Gene Set Enrichment Analysis
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inGSEA: An Improved Method for Gene Set Enrichment Analysis Using a Weighted Integral Statistic
Gene Set Enrichment Analysis (GSEA) is one of the most popular methods for transcriptomic analysis, yet its statistical power is limited when the biological pathways exhibit heterogeneous or non-concordant expression patterns. We propose an improved GSEA method, textbf{in}tegral-based GSEA (inGSEA). inGSEA introduces a novel enrichment score based on the Anderson-Darling weighted integral statistic.
Ontologizer 3: a cross-platform desktop application for frequentist and Bayesian GO enrichment analysis
We present Ontologizer 3, an easy-to-use cross-platform desktop application for Gene Ontology (GO) overrepresentation analysis. Ontologizer 3 offers two complementary methods. The first is a frequentist approach that evaluates GO terms individually using a one-sided Fisher's exact test, yielding term-level significance values.
BRAINCELL-AID: An Agentic AI Created Brain Cell Type Resource for Community Annotation
arXiv:2510.17064v4 Announce Type: replace Abstract: Single-cell RNA sequencing has transformed our ability to identify diverse cell types and their transcriptomic signatures. However, annotating these signatures-especially those involving poorly characterized genes-remains a major challenge. Traditional methods, such as Gene Set Enrichment Analysis (GSEA), depend on well-curated annotations and often perform poorly in these contexts.
Whole-genome duplication shaped cell-type evolution in the vertebrate brain
Abstract The complex brains of vertebrates have more cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution1, but it is unclear whether the duplicated genes (ohnologues) facilitated cell-type evolution. Here using brain single-cell transcriptomes from five chordates—human2, mouse3, lizard4, lamprey5 and amphioxus—we report that many cell-type families with conserved core transcription factors in vertebrates do not show...
Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer
Abstract BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1,2,3.
Transcriptomic, Specific Marker, and Pathway Analysis of Smooth Muscle Cell Foam Cells Compared to Macrophage Foam Cells in Human Atherosclerosis
BACKGROUND: Smooth muscle cells (SMCs) comprise the majority of cells in human atherosclerotic lesions and are thought to be a major source of cholesterol-overloaded foam cells in human and mouse atheromas. However, the transcriptomic profile, specific markers, and biologic itinerary of SMC foam cells relative to macrophage foam cells remain poorly defined. METHODS: Single-cell RNA sequencing (scRNA-seq) was performed on fresh coronary artery segments from heart transplant recipients with...
A prognostic human brain network for diffuse midline glioma
Abstract Diffuse midline gliomas (DMGs) are near-universally lethal tumours of the childhood central nervous system1,2. In animal models, DMGs form brain-wide integrated networks through neuron-to-glioma synapses3,4,5,6 and glioma-to-glioma gap junctional coupling3. This extensive connectivity robustly promotes the growth and invasion of DMG3,4,5,6,7,8,9 and other glial malignancies10,11,12 through paracrine mechanisms and direct neuron-to-glioma synapses.
Gene ancestries reveal diverse microbial associations during eukaryogenesis
Abstract The origin of eukaryotes remains a central enigma in biology1. Continuing debates agree on the pivotal role of a symbiosis between an alphaproteobacterium and an Asgard archaeon2,3. However, the nature, timing and contributions of other potential bacterial partners4,5,6 and the role of interactions with viruses7,8,9 remain contentious.
The genetics of transcriptional responses to stress in yeast
Alteration of gene expression levels is a key cellular strategy for responding to internal and external challenges. While expression quantitative trait loci (eQTLs) are known to influence steady-state transcript levels, their role in mediating rapid physiological transitions remains poorly understood. Using a high-throughput, "one-pot" single-cell RNA-seq approach, we mapped eQTLs in yeast immediately before and after two acute environmental shifts: salt perturbation of actively cycling...
Ignet 2.0 and Vignet: An Ontology-Driven Web Platform for Biomedical Gene Interaction Discovery and Visualization
Background: The expansion of biomedical literature demands systematic ontology-guided discovery of gene interactions, vaccine mechanisms, drug associations, and adverse events. Existing platforms such as STRING, DisGeNET, and PubTator fall short of providing a unified, freely accessible system that integrates ontology-based semantic interaction classification, vaccine-focused heterogeneous network construction, and Artificial Intelligence-assisted evidence retrieval. Ignet 2.0 and Vignet are...