PacBio and UC Davis researchers introduce a new long-read 3C method
28 Jan 2026
PacBio and UC Davis researchers have introduced CiFi, a new community-developed long-read 3C method that enables chromosome-scale haplotype-resolved genome assemblies from a single SMRT cell, even when sample material is limited.
By integrating chromatin conformation capture (3C) with PacBio HiFi long-read sequencing, CiFi delivers multi-contact reads and longer fragments that significantly increase the information content of proximity ligation experiments in a single Revio sequencing run.
Researchers in the Megan Dennis Laboratory at the University of California, Davis, have shown1 how CiFi addresses long-standing limitations of short-read Hi-C by generating long, highly accurate reads that capture multiple chromatin interactions within a single molecule. The new method offers several advantages tailored to the needs of genome biology, biodiversity studies, and functional genomics.
These include improved mapping in repetitive regions, removing obstacles around low input performance, enabling multi-contact resolution, and saving project time and complexity through single platform simplicity.
When paired with Revio SPRQ chemistry, CiFi makes it possible to generate reference-quality assemblies using fewer cells, fewer libraries, and fewer sequencing runs. This lowers barriers for genome projects that have been limited by cost, complexity, or sample availability.
Traditional Hi-C approaches typically capture only two interacting genomic fragments per read pair and often struggle in repetitive or structurally complex regions. CiFi overcomes these limitations by producing long, concatemeric HiFi reads that can contain many interacting chromatin fragments, substantially increasing contact density while maintaining the accuracy of PacBio HiFi sequencing.
In a demonstration of the method’s capabilities, UC Davis and PacBio applied the CiFi developed workflow to the prairie and meadow vole. The resulting uncurated assemblies achieved scaffold N50 values exceeding one hundred million base pairs, with telomeric sequence detected at both ends of many scaffolds.
These results show that the UC Davis developed CiFi method, combined with HiFi sequencing, can routinely deliver chromosome scale, reference quality assemblies using only one sequencing run.
“CiFi expands our multiomics capabilities, increasing what we can do on HiFi sequencing systems without new hardware and unlocking new customer use cases,” said David Miller, Vice President of Global Marketing at PacBio. “The work from the Megan Dennis Lab at UC Davis shows what becomes possible when innovative chromatin capture methods are paired with the accuracy of HiFi sequencing.”
Megan Dennis, PhD, Associate Professor at UC Davis, added, "We developed CiFi to make high-accuracy, multi-contact chromatin capture accessible to researchers working with limited or challenging samples. By combining 3C with HiFi sequencing, we can resolve chromatin architecture across complex genomic regions and generate chromosome-scale assemblies with greater confidence and far less input.”
References
1. McGinty SP, Kaya G, Sim SB, Makunin A, et al. CiFi: accurate long-read chromosome conformation capture with low-input requirements. Nat Commun 17, 215 (2026).