Executive Director's Message

Welcome to the Bioinformatics Institute in Singapore!

A little more than a decade ago, the first draft of the essentially complete human genome was published. Whereas the presentation of the draft was celebrated with great pomp, the reviews summarising the achievements thereafter hardly made it into the headlines. Not surprisingly, the outcome with regard to cures for not yet treatable diseases or new biotechnologies has not nearly reached the expectations.

For the insider, this development was not a major surprise (see also JBCB 10(5):1271001, 2012). In 2001, about half of the known protein-coding genes in human was functionally not characterised and, although our biological knowledge is as large as never before in human history, neither the list of known gene function has not become much longer in the mean time nor has the scale of function discovery increased. Most of the human genome (98.5%) is not protein-coding and this "rest" is also actively transcribed; yet, the world of non-coding RNAs' functions remains enigmatic for the most part. On the positive side though, the knowledge of the human genome sequence allows assessing how much of the human biology at the molecular mechanism level is still unknown and it appears that it is surely more than half of it.

As this situation does not promise immediate success for many pharmaceutical and biotechnological applications at the moment, it provides great opportunities for bioinformatics and computational biology. Although life sciences are not truly a theoretical discipline since the extrapolation depth is small due to the fragmentary knowledge of biomolecular mechanisms, there are a few increasingly important research areas such as studies of sequences, expression profiles, 3D structures and bioimages where the application of quantitative, mathematical concepts has become instrumental for the discovery and for progress in biological theory, for the prediction of function of genes and their interaction in pathways and networks. For example, the concept of sequence homology as common evolutionary ancestry leading to sequence similarity with resembling protein structure and function of proteins was considered obscure when it was first developed; yet, it is at life science's main stage today.

This development has mainly been fuelled by DNA sequencing but also by other high-throughput experimental techniques. The key task in life sciences now is the interpretation of nonunderstood genomic sequences in terms of biological function and mechanisms and especially the characterisation of functionally not yet annotated genes. We can jokingly say that computational biologist would have lots of biological data for analysis for decades to come even if experimentation in life science or clinical work had stopped from now on completely.

The Bioinformatics Institute (BII), originally founded by Dr. Gunaretnam Rajagopal in 2001 as IT services and bioinformatics support unit, has experienced a transformation into a biological research organisation since my arrival in August 2007. The scientific mission involves computationally biology driven life science research aimed at the discovery of biomolecular mechanisms. Besides the actual theoretical studies on biological data, this includes also the development of appropriate computerbased theoretical research tools.

Our work would be incomplete without the experimental verification of our own hypotheses and the application of the results. For this purpose, we have two options. On the one hand, we extensively collaborate with experimental and clinical groups from academia in Singapore and abroad as well as with pharmaceutical and biotechnological industry. Alternatively, BII also has its own experimental facilities.

BII has currently about 20 small and medium-sized independent research teams most of them led by first-time principal investigators (among them 10 new since 2013). The groups are organised in four basic research divisions (including (i) analysis of genome sequences, gene expression and RNA biology, (ii) protein sequence analysis and function prediction of uncharacterised genes, (iii) protein 3D structure modelling and (iv) imaging informatics - computer-supported analysis of microscopic images of cells and tissues with labelled molecules and a fifth division of translational research, new since December 2013. The latter division also houses a large library of more than 100,000 microbiological, fungal and plant species for future genomics and system biology research. In addition, we also have two cross-divisional programs with clinical focus ("Cancer Biomarkers" headed by Vladmir Kuznetsov and Human Infectious Diseases headed by Sebastian Maurer-Stroh).

Important scientific discoveries have been made by BII researchers. To name just a few, Vivek Tanavde was involved in the discovery of the role of the primatespecific exonic microRNA-198 in wound healing (Nature, 2013, doi: 10.1038/ nature11890). 2014 saw the discovery of Gpaa1/Gaa1 as metallo-peptidessynthetase as part of the transamidase complex in the GPI lipid anchor pathway (Eisenhaber et al., Cell Cycle, 2014, 13, 1912; N&V by Taroh Kinoshita in Cell Cycle, 2014, 13, 1838). Lee Hwee Kuan and colleagues have identified new subgroups of primary angle-closure glaucoma with automated analysis of images from an Asian clinical study cohort. We celebrated Chandra Verma having published more than 100 scientific papers during his first ten years at BII. To note, BII's influenza research spearheaded by Sebastian Maurer-Stroh, associated with the WHO surveillance effort and with GISAID, has generated, besides more than 20 scientific publications, the first mentioning of BII in the general press for scientific successes in context with discoveries regarding the H1N1 influenza virus mutation-phenotype relationships. And the studies on the EV1 pathway in ovarian cancer by Vladimir Kuznetsov and colleagues have the potential to yield new and early diagnostics tools for ovarian cancer.

Further hopeful signs that BII is on the right track towards scientific excellence are provided by the general outcome of scientific publications. That has about doubled since 2007 and has reached a new plateau since 2010 with well above 70 scientific publications per year, quite an achievement for about 100 faculty members, scientists, supporting staff, students, etc. working at BII at present. ~75% of all papers published by BII in 2001-2014 have come out during the years 2008-2014 (468 out of 624). Among the papers with impact factor>5, the fraction is even ~83% (117 out of 141). This is the more remarkable since almost none bioinformatics journal falls into this category; thus, we increasingly outreach into general biological/medical publications. Finally, the quality of BII's research leads to a handful of patents every year and has attracted biotech and pharma companies for collaborations with research collaborations agreements worth of many millions SGD. Through SPRING- A*STAR's GET-UP program, BII has successfully commercialised several "Made in Singapore" nucleic acid research kits under a local SME (Quintech Life Sciences Pte Ltd., also distributed by BSF A*STAR). SINSA is the first spin-off that has seen its birth with BII's participation (with Chandra Verma's group).

BII is one of the pioneering institutes to move bioinformatics into mobile apps, an initiative spearheaded by Samuel Gan. With the widely covered "DNAapp" in over 80 international newspapers, and the new "Gelapp", bioinformatics are now moving into smartphones and "phablets"; thus, increasing convenience and accuracy in the experimental lab. These apps have been downloaded by over 2000 scientists all over the world in just a few months.

BII is an attractive place for spending the sabbatical year (e.g., Prof. Andreas Wagner from the University of Zurich during 2012/2013). We also want to increase the number of PhD students in BII. Therefore, we joined with the School of Computer Engineering (SCE) of the Nanyang Technological University (NTU) in Singapore and launched a PhD program for Bioinformatics and Computational Biology that is now open for applicants. Interested good students are strongly encouraged to apply.

The annual life cycle of BII culminates in the annual BII Scientific Conference, the BII Scientific Advisory Board visit and the BII Dinner Party, all during three consecutive days in February/March. Traditionally, the concluding festive evening is crowned with the "Added Dimension Lecture" where renowned scientists speak about their very personal experiences and views on science, life and society. In 2010, Sir Tom Blundell talked about his endeavours in communal politics, world travel and crystallography. In 2011, Prof. Wong Limsoon informed us about the difficult beginnings of bioinformatics in Singapore and his personal role in the process two decades ago. Nobel Laureate Sydney Brenner contemplated about serendipity and the selection of research tasks in 2012. Prof. Bertil Andersson, President of Nanyang Technological University, made us laugh with anecdotes from his work in the Nobel Committee in 2013. In 2014, Michael Sheetz elaborated about difficulties with interdisciplinary science, conditions for creativity and his own "dumb luck" in the system.

The members of our institute are united in making BII a success story and I invite you to join us in this endeavour that will open new frontiers in biology and other life sciences as well as their applications for the benefit of society. In this context, enhanced cooperation with clinical research and life science-related industry will go hand in hand with the growing reputation of BII for good science.

Dr. Frank Eisenhaber
Executive Director
Bioinformatics Institute

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