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Results for “single-cell network medicine”

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PubMed2025

Network-based drug repurposing for psychiatric disorders using single-cell genomics.

Neuropsychiatric disorders lack effective treatments due to a limited understanding of the underlying cellular and molecular mechanisms. To address this, we integrated population-scale single-cell genomics data and analyzed 23 cell-type-level gene regulatory networks across schizophrenia, bipolar disorder, and autism. Our analysis revealed potential druggable transcription factors co-regulating known risk genes that converge into cell-type-specific co-regulated modules. We applied graph neural networks on those modules to prioritize novel risk genes and leveraged them in a network-based drug repurposing framework to identify 220 drug molecules with the potential for targeting specific cell types. We found evidence for 37 of these drugs in reversing disorder-associated transcriptional phenotypes. Additionally, we discovered 335 drug-cell quantitative trait loci (eQTLs), revealing genetic variation's influence on drug target expression at the cell-type level. Our results provide a single-cell network medicine resource that provides potential mechanistic insights for advancing treatment options for neuropsychiatric disorders.

Drug Repositioning↗

PubMed2026

The Inflammation-Thrombosis Genetic Axis in Abdominal Aortic Aneurysm: A Shared Roadmap to Precision Medicine.

Abdominal Aortic Aneurysm (AAA) is characterized by persistent inflammation, extracellular matrix loss, and intraluminal thrombus formation, yet the genetic links among these processes remain incompletely defined. Here, we examine evidence that genetic variation can influence inflammatory and thrombotic responses at the same time. Findings from genome-wide association studies are considered alongside transcriptomic, proteomic, single-cell, epigenetic, and experimental data. Particular attention is given to candidate genes and signaling networks relevant to AAA susceptibility, enlargement, and rupture. The available evidence supports a model in which inherited susceptibility alters the balance between vascular inflammation, coagulation, fibrinolysis, and wall repair. However, many reported loci still lack functional confirmation, and most genetic data come from populations of European ancestry. Defining the causal variants and the cells in which they act will be necessary before these findings can be used for individualized screening or treatment.

abdominal aortic aneurysm↗

PubMed2026

TCGA-based identification of prognostic biomarkers and candidate traditional Chinese medicine compounds in papillary thyroid carcinoma: An observational study.

This study aimed to identify prognostic genes associated with papillary thyroid carcinoma (PTC) and explore candidate traditional Chinese medicine (TCM) compounds using integrated bioinformatics and molecular docking. In this observational study, PTC gene expression profiles and clinical data were obtained from The Cancer Genome Atlas. Differentially expressed genes were screened using differential-expression sequencing (DESeq2), followed by protein-protein interaction network analysis to identify hub genes. Their expression, diagnostic value, immune relevance, prognostic significance, protein-level validation, and single-cell distribution were assessed using gene expression profiling interactive analysis, receiver operating characteristic analysis, immune infiltration analysis, Kaplan-Meier survival analysis, the human protein atlas, and single-cell RNA-sequencing data. Candidate TCM compounds were predicted using symptom mapping (SymMap) and the TCM Systems Pharmacology Database and Analysis Platform, and molecular docking was performed to evaluate potential ligand-target interactions. Five hub genes, colony-stimulating factor 2, apolipoprotein E, fibronectin 1 (FN1), collagen type I alpha 1 chain (COL1A1), and intercellular adhesion molecule 1, were identified and found to be significantly upregulated in PTC tissues, with diagnostic value in receiver operating characteristic analysis. Immune infiltration analysis showed associations with macrophages, dendritic cells, and T helper 1 cells, whereas single-cell analysis demonstrated heterogeneous expression across immune and stromal cell populations, including fibroblasts. Higher FN1 and COL1A1 expression was associated with poorer outcomes. Immunohistochemistry supported the expression patterns, while single-cell analysis provided exploratory cell-type-level context for the cellular distribution of selected genes. Ginseng and Smilax glabra were predicted as common candidate TCMs, and docking suggested favorable binding between their active compounds and selected hub targets. Colony-stimulating factor 2, apolipoprotein E, FN1, COL1A1, and intercellular adhesion molecule 1 may be biologically relevant hub genes in PTC, while FN1 and COL1A1 may have prognostic value. Predicted TCM compounds provide preliminary computational evidence for possible compound-target interactions, requiring experimental and clinical validation.

Female↗

PubMed2026

Epigenetic and Transcriptional Regulatory Networks Underlying Psoriasis Pathogenesis.

Psoriasis is a chronic, immune-mediated dermatologic disorder characterized by the hyperproliferation of keratinocytes and dysregulated immune signaling. Although genome-wide association studies have identified susceptibility loci, the multifactorial nature of the disease underlines the importance of nongenetic regulatory mechanisms. Among these epigenetic modifications are those that critically link genetic predisposition with environmental stimuli. This review offers an in-depth overview of the current insights into the role of epigenetic regulation in the pathophysiology of psoriasis. Key mechanisms, including aberrant DNA methylation, histone post-translational modifications (eg, H3K27ac, H3K4me3), and dysregulated noncoding RNAs, are discussed in the context of inflammatory signaling and immune cell function. This review also explores how environmental factors such as UV radiation and air pollution induce the epigenetic reprogramming that perpetuates the proinflammatory state. Furthermore, it highlights the translational potential of targeting epigenetic regulators and epigenome-editing technologies, including clustered regularly interspaced short palindromic repeats (CRISPR) fusion systems, as precision therapeutic strategies. In parallel, advances in single-cell epigenomics, spatial transcriptomics, and the profiling of circulating biomarkers offer novel diagnostic tools. Despite advances, challenges persist, including the limited predictive value of preclinical models and variable epigenetic profiles. Positioning epigenetics as the bridge between genetic risk, environmental triggers, and therapeutic advances, this review presents a framework for precision medicine in psoriasis.

Humans↗

PubMed2026

High-Content CRISPR Screening: Methods and Applications.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screening has become a central technology in functional genomics, enabling genome-scale interrogation via pooled perturbations. Early CRISPR screens employed survival or simple phenotypic readouts to identify essential genes and drug resistance mechanisms. However, as biological questions have shifted toward understanding regulatory networks, cellular heterogeneity, and context-dependent gene functions, there has been increasing demand for screening strategies capable of capturing complex cellular phenotypes beyond cell fitness. Recent advances in single-cell sequencing, high-content imaging, and spatial transcriptomics have expanded the resolution of CRISPR screening by enabling multidimensional phenotypic characterization following genetic perturbation. By integrating pooled perturbations with diverse readouts, these approaches systematically map targeted gene edits to transcriptional states, cellular phenotypes, and microenvironmental contexts. Meanwhile, innovations in library design, delivery, and computational pipelines have further improved the robustness and interpretability of high-content screening platforms. This review synthesizes the methodological evolution of CRISPR screening, emphasizing advances in perturbation strategies, delivery systems, and multimodal readouts. Representative applications spanning oncology, immunotherapy, developmental biology, neurobiology, and infectious diseases are delineated to demonstrate refined gene network annotations. Additionally, existing technical bottlenecks, such as scalability, cost constraints, and in vivo limitations, are critically assessed. Finally, future directions are proposed to facilitate the development of precise medicine.

CRISPR screening↗

PubMed2026

Next-generation brain proteomics: Integrating single-cell, spatial, and multi-omics for clinical biomarker discovery.

The mammalian brain's functional complexity arises from the sophisticated architecture of neurons and glia. This network is essentially defined by its dynamic proteome, which reveals the functional execution underlying neural computation and disease. This review integrates the technological leap in neuroproteomics. It has moved beyond bulk tissue proteome cataloguing to high-sensitivity single-cell and spatial resolution. We detail how next-generation platforms, such as TIMS-PASEF and Orbitrap-Astral, have enabled deeper and faster phenotypic profiling of limited brain samples. However, the proteome coverage remains constrained by dynamic range, sample loss, ionisation bias and incomplete detection of low-abundance regulatory proteins. We further examine how such studies have revealed the proteomic remodelling that drives lineage specification and synaptic plasticity by linking temporal protein expression waves to biological function. Crucially, we delineate the clinical translational trajectory, illustrating how aberrant signatures are verified in cerebrospinal fluid (CSF) and validated in plasma to support precision medicine. Finally, we argue for the necessity of "fused" multi-omics integration and Artificial Intelligence (AI) to decode the non-linear molecular logic of brain pathology.

Humans↗

PubMed2026

CRISPR-Enabled functional genomics in hPSCs-derived neural models for autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a genetically heterogeneous neurodevelopmental condition in which hundreds of individually rare risk variants converge on a small number of shared biological pathways, including synaptic scaffolding, chromatin remodeling, excitation-inhibition balance, and cellular energy metabolism. Translating this genetic heterogeneity into mechanistic insight requires experimental systems capable of interrogating individual gene functions in human-relevant neural contexts at scale. CRISPR-enabled functional genomics in human pluripotent stem cell (hPSC)-derived neural models, spanning neural progenitors, cortical and inhibitory neurons, astrocytes, microglia, and brain organoids, provides precisely this capability. By integrating pooled perturbation screens with multimodal readouts including single-cell and spatial transcriptomics, chromatin accessibility profiling, proximity labeling proteomics, multi-electrode array electrophysiology, and metabolic flux analysis, these platforms enable systematic, causal mapping of ASD gene function at system resolution. Early applications have already revealed convergent mechanisms: BAF complex disruption expands the ventral progenitor pool and biases its fate toward oligodendrocyte and interneuron lineages; ADNP loss impairs microglial synaptic pruning through altered endocytic trafficking; and mTOR pathway dysregulation in PTEN- and TSC2-perturbed models links genetic risk directly to metabolic and mitochondrial dysfunction. Computational frameworks including MIMOSCA and SCEPTRE enable causal network reconstruction and pseudotime inference from these datasets, moving the field from gene lists toward pathway-level models of ASD pathobiology. Translational applications leverage isogenic iPSC panels and variant-level base and prime editing to stratify ASD variants by functional impact, informing gene therapy design for haploinsufficient targets such as CHD8 and SCN2A via AAV or antisense oligonucleotide delivery. Remaining challenges, including model developmental immaturity, batch variability, and the difficulty of modeling polygenic risk, are addressed by a roadmap integrating spatial perturbomics, AI-driven causal inference, and population-scale standardized biobanks. This review synthesizes the current state of CRISPR-based functional genomics in human stem cell neural models as a coherent experimental framework for converting ASD genetic associations into mechanistic understanding and therapeutic opportunity.

Humans↗

PubMed1996

Genotoxicity of the laxative drug components emodin, aloe-emodin and danthron in mammalian cells: topoisomerase II mediated?

1,8-Dihydroxyanthraquinones are under debate as plant-derived carcinogens that are found in laxatives, food colors, and possibly vegetables. Published genotoxicity data are controversial, and so three of them (emodin, danthron and aloe-emodin) were tested in a number of in vitro assay systems. All three compounds induced tk-mutations in mouse lymphoma L5178Y cells. Induction of micronuclei also occurred in the same cell line, and was dose-dependent, with the potency ranking being danthron > aloe-emodin > emodin. In a DNA decatenation assay with a network of mitochondrial DNA of C. fasciulata, all three test compounds inhibited the topoisomerase II-mediated decatenation. Danthron and aloe-emodin, but not emodin, increased the fraction of DNA moving into comet tails when tested at concentrations around 50 microM in single-cell gel-electrophoresis assays (SCGE; comet assay). Comet assays were also used in modified form to determine whether pretreatment of the cells with the test compounds would reduce the effects of etoposide, a potent topoisomerase II inhibitor. All three test chemicals were effective in this pretreatment protocol, with danthron again being the most potent. Given clearcut evidence of their genotoxic activity, further research on the human cancer risk of these compounds may be warranted.

Aloe↗