PPMS: A framework to Profile Primary MicroRNAs from Single-cell RNA-sequencing datasets.

MOTIVATION: Single-cell/nuclei RNA-sequencing (scRNA-seq) technologies can simultaneously quantify gene expression in thousands of cells across the genome. However, the majority of the noncoding RNAs, such as microRNAs (miRNAs), cannot currently be profiled at the same scale. MiRNAs are a class of small noncoding RNAs and play an important role in gene regulation. MiRNAs originate from the processing of primary transcripts, known as primary-microRNAs (pri-miRNAs). The pri-miRNA transcripts, independent of their cognate miRNAs, can also function as long noncoding RNAs, code for micropeptides or even interact with DNA, acting like enhancers. Therefore, it is apparent that the significance of scRNA-seq pri-miRNA profiling expands beyond using pri-miRNA as proxies of mature miRNAs. However, there are no computational methods that allow profiling and quantification of pri-miRNAs at the single-cell-type resolution. RESULTS: We have developed a simple yet effective computational framework to profile pri-MiRNAs from single-cell RNA-sequencing datasets (PPMS). Based on user input, PPMS can profile pri-miRNAs at cell-type resolution. PPMS can be applied to both newly produced and publicly available datasets obtained via single cell or single-nuclei RNA-seq. It allows users to (i) investigate the distribution of pri-miRNAs across cell types and cell states and (ii) establish a relationship between the number of cells/reads sequenced and the detection of pri-miRNAs. Here, to demonstrate its efficacy, we have applied PPMS to publicly available scRNA-seq data generated from (i) individual chambers (ventricles and atria) of the human heart, (ii) human pluripotent stem cells during their differentiation into cardiomyocytes (the heart beating cells) and (iii) hiPSCs-derived cardiomyocytes infected with severe acute respiratory syndrome coronavirus 2.

Increased admission serum total bile acids can be associated with decreased 3-month mortality in patients with acute ischemic stroke.

BACKGROUND: Bile acids (BAs) not only play an important role in lipid metabolism and atherosclerosis but also have antiapoptotic and neuroprotective effects. However, few studies have focused on the relationship of the total bile acid (TBA) levels with the severity and prognosis of acute ischemic stroke (AIS). OBJECTIVES: The aim of this study was to investigate the potential associations of the fasting serum TBA levels on admission with the stroke severity, in-hospital complication incidence and 3 -month all-cause mortality in patients with AIS. METHODS: A total of 777 consecutive AIS patients were enrolled in this study and were divided into four groups according to the quartiles of the serum TBA levels on admission. Univariate and multivariate logistic regression analyses were used to explore the relationship between the fasting TBA levels and the stroke severity, in-hospital complications, and 3-month mortality in AIS patients. RESULTS: Patients in group Q3 had the lowest risk of severe AIS (NIHSS > 10) regardless of the adjustments for confounders (P < 0.05). During hospitalization, 115 patients (14.8%) had stroke progression (NIHSS score increased by ≥ 2), and 222 patients (28.6%) developed at least one complication, with no significant difference among the four groups (P > 0.05). There was no significant difference in the incidence of pneumonia, urinary tract infection (UTI), hemorrhagic transformation (HT), gastrointestinal bleeding (GIB), seizures or renal insufficiency (RI) among the four groups (P > 0.05). A total of 114 patients (14.7%) died from various causes (including in-hospital deaths) at the 3-month follow-up, including 42 (21.3%), 26 (13.3%), 19 (9.9%) and 27 (13.9%) patients in groups Q1, Q2, Q3 and Q4 respectively, with significant differences (P = 0.013). After adjusting for confounding factors, the risk of death decreased (P -trend < 0.05) in groups Q2, Q3, and Q4 when compared with group Q1, and the OR values were 0.36 (0.16-0.80), 0.30 (0.13-0.70), and 0.29 (0.13-0.65), respectively. CONCLUSIONS: TBA levels were inversely associated with the 3-month mortality of AIS patients but were not significantly associated with the severity of stroke or the incidence of complications.