Single Cell Tri-Channel Processing (scTRIP)
Dr Jan Korbel, EMBL; Dr Ashley Sanders, EMBL
Structural variation (SV), such as deletions, duplications, inversions or translocations in the DNA, is a major source of genetic variation and plays a role in numerous diseases. Therefore, the discovery of SVs can help to better understand disease, enable precision medicine approaches, and allow for quality control in gene and cell therapy applications. Studying SVs with current methods is often limited by the high cost associated with the requirement for high coverage in sequencing. Furthermore, the discovery of SVs, especially in repetitive regions, remains challenging, and many SVs fully escape detection with current methods. Last but not least, methods to study SVs in single cells have been lacking. Such methods, however, would be extremely relevant for measuring karyotypic abnormalities, for example to assess the integrity of cells following therapeutic genome editing.
Scientists of the EMBL Heidelberg have developed single-cell tri-channel processing (scTRIP), a method that allows for the systematic, detailed and accurate detection of SVs which includes all known forms of karyotypic abnormality in single cells. The technology uses strand-specific single cell sequencing, and integrates three layers of information (depth of coverage, read orientation and haplotype phase) in a Bayesian framework to call SVs in single cells by identifying a specific ‘diagnostic footprint’ for the different SV classes. Since scTRIP requires considerably less sequencing depth than other methods, the technology is not only more reliable than the current standard, but can also be performed for only a fraction of the cost. Potential applications for scTRIP are in disease classification for precision medicine, patient stratification for clinical studies, assessment of genome integrity in cell and gene therapy applications and therapeutic CRISPR-Cas9 editing, as well as in rare disease genetics.
We offer a technology evaluation program as well as licensing opportunities and consultancy services for setting up the technology with the partner.
The technology is ready to use.
A patent application has been filed in 2019.