Cancer Genomics Technology Development

$726,466ZIAFY2025CANIH

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

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Abstract

We have pressed forward with investigations of the higher order 3D structures of telomere chromatin relative to the genome. We have successfully addressed aspects of this program using a modification of the SPRITE method which is capable of identifying chromatin associations that are physiological and not necessarily governed by covalent structures. However, telomere repeats are typically discarded by most chromatin analysis pipelines including SPRITE. To address this problem, we created TelSPRITE rescuing mappable telomere repeats and appropriately modifying the SPRITE pipeline. We have successfully used TelSeq to analyze a number of cell types. Because somatic structural variants may involve telomere sequences, conventional long and short read sequencing was used to identify interstitial telomere repeats and neotelomeres. The data provide a comprehensive catalog of telomere chromatin associations and structural rearrangements that notably include a strong signal of telomere-centromere interactions. This technology can now be used to examine the behavior of telomere chromatin in cell models under various stresses (https://doi.org/10.1101/2024.11.22.624895). We continue to improve our short read sequencing data acquisition and analysis as exemplified by 35 exomes supporting a recently published collaborative study of myelodysplastic syndrome in a mouse model developed by Dr. Peter Aplan (PMID: 40614733).

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