The GPSeq and FRET-FISH methods developed in GENOMIS clearly go beyond the state-of-the-art, as they are the first methods capable of probing, respectively, genome radiality and local chromatin compaction. Importantly, GPSeq is part of a growing repertoire of methods for probing 3D genome organization, which are not derived from Hi-C. The latter has been instrumental in unraveling the fundamental design principles of genome organization across multiple species and cell types. However, neither Hi-C nor the dozens of Hi-C-derived methods that have been developed over the past decade can accurately capture certain important aspects of the higher-order organization of chromatin in the nucleus, such as the intra-nuclear placement of DNA loci. At the same time, it has been demonstrated that the localization of genes inside the nucleus affects their expression levels, indicating a strong link between spatial localization patterns of chromatin and transcription. In this sense, GPSeq fills in the previous knowledge gap by probing for larger-scale structural aspects in comparison to Hi-C and methods alike.
iFISH and Deconwolf build on pre-existing methods, however, they bring unique spins and improvements that make these tools not ‘just the next obvious step’, but rather a significant step forward, especially in terms of applications enabled by them. In particular, we believe that Deconwolf is the first tool that can truly democratize the use of fluorescence image deconvolution in multiple bioimaging applications, particularly in the rapidly growing field of imaging-based spatial omics.
In sum, GENOMIS has been a successful technology-driven project that has spun a set of innovative and impactful methods, which can now be leveraged by the 3D genome biology community and beyond.
