What is Bioinformatics?. Conceptualizing biology in terms of molecules and then applying “informatics” techniques from math, computer science, and statistics.

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• (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 searching1990 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 founded1998 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 Technology2000 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 repository2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).2004 Bioconductor: open software development for computational biology and bioinformatics2005 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 searching1990 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 founded1998 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 Technology2000 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 repository2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).2004 Bioconductor: open software development for computational biology and bioinformatics2005 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 searching1990 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 founded1998 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 Technology2000 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 repository2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).2004 Bioconductor: open software development for computational biology and bioinformatics2005 Reactome: knowledge base of biological pathways

Global alignment (toy example)

CATGATGACTGAGAT

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)

CATGATGACTGAGAT

CATGATGA-C-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)

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.

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

1978

1965 Margaret Dayhoff's Atlas of Protein Sequences 1967 Scientific director of NBIC was born1970 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 searching1990 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 founded1998 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 Technology2000 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 repository2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).2004 Bioconductor: open software development for computational biology and bioinformatics2005 Reactome: knowledge base of biological pathways

1965 Margaret Dayhoff's Atlas of Protein Sequences 1967 Scientific director of NBIC was born1970 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 searching1990 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 founded1998 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 Technology2000 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 repository2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).2004 Bioconductor: open software development for computational biology and bioinformatics2005 Reactome: knowledge base of biological pathways

1965 Margaret Dayhoff's Atlas of Protein Sequences 1967 Scientific director of NBIC was born1970 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 searching1990 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 founded1998 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 Technology2000 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 repository2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).2004 Bioconductor: open software development for computational biology and bioinformatics2005 Reactome: knowledge base of biological pathways

1965 Margaret Dayhoff's Atlas of Protein Sequences 1967 Scientific director of NBIC was born1970 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 searching1990 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 Technology2000 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 repository2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).2004 Bioconductor: open software development for computational biology and bioinformatics2005 Reactome: knowledge base of biological pathways

1965 Margaret Dayhoff's Atlas of Protein Sequences 1967 Scientific director of NBIC was born1970 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 searching1990 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 founded1998 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 Technology2000 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 repository2003 myGrid: personalised bioinformatics on the information grid (e.g, Taverna).2004 Bioconductor: open software development for computational biology and bioinformatics2005 Reactome: knowledge base of biological pathways

Bioinformatics in the Netherlands1976 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

Vlieg1999 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 bioinformatics2000 NWO-BMI (Biomolecular informatics); program committee

chaired by De Vlieg2001 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 founded2003 First BioRange proposal (Vriend, Berendsen, Hertzberger,

Tellegen) 2005 Start of BioRange (NBIC-I)2008 ……………

Publication history

http://dan.corlan.net/medline-trend.html

• Many different bioinformatic tools are freely available– BLAST, EMBOSS, EnsEMBL, GenScan, BioConductor,........

• 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

Bioinformatics tools and databases

National Center for Biotechnology Information

GenBank and other genome databases

Sequence retrieval:

Protein Structure:

3D modeling programs – RasMol, Protein Explorer

Sequence comparison programs:

BLAST GCG MacVector

Similarity Search: BLAST

A tool for searching gene or protein sequence databases for related genes of interest

The structure, function, and evolution of a gene may be determined by such comparisons

Alignments between the query sequence and any given database sequence, allowing for mismatches and gaps, indicate their degree of similarity

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

MRCKTETGAR

MRCGTETGAR

% identity

90%

CATTATGATA

GTTTATGATT

70%

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: Human Genome ProjectGene array technologyComparative genomicsFunctional genomics

Proteomics:

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

bioinformatics

students educators

researchers institutions