SDR-seq: New DNA-RNA Sequencing Tool Reveals Hidden Genetic Code Behind Diseases

Scientists at the European Molecular biology Laboratory (EMBL) have created a revolutionary genomic tool that unlocks the secrets hidden in non-coding DNA regions. The technology, called SDR-seq, represents a significant advancement in single-cell analysis by capturing both DNA variations and RNA expression from the same cell simultaneously.

For decades, researchers have struggled to study the non-coding regions of DNA, which comprise over 95% of disease-associated genetic variants yet remain largely unexplored. Traditional methods could only analyze expressed genes from coding regions, leaving the regulatory elements in non-coding DNA inaccessible to detailed investigation.

The research team, led by Dominik Lindenhofer from EMBL's Steinmetz Group, developed a novel approach using microscopic oil-water droplets that encapsulate individual cells. This method enables high-throughput analysis of thousands of cells in a single experiment, providing unprecedented scale and precision.

"SDR-seq solves a long-standing problem in genomics," explained Lindenhofer. "Current single-cell methods to study DNA and RNA in the same cell have had limited throughput, lacked sensitivity, and are complicated. Our tool works irrespective of where variants are located."

The technology's potential was demonstrated using B-cell lymphoma samples, where researchers observed how specific genetic variations correlated with more aggressive cancer states. Cells with higher variant loads showed stronger activation signals supporting tumor growth, revealing direct links between genetic makeup and disease progression.

The development involved cross-disciplinary collaboration between multiple EMBL research groups and external partners from Stanford University School of Medicine and Heidelberg University Hospital. Computational biologists created specialized decoding software, while other teams developed methods to preserve delicate RNA during the sequencing process.