EXECTIVE DIRECTOR'S MESSAGE

2018 was if not the most successful and productive year in the history of BII. Performance of an academic institution is typically measured in terms of scientific publications, discoveries and innovations as well as clinical and industry collaboration agreements. BII has done very well by any of these accounts. The total number of scientific publications in 2018 was 98 (with 32 in journals with impact factor >5; see figure), an excellent achievement for just about 140 faculty members, scientists, supporting staff and students. All groups contributed to this outcome. The contribution of several young principal investigator teams such as Samuel Gan’s (with >60 papers in the last 5 years) deserve special mentioning.

Established as mere IT and bioinformatics service unit for the research institutes within the Biomedical Research Council (BMRC) of A*STAR in 2001 (see JBCB 2014, 12(3):1471002 for the history of bioinformatics research in Singapore), BII was relaunched in 2007 upon my arrival as director as biomedical research unit. Our staff's engagement, hard work and good ideas resulted in a steady growth in BII's reputation in Singapore and in the world most obviously illustrated by a ~3 times growth of the scientific output per year compared with the earlier period (see figure).

More than 80% of all publications are the result of collaborative work with academic, clinical or industrial partners in Singapore or elsewhere in the world; thus, BII has established itself as a trusted partner in the community and, to emphasize, we are here to stay for a long time to come with our excellent research. We also provide scientific advice to Singaporean government and international organizations, clinical and industry partners. E.g., Sebastian Maurer-Stroh is involved in the infection surveillance programme of the Singaporean MOH and WHO. His team's landmark publication in Nature Ecology and Evolution (2018) found that individual immune selection has limited impact on seasonal influenza evolution. A*STAR’s Innovations in Food & Chemical Safety Programme (IFCS led by Benjamin Smith) housed in BII aims to develop cutting-edge in silico and in vitro platforms for chemical safety testing. IFCS research is carried out by Loo Lit Hsin's, Fan Hao's and other BII teams and is communicated to the US Environmental Protection Agency (EPA), European Chemicals Agency (ECHA), European Food Safety Authority (EFSA), and Health Canada.

The work at BII's outstation at PRISM (Duke-NUS) and the success of BII's clinical trial data facility for long-term storage, cleansing, versioning and analysis/interpretation of patient data (recognition especially to Wong Wing-Cheong's team) in the collaboration with SingHealth clinicians were behind the mentioning of BII as the example for A*STARSingHealth collaboration in MTI Minister S. Iswaran's address at the ceremony of signing the MOU at the 8th of December 2017.

It is notable that, for the Singaporean context, research always co-exists with the expectation of commercialization of intellectual property with all its consequences; the culture of doing science for the sake of knowledge and for understanding the objective laws governing nature and society is not yet exactly part of the local value system. The quality of BII's research leads to a handful of patents every year and has attracted biotech and pharma companies for research collaboration agreements worth of many millions SGD. Most industrial activities are driven by the translational research division with the Natural Organism Library (see Nature Biotechnology 2018, 36:570, praise to Ng Siew Bee and Yoganathan Kanagasundaram). SINSA (www.sinsalabs.com) and Sinopsee Therapeutics are spin-offs that have seen their birth with BII's participation (with Chandra Verma's group).

Figuratively speaking, current scientific developments such as the readily available omics or bioimage data blow a supportive wind into our wings. With hindsight, BII's birth was within a wave of hype around the full sequencing of the human genome in 2001. Whereas the presentation of the genome draft was celebrated with great pomp, the reviews summarizing the achievements a decade later 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. As a matter of fact, there is much more biological and clinical data (especially biomolecular sequence data) out there than it can be analysed and understood today. In cases, the data has been available since decades; yet, the mechanistic understanding has not progressed. For the insider, this development was not a major surprise (see JBCB 10(5):1271001, 2012 and Proteomics 18:e1800093, 2018). In 2001, about half of the known protein-coding genes and almost all non-coding RNAs in human were functionally not characterized 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 annual new function discovery increased (it actually decreased).

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 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. The key task in life sciences now is the interpretation of non-understood genomic sequences in terms of biological function and mechanisms and especially the characterization of functionally not yet annotated genes. We can jokingly say that computational biologist would have lots of biological (mainly omics) data for analysis for decades to come even if experimentation in life science or clinical work had stopped from now on completely.

BII's 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 computer-based theoretical research tools. E.g., Lee Hwee Kuan's team came up with a compact neural network architecture encoding a whole function in a network node (Neural Networks 2019, 110, 199). Or Samuel Gan's team excels with mobile applications tailored for life science research. Our work would be incomplete without the experimental verification of our own hypotheses and the application of the results. 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 ~15 independent research teams most of them led by first-time principal investigators. The groups are organized in three basic research divisions including (i) analysis of genome sequences, gene expression and RNA biology, protein sequence analysis and function predictio of uncharacterized genes, (ii) protein 3D structure modelling and (iii) imaging informatics – computer-supported analysis of microscopic images of cells and tissues with labelled molecules and (iv) a fourth division of translational research. The latter division also houses the Natural Organism Library of more than 160,000 microbiological, fungal and plant species for future genomics and systems biology research. Cross-divisional research programs at BII involve infectious diseases, cancer biomarkers, alternative (nonanimal testing) methods for toxicology, biotransformation of chemicals, etc.

The annual life cycle of BII culminates in the annual BII Scientific Conference and the BII Dinner Party, typically in March. Traditionally, the concluding festive evening is crowned with the "Added Dimension Lecture" (see article in this yearbook) where renowned scientists speak about their very personal experiences and views on science, life and society. To conclude, 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

February 2019