Researchers across the SMaHT Network compare six duplex sequencing technologies for detecting low-frequency somatic mutations.

The study highlights differences in sensitivity, cost, and genomic coverage while showing strong agreement in mutation rate estimates.

doi.org/10.64898/202...

Preprint: A comprehensive view of somatic mosaicism by single-cell DNA analysis.

Single-cell DNA sequencing reveals diverse somatic mutations and chromosomal changes across lung and colon cells, offering deeper insight into mosaicism across tissues.

www.biorxiv.org/content/10.1...

NIH Common Fund's SMaHT Network Q&A - Vol. 2 YouTube video by SMaHT Network

In Volume 2 of our Q&A series, SMaHT Network members discuss why studying somatic variation is so challenging and how the network is working to overcome those barriers to better understand human health and disease.

Tune in: youtu.be/ljZncMubN_w?...

Working Groups

The SMaHT Reference Assembly Working Group is developing best practices for using T2T assemblies and genome graphs to advance somatic variant analysis. 

Learn more about our working groups: smaht.org/working-grou...

scNanoSeq enables accurate detection of somatic mutations in single tumor cells, profiling 842 cells from 21 breast cancers.

Results reveal distinct evolutionary patterns and a proposed reprogramming–critical mutation co-timing (RCMC) model. 

Read the preprint: www.biorxiv.org/content/10.1...

IGGSy 2026 is coming!

July 5 - 9, join researchers from around the world to explore genome graphs, pangenomics, and metagenomics, including a dedicated Human Pangenome Project session with keynotes from speakers of varied specializations.

Registration open now!

iggsy.org

A recent preprint uses single-cell whole-genome sequencing to reveal increased somatic DNA damage in neurons from ALS, FTD, and Alzheimer’s disease, suggesting a shared mutational process in neurodegeneration.

Uncover the research behind it: www.biorxiv.org/content/10.1...

What makes the study of somatic variation technically or conceptually difficult? YouTube video by SMaHT Network

Finding somatic mutations is like spotting one changing leaf in a forest...rare, subtle, and incredibly informative.

In this Q&A, Thomas Bell, PhD, explains why that challenge is exactly what makes SMaHT’s work so exciting.

🎥: youtu.be/ydg6YYceoTM

A recent preprint introduces a technology-agnostic benchmarking resource for detecting somatic variants across variant types, tissues, and allele fractions... advancing somatic variant analysis in research and clinical settings. 

 www.biorxiv.org/content/10.1...

Stay connected with the SMaHT Network!

Our Linktree brings together all our social channels, resources, and updates in one place:
linktr.ee/smahtnetwork

Single-cell genome sequencing reveals elevated somatic mutations in neurons from ALS, FTD, and Alzheimer’s disease, suggesting shared DNA damage processes may contribute to neurodegeneration.

Uncover the research behind it: www.biorxiv.org/content/10.1...

Not all cells live the same biological story…

Learn how cellular variation influences somatic mosaicism in this Q&A with Alexej Abyzov, PhD, and other SMaHT Network members.

▶️ youtu.be/ljZncMubN_w

Single cell long read whole genome sequencing reveals somatic transposon activity in human brain The advent of single cell DNA sequencing revealed astonishing dynamics of genomic variability, but failed at characterizing smaller to mid size variants that on the germline level have a profound impact. In this work we discover previously ...

Single-cell long-read sequencing uncovers previously hidden somatic transposon activity in the human brain, revealing dynamic genomic changes missed by other methods.

Uncover the science behind it:
pmc.ncbi.nlm.nih.gov/articles/PMC...

The Somatic Mosaicism across Human Tissues (SMaHT) Network, a SMART Investment? While genetics is often considered static, low-level changes occur in an individual’s nucleotide sequence throughout a lifetime. Germline or constitutional

Low-level genetic changes accumulate in our cells over time, creating somatic mosaicism.

A Clinical Chemistry article highlights how the SMaHT Network is advancing tools, data, and resources to better understand how somatic variants shape human health.

academic.oup.com/clinchem/art...

Sharing the new MosaicSim preprint!

A tool that simulates realistic mosaic variants to help evaluate and optimize variant calling methods.

We are all mosaics: vast genetic diversity found between cells in a single person Technical advances allow researchers to trace the genetic changes that occur over time.

Recently spotlighted in @nature.com, a new BioRxiv preprint showcases a single-cell sequencing approach that reveals somatic mutations, chromosomal changes, and lineage insights often missed in bulk data.

Uncover the science behind it: www.nature.com/articles/d41586-025-03768-0

This November, we’re grateful for the collaboration and commitment that drive SMaHT’s progress.

Thank you to all who help advance our understanding of human health and disease!

Stay in the loop with the SMaHT network!

Follow all our socials to keep up with the latest updates on our website through our Linktree: linktr.ee/smahtnetwork

“Our results suggest that CTE develops through some process in addition to head trauma.” - Chris Walsh

A new @scinews.bsky.social study finds CTE has distinctive somatic mutations resembling Alzheimer’s and signs of 100+ years of excess genomic aging.

More at:
www.bumc.bu.edu/camed/news-e...

Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors of increasing age, and discovered the heterogeneous ...

As we age, tiny DNA changes called mosaic structural variants (mSVs) build up in our blood stem cells. A new study shows how they can disrupt cell function & may influence aging and disease risk.

Uncover the science behind it: pmc.ncbi.nlm.nih.gov/articles/PMC...

Somatic Mosaicism Across Human Tissues (SMaHT) The Somatic Mosaicism across Human Tissues (SMaHT) Network aims to transform our understanding of how somatic mosaicism in human cells influences biology and disease.

A lot is happening in the world of SMaHT...

From new research to exciting collaborations, we’re uncovering how our cells tell the story of who we are!

Learn more at www.smaht.org.

Wishing everyone a spook-tacular Halloween! 👻

Whether you’re celebrating or just enjoying a well-earned weekend, we hope it’s a wickedly wonderful one!

Novel correlative analysis identifies multiple genomic variations impacting ASD with macrocephaly Autism spectrum disorders (ASD) display both phenotypic and genetic heterogeneity, impeding the understanding of ASD and development of effective means of diagnosis and potential treatments. Genes affected by genomic variations for ASD converge in ...

Recent research uncovers unique genomic variation patterns linked to autism spectrum disorders, offering new insight into how genes tied to brain development and neuron function may interact in ASD.

Uncover the science behind it: pmc.ncbi.nlm.nih.gov/articles/PMC...

We're live at #ASHG2025!

Don't forget to check out SMaHT member presentations, happening this week.

We're headed to #ASHG2025 in Boston!

SMaHT members will be sharing their latest research and insights throughout the week; don't miss their presentations!

See who's presenting ⬇️

Working Groups

Our working groups are the backbone of SMaHT, driving efforts in technology development, data generation, analysis, ethics, and outreach.

Meet the teams shaping the future of somatic mosaicism research:

www.smaht.org/working-groups

Contributions of Germline and Somatic Mosaic Genetics to Thoracic Aortic Aneurysms in Nonsyndromic Individuals Thoracic aortic aneurysm (TAA) is associated with significant morbidity and mortality. Although individuals with family histories of TAA often undergo clinical molecular genetic testing, adults with n...

🫀 Genetic drivers of thoracic aortic aneurysm (TAA) uncovered that both germline and somatic mosaic variants play a role, with FLNA, NOTCH3, and FBN1 most frequently implicated.

Read the full study:
pmc.ncbi.nlm.nih.gov/articles/PMC...

We’re bringing SMaHT science to #ASHG2025!

Check out the list of network presentations below.

We'll see you in Boston!

Transgenerational transmission of post-zygotic mutations suggests symmetric contribution of first two blastomeres to human germline Little is known about the origin of germ cells in humans. We previously leveraged post-zygotic mutations to reconstruct zygote-rooted cell lineage ancestry trees in a phenotypically normal woman, term...

Novel research shows the human germline is polyclonal, tracing back to the first zygotic division… and unlike somatic tissues, lineages are balanced 50:50 across generations.

Read more: pmc.ncbi.nlm.nih.gov/articles/PMC...

Every consortium has a story...

Ours began with a shared goal: to better understand somatic mosaicism and its impact on human health. Together, we’re building a foundation of knowledge and resources to support discoveries that can shape the future of medicine.

www.SMaHT.org