Coelho, P. | Search bioRxiv

bioRxiv2023

A Machine Learning One-Class Logistic Regression Model to Predict Stemness in Single Cell Transcriptomics and Spatial Omics Datasets

Cell annotation is a crucial methodological component to interpreting single cell and spatial omics data. These approaches are often biased and manually curated. Here we harness an existing stemness model for assessing oncogenic states to transform its application to single cell and spatial omic datasets. This one-class logistic regression machine learning algorithm is used to extract transcriptomic or proteomic features from non-transformed stem cells to identify dedifferentiated cell states. We found this method identifies single cell states in metastatic tumor cell populations without the requirement of cell annotation. Finally these stemness indices are applicable across a variety of spatial transcriptomic and proteomic technologies for the identification of oncogenic cell types in the tumor microenvironment. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/539461v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@f2973forg.highwire.dtl.DTLVardef@a7aa9corg.highwire.dtl.DTLVardef@1b1ea27org.highwire.dtl.DTLVardef@183b4a5_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2022

Hypoxia shapes the immune landscape in lung injury promoting inflammation persistence

Acute Respiratory Distress Syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, has no cure. Hypoxemia is a defining feature, yet its impact on inflammation is often neglected. Patients with ARDS are monocytopenic early in the onset of the disease. Endotoxin or Streptococcus pneumoniae acute lung injury (ALI) in the context of hypoxia replicates this finding, through hypoxia-driven suppression of type I interferon signalling. This results in failed lung monocyte-derived interstitial macrophages (IM) niche expansion and unchecked neutrophilic inflammation. Administration of colony stimulating factor 1 (CSF1) rescues the monocytopenia, alters the circulating classical monocyte phenotype in hypoxic endotoxin-driven ALI and enables lung IM population expansion, thus limiting lung injury in endotoxin- and virally-induced hypoxic ALI. Hypoxia directly alters immune dynamics to the detriment of the host and manipulation of this aberrant response offers new therapeutic strategies for ARDS.

cell biology↗