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Improvements in epigenomic sequencing technologies could enhance cancer diagnostics

27 June 2016

An international research collaboration led by 香港六合彩中特网 scientists has developed ways to improve the quality and accuracy of information harvested from epigenome sequencing datasets in two new research papers published jointly in Nature Biotechnology and Nature Communications today.

DNA methylation鈥

According to the studies, epigenome sequencing technologies can allow for more comprehensive analysis of cancers - a key component in the development of targeted approaches to combat cancer.

Epigenetics is a relatively new and rapidly evolving area of cancer research and refers to chemical modifications to DNA that turn genes 鈥榦n鈥 or 鈥榦ff鈥. These modifications do not change the DNA sequence itself but the way it functions. In this way, epigenetic modifications help determine cellular identity i.e. what distinguishes a skin cell from a brain or other type of cell. Currently, sophisticated technologies exist that can be used to detect epigenetic changes in tissue samples. In many cancers, epigenetic variants are more frequent than genetic variants, so can therefore provide vital information for understanding how cancers develop and progress.聽

A key question for the researchers involved in the studies was whether epigenome sequencing technologies could be improved to detect such modifications much more comprehensively and efficiently.

鈥淥ur studies focused on measuring one of the most commonly known epigenetic modifications: DNA Methylation. This is a chemical 鈥榯ag鈥 that attaches to the genetic material (DNA) of a cell, which can alter the behaviour of that cell,鈥 explains Dr Emanuele Libertini, 香港六合彩中特网 Cancer Institute Research Associate and lead author of the studies. 鈥淲e are looking at what information can be extracted from DNA Methylation using whole-genome bisulfite sequencing (WGBS) technology. WGBS has been widely used to generate reference methylomes since 2010 and our improvements empower researchers to obtain additional information that could not be obtained before.鈥

鈥淭o achieve this, we鈥檝e developed a tool that dynamically segments WGBS methylomes into blocks of comethylation (COMETs) from which previously undetected information can be recovered. Given the high cost of WGBS, there is a clear benefit to extracting as much information as possible from a given dataset - our algorithms allow us to extract information that is not available to standard analysis. Essentially, we are offering a way to get more for less.鈥澛

Professor Stephan Beck, Head of the Medical Genomics Research Group at 香港六合彩中特网 Cancer Institute, says: 鈥淭his exciting new technology will advance our ability to understand phenotypic plasticity in health and disease, an important aspect of cancer research鈥.

This work is the result of an international collaboration involving , , and and was led by Professor Stephan Beck (香港六合彩中特网 Cancer Institute) and Dr. Rifat Hamoudi (香港六合彩中特网 Division of Surgery and Interventional Science)


Further information

Research paper 鈥業nformation recovery from low coverage whole- genome bisulfite sequencing鈥 Nature Communications

Research Paper Saturation analysis for whole-genome bisulfite sequencing dataNature Biotechnology

Companion papers:

鈥楺uantitative comparison of DNA methylation assays for large-scale validation and epigenetic biomarker development鈥 Nature Biotechnology.

鈥楥hromatin accessibility maps of chronic lymphocytic leukemia identify subtype-specific epigenome signatures and transcription regulatory networks鈥 Nature Communications


Links


Image:聽A DNA molecule that is methylated on both strands on the center cytosine. .[Details: The picture shows the crystal structure of a short DNA helix with sequence "accgcCGgcgcc", which is methylated on both strands at the center cytosine. The structure was taken from the Protein Data Bank (accession number 329D), rendering was performed with VMD and post-processing was done in Photoshop.] Credit: Christoph Bock/CeMM