Development of analytical (wet-lab) methods
- Robust, better and production-ready techniques for sample preparation for single cell analysis will be devised. In particular, we will focus on the development of methods for combined single cell genome-wide omics analyses (DNA+RNA, RNA+DNA-modification in single cells).
- Isolated single cells give exquisite insight into biological processes; however, cells do not operate in isolation. For this reason, there is a great need for technologies to study the behaviour of a group of cells at cellular or even sub-cellular resolution. A large part of our joint research efforts will focus on the development of methods for in situ transcriptome, genome and methylome analysis of tissue sections. We will work on spatial analysis of tissue sections with in situ sequencing techniques and using spatially barcoded tissues.
- Effective methodologies for the isolation of DNA/RNA from circulation compatible with NGS sample preparation techniques and kits to do this robustly and reliably.
- Methods for the isolation of high-molecular weight nucleic acids. The novel long-rang sequencing technologies only reach their full potential if the DNA that is used is of high molecular weight. Methods currently used for DNA isolation lead to a median length of the DNA molecules of 10 kb, while nanopore and optical mapping techniques can be used to sequence DNA molecules into the megabase range. Here we will develop mild DNA extraction methods for high molecular weight nucleic acids compatible with long-range sequencing instruments.
- Capturing techniques have been developed for sequencing the genomic fragments of greatest interest for combination with Illumina sequencing. Corresponding techniques for use with long-range sequencers do not exist. We will explore and develop techniques for targeted capturing of high-molecular weight DNA molecules.
EASI-Genomics partners will conduct joint, collaborative research to develop new methods or improve existing ones, with the final objective of enhancing the service offer that users can access.
Development of computational (dry-lab) methods
- Computational methods for analysis and storage of NGS data are of great importance. In many respects existing systems and approaches are insufficient to deal with the current demands and completely inadequate to deal with the demands of the future. We will develop computationally efficient pipelines, storage and deployment systems for the analysis sequencing data. The focus will be on decreasing computation time required for analysis while maintaining best-in-class quality, decreasing data footprints while keeping the data accessible, and distributable. Pipelines will be wrapped in a way that they can easily be deployed on other sites or in the cloud. This will provide huge benefit to the sequencing community and will save on the huger efforts of establishing and validating data analysis systems.
- The integration of data from multiple different types of omics experiments and robust procedures for the analysis of such assembled dataset is not trivial. Here we will focus on the development of computational methods for handling and analysis of multi-omics data.
- Scalable computational methods for single-cell analysis are also needed. We will develop computational approaches capable of dealing with data from millions of single cells, also considering multi-omic data from a single cell.
Here you find the publications resulting from method development within EASI-Genomics project