Scientists at A*STAR's Genome Institute of Singapore Catch Evolving Germs and Cancer Cells Early

Published: Mar 07, 2013

March 7, 2013 -- Scientists at A*STAR’s Genome Institute of Singapore (GIS) have developed a novel technique to precisely monitor and study the evolution of micro-organisms such as viruses and bacteria. This is an extremely important capability as it allows scientists to investigate if new drugs designed to kill them are working, and catch the development of resistance early on.

Micro-organisms and cancer cells evolve more quickly than normal human cells as their rapid life-cycles enable faster selection of advantageous mutations. Previously, scientists have had to wait for the selection process to reach maturity before they can observe mutations and assess their impact.

In this new work, led by GIS Principal Investigators Dr Niranjan Nagarajan and Dr Martin Hibberd, the sensitivity of detecting mutations has been significantly increased, thus making it possible to “catch evolution in real time”. Being able to do this means that scientists can now observe the process of mutation as it happens, and catch how the organism or cancer cell develops resistance to drugs used.

The novel method, known as LoFreq, was achieved by combining deep sequencing of DNA with computational analysis to detect mutations at extremely “LOw FREQuency” – in as few as one in 1000 cells. This approach is currently being used at the GIS to study the dengue virus, characterizing subtle shifts in the viral genome in response to new antiviral drugs.

Dr Niranjan said, “LoFreq has really allowed us to look at viral genome evolution in fine detail and we hope to use it construct better models for transmission of the dengue virus. We can also now identify key functional regions in viral genomes by highlighting spots that never mutate or mutate rapidly. In ongoing work, we are developing extensions to LoFreq that can better characterize mutations in Cancer.”

Executive Director of GIS, Prof Ng Huck Hui said, “This innovation in the computational space highlights GIS’s effort in developing unique capabilities in analyzing increasingly complex next-generation sequencing datasets. We expect that LoFreq will have wide utility in the analysis of viral, bacterial and cancer genome data.”

Research publication:

The research findings described in the press release was published in the December 2012 issue of Nucleic Acids Research under the title “LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets”.


Andreas Wilm1, Pauline Poh Kim Aw1, Denis Bertrand1, Grace Hui Ting Yeo1,

Swee Hoe Ong1, Chang Hua Wong1, Chiea Chuen Khor1, Rosemary Petric2,

Martin Lloyd Hibberd1 and Niranjan Nagarajan1

1. Genome Institute of Singapore, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore and

2. Hoffmann-La Roche, Bldg 85/521340 Kingsland Street, Nutley, NJ 07110, USA

Corresponding Author:

Niranjan Nagarajan, Tel: +65 6808 8071; Email:


Winnie Lim

Genome Institute of Singapore

Office of Corporate Communications

Tel: (65) 6808 8013


About the Genome Institute of Singapore (GIS)

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine.

The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy.

In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore’s manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry.

A*STAR oversees 20 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis as well as their vicinity. These two R&D hubs house a bustling and diverse community of local and international research scientists and engineers from A*STAR’s research entities as well as a growing number of corporate laboratories.

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