# Whole Individual Comprehensive KnowlEDge: Somatic Mosaicism across Human Tissues (WICKed SMaHT)

> **NIH NIH UM1** · BROAD INSTITUTE, INC. · 2024 · $2,831,245

## Abstract

ABSTRACT: (max 30 lines)
There is an enormous need to create a foundational dataset that will comprehensively catalog somatic
mutations across a diverse range of human tissues, to understand their type, frequency, the cells, and
anatomical compartments in which they are found, and their organizational, functional relationships and
consequences. Somatic variants can occur widely throughout the genome and across the lifespan producing
stochastic, clonal, and dynamic somatic mosaicism. A growing number of studies interrogating mutations in
normal tissues have demonstrated causal roles for somatic variants in age-related processes and both
oncologic and non-oncologic conditions, but these studies have generally been limited to few tissues or few
individuals. The broader functional consequences of somatic variation remain largely unknown. Additionally,
variants in non-coding, regulatory regions of the genome may affect gene expression in different cells or tissues
within individuals, but their patterns also reflect a lifetime of exposures to certain mutational signatures, with
likely differences between tissues and individuals.
Recent advances in genomics provide an opportunity to build a somatic mutation catalog for human tissues and
organs. A cross-tissue catalog of human somatic mutations at high cellular and genetic resolution will provide
an extraordinary opportunity to discover the processes underlying normal tissue function, and leading to
disease, but the development of such a catalog requires state-of-the-art, and novel, experimental and
computational frameworks. As a Genome Characterization Center (GCC) for the Somatic Mosaicism across
Human Tissues (SMaHT) program, our project will contribute to the characterization, and creation of a resource
catalog of somatic variation across human tissues at scale. We will (1) work with the Tissue Procurement
Centers and the network to share tissue sampling protocols; (2) collaborate with other GCCs to undertake
benchmarking of samples across centers to compare production data and pipelines; (3) generate core assays
(short and long-read DNA sequencing and RNA sequencing) across 750 samples, and an additional duplex
sequencing assay across ~250 samples; (4) QC and analyze all data and submit to the Data Analysis Center;
and (5) collaborate across the network broadly on benchmarking comparisons, the development of common
analytical pipelines and QC metrics, and to perform joint data analysis. Our GCC brings together a team with
expertise in human genetics/genomics, production science, computational biology, novel technologies, and the
characterization and interpretation of somatic mutations. We will help create a somatic data resource for the
scientific community that will catalyze studies to understand cellular and tissue changes during human
development, aging, and disease variant interpretation.

## Key facts

- **NIH application ID:** 10834273
- **Project number:** 5UM1DA058235-02
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** KRISTIN ARDLIE
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,831,245
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834273

## Citation

> US National Institutes of Health, RePORTER application 10834273, Whole Individual Comprehensive KnowlEDge: Somatic Mosaicism across Human Tissues (WICKed SMaHT) (5UM1DA058235-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10834273. Licensed CC0.

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