Bioinformatics Summer School 20-24 June 2011 EBI-Wellcome Trust Bioinformatics Summer School 20-24 June 2011

University of Manchester Concepts, historical milestones & the central place of bioinformatics in modern biology: a European perspective 4/27/2017 Teresa K.Attwood University of Manchester

University of Manchester Concepts, historical milestones & the central place of bioinformatics in modern biology: a personal perspective from a European 4/27/2017 Teresa K.Attwood University of Manchester

University of Manchester Concepts, historical milestones & the central place of bioinformatics in modern biology: a personal perspective from a European 4/27/2017 Teresa K.Attwood University of Manchester

University of Manchester Overview Where the term bioinformatics originated Where the ‘modern’ concept originated Some key milestones & people Its place in‘the new biology’ 4/27/2017 Teresa K.Attwood University of Manchester

University of Manchester Disclaimer Bear in mind that this is a personal view That it’s hard to step out of a situation & look back in & remain objective to separate the European & American histories Observers from different perspectives will see & tell the story differently! So this is just my perspective… & it’s bound up with sequences & dbs 4/27/2017 Teresa K.Attwood University of Manchester

Origin of bioinformatics The origin of the term ‘bioinformatics’ has been attributed to Paulien Hogeweg Dutch theoretical biologist With Ben Hesper, she coined the term in the early ‘70s, defining its meaning as “the study of informatic processes in biotic systems” Hogeweg, P. (2011) The roots of bioinformatics in theoretical biology. PLoS Computational Biology, 7(3), e1002021 The term failed to gain traction for ~20 years 4/27/2017 Teresa K.Attwood University of Manchester

Origin of bioinformatics The origins of the ‘modern’ concept of bioinformatics are rooted in sequence analysis Driven by the desire to collect annotate & analyse them systematically (i.e., using computers)! This concept of‘bioinformatics’ was barely known pre 1990… 4/27/2017 Teresa K.Attwood University of Manchester

Key milestones 1950 1960 1970 1980 1990 2000 2010 CSD insulin GIVEQCCASVCSLYQLENYCN FVNQHLCGSHLVEALYLVCGERGFFYTPKA CSD 1950 1960 1970 1980 1990 2000 2010 insulin ribonuclease Dayhoff Atlas

University of Manchester Margaret Dayhoff 1925-1983 Pioneer of computer methods to compare protein sequences & to derive evolutionary histories from alignments Particular interest in deducing evolutionary connections from sequence evidence 4/27/2017 Teresa K.Attwood University of Manchester

Teresa K.Attwood University of Manchester Margaret Dayhoff Collected all the known protein sequences made them available to the scientific community In 1965, she compiled a book the Atlas of Protein Sequence and Structure 4/27/2017 Teresa K.Attwood University of Manchester

University of Manchester Margaret Dayhoff 4/27/2017 Teresa K.Attwood University of Manchester

Key milestones 1950 1960 1970 1980 1990 2000 2010 CSD PDB ARPAnet email 1950 1960 1970 1980 1990 2000 2010 insulin ribonuclease DNA sequencing Dayhoff Atlas Auto DNA sequencing Auto protein sequencers 65 7

Data overload in the USA 4/27/2017 Teresa K.Attwood University of Manchester

Data overload in the USA 4/27/2017 Teresa K.Attwood University of Manchester

Data overload in Europe While the US debated where to locate a new centralised resource, EMBL acted… The 1st nucleotide sequence database was thus based in Heidelberg this was the EMBL data library preceded the 1st release of GenBank by ~6 months 4/27/2017 Teresa K.Attwood University of Manchester

Data overload in Europe Copies of the EMBL data library & GenBank were being maintained in Cambridge together with their search tools, etc. Researchers were given access to the dbs via an integrated system “this system is presently being used by over 30 researchers in 8 departments in the University & in local research institutes. These users can keep in touch with each other via the MAIL command”! 4/27/2017 Teresa K.Attwood University of Manchester

Key milestones 1950 1960 1970 1980 1990 2000 2010 EMBL, GenBank PIR CSD PDB ARPAnet Internet email 1950 1960 1970 1980 1990 2000 2010 insulin ribonuclease DNA sequencing Dayhoff Atlas Auto DNA sequencing Auto protein sequencers 65 7 568 859

University of Manchester Enter Amos Bairoch A crazy postgrad student in Switzerland interested in space exploration & the search for ET life His project was to develop software to analyse protein & nucleotide sequences PC/Gene 4/27/2017 Teresa K.Attwood University of Manchester

University of Manchester Amos Bairoch He published his 1st paper in 1982 a letter to the BJ Suggested use of checksums to “facilitate the detection of typographical & keyboard errors” 4/27/2017 Teresa K.Attwood University of Manchester

University of Manchester Amos Bairoch Why did he do this? In developing PC/Gene, he also needed to supply a db The Atlas wasn’t available electronically typed in >1,000 protein sequences some from the literature most from the Atlas by 1981, this was a large book, plus several supplements, listing 1,660 proteins 4/27/2017 Teresa K.Attwood University of Manchester

University of Manchester Amos Bairoch In 1983, he acquired a computer tape of the EMBL databank this was version 2, with 811 sequences In 1984, he received the 1st available computer tape copy of the Atlas (which quickly became the PIR-PSD) but he was deeply unhappy with the PIR format 4/27/2017 Teresa K.Attwood University of Manchester

University of Manchester Amos Bairoch So he decided to convert the PIR database into the semi-structured format of EMBL part manually & part automatically the result was PIR+ it was distributed as part of PC/Gene (now commercial) In summer 1986, he decided to release the database independently of PC/Gene so that it would be available to all, free of charge 4/27/2017 Teresa K.Attwood University of Manchester

University of Manchester Amos Bairoch The new database was called Swiss-Prot The 1st release was made on 21 July 1986 the exact number of entries is unknown, as he can’t find the original floppy disks! 4/27/2017 Teresa K.Attwood University of Manchester

Key milestones 1950 1960 1970 1980 1990 2000 2010 EMBL, GenBank Swiss-Prot PROSITE PRINTS EMBL, GenBank PIR CSD PDB ARPAnet Internet email 1950 1960 1970 1980 1990 2000 2010 insulin ribonuclease DNA sequencing Dayhoff Atlas Auto DNA sequencing Auto protein sequencers 65 7 568 859 3,900

University of Manchester Global data overload The number of sequences was growing The number of structures was growing So was the number of protein family signatures Two extraordinary developments had yet to take place what were they? 4/27/2017 Teresa K.Attwood University of Manchester

Key milestones 1950 1960 1970 1980 1990 2000 2010 Swiss-Prot PROSITE PRINTS FlyBase TrEMBL Pfam InterPro EMBL, GenBank PIR CSD PDB ARPAnet Internet email www 1950 1960 1970 1980 1990 2000 2010 insulin ribonuclease DNA sequencing Dayhoff Atlas C.elegans genome H.sapiens genome HT DNA sequencing S.cerevisae genome H.influenzae genome Auto DNA sequencing Auto protein sequencers D.melanogaster genome 65 7 568 859 3,900 105,000 2,423

InterPro Prosite PRINTS ProDom Profiles PIRSF HAMAP Gene3D TIGRFAM SUPERFAMILY InterPro is an integrated documentation resource for protein families, domains & sites. By uniting databases that use different methodologies & a varying degree of biological information, InterPro capitalises on their individual strengths, producing a powerful integrated database & diagnostic tool. Naïvely, we wanted to make life easier! We aimed to: simplify & rationalise protein family analysis; centralise & streamline the annotation process; & reduce manual annotation burdens; &, in the wake of all the genome projects, to facilitate automatic functional annotation of uncharacterised proteins. In fact (& now with 11 partners) we made life a lot harder! But that’s another story TIGRFAM PANTHER Profiles Pfam SMART Teresa K.Attwood

Key milestones 1950 1960 1970 1980 1990 2000 2010 EMBnet NCBI ELIXIR EBI SIB Swiss-Prot PROSITE PRINTS FlyBase TrEMBL Pfam InterPro UniProt ENA EMBL, GenBank PIR CSD PDB ARPAnet Internet email www 1950 1960 1970 1980 1990 2000 2010 insulin ribonuclease DNA sequencing Dayhoff Atlas C.elegans genome H.sapiens genome HT DNA sequencing S.cerevisae genome H.influenzae genome Auto DNA sequencing Auto protein sequencers D.melanogaster genome 65 7 568 859 3,900 105,000 2,423 15.4M 500B

Key milestones 1950 1960 1970 1980 1990 2000 2010 EMBnet NCBI ELIXIR EBI SIB Swiss-Prot PROSITE PRINTS FlyBase TrEMBL Pfam InterPro UniProt ENA EMBL, GenBank PIR CSD PDB hundreds more ARPAnet Internet email www 1950 1960 1970 1980 1990 2000 2010 insulin ribonuclease DNA sequencing Dayhoff Atlas C.elegans genome H.sapiens genome S.cerevisae genome thousands more HT DNA sequencing H.influenzae genome Auto DNA sequencing Auto protein sequencers D.melanogaster genome billions more 65 7 568 859 3,900 105,000 2,423 15.4M 500B

Red Line Growth of EMBL since its inception Scary monsters! By 2020, NGS will be producing data at a million times the current rate Green Line Growth of manually annotated Swiss-Prot Blue Line Growth of PDB 4/27/2017

The central place of bioinformatics in modern biology Hopefully, this potted history speaks for itself In the last 30 years, bioinformatics has given us the first ‘complete’ catalogues of DNA & protein sequences including genomes & proteomes of organisms across the Tree of Life software to analyse biological data on an unprecedented scale & hence tools to help understand more about evolutionary processes in general our place on the Tree of Life in particular &, ultimately, more about health & disease It isn’t a panacea, but its contribution has been huge 4/27/2017 Teresa K.Attwood University of Manchester

University of Manchester Recommended reading A.B.Richon. A short history of bioinformatics (http://www.netsci.org/Science/Bioinform/feature06.html) A.Bairoch (2000) Serendipity in bioinformatics, the tribulations of a Swiss bioinformatician through exciting times. Bioinformatics, 16(1), 48-64. M.Ashburner (2006) Won for all – How the Drosophila genome was sequenced. Cold Spring Harbor Laboratory Press. B.J.Strasser (2008) GenBank – Natural history in the 21st century? Science, 322, 537-538. What makes us the same but different from each other 4/27/2017 Teresa K.Attwood University of Manchester Teresa K.Attwood