# Comprehensive Somatic Variant Characterization at the HGSC

> **NIH NIH UM1** · BAYLOR COLLEGE OF MEDICINE · 2024 · $2,750,000

## Abstract

Studies of somatic mutations have so far focused on pathogenic variation, leading to cancer or severe
disease. The Somatic Mosaicism Across Human Tissues (SMaHT) program will now expand knowledge of
this critical class of genomic variation in normal tissues and build a comprehensive understanding of the
biology of somatic variation in all contexts. The Genome Characterization Center at the Baylor College of
Medicine Human Genome Sequencing Center (HGSC) will characterize variation in 750 tissue samples - 1/3
of the Program’s 15 samples from each of 150 individuals. Novel steps have been incorporated into our study
design to enable comprehensive discovery of somatic mutations. Both common core assay types (WGS
short-read, long read and bulk RNAseq) and two additional assays (nanoSeq and snRNAseq) that our group
specializes will be used for data generation. Benchmark standards, harmonized data structures and SOPs
will be created in collaboration with other Network members using established state-of-the-art methods for
discovery and orthogonal approaches for technical validation. New technologies that satisfy performance
criteria will be introduced into production. Statistical models will guide tissue-subsampling and sequencing
strategies, set the current thresholds with further room for improvement. NanoSeq and single nuclear RNA
procedures will each be modified for enhanced performance and close collaboration with investigators
developing additional tools will ensure optimal discovery. Local analyses will generate lists of putative
variants, with a particular focus upon characterization of long read sequence data. The latter will enable
modelling of transposition events, revealed within evidence for structural variation, as well as changes in
patterns of epigenetic marks. All data will be subjected to rigorous QA/QC, in collaboration with the DAC, and
mirrored in the centralized data repository.

## Key facts

- **NIH application ID:** 10834230
- **Project number:** 5UM1DA058229-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Harsha Vardhan Doddapaneni
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,750,000
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834230

## Citation

> US National Institutes of Health, RePORTER application 10834230, Comprehensive Somatic Variant Characterization at the HGSC (5UM1DA058229-02). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/10834230. Licensed CC0.

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