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Biology subjects

Johnson, K. D.

Publications and source records attributed to Johnson, K. D..

2 recordsLinked to original sources

MLG: Multilayer graph clustering for multi-condition scRNA-seq data

Single-cell transcriptome sequencing (scRNA-seq) enabled investigations of cellular heterogeneity at exceedingly higher resolutions. Identification of novel cell types or transient developmental stages across multiple experimental conditions is one of its key applications. Linear and non-linear dimensionality reduction for data integration became a foundational tool in inference from scRNA-seq data. We present Multi Layer Graph Clustering (MLG) as an integrative approach for combining multiple dimensionality reduction of multi-condition scRNA-seq data. MLG generates a multilayer shared nearest neighbor cell graph with higher signal-to-noise ratio and outperforms current best practices in terms of clustering accuracy across large-scale bench-marking experiments. Application of MLG to a wide variety of datasets from multiple conditions highlights how MLG boosts signal-to-noise ratio for fine-grained sub-population identification. MLG is widely applicable to settings with single cell data integration via dimension reduction.

genomics↗

GATA2 deficiency during embryogenesis elevates Interferon Regulatory Factor-8 to subvert a progenitor cell differentiation program

Cell type-specific transcription factors control stem and progenitor cell transitions by establishing networks containing hundreds of genes and proteins. Network complexity renders it challenging to discover essential versus modulatory or redundant components. This scenario is exemplified by GATA2 regulation of hematopoiesis during embryogenesis. Previously, we demonstrated that loss of Gata2, -77 enhancer disrupts the GATA2-dependent genetic network governing erythro-myeloid differentiation. The aberrant network includes the transcription factor Interferon Regulatory Factor-8 and a host of innate immune regulators. Mutant progenitors lose the capacity to balance production of diverse myelo-erythroid progeny. To elucidate mechanisms, we asked if IRF8 is essential, contributory or not required. Irf8 ablation, in the context of the -77 mutant allele, reversed granulocytic deficiencies of -77-/- embryos and rescued an imbalance of dendritic cell progenitors. Despite many dysregulated components that control vital processes, including transcription and signaling, aberrant elevation of a single transcription factor deconstructed the differentiation program.

developmental biology↗