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Results for “Colocalization analysis”

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At least 19 recordsLinked to original sources

PubMed2004

Colocalization analysis yields superior results after image restoration.

Colocalization analysis is a powerful tool for the demonstration of spatial and temporal overlap in the distribution patterns of fluorescent probes. In unprocessed images, background affects image quality by impairing resolution and obscuring image detail in the low-intensity range. Because confocal images suffer from background levels up to 30% maximum intensity, colocalization analysis, which is a typical segmentation process, is limited to high-intensity signal. In addition, noise-induced, false-positive events ("dust") may skew the results. Therefore, suppression of background is crucial for this type of image analysis. Analysis of synthetic and biological objects demonstrates that median filtering is able to eliminate noise-induced colocalization events successfully. Its disadvantages include the occasional generation of false-positive and false-negative results as well as the inherent impairment of resolution. In contrast, image restoration by deconvolution suppresses background to very low levels (<10% maximum intensity), which makes additional objects in the low-intensity but high-frequency range available for analysis. The improved resolution makes this technique extremely suitable for examination of objects of near resolution size as demonstrated by correlation coefficients. Deconvolution is, however, sensitive to overestimation of the background level. Conclusions for practical application are: (1) In raw images, colocalization analysis is limited to the intensity range above the background level. This means the higher the RS/N the better. Unfortunately, images of most biological specimens have a low RS/N. (2) Filtering improves the result substantially. The reduction of background levels and the concomitant increase of the RS/N are generated at the expense of resolution. This is a quick and simple method in cases where resolution is not a major concern. (3) If colocalization in the low-intensity range and/or maximum resolution play a role, deconvolution should be used.

Animals↗

PubMed2025

Potential therapeutic targets for ovarian hyperstimulation syndrome revealed by proteome-wide mendelian randomization and colocalization analysis.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication associated with assisted reproductive technologies, characterized by metabolic, immune and vascular disorders. Understanding the molecular mechanisms underlying OHSS could reveal potential therapeutic targets and improve patient outcomes. In this study, We aimed to utilize proteome-wide Mendelian randomization (MR) and colocalization analysis to identify plasma proteins associated with OHSS and evaluate their potential as therapeutic targets through druggability assessment. We employed proteome-wide MR analysis summary data-based Mendelian randomization (SMR) analysis and phenome-wide association study (PheWAS) analysis to establish causal relationships between plasma proteins and OHSS. Colocalization analysis confirmed overlaps between proteins and genetic signals associated with OHSS. Pathway and network analyses were conducted to explore biological functions and protein interactions, while drug-target databases were queried for potential therapeutic interventions. Our results showed that 4 key proteins, including Suprabasin (SBSN), SLAMF4 (CD244), Enolase 3 (ENO3) and Thioredoxin domain-containing protein 12 (TXNDC12) were identified as significant contributors to OHSS. Pathway enrichment and interaction analyses further supported their involvement in metabolic, immune and structural pathways related to OHSS. Drug availability for colocalized proteins reveled potential drug targets for ENO3 (2-deoxy-D-glucose), CD244 (lenalidomide) and TXNDC12 (Auranofin), while no potential drug targets were identified for SBSN. Over all, our study identified15 plasma proteins, including SBSN, CD244, ENO3, and TXNDC12, as key contributors to the risk of OHSS through MR and colocalization analysis. These proteins were involved in metabolic regulation, immune response and antioxidant pathways, highlighting potential therapeutic targets and suggesting new directions for treatment strategies.

Humans↗

PubMed2002

Deconvolution improves colocalization analysis of multiple fluorochromes in 3D confocal data sets more than filtering techniques.

Background and noise impair image quality by affecting resolution and obscuring image detail in the low intensity range. Because background levels in unprocessed confocal images are frequently at about 30% maximum intensity, colocalization analysis, a typical segmentation process, is limited to high intensity signal and prone to noise-induced, false-positive events. This makes suppression or removal of background crucial for this kind of image analysis. This paper examines the effects of median filtering and deconvolution, two image-processing techniques enhancing the signal-to-noise ratio (SNR), on the results of colocalization analysis in confocal data sets of biological specimens. The data show that median filtering can improve the SNR by a factor of 2. The technique eliminates noise-induced colocalization events successfully. However, because filtering recovers voxel values from the local neighbourhood false-negative ('dissipation' of signal intensity below threshold value) as well as false-positive ('fusion' of noise with low intensity signal resulting in above threshold intensities), results can be generated. In addition, filtering involves the convolution of an image with a kernel, a procedure that inherently impairs resolution. Image restoration by deconvolution avoids both of these disadvantages. Such routines calculate a model of the object considering various parameters that impair image formation and are able to suppress background down to very low levels (< 10% maximum intensity, resulting in a SNR improved by a factor 3 as compared to raw images). This makes additional objects in the low intensity but high frequency range available to analysis. In addition, removal of noise and distortions induced by the optical system results in improved resolution, which is of critical importance in cases involving objects of near resolution size. The technique is, however, sensitive to overestimation of the background level. In conclusion, colocalization analysis will be improved by deconvolution more than by filtering. This applies especially to specimens characterized by small object size and/or low intensities.

Animals↗

PubMed2025

Circulating inflammatory proteins and osteomyelitis: A bidirectional Mendelian randomization and colocalization analysis.

Circulating inflammatory proteins (CIPs) have been implicated in the progression of osteomyelitis (OM); however, whether these proteins play a causal role or are merely a consequence remains unclear. This study aimed to assess the causal relationships between CIPs and OM using a bidirectional 2-sample Mendelian randomization (MR) approach. MR analyses were performed using genome-wide association study summary statistics for 91 inflammation-related proteins (n = 14,824) and OM (1881 cases and 3,91,037 controls). The inverse variance weighted method was used as the primary analytical approach, supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analyses were conducted to evaluate heterogeneity, horizontal pleiotropy, and robustness. Colocalization analysis was applied to identify shared causal variants, and pathway enrichment analysis was used to explore underlying biological mechanisms. Forward MR analysis revealed that elevated levels of tumor necrosis factor-beta (TNF-β) were significantly associated with increased OM risk (odds ratio [OR] = 1.132; 95% confidence interval [CI]: 1.052-1.217; false discovery rate [FDR] = 0.027). Conversely, decreased levels of osteoprotegerin (OR = 0.772; 95% CI: 0.671-0.889; FDR = 0.015) and adenosine deaminase (OR = 0.811; 95% CI: 0.736-0.894; FDR < 0.001) were associated with increased OM risk. Reverse MR analysis identified increased levels of interleukin-15 receptor alpha, C-X-C motif chemokine ligand 1, fms-related tyrosine kinase 3 ligand, interleukin-20, interleukin-10 (IL10), C-C motif chemokine ligand 19, and CXCL6 as being significantly associated with OM susceptibility (all FDR < 0.05). Colocalization analysis provided strong evidence for a shared causal variant between TNF-β and OM (posterior probability for hypothesis 4 = 0.999). Enrichment analyses indicated involvement of implicated proteins in Toll-like receptor signaling and T-helper 17 cell differentiation pathways. This study identified several CIPs - including TNF-β, osteoprotegerin, and adenosine deaminase - as potentially causal in OM development. These findings highlight promising targets for future immunomodulatory therapies aimed at preventing or mitigating osteomyelitis.

Humans↗

PubMed2006

A guided tour into subcellular colocalization analysis in light microscopy.

It is generally accepted that the functional compartmentalization of eukaryotic cells is reflected by the differential occurrence of proteins in their compartments. The location and physiological function of a protein are closely related; local information of a protein is thus crucial to understanding its role in biological processes. The visualization of proteins residing on intracellular structures by fluorescence microscopy has become a routine approach in cell biology and is increasingly used to assess their colocalization with well-characterized markers. However, image-analysis methods for colocalization studies are a field of contention and enigma. We have therefore undertaken to review the most currently used colocalization analysis methods, introducing the basic optical concepts important for image acquisition and subsequent analysis. We provide a summary of practical tips for image acquisition and treatment that should precede proper colocalization analysis. Furthermore, we discuss the application and feasibility of colocalization tools for various biological colocalization situations and discuss their respective strengths and weaknesses. We have created a novel toolbox for subcellular colocalization analysis under ImageJ, named JACoP, that integrates current global statistic methods and a novel object-based approach.

Journal Article↗

PubMed2004

Automated high through-put colocalization analysis of multichannel confocal images.

The laser scanning confocal microscope (LSCM) generates images of multiple labelled fluorescent samples. Colocalization of fluorescent labels is frequently examined. Here we present an example where localization of fluorescent analogues of cloned protein were referenced to fluorescent antibodies directed against the proteins of cellular compartments. Colocalization is usually evaluated by visual inspection of signal overlap or by using commercially available software tools, but there are limited possibilities to automate the analysis of large amounts of data. We developed a simple tool using Matlab to automate the colocalization procedure and to exclude the biased estimations resulting from visual inspections of images. The script in Matlab language code automatically imports confocal images and converts them into arrays. The contrast of all images is uniformly set by linearly reassigning the values of pixel intensities to use the full 8-bit range (0-255). Images are binarized on several threshold levels. The area above a certain threshold level is summed for each channel of the image and for colocalized regions. As a result, count of pixels above several threshold levels in any number of images is saved in an ASCII file. In addition Pearson's r correlation coefficient is calculated for fluorescence intensities of both confocal channels. Using this approach quick quantitative analysis of colocalization of hundreds of images is possible. In addition, such automated procedure is not biased by the examiner's subject visualization.

Automation↗

PubMed2003

Colocalization analysis of sialomucins CD34 and CD164.

Flow cytometric protocols are employed to identify and characterize hemopoietic stem/progenitor populations before transplantation. Cell surface antigens, including CD34, are employed in this process and widely used in harvest protocols, which largely ignores the potential functional role of such antigens. Transmembrane glycoprotein sialomucins, including CD34 and CD164, have been implicated in cell-to-cell interactions and activation. CD164, also expressed on early hemopoietic populations, was reported to have a possible function facilitating CD34(+) cells to adhere to bone marrow stroma. In this study, we employed high-definition laser-scanning confocal microscopy to investigate CD34 and CD164 surface co-localization patterns on bone marrow and cord blood cells and to compare the expression patterns using a three-dimensional computer-generated method developed in house. Differential interference microscopy analysis revealed bone marrow membrane activity was higher than the corresponding cord blood counterpart, perhaps indicating the marrow microenvironmental nature. Fluorescence analysis of CD34 and CD164 antigens showed both were expressed first in a halo-like pattern and second in antigen-dense pockets. Three-dimensional computer analyses further revealed that this pocketing corresponded to dense crest-like surface structures appearing to rise from the point of adherence on the slide. Further, it was found that CD34 and CD164 display strong colocalization patterns on cells expressing both antigens. The dual nature of the CD34 and CD164 antigens discovered here lends further evidence to the previous literature implicating a strong functional link between these two sialomucins, which should be considered in the transplantation arena and in the function of such sialomucins as negative regulators of cell proliferation.

Antigens, CD34↗

PubMed1999

CART peptide-immunoreactive neurones in the nucleus accumbens in monkeys: ultrastructural analysis, colocalization studies, and synaptic interactions with dopaminergic afferents.

Cocaine- and amphetamine-regulated transcript (CART) is a novel mRNA whose level of expression was found to be increased in the striatum after acute administration of psychomotor stimulants in rats. To define better the potential role of CART peptides in behavioural and physiologic changes induced by psychomotor stimulants, we analyzed the distribution, ultrastructural features, synaptic connectivity, and transmitter content of CART peptide-immunoreactive neurones in the nucleus accumbens in monkeys. Medium-sized CART peptide-immunoreactive neurones within a rich plexus of labelled varicosities were found mostly in the medial division of the shell of the nucleus accumbens in monkeys. At the electron microscope level, CART peptide immunoreactivity was exclusively associated with neuronal structures that included perikarya, dendrites, spines as well as nerve terminals packed with electron-lucent and dense-core vesicles. Most CART peptide-containing somata displayed the ultrastructural features of striatal output neurones. The majority of labelled terminals formed symmetric axodendritic synapses and displayed gamma-aminobutyric acid (GABA) immunoreactivity. CART peptide-immunoreactive somata were not immunoreactive for parvalbumin and somatostatin, two markers of striatal interneurones, nor for calbindin D-28k, a marker of a subpopulation of projection neurones. In double-immunostained sections, CART peptide-immunoreactive dendrites were found to be contacted by tyrosine hydroxylase-positive terminals which displayed the ultrastructural features of dopamine-containing boutons. These findings strongly suggest that CART peptides may be a cotransmitter with GABA in a subpopulation of projection neurones in the monkey accumbens. Furthermore, the fact that CART peptide-immunoreactive neurones receive direct synaptic inputs from dopaminergic afferents and are particularly abundant in the caudomedial division of the shell of the nucleus accumbens suggest that CART peptides might be involved in neuronal and behavioural changes that underlie addiction to psychomotor stimulants and feeding in primates.

Animals↗

PubMed2005

Simultaneous degradation estimation and restoration of confocal images and performance evaluation by colocalization analysis.

A novel method for joint restoration and estimation of the degradation of confocal microscope images is presented. The observed images are degraded due to two sources: blurring due to the band-limited nature of the optical system [modelled by the point spread function (PSF)], and Poisson noise contaminates the observations due to the discrete nature of the photon detection process. The proposed method iterates noise reduction, blur estimation and deblurring, and applies these steps in two phases, i.e. a training phase and a restoration phase. In the first phase, these three steps are iterated until the blur estimation converges. Noise reduction and blur estimation are performed using steerable pyramids, and the deblurring is performed by the Richardson-Lucy algorithm. The second phase is the actual restoration. From then on, the blur estimation is used as a criterion to measure the image quality. The iterations are stopped when this measure converges, a result that is guaranteed. The integrated method is completely automatic, and no prior information on the image is required. The method has been given the name SPERRIL (Steerable Pyramid-based Estimation and Regularized Richardson-Lucy restoration). Compared with existing techniques by both objective measures and visual observation, in the SPERRIL-restored images noise is better suppressed.

Algorithms↗

PubMed2025

Association of genetically proxied cancer-targeted drugs with cardiovascular diseases through Mendelian randomization analysis.

BACKGROUND: Cancer-targeted therapies are progressively pivotal in oncological care. Observational studies underscore the emergence of cancer therapy-related cardiovascular toxicity (CTR-CVT), impacting patient outcomes. We aimed to investigate the causal relationship between different types of cancer-targeted therapies and cardiovascular disease (CVD) outcomes through a two-sample Mendelian randomization (MR) study. METHODS: This genome-wide association study was conducted using a two-sample Mendelian randomization framework. Genetic instruments for drug target gene expression were extracted from the eQTLGen consortium (31684 individuals, 37 cohorts). Genome-wide association study (GWAS) summary statistics for 19 cardiovascular diseases were derived from the FinnGen database. Primary analysis was carried out using the summary-data-based MR (SMR) method, with sensitivity analysis for validation. Colocalization analysis identifies shared causal variants between exposure eQTLs and CVD-associated single-nucleotide polymorphisms (SNPs). RESULTS: Among the 39 drug target genes, 8 were identified with detectable cis-eQTLs and were subsequently validated through positive control analysis for further investigation. In the SMR and sensitivity analyses, genetically proxied VEGFA inhibition showed significantly strong association with stroke (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.09-1.26, p = 1.33 × 10- 5). Additionally, the inhibition of FGFR1, FLT1, and MAP2K2 exhibited suggestive association with corresponding cardiovascular disease outcomes. Nevertheless, only VEGFA expression and stroke shared a causal variant (93.6%), whereas FGFR1, MAP2K2, and FLT1 did not share causal variants with corresponding cardiovascular diseases in the colocalization analysis. CONCLUSIONS: This genetic association study revealed evidence supporting the genetic association between the use of VEGFA inhibitors and increased stroke risk, highlighting the need for enhanced pharmacovigilance. These findings underscore the delicate balance between cardiovascular toxicity risk and the benefits of cancer-targeted therapy.

Humans↗

PubMed2025

Evidence supporting the role of hypertension in the onset of migraine.

BACKGROUND: The association between hypertension and migraine remains unclear. OBJECTIVE: The aim of this study employ multi-layered evidence chain that revealed the association between hypertension and migraine. METHODS: We first strictly included data from the NHANES 1999-2004 population and applied logistic regression, subgroup analysis and RCS to assess the correlation between hypertension, SBP, DBP and migraine. Meanwhile, LDSC and Mendelian randomization were conducted based on the GWAS to determine the causal relationship between hypertension and migraine. Inverse-variance weighted (IVW) was used as the primary method. Sensitivity analysis and Colocalization analysis were performed to confirm the robustness of the results. LDSC validated the genetic correlation between traits. Enrichment analysis revealed their underlying biological mechanisms. RESULTS: After strict inclusion in NHANES, 10,743 participants were included. The logistic regression showed a significant correlation between hypertension (OR = 1.21 [95% CI, 1.08-1.36], FDR < 0.001)、DBP (OR = 1.01 [95% CI, 1.01-1.02], FDR < 0.001) and migraine. This association did not show significant group differences in subgroup. The MR results further supported the existence of a significant causal relationship between hypertension (OR = 1.77 [95% CI, 1.43-2.30], FDR < 0.001)、DBP (OR = 1.02 [95% CI, 1.01-1.03], FDR < 0.001) and migraine onset. Additionally, the RCS analysis showed a linear relationship (P non-linear = 0.897) between the two. The LDSC result showed a significant genetic correlation between the two (Rg = 0.1092, SE = 0.028, P < 0.001). CONCLUSION: The development of migraine caused by hypertension is mainly realized through high DBP.

Humans↗

PubMed2026

Mapping the Immune cell-specific gene regulatory network in bipolar disorder: A framework from scTWMR to exploratory drug-target annotation.

BACKGROUND: Although the involvement of the immune system in the genetic susceptibility of bipolar disorder (BD) is widely acknowledged, the causal relationship between gene expression in specific immune cell subtypes and BD requires systematic elucidation. METHODS: We implemented an analytical framework integrating single-cell transcriptome-wide Mendelian randomization (scTWMR) with colocalization analysis. This approach utilized cis-expression quantitative trait loci (cis-eQTLs) derived from 14 distinct immune cell types as instrumental variables to interrogate BD genome-wide association study (GWAS) summary statistics (comprising 41,917 cases and 371,549 controls). Subsequent investigations encompassed functional enrichment analysis, protein-protein interaction (PPI) network construction, phenome-wide association study (PheWAS), and performed an exploratory drug-target annotation. RESULTS: Our analysis identified 33 gene-immune cell associations. Colocalization analysis provided robust evidence (PPH4 > 90%) for shared causal variants implicating the MAD1L1, APOM, and NFKBIL1 loci. Significantly enriched biological pathways included cell cycle regulation, circadian rhythm entrainment, and neuroinflammation. The PPI network revealed a core regulatory module centered on histone-encoding and immune-related genes. Exploratory drug-target annotation nominated compounds for further investigation for compounds targeting APOM, TMEM258, and NFKBIL1. CONCLUSION: This study systematically delineates a genetically supported regulatory network of immune cell-specific gene expression in BD, predominantly implicating CD8⁺ effector T cells, plasma cells, and B cells. The findings corroborate established pathological pathways while uncovering novel cell type-specific therapeutic targets, thereby providing a genetic framework for prioritizing candidate targets for future investigation.

Bipolar disorder↗

PubMed2005

Experimental LPS-induced cholestasis alters subcellular distribution and affects colocalization of Mrp2 and Bsep proteins: a quantitative colocalization study.

Quantitative colocalization analysis is a powerful tool for reliable estimation of the colocalization of antigens. We employed it to determine the changes of colocalization of multidrug resistance protein 2 (Mrp2) and bile salt export pump (Bsep) in confocal immunofluorescence microscopy images of rat liver following lipopolysaccharide (LPS) administration. Samples were taken 2, 24, 48 hours, and 1 week after LPS challenge. Pearson's correlation coefficient (PCC), an overlap coefficient according to Manders' (MOC), and overlap coefficients k1 and k2 were used to explore changes of the degree of colocalization. In intact animals, confocal microscopy showed tight colocalization of Mrp2 and Bsep proteins exclusively at the bile canaliculi. High degree of colocalization was confirmed quantitatively. Injection of LPS resulted in the appearance of fuzzy-looking areas of fluorescence of both proteins around bile canaliculi 2 and 24 hours after administration and relocation of Mrp2 protein to the basolateral domain of hepatocytes at 48 hours. By 1 week, canalicular localization was restored morphologically. Quantitative colocalization analysis of canalicular regions showed a steady decrease of the degree of colocalization of Mrp2 and Bsep up to 48 hours with the slight increase of its value by 1 week. These findings demonstrate that Mrp2, in contrast to Bsep, is partially and reversibly relocated from canalicular to basolateral domain of hepatocytes after LPS challenge.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2025

Cross-Phenotype Genome-Wide Association Study on the Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis.

OBJECTIVE: An increased risk of primary biliary cholangitis (PBC) has been reported in patients with systemic sclerosis (SSc). Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross-phenotype genome-wide association study (GWAS) meta-analysis. METHODS: We performed cross-phenotype GWAS meta-analysis and Bayesian colocalization analysis for patients with SSc and patients with PBC. We performed both genome-wide and locus-based analysis, including tissue and pathway enrichment analyses, fine-mapping, Bayesian colocalization analyses with expression quantitative trait loci and protein quantitative trait loci (pQTL) datasets, and phenome-wide association studies. Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci. RESULTS: We detected a strong genetic correlation between SSc and PBC (global genetic correlation = 0.84, P = 1.7 × 10-6). In the cross-phenotype GWAS meta-analysis, we identified 44 nonhuman leukocyte antigens loci that reached genome-wide significance (P < 5 × 10-8). Evidence of shared causal variants between patients with SSc and patients with PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized CD40, ERAP1, PLD4, SPPL3, and CCDC113 as novel candidate causal genes. The CD40 risk locus colocalized with trans-pQTLs of multiple plasma proteins involved in B cell function. CONCLUSION: Our study supports a strong shared genetic susceptibility between SSc and PBC. Using cross-phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.

Humans↗

PubMed2025

A Multi-omics Exploration Revealing SLIT2 as a Prime Therapeutic Target for Peripheral Facial Paralysis: Integrating Single-Cell Transcriptomics and Plasma Proteome Data.

Peripheral facial paralysis (PFP) is a common neurological disorder characterized by facial-nerve dysfunction. Identifying therapeutic targets and understanding the molecular and cellular mechanisms underlying PFP are crucial for developing effective treatment strategies. This study combined Mendelian randomization (MR) analysis and single-cell RNA sequencing (scRNA-seq) to explore potential therapeutic candidates and their roles in PFP pathophysiology. The MR analysis included 1925 publicly available plasma protein cis-heritability instruments. Instrumental variables were selected for MR analysis to identify plasma proteins associated with PFP, followed by colocalization analysis to evaluate shared genetic variants between the identified proteins and PFP. After the initial identification of plasma proteins associated with Bell's palsy using MR analysis, a rat model of facial-nerve injury was established to further dissect underlying mechanisms at cellular and molecular levels. Using scRNA-seq technology, we delved deeply into cellular Heterogeneity and dynamic changes in gene expression in the facial-nerve nucleus tissues under both injured and control conditions, thereby achieving a systematic study ranging from macroscopic genetic associations to microscopic cellular functions. Finally, expression patterns were preliminarily validated by performing in vitro immunofluorescence analysis on the facial-nerve nucleus samples of SD rats. The MR analysis results identified 30 plasma proteins significantly associated with PFP, with nine target genes showing differential expression in the scRNA-seq data. Colocalization analysis demonstrated that slit guidance Ligand 2 (SLIT2), semaphorin 4D (SEMA4D), EGF containing fibulin extracellular matrix protein 1 (EFEMP1), and sprouty related EVH1 domain containing 2 (SPRED2) shared causal variants with PFP. SLIT2 was highly expressed in the microglia and inhibitory neurons in the experimental group, whereas SEMA4D showed elevated expression across multiple glial cell types in the same group. In contrast, EFEMP1 and SPRED2 showed distinct expression patterns in fibroblasts and oligodendrocytes. The role of SLIT2 has been previously well-documented in many central nervous system diseases. However, for the first time, this study detected SLIT2 alteration after facial-nerve injury. Altered intercellular signaling, particularly enhanced SLIT2-ROBO signaling between neurons and glial cells, was observed in the PFP group. Pseudotime analysis revealed dynamic SLIT2 expression during microglia and inhibitory neuron differentiation, mirroring changes in ROBO1 expression. Immunofluorescence analysis of rat facial-nerve nucleus samples verified that SLIT2 protein levels were significantly increased in the facial-nerve nuclei of injured samples. In conclusion, despite the fact that this study is primarily founded on animal models and despite notable differences existing between animals and humans in terms of the facial motor nucleus, this study successfully identified SLIT2 as potential therapeutic targets for PFP. The SLIT2-ROBO axis stands out as a particularly promising candidate. SLIT2 may play a role in modulating neuroimmune interactions and promoting nerve repair. These findings provide a foundation for future clinical studies and targeted interventions to enhance recovery from PFP. Future research should focus on human sample validation to enhance clinical translation.

Animals↗

PubMed2026

Mitochondria-Related Pathogenic Genes in Paediatric Asthma: A Multi-Omics Mendelian Randomization Study.

Mitochondrial dysfunction is implicated in asthma pathogenesis, but causal roles of mitochondrial-related genes in paediatric asthma remain unclear. We performed a multi-omics Mendelian randomization study integrating GWAS data from paediatric asthma cohorts with blood-based methylation quantitative trait loci (mQTLs), expression QTLs (eQTLs) and protein QTLs (pQTLs) datasets. Causal inference was assessed using Summary-data-based Mendelian Randomization (SMR) and HEIDI testing, complemented by colocalization analysis. Findings were validated in independent cohorts and evaluated for tissue specificity using GTEx. Functional enrichment and protein-protein interaction (PPI) network analyses were conducted. SMR analysis identified 80 methylation sites spanning 54 genes, 26 gene expressions, and three proteins significantly associated with paediatric asthma. Colocalization analysis confirmed strong evidence for 10 methylation sites (7 genes), the STX17 eQTL (PP.H4 = 0.98) and the UNG pQTL (PP.H4 = 0.84). Tissue-specific eQTL validation replicated the STX17 association. Multi-omics integration associated ALAS1 (cg13241645, cg15698299) and TXNRD1 (cg09884423) with asthma at both methylation and expression levels, with colocalization supporting both ALAS1 associations. Furthermore, integrated mQTL-eQTL analysis suggests that DNA methylation potentially regulates ALAS1 and TXNRD1 expression. Functional enrichment and network analyses revealed that these candidate genes converge on mitochondrial metabolic pathways and identified seven hub genes with potential regulatory significance (SDHB, MFN2, GLDC, PHB2, TXNRD1, ATP5MC1 and PHB). This study provides multi-omics evidence supporting a causal role for mitochondrial-related genes, particularly ALAS1 and TXNRD1, in paediatric asthma, offering new insights into pathogenesis and potential therapeutic targets.

Humans↗

PubMed2026

Refining the link between REM sleep behavior disorder and neurodegeneration: Genetic correlation, Mendelian randomization, and colocalization evidence.

Observational studies have proposed a link between isolated rapid eye movement sleep behavior disorder (iRBD) and several neurodegenerative diseases. We employed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analysis to assess the causal links between iRBD and these neurodegenerative conditions. iRBD demonstrated a positive causal association with Alzheimer disease (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 1.00-1.03, P = 1.10E-02), Parkinson disease (OR = 1.10, 95% CI: 1.03-1.16, P = 2.96E-03), and multiple sclerosis (OR = 1.09, 95% CI: 1.02-1.17, P = 1.61E-02). A strong positive genetic correlation with dementia with Lewy bodies was observed (rg = 1.6313, P = .0002), along with a causal association (OR = 1.45, 95% CI: 1.03-2.06, P = 3.53E-02), further supported by colocalization analysis. No significant causal relationship was identified between iRBD and amyotrophic lateral sclerosis (all P > .05). Additionally, reverse Mendelian randomization analyses did not reveal any causal relationships between the neurodegenerative diseases studied and iRBD. Our findings provide robust genetic evidence supporting a causal relationship between iRBD and the risk of multiple neurodegenerative diseases, highlighting the potential for shared pathophysiological mechanisms.

Humans↗

PubMed2025

MetaChrome: An Open-Source, User-Friendly Tool for Automated Metaphase Chromosome Analysis.

DNA Fluorescence In Situ Hybridization (FISH) is an essential technique to study chromosome biology and genetics, enabling precise visualization of specific genomic loci to study structural abnormalities, gene mapping, and chromosomal rearrangements. High-Throughput Imaging (HTI) can automate the analysis of DNA-FISH chromosome images, but the accurate and automated segmentation of mitotic chromosomes and simultaneous colocalization of FISH signals remains a challenge. While several commercial automated karyotyping tools partially solve these issues, open-source software that effectively combines robust chromosome segmentation with comprehensive colocalization analysis capabilities remains necessary. To address this unmet need, we developed MetaChrome, an open-source software platform built around a graphical user interface and explicitly designed for automated metaphase chromosome analysis. MetaChrome leverages fine-tuned deep learning models to automate metaphase chromosome segmentation, together with colocalization analysis of chromosome-specific FISH probes and immunofluorescent-labeled proteins. Importantly, MetaChrome achieves enhanced segmentation accuracy compared to traditional image processing methods by adopting a Cellpose segmentation model fine-tuned with manually annotated metaphase chromosome datasets. The fine-tuned model ensures precise assignment of DNA-FISH spots to individual chromosomes in an automated manner. This facilitates rapid identification of chromosomal abnormalities, reduces human error, and advances high-throughput chromosome analysis workflows, addressing a key bottleneck in chromosome biology research.

Chromosome segmentation↗