Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19.

Neurological symptoms, including cognitive impairment and fatigue, can occur in both the acute infection phase of coronavirus disease 2019 (COVID-19) and at later stages, yet the mechanisms that contribute to this remain unclear. Here we profiled single-nucleus transcriptomes and proteomes of brainstem tissue from deceased individuals at various stages of COVID-19. We detected an inflammatory type I interferon response in acute COVID-19 cases, which resolves in the late disease phase.

resVAE ensemble: Unsupervised identification of gene sets in multi-modal single-cell sequencing data using deep ensembles.

Feature identification and manual inspection is currently still an integral part of biological data analysis in single-cell sequencing. Features such as expressed genes and open chromatin status are selectively studied in specific contexts, cell states or experimental conditions. While conventional analysis methods construct a relatively static view on gene candidates, artificial neural networks have been used to model their interactions after hierarchical gene regulatory networks.

Single-cell analysis of patient-derived PDAC organoids reveals cell state heterogeneity and a conserved developmental hierarchy.

Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer mortality by 2030. Bulk transcriptomic analyses have distinguished 'classical' from 'basal-like' tumors with more aggressive clinical behavior. We derive PDAC organoids from 18 primary tumors and two matched liver metastases, and show that 'classical' and 'basal-like' cells coexist in individual organoids.

Functional States in Tumor-Initiating Cell Differentiation in Human Colorectal Cancer.

Intra-tumor heterogeneity of tumor-initiating cell (TIC) activity drives colorectal cancer (CRC) progression and therapy resistance. Here, we used single-cell RNA-sequencing of patient-derived CRC models to decipher distinct cell subpopulations based on their transcriptional profiles. Cell type-specific expression modules of stem-like, transit amplifying-like, and differentiated CRC cells resemble differentiation states of normal intestinal epithelial cells.

Single-Nucleus and In Situ RNA-Sequencing Reveal Cell Topographies in the Human Pancreas.

Background & Aims: Molecular evidence of cellular heterogeneity in the human exocrine pancreas has not been yet established because of the local concentration and cascade of hydrolytic enzymes that can rapidly degrade cells and RNA upon pancreatic resection. We sought to better understand the heterogeneity and cellular composition of the pancreas in neonates and adults in healthy and diseased conditions using single-cell sequencing approaches.

Methods: We innovated single-nucleus RNA-sequencing protocols and profiled more than 120,000 cells from pancreata of adult and neonatal human donors.