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Gerlach, M.

Publications and source records attributed to Gerlach, M..

2 recordsLinked to original sources

Information-theory-based benchmarking and feature selection algorithm improve cell type annotation and reproducibility of single cell RNA-seq data analysis pipelines

Single cell RNA sequencing (scRNA-seq) data are now routinely generated in experimental practice because of their promise to enable the quantitative study of biological processes at the single cell level. However, cell type and cell state annotations remain an important computational challenge in analyzing scRNA-seq data. Here, we report on the development of a benchmark dataset where reference annotations are generated independently from transcriptomic measurements. We used this benchmark to systematically investigate the impact on labelling accuracy of different approaches to feature selection, of different clustering algorithms, and of different sets of parameter values. We show that an approach grounded on information theory can provide a general, reliable, and accurate process for discarding uninformative features and to optimize cluster resolution in single cell RNA-seq data analysis.

bioinformatics

HIF2α is a Direct Regulator of Neutrophil Motility

Orchestrated recruitment of neutrophils to inflamed tissue is essential during initiation of inflammation. Inflamed areas are usually hypoxic, and adaptation to reduced oxygen pressure is typically mediated by hypoxia pathway proteins. However, it is still unclear how these factors influence the migration of neutrophils to and at the site of inflammation either during their transmigration through the blood-endothelial cell barrier, or their motility in the interstitial space. Here, we reveal that activation of the Hypoxia Inducible Factor-2 (HIF2) due to deficiency of HIF-prolyl hydroxylase domain protein-2 (PHD2) boosts neutrophil migration specifically through highly confined microenvironments. In vivo, the increased migratory capacity of PHD2-deficient neutrophils resulted in massive tissue accumulation in models of acute local inflammation. Using systematic RNAseq analyses and mechanistic approaches, we identified RhoA, a cytoskeleton organizer, as the central downstream factor that mediates HIF2-dependent neutrophil motility. Thus, we propose that the here identified novel PHD2-HIF2-RhoA axis is vital to the initial stages of inflammation as it promotes neutrophil movement through highly confined tissue landscapes.

immunology