Locus-specific LINE-1 expression in clinical ovarian cancer specimens at the single-cell level.

Long interspersed nuclear elements (LINE-1s/L1s) are a group of retrotransposons that can copy themselves within a genome. In humans, it is the most successful transposon in nucleotide content. L1 expression is generally mild in normal human tissues, but the activity has been shown to increase significantly in many cancers. Few studies have examined L1 expression at single-cell resolution, thus it is undetermined whether L1 reactivation occurs solely in malignant cells within tumors. One of the cancer types with frequent L1 activity is high-grade serous ovarian carcinoma (HGSOC). Here, we identified locus-specific L1 expression with 3' single-cell RNA sequencing in pre- and post-chemotherapy HGSOC sample pairs from 11 patients, and in fallopian tube samples from five healthy women. Although L1 expression quantification with the chosen technique was challenging due to the repetitive nature of the element, we found evidence of L1 expression primarily in cancer cells, but also in other cell types, e.g. cancer-associated fibroblasts. The expression levels were similar in samples taken before and after neoadjuvant chemotherapy, indicating that L1 transcriptional activity was unaffected by clinical platinum-taxane treatment. Furthermore, L1 activity was negatively associated with the expression of MYC target genes, a finding that supports earlier literature of MYC being an L1 suppressor.

Portability of Polygenic Risk Scores for Sleep Duration, Insomnia and Chronotype in 33,493 Individuals.

Polygenic risk scores (PRSs) estimate genetic liability for diseases and traits. However, the portability of PRSs in sleep traits has remained elusive. We generated PRSs for self-reported insomnia, chronotype and sleep duration using summary data from genome-wide association studies (GWASs) performed in 350,000 to 697,000 European-ancestry individuals. We then projected the scores in two independent Finnish population cohorts (N = 33,493) and tested whether the PRSs were associated with their respective sleep traits. We observed that all the generated PRSs were associated with their corresponding traits (p < 0.05 in all cases). Furthermore, we found that there was a 22.2 min difference in reported sleep between the 5% tails of the PRS for sleep duration (p < 0.001). Our findings indicate that sleep-related PRSs show portability across cohorts. The findings also demonstrate that sleep measures using PRSs for sleep behaviors may provide useful instruments for testing disease and trait associations in cohorts where direct sleep parameters have not yet been measured.