The year 2018 has become another 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 2017 was 84 (with 32 in journals with impact factor >5; this is ~38% of all publications in 2017; see figure), quite an achievement for just about 100 faculty members, scientists, supporting staff, students, etc. working at BII at present.

Notably, BII was established within the framework of the Biomedical Research Council (BMRC) of A*STAR in 2001 as a mere IT and bioinformatics service unit for the other BMRC institutes. In 2007 upon my arrival as Director, BII was provided the chance to get re-established as a biomedical research unit. The engagement, hard work and good ideas of our staff, of our Scientific Advisory Board members and of our collaborators during the following years resulted in a steady growth in reputation and impact of BII's research 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). The publication number per year has stably hovered above 80 since 2014. About 83% of all papers published by BII in 2001-2016 have come out during the years 2008-2017 (749 out of 905). Among the papers with impact factor>5, the fraction is even larger than 90% (222 out of 246). This is the more remarkable since essentially none bioinformatics journal falls into this category; thus, we do outreach into general biological/medical publications.

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 reliable and trusted partner in the community and, to emphasize, we are here to stay for a long time to come and we justify ourselves with scientific discoveries and other achievements. We also provide scientific advice to Singaporean and international organizations, clinical and industry partners.

For example, Peter Bond's team discovered a novel antiseptic and antibacterial mechanism during wound healing that involves thrombin fragments forming clots that collect pathogens and toxins together (PNAS 114, E4213). Several BII teams contribute to the A*STAR Innovations in Chemical and Food Ingredient Safety Program, which aims to develop cutting-edge in silico and in vitro platforms for chemical safety testing. BII was instrumental in developing the world’s first high-throughput screen methodology for non-animal-based kidney, lung and liver cell-based toxicity testing. Loo Lit-Hsin (honored with the LUSH prize) is leading the program's involvement in an international case study on the utility of in vitro bioactivity data for estimating chemical points-of-departure. Other partners in the case study include the US Environmental Protection Agency (EPA), European Chemicals Agency (ECHA), European Food Safety Authority (EFSA), and Health Canada.

BII's infectious disease research spearheaded by Sebastian Maurer-Stroh, associated with the WHO and MOH infectious disease surveillance effort and with GISAID, has generated, besides more than 50 scientific publications, the first and many following appearances of BII in the general press for scientific successes, last time in context with the Zika epidemic in Singapore. Singapore’s government was relieved to hear that the locally circulating Zika virus strain was not derived from a version imported from Brazil but it evolved from the Zika viruses that have circulated in the local background for many years. A recent Lancet Infectious Disease publication (vol. 17, N8, p.213) provides a full epidemiological entomological, virological and clinical analysis of the epidemic’s aftermath. Infectious disease research is ongoing in BII at a wide front and targets diseases other than influenza, too. So, Chandra Verma leads BII’s BMAD (Biomolecular Modelling and Design Division) engagement in dengue virus multi-scale structure research as part of a MOE tier 3 grant together with partners from NUS and NTU.

The work at BII’s outstation as 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 to Wong Wing-Cheong’s team) in the collaboration with SingHealth clinicians were behind the mentioning of BII as the example for A*STAR-SingHealth collaboration in MTI Minister S. Iswaran’s address at the ceremony of signing the MOU at the 8th of December 2017.

Finally, 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 activities are driven by the translational research division with the Natural Organism Library at its core. SINSA and Sinopsee Therapeutics are spin-offs that have seen their birth with BII’s participation (with Chandra Verma’s group).

It is important to see BII’s development in perspective - both locally in Singapore and in the general developments in life sciences in the world. The varying finance environments provided by the changing R&D 5-year-plans in Singapore (we are currently in RIE2020) have a profound influence on BII’s size fluctuations and research direction changes. It is also 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.

Figuratively speaking, current scientific developments such as the readily available omics data blow a supportive wind into our wings. The engagement of our scientists and support staff is important and in time as it is historically part of the biological data analysis and especially biomolecular sequence data study efforts that have become instrumental for progress in life sciences. World-wide, computational biology/bioinformatics became a broader research effort recognized to be of general importance for life science only in the early 90-ies of the 20th century. The early steps for the development of bioinformatics research in Singapore have been described elsewhere (JBCB 12(3):1471002, 2014).

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 draft was celebrated with great pomp, the reviews summarizing the achievements a decade 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. As a matter of fact, there is much more biological and clinical data (especially biomolecular sequence data) out 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 also JBCB 10(5):1271001,2012). In 2001, about half of the known protein-coding genes in human was 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 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 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. 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 small and medium-sized independent research teams most of them led by first-time principal investigators. The groups are organized in three basic research divisions including

  1. Analysis of genome sequences gene expression and RNA biology, protein sequence analysis and function prediction of uncharacterized genes,
  2. Protein 3D structure modelling
  3. Imaging Informatics: Computer-supported analysis of microscopic images of cells and tissues with labelled molecules and
  4. A fourth division of translational research

The latter division also houses a large library of more than 160,000 microbiological, fungal and plant species for future genomics and systems biology research. Crossdivisional research programs at BII involve infectious diseases, cancer biomarkers, alternative (non-animal testing) methods for toxicology, biotransformation of chemicals, etc. BII provides a Secondary Clinical Data Sink for long-term storage of clinical (trial) data, its cleansing and standardization, its primary processing and later in-depth analyses, also in cross-trial contexts.

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, Prof. Michael Sheetz elaborated about difficulties with interdisciplinary science, conditions for creativity and his own “dumb luck” in the system. In 2015, Prof. Daniel Tenen taught us about humbleness and the great role of mentors and good institutions in his personal development as successful scientist. Prof. Chong Yap Seng, the Executive Director of the Singapore Institute of Clinical Sciences was the “Added Dimension” speaker in 2016; he described scientific research from the angle of a clinician and offered lots of his own experiences as food for thought. The Added Dimension Lecture in March 2016 was delivered by Prof. Christiani Jeyakumar Henry who informed us about new science in obesity and nutrition research. For example, he provided evidence that combining protein and fat with rice lowers the glycemic index, softens blood sugar spikes and improves the physiological effect of food despite the same calories eaten.

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 2018