Search bioRxiv⌕ Search

Biology subjects

Ranganathan, V.

Publications and source records attributed to Ranganathan, V..

2 recordsLinked to original sources

CHAI: Consensus Clustering Through Similarity Matrix Integration for Cell-Type Identification

Several methods have been developed to computationally predict cell-types for single cell RNA sequencing (scRNAseq) data. As methods are developed, a common problem for investigators has been identifying the best method they should apply to their specific use-case. To address this challenge, we present CHAI (consensus Clustering tHrough similArIty matrix integratIon for single cell type identification), a wisdom of crowds approach for scRNAseq clustering. CHAI presents two competing methods which aggregate the clustering results from seven state of the art clustering methods: CHAI-AvgSim and CHAI-SNF. Both methods demonstrate improved performance on a diverse selection of benchmarking datasets, besides also outperforming a previous consensus clustering method. We demonstrate CHAIs practical use case by identifying a leader tumor cell cluster enriched with CDH3. CHAI provides a platform for multiomic integration, and we demonstrate CHAI-SNF to have improved performance when including spatial transcriptomics data. CHAI is intuitive and easily customizable; it provides a way for users to add their own clustering methods to the pipeline, or down-select just the ones they want to use for the clustering aggregation. CHAI is available as an open source R package on GitHub: https://github.com/lodimk2/chai

bioinformatics↗

Polybacterial intracellular coinfection of epithelial stem cells in periodontitis

Periodontitis affects billions of people worldwide. To address interkingdom relationships of microbes and niche on periodontitis, we generated the first sin-gle-cell meta-atlas of human periodontium (34-sample, 105918-cell), harmo-nizing 32 annotations across 4 studies1-4. Highly multiplexed immunofluores-cence (32-antibody; 113910-cell) revealed spatial innate and adaptive immune foci segregation around tooth-adjacent epithelial cells. Sulcular and junctional keratinocytes (SK/JKs) within epithelia skewed toward proinflammatory phe-notypes; diseased JK stem/progenitors displayed altered differentiation states and chemotactic cytokines for innate immune cells. Single-cell metagenomics utilizing unmapped reads revealed 37 bacterial species. 16S and rRNA probes detected polybacterial intracellular pathogenesis ("co-infection") of 4 species within single cells for the first time in vivo. Challenging coinfected primary human SK/JKs with lipopolysaccharide revealed solitary and synergistic ef-fects. Coinfected single-cell analysis independently displayed proinflammatory phenotypes in situ. Here, we demonstrate the first evidence of polybacterial intracellular pathogenesis in human tissues and cells--potentially influencing chronic diseases at distant sites.

cell biology↗