Bioinformatics in Switzerland - In-Silico Analysis of Proteins

Bioinformatics in Switzerland

From BIONET to SIB

1984
-
2000

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Obscurantism, Swiss style


Biology students are forbidden to take
computer science courses (CVJ, circa 1970,
Manuel Peitsch, circa 1980)


Sequence analysis is not considered to be
an acceptable study area for a PhD (Philipp
Bucher, circa 1980)


A well
-
known Swiss scientist claims that he
can find patterns and restriction sites in a
sequence faster by eye than with a
computer (circa 1985)

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

But in the meantime…


Amos Bairoch teaches himself computer science,
and convinces his boss (Robin Offord) that
bioinformatics is a legitimate field of study


Philipp Bucher gets trained in sequence analysis
with Ed Trifonov (Weizmann Inst) and Sam Karlin
(Stanford)


CVJ learns basic computer science at UNC Chapel
Hill and UC San Francisco


Ron Appel gets his education as a computer
scientist in Geneva


Manuel Peitsch gets trained in molecular modeling
with Jacob Maizel (NCI, Frederick)

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Beginnings


1982: Amos starts BIONET, a group of hackers,
biologists and software pirates in Geneva and
Lausanne


1983: Staden package installed for ISREC on a
computer at EPFL


1983
-
4: microcomputers (Sirius/Victor) find their
way into some biology labs in Switzerland


1984: first release of the ancestor of PC
-
Gene


1984: Manuel Peitsch (undergraduate) starts
developing software on a microcomputer at ISREC


Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Problem #1: infrastructure


Obscurantism redux: biologists do not need
mainframe computers!


Real issues:


Enough storage for local copies of sequence databases


Enough CPU power and memory to search through
databases (FASTA, then BLAST)


Robust software suite for sequence analysis (GCG,
Intelligenetics, Staden, etc)


Administrator level access for software maintenance,
database updates, etc.


1984
-
2003: constant battle to have access to
sufficient computing resources

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Infrastructure
–

a continuing saga


1984
-
1998: repeatedly rejected attempts to use the computer
center of the U. of Lausanne


1985
-
1988: access to the computer and software of the
Friedrich Miescher Inst. (Basel), but at a cost!


1989
-
2003: series of agreements and collaborations with a.o.


The Swiss EMBnet node in Basel


Epidemiologists at the Medical Faculty


Pharmacists at the Natural Science Faculty


The Swiss National Scientific Computing Centre


The Ludwig Institute for Cancer Research


2003: inauguration of the Vital
-
IT Centre, HPC facility
dedicated to life science research


Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Nucleotide sequence databases


Distribution of data was a real issue
–

had to
rely on 9 mm tapes, and later CDs sent by
post from Heidelberg


Swiss EMBnet node (1988, Reinhard Doelz,
Basel) created distribution mechanism
(HASSLE, FTP), but international network
bandwidth remained a major problem


Proper mirroring of databases has become
“easy” only thanks to the evolution of the
Internet into a well
-
connected, high
-
speed
network


Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Personalities and achievements


Switzerland has been lucky to be
home to a few scientists and politicians
with a real vision and commitment to
bioinformatics


… and apologies to those I may have
forgotten

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Milestones in Swiss bioinformatics
-

1


1986: Swiss
-
Prot 1.0 !!!


1988: founding of Swiss EMBnet node, run
by Reinhard Doelz (Basel)


Development of HASSLE protocol, incorporating
many features of modern Grid computing


1989: collaboration between Ron Appel and
Amos Bairoch creates a bioinformatics
center focussed on proteomics

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Milestones in Swiss bioinformatics
-

2


1990: creation of a bioinformatics
group at ISREC


Philipp Bucher, with primary interest in
the analysis of promoters (EPD) and of
sequence motifs


Roland Luethy, with primary interest in
the analysis of sequence
-
structure
relationships

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Milestones in Swiss bioinformatics
-

3


1991: first version of Swiss
-
Model, an automated
server for producing 3D models (Manuel Peitsch)


1991: The first Entrez client outside the US is
installed in Lausanne (Manuel Peitsch)


1993: ExPASy goes live as the first Web server
dedicated to life sciences


Among first servers offering database search services


Among first applications of “push” technology (Swiss
-
Shop)


Integration and “portal” concept at the core of the server

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Milestones in Swiss bioinformatics
-

4


1992: Gaston Gonnet and Steven Benner use the “all
against all” protein sequence comparison approach to derive
novel substitution matrices


1993: Swiss
-
2DPAGE pioneers the concept of providing a
common framework for federating data from multiple sources
(Ron Appel)


1996: First version of Swiss.PdbViewer, a public domain 3D
viewer and modelling environment (Nicolas Guex)


1997: MOLLUSCS, an early implementation of distributed
sequence database searches on a Linux PC cluster
(Thomas Junier, Christian Iseli)


1998: 3D
-
Crunch, an effort to produce genome
-
scale high
-
quality protein structure models (Nicolas Guex, Manuel
Peitsch)


Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Switzerland and the EBI


Bernhard Hirt was Chairman of the EMBL Council
during the period when EBI was conceived and
created (1991
-
1994)


Developing the concept


Outlining funding model (problems with EC!)


Selection of the site: Hinxton, because of superior Internet
connectivity!


Paolo Zanella (U. of Geneva & CERN) first Director


Collaboration with SWISS
-
PROT at center of EBI
database group activities


Amos Bairoch and Klaus Müller members of the
Advisory Board defining initial EBI activities

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

The rocky road to SIB


A series of funding crises


1991: both EMBnet.ch and Swiss
-
Prot try to get support for their
activities
–

Swiss
-
Prot receives some funding from SNF


1996: EMBnet.ch in Basel throws in the towel, Swiss
-
Prot fails to receive
expected EC funding
–

international outcry


1996
-
2000: BandAid solutions keep services going, Swiss
-
Prot goes
commercial


A series of initiatives


Push from Swiss Govt to merge service activities with existing
Academies or to create a fundable institution


Trying to create a consensus within and between the Universities of
Lausanne and Geneva


Birth of an institution


30 March 1998: the Geneva Cantonal Govt sponsors the creation of a
new non
-
profit Foundation, the SIB


15 May 1998: first meeting of the SIB Foundation Council


1 Jan 2000: Federal funding starts

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Behind the scenes
-

Geneva


Robin Offord (Professor, Biochemistry)


Supported Amos and his work through many difficult times


Was instrumental in lobbying the Government for
resources and support


Denis Hochstrasser (Professor, Hospital Labs)


Gave the impetus for the development of proteomics


Major force in founding SIB, Genebio, Geneprot


Guy
-
Olivier Segond (politician)


Realized the importance of bioinformatics for the
development of Geneva


Forced Universities and political authorities to create SIB

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Behind the scenes
-

Lausanne


Bernhard Hirt (Director, ISREC)


Supported development of bioinformatics at ISREC and
University of Lausanne


Provided help for Swiss
-
Prot during several crises


Chairman of EMBL Council, instrumental in creating and
siting EBI


Lloyd Old (Director, Ludwig Inst. Worldwide)


Provided generous support to start the SIB groups in
Lausanne


Daniel Mange (Professor of Computer Science)


Realized importance of biological models for computer
science (bio
-
inspired computing)

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Behind the scenes
-

Basel


Thomas Bickle (Professor, Biozentrum)


Obtained support and funding for first Swiss EMBnet node


Participated in creation of bioinformatics groups


Gian
-
Reto Plattner (Professor of Physics and
Senator)


Obtained funding and support for bioinformatics at
University of Basel


Member of the SIB Executive Board


Joachim Seelig (Director, Biozentrum)


Ensured support from the Swiss National Fund


Andreas Engel (Professor, Biozentrum)


Oversaw development of bioinformatics at Biozentrum

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Behind the scenes
-

more


Charles Kleiber, Secretary of State for
Education and Research


Jean
-
Raoul Scherrer (Geneva
University Hospital)


Christian Pellegrini (U. of Geneva)


Paul Herrling (Novartis)


Jonathan Knowles (Glaxo, Roche)

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Lessons learned from SIB


A bottom
-
up approach often works better than top
-
down


Scientists working together can accomplish more than
ministries handing down decisions


Funding is important, but cannot replace
enthousiasm and commitment


Much of the landmark work performed by current SIB
group leaders was done “outside of working hours” and
not specifically funded


A well
-
funded Institute needs professional
management


It is not enough to do good science and provide efficient
services, you have to produce the documents that prove it

Swiss
-
Prot 20th anniversary

Fortaleza, Brazil

Ron Appel

Amos Bairoch

Philipp Bucher

Manuel Peitsch

Victor Jongeneel

Nicolas Guex

Torsten Schwede

Mike Primig

Cédric Notredame

Mauro Delorenzi

Olivier Michielin

Bastien Chopard

Erik van Nimwegen

Mihaela Zavolan

Marc Robinson
-
Rechavi

Sven Bergmann

Evgeni Zdobnov

Bernard Moret

Joerg Stelling

Gaston Gonnet

Ernest Feytmans