SMaHT Network advances approaches for finding rare DNA mutations within the body

Somatic mutations, the DNA changes that occur as our bodies grow and age, not only hold an important key to cancer, but are emerging as the seeds of a wide range of common, non-cancerous diseases.  The Somatic Mosaicism across Human Tissues (SMaHT) Network, a National Institutes of Health Common Fund initiative to catalog all the normal processes of somatic mutation, has published its first comprehensive benchmarking study in Cell. The study developed and calibrated new sequencing technologies, experimental approaches and computational methods that now make it possible to detect different types of somatic mutations with greater sensitivity and specificity than ever before. The study is foundational for upcoming disease studies probing these genetic changes.

Researchers at Baylor College of Medicine’s Human Genome Sequencing Center led three grant projects to develop state-of-the-art tools that enable study of these important somatic changes.  

For the major Cell paper summarizing all the Networks findings, Baylor scientists led by Dr. Chenghang (Chuck) Zong, Dr. Harshavardhan Doddapaneni and Dr. Richard Gibbs made major contributions in developing new ‘duplex’ DNA sequencing methods that can accurately detect somatic mutations that exist in single DNA molecules isolated from bulk tissue samples or single cells. Dr. Fritz Sedlazeck and Dr. Christopher Grochowski led work providing new ways to detect large DNA changes called somatic structural variants, and Dr. Rui Chen led analysis of data from single cells. These new methods now enable a complete and integrated view of the normal patterns of somatic mosaicism and pave the road for studying the role of somatic mutations in common human diseases.

The work has a banner authorship of ‘The Somatic Mutation across Human Tissues Network’, with a full list of all contributors listed in the paper.

Also in this issue of Cell, Dr. Margaret A. Goodell and Jacey R. Pridgen wrote an accompanying commentary summarizing the findings of these and other upcoming SMaHT Network papers and the potential implications for understanding aging and human health.

“Every cell in the human body carries its own genome, shaped by mutations acquired over a lifetime, yet this vast somatic variation has been nearly impossible to measure,” they wrote. “The SMaHT Network now delivers benchmarked tools and the first body-wide map of somatic mosaicism, establishing a baseline of ‘normal’ against which its roles in development, aging and disease can finally be tested.”

Read the full commentary in this edition of Cell.

Baylor lead contributors:

• Dr. Chenghang (Chuck) Zong, associate professor in the Department of Molecular and Human Genetics and McNair Scholar
• Dr. Harshavardhan Doddapaneni, associate professor in the Human Genome Sequencing Center
• Dr. Richard Gibbs, founding director of the Human Genome Sequencing Center and Wofford Cain Professor in Molecular and Human Genetics
• Dr. Fritz Sedlazeck, associate professor in the Human Genome Sequencing Center
• Dr. Christopher Grochowski, assistant professor in the Human Genome Sequencing Center

Commentary contributors:

• Dr. Margaret A. Goodell, chair of the Department of Molecular and Cellular Biology and Thomas C. Thompson Chair in Molecular and Cellular Biology at Baylor College of Medicine
• Jacey R. Pridgen, M.D./Ph.D. student in the Goodell Lab