Trial eligibility, treatment patterns and outcome for venetoclax-based therapy in AML: a prospective cohort study.

Venetoclax (Ven) plus hypomethylating agents are considered standard-of-care for patients with acute myeloid leukemia (AML) judged ineligible for intensive chemotherapy (IC). Real-world studies complement clinical trials, since patterns of patient selection, treatment-exposure and post-remission management may vary. This prospective observational multi-center study included 209 newly diagnosed IC-ineligible patients with a median age 75 years (interquartile range, 71-81 years).

Evidence for compensatory evolution within pleiotropic regulatory elements.

Pleiotropy, measured as expression breadth across tissues, is one of the best predictors for protein sequence and expression conservation. In this study, we investigated its effect on the evolution of regulatory elements (CREs). To this end, we carefully reanalyzed the Epigenomics Roadmap data for nine fetal tissues, assigning a measure of pleiotropic degree to nearly half a million CREs.

Generation and characterization of inducible KRAB-dCas9 iPSCs from primates for cross-species CRISPRi.

Comparisons of molecular phenotypes across primates provide unique information to understand human biology and evolution, and single-cell RNA-seq CRISPR interference (CRISPRi) screens are a powerful approach to analyze them. Here, we generate and validate three human, three gorilla, and two cynomolgus iPS cell lines that carry a dox-inducible KRAB-dCas9 construct at the AAVS1 locus. We show that despite variable expression levels of KRAB-dCas9 among lines, comparable downregulation of target genes and comparable phenotypic effects are observed in a single-cell RNA-seq CRISPRi screen.

The effect of background noise and its removal on the analysis of single-cell expression data.

Background: In droplet-based single-cell and single-nucleus RNA-seq experiments, not all reads associated with one cell barcode originate from the encapsulated cell. Such background noise is attributed to spillage from cell-free ambient RNA or barcode swapping events.

Results: Here, we characterize this background noise exemplified by three scRNA-seq and two snRNA-seq replicates of mouse kidneys.