WashU Medicine Verifies Sequencing Tools to Map Human Genetic Mosaicism
Washington University School of Medicine researchers have confirmed the accuracy of genetic tools designed to identify rare DNA changes that build up in human cells over time, News-Medical reported. These somatic variations, which create genetic differences between tissues within the same person, affect aging and cancer risk.
The findings form part of the Somatic Mosaicism across Human Tissues (SMaHT) Network, an initiative supported by the National Institutes of Health Common Fund. WashU Medicine operates as the national coordinating center for the project, led by principal investigator Ting Wang. The institution also serves as the largest of five data production centers, contributing more than 25% of all data produced by the network since its launch in 2023.
Combining Three Sequencing Strategies for Complete Tissue Profiles
To capture the full spectrum of somatic mosaicism, researchers evaluated three distinct sequencing methods. The team determined that combining bulk sequencing, single-cell sequencing, and duplex sequencing yields the most comprehensive picture of genetic changes within human tissues.
Researchers used data from the Human Pangenome Reference Consortium in one study, demonstrating that pangenome sequences can identify somatic DNA variation across tissues. In a second study led by Sheng Chih (Peter) Jin, an assistant professor of genetics at WashU Medicine, investigators utilized data from the International HapMap Project to synthetically create millions of known somatic mutations. This resource tests the accuracy of computational tools in identifying rare mutations across various tissue types with high statistical sensitivity and specificity.
Did you know?
WashU Medicine contributes over 25% of all sequencing data produced by the SMaHT Network since the initiative launched in 2023.
Expanding the Scope to 150 Human Donors
With the accuracy of their computational tools verified in a flagship paper published in Cell and supporting studies in Cell Genomics, the research team is moving to the next phase of the project. Investigators plan to analyze multiple tissue samples from 150 human donors representing diverse ancestries and multiple life stages. Wang noted that establishing this reference spectrum of normal somatic variation is a necessary step before researchers can determine what leads to disease and how to mitigate it.
Frequently Asked Questions
What is somatic mosaicism?
Somatic mosaicism occurs when DNA changes accumulate in some cells of the body during a person’s lifetime rather than being present in all cells from birth. These variations create genetic differences between different tissues within the same individual.
How many data production centers are in the SMaHT Network?
The network includes five data production centers supported by the National Institutes of Health Common Fund, with Washington University School of Medicine operating as the largest contributor.
What are the three sequencing methods used in the study?
The validated approaches include bulk sequencing, single-cell sequencing, and duplex sequencing, which researchers combine to generate a comprehensive picture of mosaicism within tissues.
How many donors will be analyzed in the next phase of the project?
Researchers are working toward analyzing multiple tissue samples from 150 human donors spanning diverse ancestries and life stages.
Kong, N., et al. published their findings on a pangenomic method for establishing a synthetic somatic variant resource in Cell Genomics.
Keep reading