Molecular omics最新文献

{"title":"DeSciDe: a tool for unbiased literature searching and gene list curation unveils a new role for the acidic patch mutation H2A E92K","authors":"Cameron J. Douglas and Ciaran P. Seath","doi":"10.1039/D5MO00160A","DOIUrl":"10.1039/D5MO00160A","url":null,"abstract":"<p >Omics analysis has become an indispensable tool for researchers in the life sciences, enabling the study of DNA, RNA, and proteins and how they respond to cellular stimulus. Many methods of data analysis exist for the generation and characterization of gene lists, however, selection of genes for further investigation is still heavily influenced by prior knowledge, with practitioners often studying well characterized genes, reinforcing bias in the literature. Here, we have developed an open-source, R package for impartial ranking of gene lists derived from omics analysis that we term deciphering scientific discoveries (DeSciDe). We applied a pipeline that sorts a gene list first by precedence, which we define as co-occurrence of the gene with pre-defined search terms in publications. We then rank gene lists by connectivity, an underutilized metric for how related a gene is to other enriched genes. The combination of these rankings by scatterplot provides a method for gene selection by simple visual analysis. We apply this analysis method to published Omics datasets, identifying novel avenues for investigation. Further, using this method we have been able to assign a novel loss of function role for the histone mutation H2A E92K.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 760-767"},"PeriodicalIF":2.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12599656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145489182","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}

{"title":"Mapping the Helichrysum metabolome: uncovering species-specific chemistry through an AI-guided LC-MS/MS workflow","authors":"Motseoa Mariam Lephatsi, Mpho Susan Choene, Abidemi Paul Kappo, Ntakadzeni Edwin Madala and Fidele Tugizimana","doi":"10.1039/D5MO00118H","DOIUrl":"10.1039/D5MO00118H","url":null,"abstract":"<p > <em>Helichrysum</em> species, of which 35% are native to South Africa, are renowned for their diverse medicinal properties, yet their chemical composition remains largely unexplored. As such, continuous efforts are needed to comprehensively characterize the phytochemistry of <em>Helichrysum</em> species which will subsequently contribute to the discovery and exploration of <em>Helichrysum</em>-derived natural products for drug discovery. Thus, a computational metabolomics work is reported herein to comprehensively characterize the metabolic landscape of three medicinal species (<em>H. italicum</em>, <em>H. petiolare</em>, and <em>H. splendidum</em>), which are less studied. The metabolites were extracted using hexane, ethyl acetate, and methanol and analyzed on a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. Different solvents were utilized to increase metabolome coverage in <em>Helichrysum</em> species. Spectral data were mined using molecular networking (MN) strategies. The results revealed that multiple extraction methods provide a more comprehensive analysis of the metabolome of the three plants. The measured metabolome of <em>Helichrysum</em> species is rich in phenylpropanoids, lipids and lipid-like molecules, pointing to a rich chemistry with potential bioactivities. Comparative analysis of the <em>H. italicum</em>, <em>H. petiolare</em> and <em>H. splendidum</em> metabolomes revealed that the flavonoid glucoside and triterpenoid profiles of the three species differ distinctively. These results expand the knowledge base on the chemistry of <em>Helichrysum</em> plants and provide deconvoluted details of the various chemical classes that differentially define the metabolome of the <em>Helichrysum</em> plants. Such actionable insights point to <em>Helichrysum</em>'s potential as a valuable source of natural compounds with promising medicinal properties.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 747-759"},"PeriodicalIF":2.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/mo/d5mo00118h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482647","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}

{"title":"Hypoxia-induced alterations in lipid polyunsaturation and associated proteins drive aggressive metastasis in pancreatic cancer via the PPAR/hypoxia pathway","authors":"Prema Kumari Agarwala, Avinash Singh, Sanjeeva Srivastava and Shobhna Kapoor","doi":"10.1039/D5MO00111K","DOIUrl":"10.1039/D5MO00111K","url":null,"abstract":"<p >In pancreatic ductal adenocarcinoma, hypoxia is a crucial component of the tumour microenvironment and is associated with worse clinical outcomes. Adaptation to extreme hypoxic settings is based on abnormal lipid metabolism, but insights into how hypoxia-regulated lipid changes link with aggressive migratory potential in pancreatic cancer are lacking. This study investigates the molecular processes, pathways, and critical proteins involved in hypoxia-induced lipidic and polyunsaturated fatty acid alterations in pancreatic cancer. Our findings elucidate increased multilayer unsaturation in FA chains of major lipid classes associated with greater migration and invasion, as well as higher abundances of particular desaturases. The expression of these proteins was verified in clinical tumour samples by unsaturated fatty acid biosynthesis-related gene enrichment score. High unsaturated fatty acid clusters were shown to be associated with a low survival rate. Pathway correlation and protein–protein interaction analysis indicated that the PPAR-hypoxia axis and SCD/FADS2/APOC3-HDLBP protein network are implicated in mediating the observed alterations in lipid pools and poly-unsaturation levels in pancreatic cancer under hypoxia. These results provide novel therapeutic targets in pancreatic cancer while improving our understanding of hypoxia-induced migratory potential in pancreatic cancer.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 736-746"},"PeriodicalIF":2.4,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438422","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}

{"title":"Global spinal cord peptidome profiling in response to osteoarthritis in rats","authors":"Gaoyuan Lu, Marilyn Frézier, Colombe Otis, Vu Ngoc Huong Tran, Bertrand Lussier, Guillaume Saint-Jean, Helene Beaudry, Eric Troncy and Lingjun Li","doi":"10.1039/D5MO00152H","DOIUrl":"10.1039/D5MO00152H","url":null,"abstract":"<p >Osteoarthritis (OA) is a complex and increasingly prevalent condition, affecting an estimated 600 million people worldwide and significantly reducing quality of life. Understanding OA as both an inflammatory and neurological disease presents challenges for diagnosis and treatment, as no curative therapy is currently available. The neuroactive effects of OA pain on neuropeptide systems, particularly within the spinal cord, remain underexplored, impeding therapeutic advances. Mass spectrometry (MS) was employed to characterize the spinal cord peptidome in a validated rat model of OA pain. The peptidome was analyzed longitudinally over 84 days using the Montreal Induction of Rat Arthritis Testing (MI-RAT©; <em>n</em> = 20) model, compared to arthrotomic (Sham; <em>n</em> = 4) and healthy (Naive; <em>n</em> = 9) groups. Label-free peptidome profiling using liquid chromatography coupled with tandem MS (LC-MS/MS) revealed dynamic changes in endogenous spinal peptides during OA progression, leading to the identification of 624 peptides derived from 29 prohormone precursors. The findings reveal substantial changes in peptide levels in the spinal cord, particularly involving neuropeptide substance P and peptides derived from proenkephalin, calcitonin gene-related peptide, and somatostatin. These results provide novel insights into the molecular mechanisms underlying OA-associated pain and identify potential targets for new therapeutic interventions in neurological pain conditions.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 645-656"},"PeriodicalIF":2.4,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145391689","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}

{"title":"Nucleolin perturbation alters membrane lipid homeostasis","authors":"Eitan Erez Zahavi, Ida Rishal, Juan A. Oses-Prieto, Alexander Brandis, Sergey Malitsky, Maxim Itkin, Šárka Pokorná, Florencia Cabrera-Cabrera, Natjan-Naatan Seeba, Robert Risti, Aivar Lõokene, Anthony H. Futerman, Alma L. Burlingame, Mike Fainzilber and Indrek Koppel","doi":"10.1039/D5MO00088B","DOIUrl":"10.1039/D5MO00088B","url":null,"abstract":"<p >AS1411 is a G-rich DNA aptamer that targets the multifunctional RNA-binding protein nucleolin. AS1411 has both antiproliferative and cell size-regulating activities and has been evaluated for clinical utility, reaching phase II trials as an anticancer agent. The mechanisms underlying cell size effects of AS1411 are not well understood and broad characterization of its molecular effects is lacking. Here, we used a multi-omics approach to profile transcriptome, proteome and lipidome changes in AS1411-treated NIH-3T3 cells, which increase in size in response to the aptamer. We found that AS1411 caused downregulation of cholesterol biosynthesis pathway enzymes at both mRNA and protein levels, without an accompanying reduction in cellular cholesterol levels or cholesterol uptake. In addition, AS1411 induced changes in several lipid classes, including increases in phosphatidylethanolamine levels. Ratiometric imaging of Di-4-ANEPPS-labeled cells showed that AS1411 decreases the fluidity of intracellular membranes. Thus, aptamer engagement of nucleolin affects lipid biosynthesis and homeostasis, likely contributing to its roles in cell size control.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 723-735"},"PeriodicalIF":2.4,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12560814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145378130","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}

{"title":"Mass spectrometry-based profiling of phosphoinositide: advances, challenges, and future directions","authors":"Yuki Ishino, Yuta Shimanaka, Junken Aoki and Nozomu Kono","doi":"10.1039/D5MO00115C","DOIUrl":"10.1039/D5MO00115C","url":null,"abstract":"<p >Phosphoinositides (PIPs), the phosphorylated derivatives of phosphatidylinositol (PI), are low-abundance yet critical components of eukaryotic membranes. They play pivotal roles in a wide array of cellular processes, including signal transduction, membrane trafficking, and cell motility. The seven PIP subclasses, generated by phosphorylation at the 3-, 4-, and 5-positions of the inositol ring, are tightly regulated in both spatial and temporal contexts. Dysregulation of PIP metabolism is associated with a range of diseases, including cancer, myopathy, and neurodegenerative and developmental disorders. While the importance of phosphorylation of the inositol ring is well established, recent studies have clarified the role of the fatty acyl chain composition of PIPs. This has resulted in a growing interest in analytical techniques that can determine fatty acyl chain profiles of PIPs. Over the past three decades, substantial advances have been made in mass spectrometry-based techniques, enabling detailed characterization of PIP molecular species, including their phosphate regioisomers. This review provides an overview of the development of mass spectrometric methods for analyzing PIPs, with a particular focus on those enabling the separation of PIP regioisomers and the profiling of their acyl chain composition.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 536-544"},"PeriodicalIF":2.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/mo/d5mo00115c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145378119","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}

{"title":"The omics revolution in obesity: from molecularsignatures to clinical solutions","authors":"Mohammad Mustafa, Amr A. Arafat, Waleed Alhazzani, Faisal Kunnathodi, Sarfuddin Azmi, Riyasdeen Anvarbatcha, Ishtiaque Ahmad and Haifa F. Alotaibi","doi":"10.1039/D5MO00074B","DOIUrl":"10.1039/D5MO00074B","url":null,"abstract":"<p >Obesity is a multifactorial condition projected to affect over half of the global population by 2035, posing significant clinical and socioeconomic challenges. Traditional metrics such as body mass index lack precision in predicting individual risk, disease progression, and therapeutic response due to the heterogeneous nature of obesity. Advances in omics technologies such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics have enabled the identification of molecular subtypes and candidate biomarkers that offer deeper insights into obesity pathophysiology. Genomic studies have revealed hundreds of loci associated with obesity related traits, while polygenic risk scores offer modest improvements in early risk prediction. Epigenomic profiling, particularly deoxy ribose nucleic acid (DNA) methylation signatures such as those at carnitine palmitoyl transferase 1A (<em>CPT1A</em>) and hypoxia inducible factor 3 subunit alpha (<em>HIF3A</em>), has uncovered modifiable pathways linked to adiposity and metabolic dysfunction. These findings are increasingly being integrated with other omics layers to improve stratification and therapeutic targeting. Metabolomic subtypes, including ceramide driven insulin resistance and branched chain amino acid (BCAA) dominant dysregulation, have shown potential in guiding treatment selection, such as sodium glucose cotransporter 2 (SGLT2) inhibitors or glucagon like peptide-1 (GLP-1) agonists. Proteomic markers like proprotein convertase subtilisin/kexin type 9 (<em>PCSK9</em>) and retinol binding protein 4 (<em>RBP4</em>) are being evaluated for cardiovascular risk stratification independent of body mass index (BMI). Integrative multiomics frameworks and AI driven models are beginning to bridge molecular data with clinical phenotypes, enabling patient stratification and risk modeling. However, most findings remain in research grade environments, and clinical translation is limited by cohort diversity, data harmonization challenges, and the lack of standardized validation protocols. This review synthesizes evidence from single and multiomics studies, highlights emerging biomarkers and molecular subtypes, and discusses the potential of omics guided frameworks to inform precision obesity care.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 582-593"},"PeriodicalIF":2.4,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355278","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}

{"title":"Cytokine-induced memory-like responses in endothelial cells link chronic inflammation to vascular disease risk","authors":"Kieu T. T. Le, Nick Keur, Heleen Middelkamp, Thuy Linh Do, Albert van den Berg, Valeria Orlova, Leo A.B. Joosten, Mihai G. Netea, Cisca Wijmenga, Iris Jonkers, Sebo Withoff, Andries D. Van der Meer and Vinod Kumar","doi":"10.1039/D5MO00136F","DOIUrl":"10.1039/D5MO00136F","url":null,"abstract":"<p >Chronic inflammation plays a central role in the progression of both infectious and vascular diseases, yet its impact on endothelial cells (ECs), which form the interface between blood and tissue, remains poorly understood. Given their constant exposure to inflammatory cytokines such as TNF-α and IFN-γ, we set out to investigate how cytokine induced inflammation shapes EC function at the molecular level. Using primary human umbilical vein endothelial cells (HUVECs), we modeled repeated cytokine exposure to simulate a chronically inflamed microenvironment. Transcriptomic and epigenetic profiling revealed that ECs respond to this chronic stimulation with durable transcriptional and chromatin changes. These responses included phenotypes resembling immune cell priming, training, and tolerance, which are commonly associated with innate immune memory, a phenomenon whereby innate immune cells mount altered responses following previous stimulation. Although we did not observe classical trained immunity pathways, several genes known to mediate immune training, including <em>TLR2</em>, <em>IL1B</em>, and <em>HDAC9</em>, exhibited enhanced activation following TNF-α re-exposure. IFN-γ stimulation uniquely induced sustained expression and chromatin accessibility at MHC class II loci, suggesting cytokine-specific modes of reprogramming. Functionally, re-stimulated ECs exhibited enhanced monocyte adhesion in a 3D vessel-on-chip model, highlighting the relevance of these molecular changes to vascular inflammation. Moreover, the regulatory regions altered by cytokine exposure were enriched for disease-associated SNPs, particularly those linked to COVID-19, sepsis, and cardiovascular disorders. In summary, these findings reveal that repeated exposure to cytokines as seen in chronic inflammation can induce memory-like responses in ECs and suggest that endothelial reprogramming may contribute to vascular dysfunction.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 706-722"},"PeriodicalIF":2.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286263","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}

{"title":"An altered proteome in ovarian cancer stem-like cells: profiling of the mDivi-1 induced proteome and its clinical significance","authors":"Manita Raina, Tejan Lodhiya, Rahail Ashraf, Kalpana Tankay, Arunaja K., Raju Mukherjee and Sanjay Kumar","doi":"10.1039/D5MO00098J","DOIUrl":"10.1039/D5MO00098J","url":null,"abstract":"<p >A three-dimensional (3D) spheroid culture mimics <em>in vivo</em> conditions and reproduces the tumor microenvironment, thus providing more physiological relevance to disease conditions. Mapping the proteome profile in 3D-cultured ovarian cancer (OC) spheroids helps identify novel and potential therapeutic targets in ovarian cancer stem cells. We used mass-spectrometry-based comparative proteome profiling for two-dimensional (2D)-cultured adherent and 3D-cultured OC spheroids and identified 94 upregulated and 54 downregulated proteins in 3D-cultured A2780 spheroids compared to 2D-cultured adherent A2780 cells. In SKOV-3 cells, we identified 127 upregulated proteins and 192 downregulated proteins in 3D-cultured spheroids compared to 2D-cultured adherent cells. The differentially expressed proteins were enriched in proteins regulating oxidative phosphorylation, the acetyl-CoA metabolic process, RNA polymerase core enzyme binding, and growth factor binding. In addition, we also mapped the proteome profile after the treatment with a mitochondrial fission inhibitor, mDivi-1, of 3D-cultured cells and defined the correlation between significantly upregulated and downregulated genes and their association with the progression-free survival of OC patients.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 621-632"},"PeriodicalIF":2.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252051","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}

{"title":"Multi-omics data integration for topology-based pathway activation assessment and personalized drug ranking","authors":"Nicolas Borisov, Yaroslav Ilnytsky, Boseon Byeon, Olga Kovalchuk and Igor Kovalchuk","doi":"10.1039/D5MO00151J","DOIUrl":"10.1039/D5MO00151J","url":null,"abstract":"<p >Although multi-omics analysis is popular for revealing diverse physiological effects and biomarkers in many branches of state-of-the-art molecular and cell biology and bioinformatics, there is still no consensus on a gold standard protocol for the integration of various multi-omics profiles into a uniformly shaped system bioinformatics platform. In the current study, we performed the integration of data on DNA methylation, and the expression of coding RNA (mRNA), micro-RNA (miRNA), and long non-coding RNA into a joint platform for calculation of signaling pathway impact analysis (SPIA) and drug efficiency index (DEI). We found that the mirrored and balanced DEI values fitted the DNA methylome data better than the original DEI. Additionally, the protein-coding mRNA-based values correlated more strongly with antisense lncRNA-based values than with miRNA-based values. The whole correlation between the mRNA-based and antisense lncRNA-based values was generally positive. This platform allowed integrative analysis of several levels of gene expression regulation of protein-coding genes and their regulators, including methylation and noncoding RNAs.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 678-689"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/mo/d5mo00151j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200260","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}