Biology subjects

Kearns, N.

Publications and source records attributed to Kearns, N..

3 recordsLinked to original sources

bioRxiv2025

g.nome, A Transparent Bioinformatics Pipeline that Enables Differential Expression and Alternative Splicing Analysis by Non-Computational Biologists

Reproducibility and accessibility are cardinal principles in the rapidly evolving field of bioinformatics. As the collection of biological data grows, proper use of pipelines to analyze datasets can become a bottleneck restricting efficient analysis. Biologists who collect data and test hypotheses may not have strong computational backgrounds and may not be able to fully understand the underlying strengths and weaknesses of computational approaches or fully exploit their data. Some data may be misunderstood and, perhaps more importantly, critical findings may remain unobserved. High throughput RNA sequencing (RNAseq) has advanced our understanding of transcriptomics across diverse applications. Here we introduce g.nome, a bioinformatics platform that integrates contemporary tools necessary for independent analysis. A user-friendly graphical interface simplifies running jobs and allows simplified analysis of different datasets by non-bioinformaticians. g.nome was used to analyze the consequences of localizing the critical RNAi factor argonaute (AGO) to nuclei of colorectal cancer cell line HCT116. Analysis using the pipeline facilitated the straightforward identification of splicing changes and the prioritization of these splicing changes for validation and further experimental analysis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/652286v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@f0fa7org.highwire.dtl.DTLVardef@ccac5borg.highwire.dtl.DTLVardef@147c331org.highwire.dtl.DTLVardef@5fe66c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2023

TRAFfic signals: High-throughput CAR discovery in NK cells reveals novel TRAF-binding endodomains that drive enhanced persistence and cytotoxicity

Natural killer (NK) cells are a promising alternative therapeutic platform to CAR T cells given their favorable safety profile and potent killing ability. However, CAR NK cells suffer from limited persistence in vivo, which is, in part, thought to be the consequence of limited cytokine signaling. To address this challenge, we developed an innovative high-throughput screening strategy to identify CAR endodomains that could drive enhanced persistence while maintaining potent cytotoxicity. We uncovered a family of TRAF-binding endodomains that outperform benchmarks in primary NK cells along dimensions of persistence and cytotoxicity, even in low IL-2 conditions. This work highlights the importance of cell-type-specific cell therapy engineering and unlocks a wide range of high-throughput molecular engineering avenues in NK cells.

immunology↗

bioRxiv2022

Dissecting the Human Leptomeninges at single-cell resolution

Emerging evidence shows that the meninges conduct essential immune surveillance and immune defense at the brain border, and the dysfunction of meningeal immunity contributes to aging and neurodegeneration. However, no study exists on the molecular properties of cell types within human leptomeninges. Here, we provide the first single nuclei profiling of dissected postmortem leptomeninges from aged individuals. We detect diverse cell types, including unique meningeal endothelial, mural, and fibroblast subtypes. For immune cells, we show that most T cells express CD8 and bear characteristics of tissue-resident memory T cells. We also identify distinct subtypes of border-associated macrophages (BAMs) that display differential gene expressions from microglia and express risk genes for Alzheimers Disease (AD), as nominated by genome-wide association studies (GWAS). We discover cell-type-specific differentially expressed genes in individuals with Alzheimers dementia, particularly in fibroblasts and BAMs. Indeed, when cultured, leptomeningeal cells display the signature of ex vivo AD fibroblasts upon amyloid-{beta} treatment. We further explore ligand-receptor interactions within the leptomeningeal niche and computationally infer intercellular communications in AD. Thus, our study establishes a molecular map of human leptomeningeal cell types, providing significant insight into the border immune and fibrotic responses in AD.

genomics↗