages available
– Spotfire, Rosetta Resolver, Genelogic, ......
•
Bioinformaticians write their own tools for specialized tasks
Sequence retrieval:
National Center for Biotechnology Information
GenBank and other genome databases
Sequence comparison programs:
BLAST
GCG
MacVector
Protein Structure:
3D modeling programs – RasMol,
Protein Explorer
Similarity Search: BLAST
A tool for searching gene or protein sequence
databases for related genes of interest
Alignments between the query sequence and any
given database sequence, allowing for mismatches
and gaps, indicate their degree of similarity
The structure, function, and evolution of a gene may
be determined by such comparisons
http://www.ncbi.nlm.nih.gov/BLAST/
% identity
CATTATGATA
70%
GTTTATGATT
MRCKTETGAR
90%
MRCGTETGAR
Strengths:
Accessibility
Growing rapidly
User friendly
Weaknesses:
Sometimes not up-to-date
Limited possibilities
Limited comparisons and information
Not accurate
Need for improved Bioinformatics
Genomics:
Proteomics:
Human Genome Project
Gene array technology
Comparative genomics
Functional genomics
Global view of protein
function/interactions
Protein motifs
Structural databases
Data Mining
Handling enormous amounts of data
Sort through what is important and what is not
Manipulate and analyze data to find patterns and
variations that correlate with biological function
educators
students
bioinformatics
researchers
institutions