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Human Genome Organisation (HUGO) 13th Human Genome Meeting...more Asia-Pacific Regional S.pombe Meeting 2008, Singapore 25 - 27 July 2008...more Systems Biology, Integrative Biology, Predictive Biology Date: 22/06/2005   This commentary by Prof Edison T Liu Executive Director at the Genome Institute of Singapore, first appeared in Cell May 20 2005 (Vol. 121) The commentary empbodies the GIS philsopohy on science, integration, and the systems approach The pursuit of science is based on empiricism enabled by advancing technologies. Theories then emerge that unify our understanding of natural order. The trinity of experimentation, theory, and technology that underlies the scientific method cannot be placed into a hierarchy of importance. Theoretical fields quickly lose substance in the absence of robust experimentation, and theoretical conundrums cannot be resolved without experimentation using advanced technologies. Physics is perhaps the most mature of the experimental sciences in exploiting the interface between theory, experimentation, and technology. Quantum and relativity theories revolutionized physics and engineering, but high-energy physics is a discipline made possible by the technology of the linear accelerator. The advantage of physics over other experimental sciences is the ability to use first principles to calculate more complex models of the physical world. These models are then used to predict unforeseen physical events. Fundamental to this is the ability to precisely quantify physical observations and to render them mathematically transformable. This progression from observation, to theory, to prediction has been the driving force in humanity's fascination with science. Not only do we have an inherent appetite for knowledge that motivates us to explore, but we also have a desire to extract reason from perceived chaos in order to construct models that can predict our future. In this past century, biology has transformed from a primarily empiric and observational field to one based on fundamental principles. The foundations for this change may be attributed to a great degree to the discovery of the true structure of DNA, and followed by the recent ability to sequence entire genomes. We are now poised to advance further into predictive theory with the new discipline of systems biology. Systems biology can be different things to different people, but there is a common understanding that this discipline seeks to explain biologic phenomenon, not on a gene-by-gene basis, but through the net interactions of all cellular and biochemical components within a cell or organism. Operationally, systems biology requires the ability to digitalize biological output so that it can be computed, the computational power to analyze comprehensive and massive datasets, and the capacity to integrate heterogeneous data into a usable knowledge format. Thus, systems biology can be described as "integrative biology" with the ultimate goal of being able to predict de novo biological outcomes given the list of the components involved. An example of this approach is seen in the work by Davidson and colleagues. After identifying the important components for developmental specification for sea urchin endomesodermal differentiation (Davidson et al., 2002a), they defined the genetic network for endomesodermal specification on a genome-wide scale (Davidson et al., 2002b; Bolouri and Davidson, 2003). By describing the network as a precise functional model mapped by a control diagram, they advanced the prospects of forward engineering of a complex biological process. In this aspect, systems biology is also "predictive biology." The Genome Institute of Singapore, founded in 2001, is focused on integrative and systems approaches to resolving biological questions of medical importance. We seek to integrate biological and analytical systems to generate large-scale and precise data about dynamic cellular processes (Wei et al., 2005; Peng et al., 2005; Lin et al., 2004). We, and others, believe that this approach not only can provide an unbiased and complete dataset about a biological system, but when analyzed appropriately, can give insights as to the interconnections of molecular components and the hierarchy of importance of the often large number of involved molecules and pathways (Liu, 2004; Hood et al., 2004). To this end, we have focused on the dynamics of the transcriptome using genomic tools (Ng et al., 2005; Ruan et al., 2004). This strategy was selected in large part because the technologies for precisely assessing the transcriptome in a highly multiplexed fashion and the accompanying computational tools are within reach. The most proximal read-outs of transcriptional activity, either DNA binding by a transcription factor or the level of the resultant transcripts, can be readily assessed on a genome-wide scale and easily subjected to digitalization. Moreover, unlike the proteome, the transcriptome currently can be examined dynamically in time course experiments over many conditions to accelerate data accession. Therefore, the first set of criteria for systems biology, dense datasets cast in a digital format, can be satisfied. The greatest challenges in establishing this systems approach are not biological but computational and organizational. The computational issues are centered on the search and analysis of massive amounts of data (e.g., the behavior of all transcripts in a number of species over time in conditions interrogating several biological processes), on integration of heterogeneous databases (e.g., protein-protein interaction with RNA expression information with knowledge of biochemical pathways), and on large-scale data-presentation systems interpretable to bench biologists. Ultimately, the importance of any computational approach will be judged not on its mathematical beauty but by how it can be used to predict new biological phenomenon. To this end, the close physical interaction between computationally derived biological theory and experimentation will be essential for accelerating progress in the field. Traditionally, bioinformatics resided in a computer science or biostatistics department, biology in a biochemistry department, and a genomics center functionally and administratively disjointed from the two. This is an unfortunate disconnect and will need organizational realignment. Regarding data presentation, it is not reasonable to expect computational sophistication in an entire generation of biologists not raised in such an environment. The success of products that provide more natural interfaces between humans and computers shows the appeal (and the need) of bringing technology to the nonexpert users. Thus, we believe there will be a demand for a simplified interface specifically tailored to enable biologists to make use of such massive digitalized biological data. Equally important for systems biology to flourish is an organizational structure and social culture that encourages collective effort and iterative experimentation between the wet laboratory and computational modeling. The current funding systems and departmental structures have a challenging task ahead. Grants for individual principal investigators (PI) are small compared to the experimental and infrastructural needs to mount significant efforts in systems biology. Thus far, grants have been administered such that incremental advances by the individual scientist, rather than an individual's contribution to larger efforts that may have much greater scientific impact, are rewarded. Funding for critical infrastructure and technology development is often bypassed as lacking scientific content. Departmental promotion procedures have tended to encourage PI insularity by discounting participation in collaborative projects focusing solely on individual effort. Graduate student training, centered on serving an individual PI's projects and demarcated by classical departmental boundaries, has not responded to the educational needs in integrative biology. Systems biologists require crossdisciplinary training that is difficult under current departmental structures. For these reasons, we have spent a great deal of energy in crafting the cultural state of our institute, which prizes flexibility, individual intensity, and collective impact (http://www.gis.a-star.edu.sg/homepage/). The Genome Institute of Singapore specifically recognizes technology-focused scientists to be as important as biology centric investigators, but we demand that technologists team with biologists to address fundamental biological questions. We devote much time to achieving consensus as to the major scientific questions we will attack together as a community. We focus on data integration so that individual efforts can be harvested for collective reasoning, though admittedly, we are still far away from the ideal. Then, our individual performance is judged not only on excellence in our personal science but also on how we contribute to the advance of our collective goals. Our project-based internal funding has allowed us as an institution to focus on the biological question rather than managing territorial claims amongst investigators. And in a project-driven culture, a postdoctoral fellow can lead a program as much as a senior group leader. We actively encourage joint mentorship for our postdoctoral fellows and graduate students, often between a technology-oriented and a biology-focused investigator or between an informatics scientist and a biologist. Without such organizational changes, the important cultural conditions for a robust systems biology environment will not flourish. An important factor facilitating this cultural change has been block funding from a single source so that we can coordinate projects on a large scale with a long time horizon. The excitement over the systems approach to biology and medicine is justified. The ability to predict more logical outcomes in complex systems is the grand enticement. The only limitations to our success are what we, ourselves, place before us.  Event/Seminar 02 Apr 2008 Joint 7th Human Genome Organisation (HUGO) - Pacific Meeting and the 8th Asia-Pacific Conference on Human Genetics...more 21 May 2007 AACR Centennial Conference...more 12 Feb 2007 GIS Invited Speakers Series 2007...more 10 May 2006 Genome Institute of Singapore Open House...more 17 Mar 2006 Genetic variation and Individul landscape of gene expression...more 03 Feb 2006 Seminar: How the Epigenome Changes in Cancer...more  News Article 13 Jun 2008 Bio-Medicine: Wealth of genomic hotspots discovered in embryonic stem cells...more 09 Jun 2008 Novel Therapeutic Strategy For Colon Cancer Treatment...more 17 Mar 2008 Biotech Business Week – Cell Biology; Molecular alliance that sustains embryonic stem cell state...more 11 Mar 2008 Channel NewsAsia - Research on SARS spawns new techniques to develop diagnostic kits for other diseases...more 06 Mar 2008 News-Medical.Net – Molecular alliance that sustains embryonic stem cell state...more 05 Mar 2008 Genetic Engineering & Biotechnology News - Molecular alliance identified that sustains embryonic stem-cell state ...more 05 Mar 2008 MediLexicon - Embryonic stem cell state sustained by molecular alliance ...more 05 Mar 2008 Medical News Today - Embryonic stem cell state sustained by molecular alliance...more 05 Mar 2008 Cloning Resources – Molecular alliance that sustains embryonic stem cell state ...more 04 Mar 2008 Science Daily - Molecular alliance that sustains embryonic stem cell state identified....more 04 Mar 2008 Omniomix - Molecular alliance that sustains embryonic stem cell state...more 04 Mar 2008 Physorg - Molecular alliance that sustains embryonic stem cell state...more 04 Mar 2008 Biology News Net – Molecular alliance that sustains embryonic stem cell state...more 03 Mar 2008 BioSpectrum Asia Edition - Singapore scientists shed light on molecular alliance in key proteins...more 01 Feb 2008 Bio.IT World - From Genomes to Systems; Edison Liu talks about Singapore, HUGO, and predictive biology....more 20 Jan 2008 (Lianhe Zaobao) Minister Khaw’s visit to Biopolis ...more 17 Oct 2007 The Straits Times: Genome Institute gets US grants...more 10 Oct 2007 Medical News Today: Full-Scale ENCODE Project will survey entire human instruction book...more 01 Oct 2007 People Watch-NCI and NHGRI Grants (Ed and Yijun)...more 01 Oct 2007 Singapore Scientists Discover Protein Modifications to Develop Stem Cells into Specialized Body ...more 24 Sep 2007 The Straits Times: Bird flu detector: 10 times faster, 100 times cheaper...more 14 Sep 2007 Lianhe Zaobao: NSTA Awards...more 01 Sep 2007 The Straits Times: Science Talk- Why setting the right rules on health products is critical...more 01 Sep 2007 Biomed-Asia: GIS identifies genetic risk factors for breast cancer...more 30 Aug 2007 The Straits Times: Singapore don to head top global genome organization...more 15 Aug 2007 Dengue Digest: Expansion of the Singapore Dengue Consortium...more 13 Aug 2007 Biospectrum Asia Edition:: Scientists' discovery of DNA replication behaviour in complex organisms may be the forerunner to leaps in genomic discoveries...more 29 Jun 2007 The New Paper: Why no vaccine?...more 23 Jun 2007 Straits Times: Research group pools strengths for faster results...more 23 Jun 2007 Straits Times: Science Talk (by Martin Hibberd & Ooi Eng Eong)...more 22 Jun 2007 Today: Dengue early-warning system a possibility...more 22 Jun 2007 Straits Times: Dengue research gets more muscle...more 22 Jun 2007 Lianhe Zaobao: 11 organizations signed MOU to form Singapore Dengue Consortium...more 21 Jun 2007 Channel NewsAsia: Consortium set up to investigate anti-dengue strategies...more 21 Jun 2007 Bernama: Scientific Bodies band together to fight dengue...more 02 Jun 2007 The Straits Times: Researchers here help to decode breast cancer genes...more 02 Jun 2007 The Straits Times: Scientists stumped by 2 dengue findings here...more 01 Jun 2007 Time Out Singapore: What it's like to be a...Stem–cell researcher...more 29 May 2007 Medical News Today: 1st Confirmed Common Genetic Risk Factors for Breast Cancer Uncovered by Genome Institute of Singapore and Partners...more 28 May 2007 The Star Online: Researchers find big batch of breast cancer genes...more 28 May 2007 Los Angeles Times: 4 more breast cancer genes discovered...more 28 May 2007 Channel NewsAsia: More surviving cancer, trend likely to continue: NCC...more 01 May 2007 Biomed-Singapore: Dengue's effects on the immune system...more 28 Apr 2007 The Straits Times Interactive: She can work anywhere...more 01 Apr 2007 Spotlight: Singapore Dr Edison Liu is pushing Science to the highest level at Singapore's Cancer Syndicate and Genome Institute...more 11 Mar 2007 STI Home: 'This is the most exciting place to do science'...more 11 Mar 2007 STI Home: Biomedical push kept 2 talented locals here...more 04 Mar 2007 Biology News Net - Molecular alliance that sustains embryonic stem cell state...more 01 Mar 2007 BioSpectrum: What is next in biotechnology?...more 26 Feb 2007 BioSpectrum Asia: GIS & KI Collaboration...more 24 Feb 2007 The Straits Times Interactive: Worming its way into biomedical research...more 10 Feb 2007 ST Sat Special: Making 'new' mice to use as disease-busters...more 09 Feb 2007 Yahoo Asia News: A*STAR awards grants worth S$10m for 17 research projects...more 08 Feb 2007 Biomed-Singapore: Predicting breast cancer survival from genetic fingerprints...more 08 Feb 2007 Biomed-Singapore: Creating safer and cheaper therapeutic options for stem cells...more 20 Jan 2007 The Straits Times Interactive: Singapore team creates 'less risky' stem cells...more 17 Jan 2007 Research scientists have found a way to enhance the development of human embryonic stem cells-based therapies...more 15 Jan 2007 BioSpectrum Asia Edition (Online)...more 22 Dec 2006 ARET RUNDT (Danish magazine – Engineering Weekly)...more 23 Nov 2006 Local researchers discover mutated gene which increases risk of Parkinson's...more 23 Sep 2006 SITNews: Micro gene material found...more 22 Sep 2006 Researchers discover importance of molecule in study of diseases...more 22 Sep 2006 IBM & Genome Institute of Singapore Research Enhances View of microRNAs’ Influence in Cells...more 17 Aug 2006 Singapore Acts as Haven for Stem Cell Research...more 09 Aug 2006 Lianhe Zhaobao Interview with Lisa...more 31 Jul 2006 Flu test labs on US ships, thanks to S'pore firm...more 31 Jul 2006 Stem Cell Central...more 11 Jul 2006 A dogged pursuit of talent pays dividends...more 11 Jul 2006 Clubs pay the price: report shows luck determines football managers’ tenure...more 01 Jul 2006 Singapore’s Model System...more 18 Apr 2006 Singapore's Twin Threats...more 03 Mar 2006 Singapore creates R&D role models...more 17 Nov 2005 GIS scientist wins “Most Inspiring Woman” Award ...more 18 Oct 2005 Singapore Prime Minister Lee Hsien Loong visits GIS...more 27 Sep 2005 Singapore scientists invent quick bird flu test...more 12 Sep 2005 GIS scientist wins NUS Centennial Genesis Award...more 01 Sep 2005 GIS participates in EDEN, a multi-agency collaborative study on dengue...more 11 Apr 2005 World looks to Singapore for inspiration...more 10 Jan 2005 Singapore biomedical researchers get $48m boost from A*STAR...more 17 Nov 2004 Over 700 attend 5th HUGO Pacific Meeting...more 25 Oct 2004 Nature Methods highlights GIS Scientists work...more 05 Jun 2004 Chip developed here to trace Sars mutations...more 10 Dec 2003 The virus that changed my world...more 17 Jul 2003 Roche Diagnostics Launches SARS Research Kit...more 24 May 2003 $300,000 raised for joint research effort to fight bug...more 22 May 2003 GIS partners giant pharmarceutical Roche to develop SARS detection tool...more 10 May 2003 Scientists Say SARS Has Undergone Genetic Changes...more 09 May 2003 U.S. to distribute SARS tests...more 09 May 2003 SARS death rate adjusted higher...more 09 May 2003 Many SARS Theories, Still No Cure...more 09 May 2003 Stability reported in SARS...more 09 May 2003 Many SARS Theories, Still No Cure...more 09 May 2003 Study Analyzes How SARS Virus Changed As It Spread Across the Globe...more 09 May 2003 Research warns Sars may be here to stay...more 09 May 2003 SARS virus genome is "double-edged sword"...more 09 May 2003 Sars "here to stay"...more 09 May 2003 Medics say the SARS virus may be here to stay...more 09 May 2003 Genome Institute says SARS virus has mutated, now 2 different strains...more 09 May 2003 Study suggests the SARS virus is not mutating much...more 09 May 2003 Study of SARS Genome Shows No Big Mutations...more 09 May 2003 Study shows little mutation in SARS virus...more 09 May 2003 Virus is robust and deadly to over 65s...more 09 May 2003 SARS Not Evolving Into Less Deadly Virus...more 19 Apr 2003 Testing for the virus: Hopes - and realities...more 18 Apr 2003 S'pore scientists map Sars virus genetic code...more 18 Apr 2003 Scientists crack genetic code of virus...more 17 Apr 2003 In 2 to 6 weeks, tests could detect virus 10 to 100 times faster...more 16 Apr 2003 Light at end of tunnel?...more 16 Apr 2003 Genome Institute of Singapore to release SARS diagnostic kit by this week...more 16 Apr 2003 S'pore-made Sars test by this week...more 27 Mar 2003 Tackling the Transcriptome...more 02 Mar 2003 Closer to God than ever before...more 03 Jan 2003 Ambition in A Test Tube...more 01 Jan 2003 Tiny Fish May Hold Key To Cancer Cure...more 01 Jan 2003 Gene institute headhunts experts from around globe...more 01 Jan 2003 Singapore's Genome Institute Draws Asian Talent With Expensive Equipment...more 03 Dec 2002 S'pore launches tissue, DNA bank...more 03 Dec 2002 National tissue bank to be set up...more 29 Oct 2002 Biomedical Asia New national body to push cancer research...more 21 Jun 2002 New Home for Genome Institute Aims To Attract International Scientists...more 20 Jun 2002 Teachers' Peek Into A New World...more 11 May 2002 Biomedical Hub Will Provide At Least 4,000 Jobs: Philip Yeo...more 10 May 2002 Money No Object To Luring Scientists To Singapore...more  Press Release 29 Apr 2008 Scientists form International Cancer Genome Consortium...more 17 Mar 2008 2008 Scientists make surprising discovery on biodiversity and biogeography of phages in modern stromatolites and thrombolites, which may lead to the discovery of viruses....more 17 Mar 2008 Scientists make surprising discovery on biodiversity and biogeography of phages in modern stromatolites and thrombolites, which may lead to the discovery of viruses...more 03 Mar 2008 Scientists in Singapore shed light on the molecular alliance between key proteins that play a role in sustaining the embryonic stem cell state....more 03 Mar 2008 Scientists in Singapore shed light on molecular alliance between key proteins that play a role in sustaining the embryonic stem cell state...more 03 Mar 2008 Scientists in Singapore shed light on molecular alliance between key proteins that play a role in sustaining the embryonic stem cell state...more 07 Nov 2007 Researchers chart the genetic mechanisms behind the genesis of fat cells...more 07 Nov 2007 Drug slows prostate tumor growth by keeping Vitamin A active...more 05 Nov 2007 Rare Cancer-causing syndrome found, for the first time, in Singapore...more 05 Nov 2007 Curry-derived molecules might be too spicy for colorectal cancers...more 05 Nov 2007 Antioxidants could provide all-purpose radiation protection...more 01 Nov 2007 Emerging therapies with a focus on Asian populations mark the AACR Centennial Conference on Translational Cancer Medicine: From Technology to Treatment, Singapore on November 4-8 2007...more 18 Oct 2007 Singapore scientists discover new regulators that maintain embryonic stem cells’ unique epigenetic character...more 16 Oct 2007 Genome Institute of Singapore secures prestigious NIH grants for research on advanced DNA technologies....more 05 Oct 2007 Hallmark features of human embryonic stem cells controlled by protein modifications that influence gene expression but do not alter DNA...more 03 Oct 2007 Enhancing the genomic medicine particularly in developing countries: priorities of HUGO’s new president, Dr. Ed Liu of Singapore ...more 08 Aug 2007 Scientists’ discovery of DNA replication behaviour in complex organisms may be the forerunner to leaps in genomic discoveries...more 24 Nov 2006 Scientists discover a "genetic grade signature" for improved prediction of breast cancer recurrence...more 22 Sep 2006 IBM & Genome Institute of Singapore Collaboration May Lead to Better Understanding of Cell Process Regulation...more 17 Sep 2006 Master Regulator of Stem Cell Genes Discovered...more 14 Mar 2006 Unveiling the treasure maps in stem cells...more 18 Jan 2006 A*STAR scientists unravel more mysteries of p53...more 11 Jan 2006 Common plant virus found to reside in human gut...more 20 Dec 2005 National Grid Proves to be a Powerful Tool for Biomedical Research...more 12 Sep 2005 Singapore scientists discover "genetic fingerprint" that predicts cancer patients' survival...more 15 Aug 2005 International study suggests possible link between evolution and cancer...more 28 Jul 2005 GIS scientists develop robust and specific primers to detect avian flu...more 26 Jul 2005 Singapore researchers identify protein that could be used to control Hepatitis B virus...more 13 Apr 2005 A New Way of Looking At Cancer...more 31 Mar 2005 Novel analysis helps uncover web of mysteries within the Human Genome...more 07 Dec 2004 Singapore scientists develop new synthetic protein that targets and kills cancer cells...more 19 Nov 2004 HUGO Pacific Pan-Asian SNP Initiative to Explore Genetic Diversity for Pan-Aisan Populations...more 09 Nov 2004 Biopolis plays host to Asia Pacific Meeting on human genetics...more 22 Oct 2004 Singapore scientists Awarded USD 1 million grant by US NIH to further work on Human Genome...more 21 Sep 2004 GIS develops new method to decipher gene...more 17 Sep 2004 Accolades for Cutting Edge Reearch: 11 Outstanding Research Talent Accorded Singapore's Highest Honour in Science and Technolog...more 04 Jun 2004 Microarray to "Fingerprint" SARS Virus...more 19 May 2004 S*BIO and the Genome Institute of Singapore set to collaborate on developing new drugs in the area of cancer...more 20 Nov 2003 SUN Microsystems unveils the SUN-GIS Centre of Excellence in Digital Biology...more 20 Jun 2003 Six Companies form the Singapore Dengue Consortium...more 21 May 2003 GIS partners giant pharmarceutical Roche to develop SARS detection tool...more 09 May 2003 New findings reveal mutating abilities of SARS virus...more 17 Apr 2003 Singapore scientists determine complete genetic code of SARS virus...more 15 Apr 2003 Singapore scientists reveal genetic code of SARS virus...more 31 Jan 2003 Singapore Poised to become Leading Biomedical Sciences Hub Says leading US Researcher who takes top post at Singapore Genomics...more 21 Jun 2001 Singapore Genomics Programme is now Genome Institute A New Name To Better Reflect Its Role as a Research Institute...more  Speeches 17 Nov 2004 Keynote Address by Singaproe Deputy Prime Minister Dr Tony Tan at the Gala Dinner, 5th HUGO Pacific Meeting...more 17 Nov 2004 Opening address by Professor Tan Chorh Chuan at the Opening Plenary of the 5th HUGO Pacific Meeting...more 29 Oct 2003 Keynote Address by Singapore Deputy Prime Minister Dr Tony Tan at the Biopolis Opening...more 02 Dec 2002 Opening address by Prof Edison Liu, Director Singapore TIssue Network & Executive Director Genome Institute of Singapore...more 02 Dec 2002 Opening Speech by Prof Tan Chorh Chuan, Chairman Singapore Tissue Network Steering Committee at the Launch of the Singapore Tissue Network...more 02 Dec 2002 Welcome address by Mr Philip Yeo, Chairman A*STAR at the Launch of the Singapore Tissue Network...more 10 May 2002 Opening address by Mr Philip Yeo, Chairman ASTAR at the GIS Opening ...more 10 May 2002 Opening Speech by Professor Robert Weinberg, Chairman of the GIS Scientific Advisroy Board at the GIS Opening ...more 10 May 2002 Welcome Address by Professor Edison Liu, Executive Director, GIS at the GIS Opening Ceremony...more 29 Sep 2000 Welcome Address By Mr Philip Yeo, Chairman A*STAR at the Inaugural Symposium of the Singapore Genomics Program...more  Views 22 Jun 2005 Systems Biology, Integrative Biology, Predictive Biology...more