# Inferring the structure and evolution of tandem duplication towers

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $51,752

## Abstract

PROJECT SUMMARY
Complex structural variants (SVs) are a class of mutations consisting of clustered DNA copy number changes
and rearrangements. These alterations can produce driver mutations in cancer but have been underexplored
due to the analytical limitations of bulk short read sequencing. There is an urgent need for new computational
tools that can apply long-range and single cell genomic profiles to structural variant analysis. Genome graphs
are a computational framework that can be extended to these new data modalities to study the allelic structure
and evolution of complex SVs. Recent genome graph analysis of pan-cancer whole genomes by our lab identified
a novel complex structural variant pattern termed pyrgo. Pyrgo consist of “towers” of clustered tandem
duplications and are enriched in prostate and ovarian adenocarcinomas. In Aim 1, we will construct haplotype
graphs to characterize the allelic structure of pyrgo. Haplotype graphs represent allele-specific genomic
segment and junction copy numbers and will be inferred from long range profiling data. Using these graphs, we
will characterize the parental and somatic allele structure of pyrgo duplications in pan-cancer genomes. We will
identify associations between allelic structure and cell-of-origin, prior systemic therapy, and genomic features
such as chromatin loops and replication timing. In Aim 2, we will construct single cell genome graphs that
recapitulate the evolution of pyrgo. Single cell genome graphs are a set of phylogenetically linked genome
graphs representing the structural variants present in individual cells, along with the ancestral subclone in which
each aberrant genomic junction first arose. These graphs will be inferred from single cell whole genome profiles.
We will use single cell genome graphs to model the acquisition of tandem duplications comprising pyrgo during
tumor evolution in ovarian adenocarcinoma tissue samples.

## Key facts

- **NIH application ID:** 10536029
- **Project number:** 1F30CA268747-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Zi-Ning Choo
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536029

## Citation

> US National Institutes of Health, RePORTER application 10536029, Inferring the structure and evolution of tandem duplication towers (1F30CA268747-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10536029. Licensed CC0.

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