Search bioRxiv⌕ Search

Biology subjects

Herzenberg, L. A.

Publications and source records attributed to Herzenberg, L. A..

3 recordsLinked to original sources

MUDflow: Combining Neural Networks, UMAP and DBM Clustering to Identify Cell Populations Accurately, Quickly and Easily in Mass and Fluorescence Cytometry

Identifying cell populations in flow cytometry data is mostly done via a "manual gating" method that often lacks verifiability and reproducibility, even in the hands of experienced investigators. Recently developed automatic gating methods have been shown to have good performance in cell population identification, but may require fine-tuned setup from experts or struggle to identify small populations. Here, we introduce an easily trainable multilayer perceptron neural network for automatic gating (MLPgater). Compared to the three popular automatic gating methods LDA, FlowSOM and PhenoGraph on three mass and six fluorescence cytometry datasets, MLPgater is most accurate by a substantial margin, tied with LDA as the fastest and uniquely able to replace manual gating except for training purposes. Furthermore, we show that combining MLPgater with UMAPs guided dimensionality reduction feature and DBMs clustering (MUDflow) effectively detects new populations that did not exist or were not identified in the training set.

bioinformatics↗

Automatic Phenotyping Using Exhaustive Projection Pursuit

One of the most common objectives in the analysis of flow cytometry data is the identification and delineation of phenotypes, distinct populations of cells with shared characteristics in the measurement dimensions. We have developed an automated tool to comprehensively identify these cell populations by Exhaustive Projection Pursuit (EPP). The method evaluates all two-dimensional projections among the suitable data dimensions and creates an optimized sequence of statistically significant gating regions that identify all phenotypes supported by the data. We evaluate the results of EPP on four well characterized data sets from the literature. The C++ code for EPP can be called from any computing environment. We illustrate this with a MATLAB utility that integrates EPP with FlowJo. All source code is freely available.

bioinformatics↗

Hematopoietic stem cell requirement for macrophage regeneration is tissue-specific

Tissue-resident macrophages (TRM{Phi}) are important immune sentinels responsible for maintaining tissue and immune homeostasis within their specific niche. Recently, the origins of TRM{Phi} have undergone intense scrutiny where now most TRM{Phi} are thought to originate early during embryonic development independent of hematopoietic stem cells (HSCs). We previously characterized two distinct subsets of mouse peritoneal cavity macrophages (Large and Small Peritoneal Macrophages; LPM and SPM, respectively) whose origins and relationship to both fetal and adult long-term (LT)-HSCs have not been fully investigated. Here we employ highly purified LT-HSC transplantation and in vivo lineage tracing to show a dual ontogeny for LPM and SPM, where the initial wave of peritoneal macrophages is seeded from yolk sac-derived precursors, which later require LT-HSCs for regeneration. In contrast, transplanted fetal and adult LT-HSCs are not able to regenerate brain-resident microglia. Thus, we demonstrate that LT-HSCs retain the potential to develop into TRM{Phi}, but their requirement is tissue-specific.

immunology↗