WashU Medicine verifies tools for rare somatic DNA variants

Researchers at Washington University School of Medicine in St. Louis (WashU Medicine) and partners in the Somatic Mosaicism across Human Tissues (SMaHT) Network have verified the accuracy of computational tools for detecting rare somatic DNA variants, according to newswise.com. newswise.com The results appear in a package of papers in Cell Press journals: one in Cell and two in Cell Genomics, led or co-led by WashU Medicine. newswise.com The network is supported by the NIH Common Fund. newswise.com

Somatic mosaicism is the set of DNA changes that arise during a person's lifetime in only some cells, so tissues within one person differ genetically. Unlike inherited variants, which are present in every cell, these changes are rare and hard to measure. They alter how cells operate and are linked to aging and disease, especially cancer. newswise.com

Benchmarking detection tools

The main goal of this first set of studies was to confirm that the tools developed by the scientists identify all the rare DNA changes in an individual's mosaic with high statistical sensitivity and specificity. newswise.com Ting Wang, PhD, who leads the network's national organizing center at WashU Medicine, said a reference spectrum of normal somatic variation is needed before researchers can examine what leads to disease. newswise.com WashU Medicine is the largest of five data production centers and has contributed more than 25% of the data produced since the network launched in 2023. newswise.com

In a Cell Genomics study led by Wang, the team used sequencing data from the Human Pangenome Reference Consortium. These data had previously been used mainly to find inherited variants; the study is the first to show they can also identify somatic variation in any tissue. newswise.com

Synthetic mutations and sequencing strategies

In the second Cell Genomics study, led by Sheng Chih (Peter) Jin, PhD, the group used data from the International HapMap Project, an NIH-funded sequencing project that ran from 2002 to 2010. Jin said the approach creates millions of known somatic mutations synthetically, which serve as a resource for testing how accurately rare mutations are found. newswise.com

The Cell paper, co-led with the Mayo Clinic, summarizes the results of the whole package. newswise.com The researchers conclude that bulk sequencing, single-cell sequencing and duplex sequencing are complementary, and that combining them gives a more complete picture of mosaicism within tissues. newswise.com

With the accuracy of the technologies verified, the researchers are now working to analyze multiple tissue samples from 150 human donors of diverse ancestries and across several life stages. newswise.com

WashU Medicine verifies accuracy of tools for detecting rare somatic DNA variants across human tissues

Benchmarking detection tools

Synthetic mutations and sequencing strategies

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