Great paper in Cancer Discovery: Nucleosome Patterns in Circulating Tumor DNA Reveal Transcriptional Regulation of Advanced Prostate Cancer Phenotypes, PMID: 36399432.
The precision medicine challenge in prostate cancer seems to be that in the course of therapy that targets androgen receptor pathway, prostate cancer can mutate into neuroendocrine type that does not use that pathway to abnormally increase cell proliferation. When this happens, the standard therapy is futile, but abandoning the standard therapy by mistake can be fatal.
The methods described in the paper lead to an impressive quality of diagnosis, “accuracies of 97% for dominant phenotypes and 87% for mixed clinical phenotypes”. For a data analyst, several analytic approaches with novel elements are described in sufficient detail to guide similar investigations that are based on cfDNA and the distribution of active TSSs, active enhancers and transcription factor binding sites. The authors also point to possible ways for further improvements, for example: “…nucleosome positioning and spacing are dynamic in active and repressed gene regulation. A detailed understanding of the nucleosome patterns and accessible chromatin associated with transcriptional regulation in tumor phenotypes has not been fully explored in cfDNA.”
Jieun Jeong (정지은), Ph.D. 