Exploration of fragmentomics for monitoring disease progression in Neurofibromatosis patients
Introduction
Neurofibromatosis 1 (NF1) is a common genetic disorder mutation characterized by tumor growth on nerve cells and other parts of the body. Those diagnosed with NF1 are significantly more at risk of developing malignant peripheral nerve sheath tumor (MPNST) which is aggressive and very difficult to treat. A poor prognosis for MPNST demands innovation in early detection and monitoring. Here we explore leveraging the analysis of DNA fragment size and sequence patterns from cell-free DNA (“fragmentomics”) found in the bloodstream for the purposes of NF1 patient monitoring.
Methods
We considered various approaches, including end motifs of sequence alignment data from 12 samples from 11 patients. Working under an assumption that shorter fragments will be enriched from tissue sources of interest, we also performed all analyses on fragments below certain size thresholds. We looked at the distribution landscape of end-motifs across all patients and generated correlation biplots based on those end-motifs. We also considered the motif diversity scores (MDS) of the end-motifs from patients with NF1-associated MPNST (MPNST) and patients with NF1 without MPNST (non-MPNST) (based on Shannon entropy).
Results
We found that in the correlation biplot, there is a distinction between MPNST and non-MPNST samples. Additionally, when looking at the MDS between MPNST and non-MPNST samples, the median MPNST score was distinctly higher than that of non-MPNST scores. No significant difference was found between data filtered by fragment size and the full set data that was not filtered.
Conclusion
We found a notable difference between the fragment characteristics from samples with MPNST and no MPNST. We are planning an analysis of a larger cohort of patient samples in which we will also explore the informativeness of preferred ends.