More advanced analyses of archived patient samples with new assay

Analysis of tissues samples from patients is one of the most important ways for disease diagnosis. For more than 130 years, the gold standard for clinical tissue preservation has been formalin-fixed paraffin-embedded (FFPE) samples and today, an estimated 400 million to 1 billion FFPE samples are stored across hospitals and research centres worldwide. These samples capture the most critical clinical moments – diagnosis, treatment response, relapse, and metastasis – but until now, they have been inaccessible to single-cell chromatin accessibility methods due to severe DNA damage caused by formalin fixation.

The new technology developed by the IGP researchers, called scFFPE-ATAC, overcomes this barrier and enables researchers to recover chromatin accessibility signals from highly fragmented DNA. It also allows profiling of thousands of single cells simultaneously.

“We validated the method across multiple model systems and clinical samples. In mouse FFPE spleen tissue, scFFPE-ATAC recovered chromatin landscapes that closely matched fresh tissue profiles – something conventional methods could not achieve. In human lymph nodes archived for 8–12 years, the method resolved major immune cell types and identified their distinct regulatory programmes,” says senior author Dr. Xingqi Chen.

Spatial comparison

The researchers also applied scFFPE-ATAC to FFPE human lung cancer samples taken from both the tumour centre and the invasive edge. The spatial comparison revealed distinct regulatory trajectories and transcription factor networks associated with tumour progression.

In another application, the team profiled paired FFPE samples from patients with follicular lymphoma who later relapsed or transformed into diffuse large B-cell lymphoma, uncovering epigenetic changes linked to these events.

The development of scFFPE-ATAC marks a major step forward for retrospective studies, spatial epigenomics, and long-term clinical sample research.

“With scFFPE-ATAC, we can now explore single-cell epigenetic regulation in precisely the samples clinicians collect and store every day. This technology transforms FFPE archives into a powerful resource for understanding disease mechanisms, tumour evolution, and therapy resistance. It opens the door to new discoveries in biomedical science and precision oncology,” says Xingqi Chen.

The study was published in the journal Nature Communications.