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Researchers Develop System To Identify Treatment Target For Cancer

World Affairs – Health
open eyes opinion {source: SGgov/Genome Institute of Singapore}

Background Note:
The research findings described in this article can be found in the Nucleic Acids Research journal, under the title, “Patient-specific driver gene prediction and risk assessment through integrated network analysis of cancer omics profiles” by Denis Bertrand1,†, Kern Rei Chng1,†, Faranak Ghazi Sherbaf2,†, Anja Kiesel1, Burton K. H. Chia1, Yee Yen Sia2, Sharon K. Huang3, Dave S.B. Hoon3, Edison T. Liu2,4, Axel Hillmer2 and Niranjan Nagarajan1.

1. Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore,

2. Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore 138672, Singapore,

3. Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, CA 90404, USA

4. The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA.
† These authors contributed equally to the paper as first authors.

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13th February 2015

A*STAR RESEARCHERS DEVELOP EXPERT SYSTEMS FOR IDENTIFYING TREATMENT TARGETS FOR CANCER AND RARE DISEASES

Singapore – In recent months, several national initiatives for personalized medicine have been announced, including the recently launched precision medicine initiative in the US, driven by rapid advances in genomic technologies and with the promise of cheaper and better health care. Significant challenges remain, however, in the management and analysis of genetic information and their integration with patient data. The sheer scale and complexity of this data, generated using cutting-edge technologies such as next generation DNA sequencing, requires the development of new computer algorithms and systems that can mine this data to get actionable knowledge.

Now, scientists at A*STAR’s Genome Institute of Singapore (GIS) have reported another breakthrough in the development of expert systems that can trawl large data-sets, integrating complex disease information to guide doctors in the diagnosis and treatment of diseases. The latest in this series is the development of a system called OncoIMPACT that combines cancer omics data and models learned from hundreds of patients to better sift through genetic mutations and pick potentially causal ones.

The lead investigator in this study, Dr Niranjan Nagarajan, Associate Director of Computational and Systems Biology at the GIS, noted, “We are particularly excited about OncoIMPACT’s ability to take into account the unique genetic makeup of each patient to predict treatment targets. It allows us to crunch massive cancer genome data-sets in an integrative and model-driven fashion to distill them down to the few key driver mutations.”

Assistant Professor Johannes Schumacher from the Institute of Human Genetics at the University of Bonn, added: “The integration of different ‘omics’ data-sets for the identification of cancer driver genes is a challenge. OncoIMPACT fills a gap in integrative analyses and provides the opportunity to revisit large complex data-sets for the identification of disease driving genes.”

The team of researchers at A*STAR have applied OncoIMPACT to more than a thousand cancers such as melanomas, glioblastomas, prostate, bladder and ovarian cancers, and are in the process of building a complete map of driver mutations across cancers. They also demonstrated a proof-of-concept in this study for using driver mutation signatures to predict clinical outcomes for cancer patients. This is an exciting alternative to currently available tests based on RNA and protein levels as DNA can be more reliably assayed, and the team plans to develop this work further.

Dr Nagarajan remarked, “Our hope is to create a resource for cancer researchers and clinicians in Singapore and around the world. We envisage a future where expert systems such as OncoIMPACT can leverage genomic data generated worldwide and contribute to personalized and targeted medicine in Singapore.”

Dr Gopal Iyer, Principal Investigator of the Cancer Therapeutics Research Laboratory at the National Cancer Centre of Singapore (NCCS) noted, “With the availability of large amounts of genetic data, it is difficult to focus our attention on the real cause and drivers in cancers. There are a number of algorithms that help narrow this search down in groups of cancers.

OncoIMPACT, however, is different as it can focus these analyses on a single patient. This is the first step for true treatment individualization: if we can uncover the drivers behind a tumor in a specific patient, we can ask if this can then be treated with specific drugs.” OncoIMPACT is the latest in the series of expert systems from the GIS and follows the recent publication of Phen-Gen – the first such system to cross-reference patient’s symptoms with genome sequence to detect causal genes for rare diseases. Both methods fall in the emerging area of integrative omics, where complex, multi-dimensional data-sets are jointly analysed with sophisticated algorithms to reveal novel biological and medical insights.

The development of OncoIMPACT was recently published in the journal Nucleic Acids Research, while Phen-Gen’s development was published in Nature Methods in August 2014.

About A*STAR’s 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 achieve extraordinary improvements in human health and public prosperity.

Established in 2000 as a center for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards academic, economic and societal impact.

The key research areas at the GIS include Human Genetics, Infectious Diseases, Cancer Therapeutics and Stratified Oncology, Stem Cell and Regenerative Biology, Cancer Stem Cell Biology, Computational and Systems Biology, and Translational Research.

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. For more information about GIS, please visit: www.gis.a-star.edu.sg

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 catalyzing new growth industries.

A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry. A*STAR oversees 18 bio-medical 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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