Periodic Reporting for period 1 - CONAN (COmplete Nucleic acid ANalysis at genome scale using ultra high throughput sequencing)
Reporting period: 2016-07-01 to 2016-12-31
Next Generation Sequencing (NGS) instruments have enabled scientists to decode the basic sequence of DNA on a massive scale and to unlock major discoveries in areas as diverse as human health, evolution, and ecology. However, being able to read the four bases of DNA is far from sufficient to be able to understand all of the genetic world around us. In human genetics, for example, even though many tens of thousands of human genomes have now been sequenced, a large fraction of human genetic variation cannot be well correlated to common human diseases (e.g. heart disease, cancer, obesity, etc.). In recent years, new levels of genetic complexity have been uncovered with the discovery of different types of molecular switches that control the activity of the genes encoded by DNA. Two types of molecular switches are extremely important in modulating genetic activity: (1) variations in the different forms of RNA, and (2) the base-modifications – a set of chemical groups can be added to the bases of both DNA and RNA. It is now clear that full genome analysis requires the sequencing of not only DNA, but also RNA and the base modifications on these molecules. Current NGS instruments are very good for reading DNA sequence, but are severely limited in their capacity to analyse RNA and base-modifications.
PicoSeq (recently renamed as ‘Depixus’) is developing a technology platform on which it is possible to sequence both DNA and RNA and detect analyse both DNA/RNA sequence and base-modifications – in other words it is capable of ‘complete nucleic acid analysis’. This technology, known as SIMDEQTM (short for SIngle-molecule Magnetic DEtection and Quantification) has the capacity to transform genetic analysis. The technology is based on the work of the Croquette lab at France’s prestigious Ecole Normale Supérieure. Depixus was established in 2012 to further develop and commercialise the technology.
It has already been shown that SIMDEQTM can be used to extract sequence and base-modification information from both DNA and RNA. However, the current instrument prototypes on which these experiments have been performed are severely limited in their throughput (i.e. the number of nucleic acid molecules that can be analysed per unit time). Development of a commercial grade SIMDEQTM system requires significant improvements to throughput.
The ultimate goal of this COmplete Nucleic acid ANalysis (CONAN) project is to develop a version of the SIMDEQTM system capable of operating at high-throughput. This will be achieved by applying advanced manufacturing technologies, common in the micro-electronics industry, to the development of a MEMS-based biochip (‘SIMDEQTM Digital’).
The ultimate goal of this COmplete Nucleic acid ANalysis (CONAN) project is to develop a version of the SIMDEQTM system capable of operating at high-throughput. This will be achieved by applying advanced manufacturing technologies, common in the micro-electronics industry, to the development of a MEMS-based biochip (‘SIMDEQTM Digital’).