Biology subjects

Kho, A. T.

Publications and source records attributed to Kho, A. T..

3 recordsLinked to original sources

bioRxiv2026

Asthma Exacerbations: Integrative Analysis of miRNA Activity Using Single-Cell Transcriptomics

BackgroundAsthma exacerbations are caused by dysregulated cellular interactions between airway and immune cell populations. Circulating microRNAs (miRNAs) are potential biomarkers for asthma exacerbations; however, their target airway cells remain poorly defined. ObjectiveTo identify the cell types that are regulated by the circulating microRNAs linked to asthma exacerbations and the extent to which the cells are regulated by miRNAs. MethodsWe integrated a curated panel of exacerbation-associated circulating miRNAs with single-cell RNA sequencing (scRNA-seq) profiles from induced sputum of 16 asthma patients and 8 healthy controls. Experimentally validated miRNA-target interactions were combined with cell-type-specific differential expression. Elastic Net regression and SHAP analysis quantified gene-level regulatory contributions, yielding a composite Regulation Strength metric. Findings were validated against four independent GEO datasets. ResultsImmune cells, including monocytes, dendritic cells, and macrophages, demonstrated the strongest statistically significant miRNA regulatory signals, in contrast to airway epithelial cells.hsa-miR-222-3p showed opposing regulatory effects in mature versus alveolar macrophages, indicating differentiation-state-dependent activity, while B_Plasma cells showed no detectable regulatory effect from any miRNA tested. Independent GEO validation confirmed higher expression of protective miRNAs (hsa-miR-126-3p, hsa-miR-146b-5p) in healthy individuals, consistent with prior CAMP cohort associations. ConclusionCirculating miRNAs show cell-type-specific regulatory activity, strongest in monocytes, dendritic cells, and macrophages. hsa-miR-222-3p showed opposing regulatory directions between macrophage subtypes, while B_Plasma cells showed no effect, validated across independent GEO cohorts.

bioinformatics↗

bioRxiv2019

COMPASS: a COMprehensive Platform for smAll RNA-Seq data analySis

BackgroundCirculating RNAs are potential disease biomarkers and their function is being actively investigated. Next generation sequencing (NGS) is a common means to interrogate the small RNAome or the full spectrum of small RNAs (<200 nucleotide length) of a biological system. A pivotal problem in NGS based small RNA analysis is identifying and quantifying the small RNAome constituent components. Most existing NGS data analysis tools focus on the microRNA component and a few other small RNA types like piRNA, snRNA and snoRNA. A comprehensive platform is needed to interrogate the full small RNAome, a prerequisite for down-stream data analysis.\n\nResultsWe present COMPASS, a comprehensive modular stand-alone platform for identifying and quantifying small RNAs from small RNA sequencing data. COMPASS contains prebuilt customizable standard RNA databases and sequence processing tools to enable turnkey basic small RNA analysis. We evaluated COMPASS against comparable existing tools on small RNA sequencing data set from serum samples of 12 healthy human controls, and COMPASS identified a greater diversity and abundance of small RNA molecules.\n\nConclusionCOMPASS is modular, stand-alone and integrates multiple customizable RNA databases and sequence processing tool and is distributed under the GNU General Public License free to non-commercial registered users at https://regepi.bwh.harvard.edu/circurna/ and the source code is available at https://github.com/cougarlj/COMPASS.

bioinformatics↗

bioRxiv2017

Sexual dimorphism of complement-dependent microglial synaptic pruning in the developing brain

Sexual dimorphism has been reported in the prevalence, onset and progression of neurodevelopmental and neurodegenerative disorders. We hypothesize that immunological signaling in the developing brain, notably the complement cascade underlying microglial synaptic pruning, could be one mechanism for this dimorphism. Here we show that genes differentially expressed between male and female normal cortical development are enriched for pathways associated with the activation of the innate immune system, complement cascade and phagocytic processes. Specifically, the male brain is enriched for the expression of genes associated with phagocytic function of microglia through complement-dependent synaptic pruning especially at the developmental stages before birth. Our results suggest the existence of a common regulatory module involved in both prenatal immune activation in males and postnatal immune activation in females. The activation of immune pruning pathways at different stages of normal male and female development could provide valuable insights about critical periods of plasticity and refinement in the human cortex that could explain the different vulnerabilities of males and females to neurological disorders.

neuroscience↗