On Dec. 10, 2025, researchers from Gladstone Institutes and Stanford University announced they have leveraged a comprehensive method of probing every gene in a cell to connect diseases and other traits with their underlying genetic machinery. These maps could clarify confusing biology and pinpoint disease-causing genes that are ripe for intervention.

For decades, researchers have leaned on “genome-wide association studies,” which analyze genomes from thousands of people to statistically link DNA anomalies with diseases and other traits. These projects have provided a wealth of data, but the information isn’t always actionable—particularly when it comes to complex traits that are rooted in many genes.

“Even with these studies, there remains a huge gap in understanding disease biology on a genetic level,” says first author Mineto Ota, MD, PhD. Ota is a postdoctoral scholar in Marson’s Gladstone lab, as well as in the lab of Stanford scientist Jonathan Pritchard, PhD. “We understand that many variants are associated with disease; we just don’t understand why.”

The team queried two separate databases. The first was derived from a human leukemia cell line often used to model red blood cell traits. An MIT researcher with no role in the current study had previously disabled every gene in the cell line, one by one, mapping how each loss affected genetic activity.

Marson and his team combined those findings with data from the UK Biobank, which contains genomic sequences of more than 500,000 people. Ota mined the data for people who had genetic mutations that reduced function in a way that altered their red blood cells. By combining these datasets, the team was able to comprehensively map the gene networks that affect red blood cell traits, illuminating an incredibly complex genomic landscape. Now they had a starting point, a destination, and the web of roads in between.

They found that some genes act on multiple mechanisms, diminishing some biological activities while boosting others. A good example is SUPT5H, a gene linked to beta thalassemia, a blood disorder that affects hemoglobin production and can cause moderate to severe anemia. The researchers linked SUPT5H to three essential blood-cells programs: hemoglobin production, cell cycle, and autophagy. Importantly, they also highlighted how the gene affects those programs—by either boosting or minimizing gene activity.

The ability to reveal the detailed genetic mechanisms that control cells could have a profound impact on biological discovery and drug development. While the study uncovered a number of ways gene networks influence blood cell function, those findings are secondary to the method itself. The research team—and possibly many others in the life science community—can now conduct similar research in a variety of human cells to tease out the molecular signatures that drive disease. The new genomic mapping technique was published in Nature