Molecular omics最新文献

Identification of Novel Salivary Metabolite Biomarkers for Oral Squamous Cell Carcinoma Using Untargeted UHPLC-MS/MS Metabolomic Profiling. 使用非靶向UHPLC-MS/MS代谢组学分析鉴定口腔鳞状细胞癌的新型唾液代谢物生物标志物

IF 2.4 4区生物学

Molecular omics Pub Date : 2026-10-19 DOI: 10.1093/molecular-omics/aaiag024

Asha Selvaraj, Alycia Devasagayam, Stalin Selvaraj

{"title":"Identification of Novel Salivary Metabolite Biomarkers for Oral Squamous Cell Carcinoma Using Untargeted UHPLC-MS/MS Metabolomic Profiling.","authors":"Asha Selvaraj, Alycia Devasagayam, Stalin Selvaraj","doi":"10.1093/molecular-omics/aaiag024","DOIUrl":"https://doi.org/10.1093/molecular-omics/aaiag024","url":null,"abstract":"This study aimed to identify candidate salivary metabolites for differentiating oral squamous cell carcinoma (OSCC) patients from healthy controls. Untargeted metabolomics was performed using an Orbitrap UHPLC-MS/MS system on saliva samples from nine OSCC patients and nine healthy controls following ethical approval. A total of 1,105 metabolite features, including those detected in quality control samples, were identified. Sequential filtering to exclude non-endogenous or non-human-associated compounds retained 291 endogenous metabolites. Following further preprocessing, 75 metabolite features were subjected to downstream statistical analysis using MetaboAnalyst 6.0. Of these, 34 metabolites exhibited differential abundance based on a nominal p value < 0.05 and a fold-change threshold of >1.2, comprising 21 upregulated and 13 downregulated metabolites. The ten most significantly upregulated metabolites were prioritized for further evaluation. L-iditol, lignoceric acid, D-glucose 1-phosphate, ManGlcNAc2, and Man3GlcNAc2 emerged as candidate discriminatory features. Receiver operating characteristic (ROC) analysis demonstrated promising discriminatory performance, with a three-metabolite panel comprising Man3GlcNAc2, lignoceric acid, and ManGlcNAc2 achieving an area under the curve (AUC) of 1.0 within this discovery cohort. Nevertheless, this apparently perfect discrimination should be interpreted cautiously because of the small sample size, potential overfitting, and exploratory nature of the analysis. The identified metabolites represent preliminary candidate biomarkers rather than clinically validated diagnostic markers. Larger independent cohorts, appropriate disease-control groups, and targeted analytical validation are essential to establish their reproducibility, disease specificity, and potential clinical utility for OSCC detection and monitoring.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224621","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

Reference-based cell type deconvolution using self-supervised contrastive learning in spatial transcriptomics with ctdecon. 基于参考的细胞类型反卷积在Ctdecon空间转录组学中的应用。

IF 2.4 4区生物学

Molecular omics Pub Date : 2026-09-21 DOI: 10.1093/molecular-omics/aaiag023

Jing Lin, Aijing Feng, Yankun Cao, Yuan Chen, Zhiyi Wang, Zhi Liu, Xian Zhao

{"title":"Reference-based cell type deconvolution using self-supervised contrastive learning in spatial transcriptomics with ctdecon.","authors":"Jing Lin, Aijing Feng, Yankun Cao, Yuan Chen, Zhiyi Wang, Zhi Liu, Xian Zhao","doi":"10.1093/molecular-omics/aaiag023","DOIUrl":"10.1093/molecular-omics/aaiag023","url":null,"abstract":"It is important to analyse the cell types in the spatial domain at the single-cell resolution, especially in spatial transcriptomics (ST). It is also key to present the cell types distributed in the spatial domain. Here, we introduce ctdecon, a module constructed by neural network algorithm, which can solve the problem of heavy mixing of multiple cell type signals within individual spatial spots and obtain the reasonable proportion of cell types in each spatial site. It uses the cell types referenced by scRNA-seq to quantify the proportion of cell types in ST, which greatly improves the performance. Different from the existing methods that only rely on gene expression, ctdecon integrates the spatial correlation of cell types to improve the performance of deconvolution, and yields consistent results relative to traditional methods in solving mixed cell types. Ctdecon can minimize the reconstruction error while maintaining biological rationality and ensure the generalization ability of technical noise. In addition, ctdecon can directly provide a cell type map with spatial resolution, which can directly identify the location and proportion of cell distribution.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081184","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

Baseline cellular state shapes the molecular impact of mutant Kirsten rat sarcoma viral oncogene homologue (KRAS) alleles in reconstituted pancreatic cancer cells. 在重建的胰腺癌细胞中，基线细胞状态塑造突变KRAS等位基因的分子影响。

IF 2.4 4区生物学

Molecular omics Pub Date : 2026-09-21 DOI: 10.1093/molecular-omics/aaiag022

Yanixa Quiñones-Avilés, Barbora Salovska, Cassandra S Markham, Yi Di, Benjamin E Turk, Yansheng Liu, Mandar Deepak Muzumdar

{"title":"Baseline cellular state shapes the molecular impact of mutant Kirsten rat sarcoma viral oncogene homologue (KRAS) alleles in reconstituted pancreatic cancer cells.","authors":"Yanixa Quiñones-Avilés, Barbora Salovska, Cassandra S Markham, Yi Di, Benjamin E Turk, Yansheng Liu, Mandar Deepak Muzumdar","doi":"10.1093/molecular-omics/aaiag022","DOIUrl":"10.1093/molecular-omics/aaiag022","url":null,"abstract":"Kirsten rat sarcoma viral oncogene homologue (KRAS) is mutated in over 90% of pancreatic ductal adenocarcinomas (PDAC), where hotspot alterations in codons 12, 13, and 61 drive tumour initiation and progression. Although distinct biochemical properties have been described for individual KRAS mutants, whether they generate unique allele-specific signalling programmes in PDAC cells remains unresolved. Here, we systematically interrogated the molecular consequences of seven common KRAS mutant variants in reconstituted isogenic, KRAS-deficient PDAC cell lines by integrated transcriptomic, proteomic, and phosphoproteomic profiling. We found that baseline cellular state, rather than allele identity, was the predominant driver of molecular variation. Comparisons with established KRAS reference signatures revealed significant but moderate overlap at the mRNA level and less so at the proteome level. Pathway analyses highlighted the interferon response and mitochondrial translation-related proteins as recurrently altered across mutant alleles, while phosphoproteomic data confirmed robust extracellular signal-regulated kinase 1/2 (ERK1/2) activity and the suppression of dual-specificity tyrosine phosphorylation-regulated kinase substrates by mutant KRAS expression. Importantly, no robust mutant allele-specific molecular programmes were identified in our KRAS-reconstituted cell lines. Together, our study establishes a comprehensive multi-omics resource for KRAS signalling in PDAC and demonstrates that cellular context exerts a stronger influence than allele identity in shaping molecular profiles, with implications for interpreting putative allele-specific signalling dependencies.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920070","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

Proteomic analysis reveals a metabolic switch and cellular remodelling in pancreatic-like cell spheroids cocultured with hepatocyte-like cells using an interconnected liver-pancreas-on-chip system. 蛋白质组学分析揭示了胰腺样细胞球体与肝细胞样细胞共培养的代谢开关和细胞重塑，使用相互连接的肝脏-胰腺芯片系统。

IF 2.4 4区生物学

Molecular omics Pub Date : 2026-09-21 DOI: 10.1093/molecular-omics/aaiag021

Amal Essaouiba, Jérôme Vicogne, Alexandre Stella, Mathieu Danoy, Anne Gonzalez de Peredo, Cécile Legallais, Yasuyuki Sakai, Rachid Jellali, Eric Leclerc

{"title":"Proteomic analysis reveals a metabolic switch and cellular remodelling in pancreatic-like cell spheroids cocultured with hepatocyte-like cells using an interconnected liver-pancreas-on-chip system.","authors":"Amal Essaouiba, Jérôme Vicogne, Alexandre Stella, Mathieu Danoy, Anne Gonzalez de Peredo, Cécile Legallais, Yasuyuki Sakai, Rachid Jellali, Eric Leclerc","doi":"10.1093/molecular-omics/aaiag021","DOIUrl":"10.1093/molecular-omics/aaiag021","url":null,"abstract":"Systemic interactions between the liver and pancreas are critical for regulating lipid and carbohydrate homeostasis. These organs are also deeply interdependent in pathological conditions such as insulin resistance, where the liver fails to respond appropriately to insulin stimulation, leading to dysfunction in both organs. To investigate the crosstalk between these tissues using human models, we developed an advanced organ-on-chip (OoC) device hosting human induced pluripotent stem cell-derived liver and pancreatic tissues. The proteomic response of pancreatic-like cell spheroids cocultured with hepatocyte-like cells was characterized. We observed that the presence of liver tissue enhanced the synthesis of proteins associated with extracellular matrix remodelling, inflammatory responses, and pro-apoptotic signalling in pancreatic cells. Conversely, monocultures of pancreatic cells exhibited a higher abundance of proteins involved in fatty acid metabolism, glycolysis, and the citrate cycle. Key pancreatic markers (GCG, TPH1, SCGN3, SCGN, CHGA, CHGB) were upregulated in monocultures, while no reduction was observed in the secretion of pancreatic hormones (IGF2, GHRL, and C-peptide). Overall, our results suggest a metabolic switch in cocultures, accompanied by cellular stress and moderate alterations in pancreatic secretion. These findings provide insights into liver-pancreas crosstalk and may guide the design of future multicellular OoC models.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818987","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

Rapid serum proteome profiling of glycation and N-glycosylation in women with a history of gestational diabetes. 妊娠期糖尿病患者糖基化和n -糖基化的快速血清蛋白质组学分析。

IF 2.4 4区生物学

Molecular omics Pub Date : 2026-07-14 DOI: 10.1093/molecular-omics/aaiag020

Philip To, Shruti Kale, Sadie Partlow, Kristina Wallenius, Agneta Holmäng, Ulrika Andersson-Hall, Erik L Allman, Sonja Hess, H Sophia Chung

引用次数: 0

Elevated urea levels in human frontotemporal dementia and amyotrophic lateral sclerosis post-mortem brain tissue: evidence of a multi-dementia pathogenic mechanism. 人类额颞叶痴呆和肌萎缩侧索硬化症死后脑组织中尿素水平升高：多重痴呆致病机制的证据。

IF 2.4 4区生物学

Molecular omics Pub Date : 2026-07-14 DOI: 10.1093/molecular-omics/aaiag019

Sasha A Philbert, Stephanie J Church, Richard D Unwin, Garth J S Cooper

{"title":"Elevated urea levels in human frontotemporal dementia and amyotrophic lateral sclerosis post-mortem brain tissue: evidence of a multi-dementia pathogenic mechanism.","authors":"Sasha A Philbert, Stephanie J Church, Richard D Unwin, Garth J S Cooper","doi":"10.1093/molecular-omics/aaiag019","DOIUrl":"10.1093/molecular-omics/aaiag019","url":null,"abstract":"Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) represent two neurodegenerative diseases on opposite sides of a movement disorder continuum. However, like many other neurodegenerative diseases, the molecular pathogenesis of FTD and ALS is not fully understood. Our group has previously reported evidence for a pervasive elevation of brain urea levels in five other dementia-causing diseases. However, brain urea levels have yet to be measured in ALS and FTD. Here, we employed ultra-high-performance liquid chromatography-tandem mass spectrometry to characterize brain urea differences between control (n = 14/12) and ALS/FTD (FTD: n = 8/9; ALS: n = 13/14) cases in post-mortem tissue from two brain regions with different levels of neuropathological burden (high versus low). Elevated urea levels were observed in both the frontal cortex (high neuropathological burden) and primary visual cortex (low neuropathological burden) in cases with FTD. Contrastingly, in cases with ALS, elevated urea was observed in the primary motor cortex (high neuropathological burden), but not the dentate nucleus (low neuropathological burden). These results not only suggest that elevated urea levels are also present in ALS and FTD but imply that elevated brain urea is linked to a multi-dementia pathogenic mechanism. In contrast to ALS, the observation of elevated urea in regions of both high and low neuropathological burden in FTD implies that this phenotype is likely widespread and, therefore, may play a larger role in the pathogenesis of disease. Such a mechanism could offer new directions for developing treatments targeting this underlying pathology.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376519","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

Platelet proteomics on less than a drop of previously frozen, non-citrate plasma. 血小板蛋白质组学检测不到一滴先前冷冻的非柠檬酸盐血浆。

IF 2.4 4区生物学

Molecular omics Pub Date : 2026-05-05 DOI: 10.1093/molecular-omics/aaiag017

Dylan Nicholas Tabang, Kathrin Korff, Kaitlin Brannon, Julia Tilburg, Komal Mandal, Arthur Viodé, Patrick W van Zalm, Arjun Ravishankar, Jin-Gyu Cheong, Oliver Schott, Ramy Arnaout, Steven Z Josefowicz, Joseph E Italiano, Hanno Steen, Kinga K Smolen

{"title":"Platelet proteomics on less than a drop of previously frozen, non-citrate plasma.","authors":"Dylan Nicholas Tabang, Kathrin Korff, Kaitlin Brannon, Julia Tilburg, Komal Mandal, Arthur Viodé, Patrick W van Zalm, Arjun Ravishankar, Jin-Gyu Cheong, Oliver Schott, Ramy Arnaout, Steven Z Josefowicz, Joseph E Italiano, Hanno Steen, Kinga K Smolen","doi":"10.1093/molecular-omics/aaiag017","DOIUrl":"10.1093/molecular-omics/aaiag017","url":null,"abstract":"Platelets are blood components not regularly analysed with proteomics due to the conventional wisdom that plasma for platelet research must be citrate-treated and freshly sampled to minimize artifactual changes. Information from platelets is complementary to plasma, specifically regarding immunophenotyping of patients with challenged immune systems due to infection or inflammation. We sought to develop a sample-sparing, high-throughput-compatible platelet proteomics workflow applicable to previously frozen, non-citrate platelet-rich plasma, in contrast to the field's standard, and test its efficacy by applying it to a COVID-19 cohort. We examined centrifugation of whole blood and platelet-rich plasma and volume requirements of plasma for platelet analysis. Platelet and platelet-poor plasma samples were analysed from a cohort of 79 patients, consisting of COVID-19 negative non-ICU and ICU controls and patients with COVID-19 over time. Conventional platelet count was successfully performed using flow cytometry on previously frozen plasma, showing minimal platelet aggregation and cell debris, demonstrating viability of previously frozen plasma for platelet proteomic analysis. Protein counts in platelets mostly mirrored trends in platelet count, except in severe COVID-19 patients within three days of admission to the ICU. Proteins dysregulated in this group compared to controls were enriched in terms related to platelet activation, phagosome, and efferocytosis. This agrees with prior reports using conventional platelet proteomics methods. Such similar findings suggest that the method developed here can utilize non-citrate, previously frozen plasma down to 0.5 μL per sample. This will make platelet proteomics studies on already collected, banked plasma samples more accessible and increase biomolecular information gained.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776383","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

Decoding the diabetic transition: a lipidomic approach for biomarker discovery in an Indian cohort. 解码糖尿病转变：在印度队列中发现生物标志物的脂质组学方法。

IF 2.4 4区生物学

Molecular omics Pub Date : 2026-05-05 DOI: 10.1093/molecular-omics/aaiag016

Sneha Singh, Rekha Nagpal, Ashutosh Kumar

{"title":"Decoding the diabetic transition: a lipidomic approach for biomarker discovery in an Indian cohort.","authors":"Sneha Singh, Rekha Nagpal, Ashutosh Kumar","doi":"10.1093/molecular-omics/aaiag016","DOIUrl":"10.1093/molecular-omics/aaiag016","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) is a significant public health burden in India, where the disease presents with unique clinical characteristics, yet data from this high-risk population remain scarce. This study aimed to conduct a lipidomic analysis to identify candidate lipid species associated with different glycemic stages using a refined untargeted lipidomics approach. A cross-sectional study of 95 individuals from Mumbai was stratified into healthy, prediabetic, newly diagnosed diabetic, and advanced diabetic groups based on glycated hemoglobin levels. An untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry approach was applied to pooled serum samples to construct a comprehensive lipid library and enable comparative profiling. A stringent filtering pipeline was implemented to ensure robust lipid identification. Our analysis identified a core lipidome of 69 species shared across all cohorts, alongside an increase in lipidomic diversity in diabetic states, with the advanced diabetic group exhibiting the highest number of unique species. Ceramides (Cer) were detected across the glycemic spectrum and exhibited a distinct remodeling pattern. Partial least squares discriminant analysis identified 20 candidate lipid species with variable importance in projection scores > 1.0, prominently including Cer, phosphatidylinositol, and hexosylceramides. Additional lipid classes of interest included sphingomyelins, triacylglycerols, acylcarnitines, and fatty acids. These hypothesis-generating findings provide a prioritized framework for future large-scale quantitative validation studies aimed at early prediction and risk stratification of T2DM in the Indian population.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691072","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

Placental metabolomics for assessment of pregnancy complications: a systematic review. 胎盘代谢组学评估妊娠并发症：一项系统综述。

IF 2.4 4区生物学

Molecular omics Pub Date : 2026-05-05 DOI: 10.1093/molecular-omics/aaiag015

Grace V Mercer, Lindsay S Cahill

{"title":"Placental metabolomics for assessment of pregnancy complications: a systematic review.","authors":"Grace V Mercer, Lindsay S Cahill","doi":"10.1093/molecular-omics/aaiag015","DOIUrl":"10.1093/molecular-omics/aaiag015","url":null,"abstract":"Metabolomics is a powerful tool for understanding biological function at the cellular level. While this omics technology has found application in areas ranging from toxicology to cancer, its potential for the study of human pregnancy complications is in its infancy. Proper placental function is critical for a healthy pregnancy and assessing placental metabolism offers a direct window into placental physiology. This review aims to analyse placental metabolomics in pregnancy complications in humans. A systematic search was completed using PubMed and Google Scholar, and the Covidence software was used for the screening process. Following title and abstract screening and full-text review, 32 articles remained and were included in this review. Multiple articles performed metabolomics using mass spectrometry and/or nuclear magnetic resonance to study pre-eclampsia, gestational hypertension, foetal growth restriction, maternal obesity, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and preterm birth. A subset of pregnancy complications was investigated in only a single study each (human immunodeficiency virus in pregnancy, neural tube defects, chromosomal disorders, chronic hypoxia, and recurrent pregnancy loss). Univariate analyses identified potential biomarkers of pregnancy complications. Multivariate analyses demonstrated that the placental global metabolic profiles could separate healthy and complicated pregnancies and identified metabolic pathways (e.g. amino acid metabolism, lipid and phospholipid metabolism) to explain pathogenesis and the mechanisms of disease. We highlight knowledge gaps and future directions, emphasizing the need for data replication and inclusion of variables such as biological sex in the field of placental metabolomics.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675129","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

Metabolite-centric identification of antimetabolite drug targets across cancer and neurodegenerative diseases. 以代谢物为中心的癌症和神经退行性疾病的抗代谢物药物靶点鉴定。

IF 2.4 4区生物学

Molecular omics Pub Date : 2026-05-05 DOI: 10.1093/molecular-omics/aaiag018

Regan Odongo, Tunahan Çakır

{"title":"Metabolite-centric identification of antimetabolite drug targets across cancer and neurodegenerative diseases.","authors":"Regan Odongo, Tunahan Çakır","doi":"10.1093/molecular-omics/aaiag018","DOIUrl":"10.1093/molecular-omics/aaiag018","url":null,"abstract":"Antimetabolites, primarily studied in cancer, are novel drugs targeting metabolic networks by mimicking and inhibiting disease-causing metabolites, enabling poly-pharmacologic effects essential for complex diseases. Moreover, predicting patients likely to positively respond to antimetabolite drugs is necessary to simplify clinical applications. However, existing computational approaches for antimetabolite target discovery lack incorporation of disease-induced metabolic state perturbations, and their applicability beyond cancer remains unexplored. We introduce MATADOR (Metabolite-centric Analysis of TArgets for Drug ORientation), a computational workflow that integrates patient-derived omic data with metabolic networks to identify, evaluate, and prioritize antimetabolite targets based on metabolic state transformation. Applying MATADOR to RNA-seq data from breast, colon, lung, and liver cancers, we achieved a 66 ± 6% sensitivity in recapturing known antimetabolite targets, strongly supported thioredoxin as a pan-cancer antimetabolite drug target, and linked top-ranked targets to poor 5-year survival in breast and liver cancers. Extending beyond cancer, MATADOR nominated metabolites with proinflammatory effects as potential antimetabolite targets in Alzheimer's and Parkinson's diseases, aligning well with their known pathological mechanisms. Finally, applying MATADOR on personalized metabolic networks, machine learning models trained on metabolic gene expression demonstrated the ability to leverage gene expression to personalize antimetabolite targets. The proposed approach may expedite prioritization and personalization of antimetabolite targets during pre-clinical studies across diseases with systemic metabolic alterations.","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840458","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