Molecular omics最新文献_第2页

Temperature- and time-dependent degradation of mouse tissue proteins: insights into RNA-binding protein stability via mass spectrometry† 小鼠组织蛋白的温度和时间依赖性降解：通过质谱分析了解rna结合蛋白的稳定性。

IF 2.4 4区生物学

Molecular omics Pub Date : 2025-07-14 DOI: 10.1039/D5MO00020C

Aiswarya Suresh, Nikhil Pallaprolu, Aishwarya Dande, Harish Kumar Pogula, Vipan Kumar Parihar and Ramalingam Peraman

{"title":"Temperature- and time-dependent degradation of mouse tissue proteins: insights into RNA-binding protein stability via mass spectrometry†","authors":"Aiswarya Suresh, Nikhil Pallaprolu, Aishwarya Dande, Harish Kumar Pogula, Vipan Kumar Parihar and Ramalingam Peraman","doi":"10.1039/D5MO00020C","DOIUrl":"10.1039/D5MO00020C","url":null,"abstract":"In proteomics research, samples are frequently stored at −20 °C and −80 °C for extended periods, and assessing protein stability under these conditions is essential. We evaluated protein stability in healthy and diseased mice liver tissues stored at 4 °C, −20 °C, and −80 °C for 0, 7, 30, 90, and 180 days. A 10% variation in protein concentrations (by day 90, p < 0.001) was observed via BCA assay across all conditions. Untargeted proteomic analysis was performed using in-solution trypsin digestion and LC-Q-Orbitrap-MS/MS, with data processed using Proteome Discoverer 2.5. Proteins were shortlisted based on ≥2 unique peptides, FDR < 1%, and abundance ratio p ≤ 0.001. Differentially expressed proteins were identified using log 2 FC ± 2, p-adj ≤ 0.05. Protein degradation varied with storage conditions. In healthy tissues, 24, 11, and 8 proteins completely degraded at 4 °C, −20 °C, and −80 °C, respectively, after 7 days, compared to 8, 2, and 3 proteins in diseased tissues. The total number of significant proteins consistently identified across all time points in healthy samples was 2570, 2711, and 2617, and in diseased samples it was 2124, 2414, and 2353 at 4 °C, −20 °C, and −80 °C, respectively. RNA-binding proteins, such as La ribonucleoprotein 1B, Reticulophagy regulator 3, and Telomerase RNA component interacting RNase, were particularly prone to degradation across all conditions within 7 days. Notably, 18 degraded proteins were reported as biomarkers in disease conditions. Although −20 °C and −80 °C provided better preservation, residual instability persisted. Optimizing storage conditions is essential to prevent degradation, particularly for biomarker discovery studies.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 5","pages":" 479-495"},"PeriodicalIF":2.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding metabolic alterations in advanced stage chronic kidney disease patients by NMR-based metabolomics† 通过核磁共振代谢组学了解晚期慢性肾病患者的代谢改变。

IF 2.4 4区生物学

Molecular omics Pub Date : 2025-06-16 DOI: 10.1039/D5MO00019J

Amrita Sahu, Upasna Gupta, Bikash Baishya, Dharmendra Singh Bhadauria and Neeraj Sinha

{"title":"Understanding metabolic alterations in advanced stage chronic kidney disease patients by NMR-based metabolomics†","authors":"Amrita Sahu, Upasna Gupta, Bikash Baishya, Dharmendra Singh Bhadauria and Neeraj Sinha","doi":"10.1039/D5MO00019J","DOIUrl":"10.1039/D5MO00019J","url":null,"abstract":"Understanding metabolic alterations in CKD is crucial, as serum creatinine-based diagnosis lacks precision, affecting key clinical decisions. In this study, a 1H NMR-based metabolomics approach was employed to distinguish between advanced-stage CKD (ASCKD) patients and healthy controls (HC), as well as within the ASCKD stages (stage 4 and stage 5). Serum samples from 52 ASCKD (S4, S5) and 25 HC were analyzed. Multivariate and univariate analysis revealed distinct metabolic patterns across groups, providing insights into CKD pathophysiology and associated pathway alterations. Compared to HC, six metabolites were significantly altered in both stage 4 and 5 CKD patients with upregulated creatinine, urea, myoinositol, choline, N,N-dimethylglycine, and downregulated tyrosine, showing potential as biomarkers with AUC above 0.8 in ROC analysis. Additionally, myo-inositol, dimethylamine, N,N-dimethylglycine, and choline correlate positively with creatinine while tyrosine correlates negatively. Amino acid metabolism was downregulated in S5 indicating more severity. Within ASCKD patients, significant alterations were observed in metabolites such as glutamate, glutamine, alanine, threonine, myo-inositol, dimethylamine, citrulline, urea, citrate, and betaine. Pathway analysis identified five distinct metabolic pathways associated with CKD progression. Consequently, we propose a panel of serum metabolites which should be monitored along with creatinine for following CKD progression. Markers of oxidative stress, inflammation, and gut dysbiosis were evident in the perturbed metabolic profile due to the systemic impact of CKD.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 5","pages":" 464-478"},"PeriodicalIF":2.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

POMC-specific modulation of metabolic and immune pathways via melanocortin-3 receptor signaling† 通过黑素皮质素-3受体信号，pomc特异性调节代谢和免疫途径。

IF 2.4 4区生物学

Molecular omics Pub Date : 2025-06-11 DOI: 10.1039/D4MO00248B

Mariya Nezhyva, Friederike A. Sandbaumhüter, Per E. Andrén and Erik T. Jansson

{"title":"POMC-specific modulation of metabolic and immune pathways via melanocortin-3 receptor signaling†","authors":"Mariya Nezhyva, Friederike A. Sandbaumhüter, Per E. Andrén and Erik T. Jansson","doi":"10.1039/D4MO00248B","DOIUrl":"10.1039/D4MO00248B","url":null,"abstract":"This proteomic study provides a nuanced mechanistic understanding of the signaling processes upon agonist binding to the melanocortin-3 receptor (MC3R). Utilizing thermal proteome profiling (TPP) combined with LC–MS, we uncovered the distinct influences of the endogenous agonists adrenocorticotropic hormone (ACTH), α-melanocyte-stimulating hormone (α-MSH), and γ-melanocyte-stimulating hormone (γ-MSH) on protein thermal stability and pathway activation. In our 2D-TPP study, transfected HEK293 cells for expression of MC3R were exposed to the three endogenous MC3R-ligands across several concentrations followed by incubation at several temperatures, centrifugation and LC–MS analysis of the resulting supernatants. This enabled us to assess the effects of type of ligand and concentration on the thermal stability of proteins in these cells. We employed a combination of multivariate analysis, differential expression, TPP and pathway analysis to deeply characterize the impact of MC3R activation on molecular mechanisms. All three ligands affected signaling pathways related to the immune system and energy homeostasis. While α-MSH significantly modulated the IL-6 pathway via STAT3, and γ-MSH prominently activated interferon signaling, ACTH uniquely affected NADPH-related proteins. All ligands shared involvement in the cAMP-PKA-CREB and varied impacts on PI3K and ERK pathways, crucial for energy metabolism. All proteomic data are available under DOI: https://doi.org/10.6019/PXD039945.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 5","pages":" 456-463"},"PeriodicalIF":2.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/mo/d4mo00248b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing colorectal cancer research through lipidomics 通过脂质组学推进结直肠癌研究。

IF 2.4 4区生物学

Molecular omics Pub Date : 2025-06-04 DOI: 10.1039/D5MO00045A

Pedro Santiago, Tânia Melo, Maria Barceló-Nicolau, Gwendolyn Barceló-Coblijn, Pedro Domingues and Rosário Domingues

{"title":"Advancing colorectal cancer research through lipidomics","authors":"Pedro Santiago, Tânia Melo, Maria Barceló-Nicolau, Gwendolyn Barceló-Coblijn, Pedro Domingues and Rosário Domingues","doi":"10.1039/D5MO00045A","DOIUrl":"10.1039/D5MO00045A","url":null,"abstract":"Colorectal cancer (CRC) is currently a global health burden, with staggering worldwide prevalence. CRC is ranked as the third most common and second deadliest cancer worldwide. With rising life expectancy population growth, CRC incidence and mortality are projected to increase, particularly among individuals under 50. This underscores the need to improve early detection of CRC. Although colonoscopy remains the preferred diagnostic technique, due to its high sensitivity and specificity for CRC its invasive nature and cost result in low adherence rates. Consequently, the scientific community is actively exploring alternative diagnostic methods, primarily through biomarkers, molecules exhibiting dysregulated levels associated with specific diseases. Lipidomics has become crucial in cancer research, as lipids play key roles in metabolic pathways driving cancer development. Recent investigations have revealed decreased levels of lipid classes such as lysophosphatidylcholine (LPC) in CRC patients compared to healthy controls, alongside an increase in specific sphingolipid species across multiple studies. In the context of CRC progression, triglycerides (TGs) stand out as the lipids that display the most pronounced differentiation among different disease stages. These lipid dysregulations present promising avenues for identifying potential therapeutic targets and innovative diagnostic methods, however, a comprehensive understanding of these processes requires further exploration.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 5","pages":" 373-389"},"PeriodicalIF":2.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/mo/d5mo00045a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterizing metabolic dysregulation in early-stage chronic kidney disease for diagnostic insights. 表征代谢失调早期慢性肾脏疾病的诊断见解。

IF 3 4区生物学

Molecular omics Pub Date : 2025-05-29 DOI: 10.1039/d5mo00018a

Upasna Gupta, Amrita Sahu, Dharmendra Singh Bhadauria, Bikash Baishya, Neeraj Sinha

{"title":"Characterizing metabolic dysregulation in early-stage chronic kidney disease for diagnostic insights.","authors":"Upasna Gupta, Amrita Sahu, Dharmendra Singh Bhadauria, Bikash Baishya, Neeraj Sinha","doi":"10.1039/d5mo00018a","DOIUrl":"https://doi.org/10.1039/d5mo00018a","url":null,"abstract":"The progressive illness known as chronic kidney disease (CKD) can often be challenging to diagnose in its early stages with conventional diagnostic approaches such as serum creatinine and albumin assessment. Early-stage CKD (stages G1-G3) is defined by a GFR of ≥30 mL min-1/1.73 m2, which indicates normal to moderately reduced kidney function with or without symptoms of impaired kidney function. Identifying possible biomarkers for early detection and personalised treatment, as well as physiological changes linked to early CKD-an area that has not been fully investigated before-is the goal of the study to address this gap. We performed a metabolomic analysis using 1H NMR on 115 human serum samples (24 healthy controls and 91 patients with early-stage CKD). MetaboAnalyst 6.0 was used for data pre-processing and statistical analyses (PCA, PLS-DA, OPLS-DA, ANOVA, and Wilcoxon Mann-Whitney test). Strong differentiation between CKD stages was achieved by random forest modelling. The KEGG database was used to perform pathway enrichment, and ROC analysis was used to evaluate the diagnostic value of important metabolites. Across CKD stages, significant changes were observed in ten different metabolites: myo-Inositol, glycerol, pyruvate, carnitine, phenylalanine, tyrosine, histidine, TMAO, 2-hydroxyisobutyrate, and 3-hydroxyisobutyrate (p < 0.05, VIP > 1). AUC values > 0.7 from ROC curves demonstrated its potential for diagnosis. Pathway analysis revealed significant dysregulation in the metabolism of inositol phosphate, tyrosine, histidine, and pyruvate, and biosynthesis of phenylalanine, tryptophan and tyrosine. This comprehensive metabolomics investigation identified potential early-stage CKD biomarkers in addition to significant metabolic abnormalities. These findings could help provide individualized care for early CKD management.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrated multi-omic analyses of bovine milk identify biomarkers of negative energy balance† 牛乳的多组学分析鉴定了负能量平衡的生物标志物。

IF 2.4 4区生物学

Molecular omics Pub Date : 2025-05-21 DOI: 10.1039/D4MO00190G

A. Leduc, A. Rau, D. Laloë, S. Le Guillou, P. Martin, M. Gelé, J. Pires, Y. Faulconnier, C. Leroux, M. Boutinaud and F. Le Provost

{"title":"Integrated multi-omic analyses of bovine milk identify biomarkers of negative energy balance†","authors":"A. Leduc, A. Rau, D. Laloë, S. Le Guillou, P. Martin, M. Gelé, J. Pires, Y. Faulconnier, C. Leroux, M. Boutinaud and F. Le Provost","doi":"10.1039/D4MO00190G","DOIUrl":"10.1039/D4MO00190G","url":null,"abstract":"Dairy cows are susceptible to negative energy balance, which can lead to metabolic disorders such as ketosis. Negative energy balance (NEB) often occurs in early lactation, but can also be due to food scarcity. Its quantification is difficult and prone to error, justifying the need to identify biomarkers instead. The effect of NEB on milk composition is known to be directly related to its intensity, impacting major and minor milk constituents. As such, one promising approach may be to identify non-invasive biomarkers in milk. To identify potential biomarkers of NEB, we performed an integrative multi-omic study of milk production and composition in two feed restriction trials of different lengths and intensities. Multivariate data integration using a redundancy analysis enabled an exploration of the linear relationships between variation in energy balance and milk production and composition. A highly correlated multi-omic signature of NEB was then identified using a multi-block partial least squares discriminant analysis. Early and late integration of data from the two feed restriction trials enabled the identification of a robust multi-omic panel of biomarkers of NEB. Taken together, these analyses showed that feed restrictions led to consistent decreases in milk yield, lactose content and uric acid concentration, as well as increased isocitrate and serotransferrin concentrations and differentially abundant microRNAs in both whole milk and milk fat globules. These findings are promising for the development of a panel of non-invasive biomarkers for monitoring animal energy status, and enhance our understanding of adaptations to NEB.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 5","pages":" 433-445"},"PeriodicalIF":2.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating N-glycan and CODEX imaging reveal cell-specific protein glycosylation in healthy human lung† 整合n -聚糖和CODEX成像揭示健康人肺细胞特异性蛋白糖基化。

IF 3 4区生物学

Molecular omics Pub Date : 2025-05-20 DOI: 10.1039/D4MO00230J

Dušan Veličković, Jeffrey Purkerson, Harsh Bhotika, Heidie Huyck, Geremy Clair, Gloria S. Pryhuber and Christopher Anderton

{"title":"Integrating N-glycan and CODEX imaging reveal cell-specific protein glycosylation in healthy human lung†","authors":"Dušan Veličković, Jeffrey Purkerson, Harsh Bhotika, Heidie Huyck, Geremy Clair, Gloria S. Pryhuber and Christopher Anderton","doi":"10.1039/D4MO00230J","DOIUrl":"10.1039/D4MO00230J","url":null,"abstract":"Identifying cell-specific glycan structures in human lungs is critical for understanding the chemistry and mechanisms that guide cell–cell and cell–matrix interactions and determining nuanced functions of specific glycosylation. Our dual-modality omics platform, which uses matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to profile glycan chemistry at 50 μm × 50 μm scale, combined with co-detection by indexing (CODEX) to provide cell identification from the exact same tissue section, is a significant step in this direction. It enabled us to detect, differentiate, and reveal chemical properties of N-glycans in the various cell types of a human lung, suggesting the cell-specific function of distinct carbohydrate moieties. This innovative technological combination bridges the gap between the specific protein glycosylation and their cellular origin, paving the way for targeted studies in the lungs and many other human tissues where glycans mediate cell–cell recognition events.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 4","pages":" 334-342"},"PeriodicalIF":3.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipid profiling: proving the geographical origin of strawberries (Fragaria × ananassa) using a non-targeted LC-IM-MS approach† 脂质分析：使用非靶向LC-IM-MS方法证明草莓（Fragaria x ananassa）的地理起源。

IF 3 4区生物学

Molecular omics Pub Date : 2025-05-16 DOI: 10.1039/D5MO00006H

Johannes Brockelt, Felix Schmauder, Marina Creydt and Markus Fischer

{"title":"Lipid profiling: proving the geographical origin of strawberries (Fragaria × ananassa) using a non-targeted LC-IM-MS approach†","authors":"Johannes Brockelt, Felix Schmauder, Marina Creydt and Markus Fischer","doi":"10.1039/D5MO00006H","DOIUrl":"10.1039/D5MO00006H","url":null,"abstract":"The strawberry, a globally traded fruit, is a prime example of how geographical origin has become an important marketing factor. Significant price differences between countries of origin make mislabeling a financially attractive form of food fraud, underlining the need for origin verification. In this context, the development of methods that can unequivocally prove the authenticity, i.e., the declared origin, is an absolute necessity. In this study, a non-targeted lipidomic approach using ion mobility combined with high resolution mass spectrometry was applied to clearly distinguish German strawberries from non-German strawberries. Using linear discriminant analysis (LDA), an accuracy of 90% was achieved. Furthermore, a detailed classification of strawberries from Central Europe (German, Dutch and Polish strawberries) as well as strawberries from Mediterranean regions (Spanish, Greek and Egyptian strawberries) was carried out with a classification accuracy of 74%. To further investigate the classification results, a total of 39 lipids were identified as relevant markers for German, Dutch and Polish strawberries as well as for Spanish, Greek and Egyptian strawberries using MS/MS measurements. A particular difficulty was the fact that the influence of climatic conditions on the metabolome is similar in countries that are geographically close to each other. Overall, the results of this study help to prevent food fraud and to confirm the authenticity of strawberries in terms of their origin.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 4","pages":" 353-364"},"PeriodicalIF":3.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/mo/d5mo00006h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integration of focal adhesion morphogenesis and polarity by DOCK5 promotes YAP/TAZ-driven drug resistance in TNBC† DOCK5整合局灶黏附形态和极性，促进了YAP/ taz驱动的TNBC耐药。

IF 2.4 4区生物学

Molecular omics Pub Date : 2025-05-12 DOI: 10.1039/D4MO00154K

Patricia Pascual-Vargas, Mar Arias-Garcia, Theodoros I. Roumeliotis, Jyoti S. Choudhary and Chris Bakal

{"title":"Integration of focal adhesion morphogenesis and polarity by DOCK5 promotes YAP/TAZ-driven drug resistance in TNBC†","authors":"Patricia Pascual-Vargas, Mar Arias-Garcia, Theodoros I. Roumeliotis, Jyoti S. Choudhary and Chris Bakal","doi":"10.1039/D4MO00154K","DOIUrl":"10.1039/D4MO00154K","url":null,"abstract":"YAP and TAZ are transcriptional co-activators that are inhibited by sequestration in the cytoplasm. Cellular signalling pathways integrate soluble, mechanical (cytoskeleton, adhesion), and geometric (cell size, morphology) cues to regulate the translocation of YAP/TAZ to the nucleus. In triple-negative breast cancer (TNBC) cells, both signalling and morphogenesis are frequently rewired, leading to increased YAP/TAZ translocation, which drives proliferation, invasion, and drug resistance. However, whether this increased YAP/TAZ translocation is due to alterations in upstream signalling events or changes in cell morphology remains unclear. To gain insight into YAP/TAZ regulation in TNBC cells, we performed multiplexed quantitative genetic screens for YAP/TAZ localisation and cell shape, enabling us to determine whether changes in YAP/TAZ localisation following gene knockdown could be explained by alterations in cell morphology. These screens revealed that the focal adhesion (FA)-associated RhoGEF DOCK5 is essential for YAP/TAZ nuclear localisation in TNBC cells. DOCK5-defective cells exhibit defects in FA morphogenesis and fail to generate a stable, polarised leading edge, which we propose contributes to impaired YAP/TAZ translocation. Mechanistically, we implicate DOCK5's ability to act as a RacGEF and as a scaffold for NCK/AKT as key to its role in FA morphogenesis. Importantly, DOCK5 is essential for promoting the resistance of LM2 cells to the clinically used MEK inhibitor Binimetinib. Taken together, our findings suggest that DOCK5's role in TNBC cell shape determination drives YAP/TAZ upregulation and drug resistance.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 5","pages":" 390-421"},"PeriodicalIF":2.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A multi-omics machine learning classifier for outgrowth of cow's milk allergy in children† 儿童牛奶过敏生长的多组学机器学习分类器。

IF 3 4区生物学

Molecular omics Pub Date : 2025-05-09 DOI: 10.1039/D4MO00245H

Diana M. Hendrickx, Mariyana V. Savova, Pingping Zhu, Ran An, Sjef Boeren, Kelly Klomp, Sumanth K. Mutte, PRESTO study team, Harm Wopereis, Renate G. van der Molen, Amy C. Harms and Clara Belzer

{"title":"A multi-omics machine learning classifier for outgrowth of cow's milk allergy in children†","authors":"Diana M. Hendrickx, Mariyana V. Savova, Pingping Zhu, Ran An, Sjef Boeren, Kelly Klomp, Sumanth K. Mutte, PRESTO study team, Harm Wopereis, Renate G. van der Molen, Amy C. Harms and Clara Belzer","doi":"10.1039/D4MO00245H","DOIUrl":"10.1039/D4MO00245H","url":null,"abstract":"Cow's milk protein allergy (CMA) is one of the most common food allergies in children worldwide. However, it is still not well understood why certain children outgrow their CMA and others do not. While there is increasing evidence for a link of CMA with the gut microbiome, it is still unclear how the gut microbiome and metabolome interact with the immune system. Integrating data from different omics platforms and clinical data can help to unravel these interactions. In this study, we integrate clinical, microbial, (meta)proteomics, immune and metabolomics data into machine learning (ML) classification, using multi-view learning by late integration. The aim is to group infants into those that outgrew their CMA and those that did not. The results show that integration of microbiome data with clinical, immune, (meta)proteomics and metabolomics data could considerably improve classification of infants on outgrowth of CMA, compared to only considering one type of data. Moreover, pathways previously linked to development of CMA could also be related to outgrowth of this allergy.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 4","pages":" 343-352"},"PeriodicalIF":3.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0