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Moving the field of clinical genomics toward a future of more effective diagnosis and treatment of cancers.

Scientists and engineers from BC Cancer Agency’s Genome Sciences Centre (GSC) have developed two new approaches for characterizing how the information in genes is expressed. Details of each method, known as ALEXA-Seq and Trans-ABySS, were recently published in separate papers in the journal Nature Methods. Each approach uses state-of-the-art sequencing technology to characterize transcriptomes—collections of all expressed genes. Both methods represent significant steps towards cost-effective surveying of all genetic information in a tumour.

The paper “Alternative expression analysis by RNA sequencing”, published in September, describes the ALEXA-seq analysis system. Most genes can be expressed as RNA in several different ways or ‘isoforms’, each of which makes a distinct version of a protein. ALEXA-seq sensitively detects isoforms within individual genes. The researchers proved the method’s value by identifying isoforms that were specific to chemotherapy-resistant colon cancer cells. This type of highly detailed information will provide a roadmap of the cancer, pointing to distinct proteins involved in the growth and development of its cells.

ALEXA icon

ALEXA: Alternative Expression Analysis

“Cancer is an umbrella term for thousands of distinct diseases, “ says Marco Marra, PhD, director, BC Cancer Agency Genome Sciences Centre. “Now we have entered an era where we can economically characterize all of the types and sub-types that fall under this massive cancer umbrella.” Marra adds, “We are already applying the ALEXA-seq approach to characterize breast cancer, multiple myeloma, lymphoma, leukemia, and other cancer types. With the knowledge gained we can propel development of personalized treatment.”

The research paper “De novo assembly and analysis of RNA-seq data”, published today in Nature Methods, describes Trans-ABySS, an approach that is highly effective in identifying novel RNA molecules—the coding mechanism for proteins. The challenge was to develop a method that could correctly reconstruct thousands of RNA sequences from short sequence reads. “With Trans-ABySS, we showed how to use assembly to reconstruct a challenging genetic jigsaw puzzle accurately from millions of tiny pieces,” says Inanc Birol, PhD, bioinformatics group leader, BC Cancer Agency Genome Sciences Centre. The team has shown that Trans-ABySS can detect known isoform irregularities in non-Hodgkin lymphoma, and are now applying the approach to survey a wider range of cancer types.

Both methods are able to detect isoforms that do not normally occur in human tissues, but, are found in cancerous tissue. If isoforms could be described efficiently in large numbers of patients, in particular types and subtypes of cancers, the resulting knowledge could be used to develop new drugs, and to predict how an individual patient should respond to particular drugs.

The rapid evolution of sequencing and computer systems have made it practical to comprehensively and efficiently produce a snapshot of entire transcriptomes, and is allowing the field of ‘clinical genomics’ to emerge. Because the human genome is large and transcriptomes are complex, developing efficient computational analysis methods remains central to progress in this area. ALEXA-seq and Trans-ABySS represent advances towards more cost-effective and efficient methods for surveying the isoforms in a tumor in order to identify those that are specific to a cancer or are associated with a particular clinical outcome.

Research Paper Citations:

Alternative expression analysis by RNA sequencing. Griffith M, Griffith OL, Mwenifumbo J, Goya R, Morrissy AS, Morin RD, Corbett R, Tang MJ, Hou YC, Pugh TJ, Robertson G, Chittaranjan S, Ally A, Asano JK, Chan SY, Li HI, McDonald H, Teague K, Zhao Y, Zeng T, Delaney A, Hirst M, Morin GB, Jones SJ, Tai IT, Marra MA. Nat Methods. 2010 Oct;7(10):793-5.

De novo assembly and analysis of RNA-seq data.Robertson G, Schein J, Chiu R, Corbett R, Field M, Jackman SD, Mungall K, Lee S, Okada HM, Qian JQ, Griffith M, Raymond A, Thiessen N, Cezard T, Butterfield YS, Newsome R, Chan SK, She R, Varhol R, Kamoh B, Prabhu AL, Tam A, Zhao Y, Moore RA, Hirst M, Marra MA, Jones SJ, Hoodless PA, Birol I. Nat Methods. 2010 Oct 10. [Epub ahead of print]


ALEXA-seq research team acknowledges the financial support received from the University of British Columbia, the Michael Smith Foundation for Health Research, the Natural Sciences and Engineering Research Council, Genome British Columbia, the Terry Fox Foundation, the Canadian Institutes of Health Research, the National Cancer Institute of Canada and the BC Cancer Foundation.

Trans-ABySS research team acknowledges the support received from Genome Canada, Genome British Columbia and the Canadian Institute of Health Research (CIHR), including the CIHR Bioinformatics Training Program for Health Research.

About the BC Cancer Agency

The BC Cancer Agency, an agency of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. The BC Cancer Foundation raises funds to support research and enhancements to patient care at the BC Cancer Agency.

About the Genome Sciences Centre

Operating under the BC Cancer Agency, the Genome Sciences Centre is Canada’s first high-throughput sequencing facility. The centre provides state-of-the-art DNA sequencing technology to support genetic research focused on improving the diagnosis and treatment of cancer. The ultimate goal of this research is to develop methods for controlling the human genes affecting the growth and suppression of cancer.

For more information, please contact: Papinder Rehncy Communications Leader BC Cancer Agency 604.877.6261

Page last modified Oct 15, 2010