Molecular omics最新文献

{"title":"An adaptable in silico ensemble model of the arachidonic acid cascade†","authors":"Megan Uttley, Grace Horne, Areti Tsigkinopoulou, Francesco Del Carratore, Aliah Hawari, Magdalena Kiezel-Tsugunova, Alexandra C. Kendall, Janette Jones, David Messenger, Ranjit Kaur Bhogal, Rainer Breitling and Anna Nicolaou","doi":"10.1039/D3MO00187C","DOIUrl":"10.1039/D3MO00187C","url":null,"abstract":"<p >Eicosanoids are a family of bioactive lipids, including derivatives of the ubiquitous fatty acid arachidonic acid (AA). The intimate involvement of eicosanoids in inflammation motivates the development of predictive <em>in silico</em> models for a systems-level exploration of disease mechanisms, drug development and replacement of animal models. Using an ensemble modelling strategy, we developed a computational model of the AA cascade. This approach allows the visualisation of plausible and thermodynamically feasible predictions, overcoming the limitations of fixed-parameter modelling. A quality scoring method was developed to quantify the accuracy of ensemble predictions relative to experimental data, measuring the overall uncertainty of the process. Monte Carlo ensemble modelling was used to quantify the prediction confidence levels. Model applicability was demonstrated using mass spectrometry mediator lipidomics to measure eicosanoids produced by HaCaT epidermal keratinocytes and 46BR.1N dermal fibroblasts, treated with stimuli (calcium ionophore A23187), (ultraviolet radiation, adenosine triphosphate) and a cyclooxygenase inhibitor (indomethacin). Experimentation and predictions were in good qualitative agreement, demonstrating the ability of the model to be adapted to cell types exhibiting differences in AA release and enzyme concentration profiles. The quantitative agreement between experimental and predicted outputs could be improved by expanding network topology to include additional reactions. Overall, our approach generated an adaptable, tuneable ensemble model of the AA cascade that can be tailored to represent different cell types and demonstrated that the integration of <em>in silico</em> and <em>in vitro</em> methods can facilitate a greater understanding of complex biological networks such as the AA cascade.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/mo/d3mo00187c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141253056","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":"Understanding pulmonary hypertension: the need for an integrative metabolomics and transcriptomics approach","authors":"Priyanka Choudhury, Sanjukta Dasgupta, Parthasarathi Bhattacharyya, Sushmita Roychowdhury and Koel Chaudhury","doi":"10.1039/D3MO00266G","DOIUrl":"10.1039/D3MO00266G","url":null,"abstract":"<p >Pulmonary hypertension (PH), characterised by mean pulmonary arterial pressure (mPAP) &gt;20 mm Hg at rest, is a complex pathophysiological disorder associated with multiple clinical conditions. The high prevalence of the disease along with increased mortality and morbidity makes it a global health burden. Despite major advances in understanding the disease pathophysiology, much of the underlying complex molecular mechanism remains to be elucidated. Lack of a robust diagnostic test and specific therapeutic targets also poses major challenges. This review provides a comprehensive update on the dysregulated pathways and promising candidate markers identified in PH patients using the transcriptomics and metabolomics approach. The review also highlights the need of using an integrative multi-omics approach for obtaining insight into the disease at a molecular level. The integrative multi-omics/pan-omics approach envisaged to help in bridging the gap from genotype to phenotype is outlined. Finally, the challenges commonly encountered while conducting omics-driven studies are also discussed.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141148744","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":"Species-level identification of enterotype-specific microbial markers for colorectal cancer and adenoma†","authors":"Ünzile Güven Gülhan, Emrah Nikerel, Tunahan Çakır, Fatih Erdoğan Sevilgen and Saliha Durmuş","doi":"10.1039/D4MO00016A","DOIUrl":"10.1039/D4MO00016A","url":null,"abstract":"<p >Enterotypes have been shown to be an important factor for population stratification based on gut microbiota composition, leading to a better understanding of human health and disease states. Classifications based on compositional patterns will have implications for personalized microbiota-based solutions. There have been limited enterotype based studies on colorectal adenoma and cancer. Here, an enterotype-based meta-analysis of fecal shotgun metagenomic studies was performed, including 1579 samples of healthy controls (CTR), colorectal adenoma (ADN) and colorectal cancer (CRC) in total. Gut microbiota of healthy people were clustered into three enterotypes (<em>Ruminococcus</em>-, <em>Bacteroides</em>- and <em>Prevotella</em>-dominated enterotypes). Reference-based enterotype assignments were performed for CRC and ADN samples, using the supervised machine learning algorithm, K-nearest neighbors. Differential abundance analyses and random forest classification were conducted on each enterotype between healthy controls and CRC–ADN groups, revealing novel enterotype-specific microbial markers for non-invasive CRC screening strategies. Furthermore, we identified microbial species unique to each enterotype that play a role in the production of secondary bile acids and short-chain fatty acids, unveiling the correlation between cancer-associated gut microbes and dietary patterns. The enterotype-based approach in this study is promising in elucidating the mechanisms of differential gut microbiome profiles, thereby improving the efficacy of personalized microbiota-based solutions.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140929577","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":"Metabolomic approaches to dissect dysregulated metabolism in the progression of pre-diabetes to T2DM†","authors":"Wenrui Ji, Xiaomin Xie, Guirong Bai, Yanting He, Ling Li, Li Zhang and Dan Qiang","doi":"10.1039/D3MO00130J","DOIUrl":"10.1039/D3MO00130J","url":null,"abstract":"<p >Many individuals with pre-diabetes eventually develop diabetes. Therefore, profiling of prediabetic metabolic disorders may be an effective targeted preventive measure. We aimed to elucidate the metabolic mechanism of progression of pre-diabetes to type 2 diabetes mellitus (T2DM) from a metabolic perspective. Four sets of plasma samples (20 subjects per group) collected according to fasting blood glucose (FBG) concentration were subjected to metabolomic analysis. An integrative approach of metabolome and WGCNA was employed to explore candidate metabolites. Compared with the healthy group (FBG &lt; 5.6 mmol L<small>⁻¹</small>), 113 metabolites were differentially expressed in the early stage of pre-diabetes (5.6 mmol L<small>⁻¹</small> ⩽ FBG &lt; 6.1 mmol L<small>⁻¹</small>), 237 in the late stage of pre-diabetes (6.1 mmol L<small>⁻¹</small> ⩽ FBG &lt; 7.0 mmol L<small>⁻¹</small>), and 245 in the T2DM group (FBG <img> 7.0 mmol L<small>⁻¹</small>). A total of 27 differentially expressed metabolites (DEMs) were shared in all comparisons. Among them, <small>L</small>-norleucine was downregulated, whereas ethionamide, oxidized glutathione, 5-methylcytosine, and alpha-<small>D</small>-glucopyranoside beta-<small>D</small>-fructofuranosyl were increased with the rising levels of FBG. Surprisingly, 15 (11 lyso-phosphatidylcholines, <small>L</small>-norleucine, oxidized glutathione, arachidonic acid, and 5-oxoproline) of the 27 DEMs were ferroptosis-associated metabolites. WGCNA clustered all metabolites into 8 modules and the pathway enrichment analysis of DEMs showed a significant annotation to the insulin resistance-related pathway. Integrated analysis of DEMs, ROC and WGCNA modules determined 12 potential biomarkers for pre-diabetes and T2DM, including <small>L</small>-norleucine, 8 of which were <small>L</small>-arginine or its metabolites. <small>L</small>-Norleucine and <small>L</small>-arginine could serve as biomarkers for pre-diabetes. The inventory of metabolites provided by our plasma metabolome offers insights into T2DM physiology metabolism.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/mo/d3mo00130j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829963","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":"A blood-based multi-omic landscape for the molecular characterization of kidney stone disease†","authors":"Weibing Pan‡, Tianwei Yun, Xin Ouyang, Zhijun Ruan, Tuanjie Zhang, Yuhao An, Rui Wang and Peng Zhu","doi":"10.1039/D3MO00261F","DOIUrl":"10.1039/D3MO00261F","url":null,"abstract":"<p >Kidney stone disease (KSD, also named renal calculi, nephrolithiasis, or urolithiasis) is a common urological disease entailing the formation of minerals and salts that form inside the urinary tract, frequently caused by diabetes, high blood pressure, hypertension, and monogenetic components in most patients. 10% of adults worldwide are affected by KSD, which continues to be highly prevalent and with increasing incidence. For the identification of novel therapeutic targets in KSD, we adopted high-throughput sequencing and mass spectrometry (MS) techniques in this study and carried out an integrative analysis of exosome proteomic data and DNA methylation data from blood samples of normal and KSD individuals. Our research delineated the profiling of exosomal proteins and DNA methylation in both healthy individuals and those afflicted with KSD, finding that the overexpressed proteins and the demethylated genes in KSD samples are associated with immune responses. The consistency of the results in proteomics and epigenetics supports the feasibility of the comprehensive strategy. Our insights into the molecular landscape of KSD pave the way for a deeper understanding of its pathogenic mechanism, providing an opportunity for more precise diagnosis and targeted treatment strategies for KSD.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140577667","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":"PerSEveML: a web-based tool to identify persistent biomarker structure for rare events using an integrative machine learning approach†","authors":"Sreejata Dutta, Dinesh Pal Mudaranthakam, Yanming Li and Mihaela E. Sardiu","doi":"10.1039/D4MO00008K","DOIUrl":"10.1039/D4MO00008K","url":null,"abstract":"<p >Omics data sets often pose a computational challenge due to their high dimensionality, large size, and non-linear structures. Analyzing these data sets becomes especially daunting in the presence of rare events. Machine learning (ML) methods have gained traction for analyzing rare events, yet there has been limited exploration of bioinformatics tools that integrate ML techniques to comprehend the underlying biology. Expanding upon our previously developed computational framework of an integrative machine learning approach, we introduce PerSEveML, an interactive web-based tool that uses crowd-sourced intelligence to predict rare events and determine feature selection structures. PerSEveML provides a comprehensive overview of the integrative approach through evaluation metrics that help users understand the contribution of individual ML methods to the prediction process. Additionally, PerSEveML calculates entropy and rank scores, which visually organize input features into a persistent structure of selected, unselected, and fluctuating categories that help researchers uncover meaningful hypotheses regarding the underlying biology. We have evaluated PerSEveML on three diverse biologically complex data sets with extremely rare events from small to large scale and have demonstrated its ability to generate valid hypotheses. PerSEveML is available at https://biostats-shinyr.kumc.edu/PerSEveML/ and https://github.com/sreejatadutta/PerSEveML.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/mo/d4mo00008k?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140577568","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":"Intact cell lipidomics using the Bruker MBT lipid Xtract assay allows the rapid detection of glycosyl-inositol-phospho-ceramides from Aspergillus fumigatus†","authors":"Aishani Chakraborty, Leila Alsharqi, Markus Kostrzewa, Darius Armstrong-James and Gerald Larrouy-Maumus","doi":"10.1039/D4MO00030G","DOIUrl":"10.1039/D4MO00030G","url":null,"abstract":"<p >Glycosyl-inositol-phospho-ceramides (GIPCs) or glycosylphosphatidylinositol-anchored fungal polysaccharides are major lipids in plant and fungal plasma membranes and play an important role in stress adaption. However, their analysis remains challenging due to the multiple steps involved in their extraction and purification prior to mass spectrometry analysis. To address this challenge, we report here a novel simplified method to identify GIPCs from <em>Aspergillus fumigatus</em> using the new Bruker MBT lipid Xtract assay. <em>A. fumigatus</em> reference strains and clinical isolates were cultured, harvested, heat-inactivated and suspended in double-distilled water. A fraction of this fungal preparation was then dried in a microtube, mixed with an MBT lipid Xtract matrix (Bruker Daltonik, Germany) and loaded onto a MALDI target plate. Analysis was performed using a Bruker MALDI Biotyper Sirius system in the linear negative ion mode. Mass spectra were scanned from <em>m</em>/<em>z</em> 700 to <em>m</em>/<em>z</em> 2 000. MALDI-TOF MS analysis of cultured fungi showed a clear signature of GIPCs in <em>Aspergillus fumigatus</em> reference strains and clinical isolates. Here, we have demonstrated that routine MALDI-TOF in the linear negative ion mode combined with the MBT lipid Xtract is able to detect <em>Aspergillus fumigatus</em> GIPCs.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/mo/d4mo00030g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140316240","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":"Implementation of multiomic mass spectrometry approaches for the evaluation of human health following environmental exposure","authors":"Christina R. Ferreira, Paulo Clairmont F. de Lima Gomes, Kiley Marie Robison‡, Bruce R. Cooper‡ and Jonathan H. Shannahan","doi":"10.1039/D3MO00214D","DOIUrl":"10.1039/D3MO00214D","url":null,"abstract":"<p >Omics analyses collectively refer to the possibility of profiling genetic variants, RNA, epigenetic markers, proteins, lipids, and metabolites. The most common analytical approaches used for detecting molecules present within biofluids related to metabolism are vibrational spectroscopy techniques, represented by infrared, Raman, and nuclear magnetic resonance (NMR) spectroscopies and mass spectrometry (MS). Omics-based assessments utilizing MS are rapidly expanding and being applied to various scientific disciplines and clinical settings. Most of the omics instruments are operated by specialists in dedicated laboratories; however, the development of miniature portable omics has made the technology more available to users for field applications. Variations in molecular information gained from omics approaches are useful for evaluating human health following environmental exposure and the development and progression of numerous diseases. As MS technology develops so do statistical and machine learning methods for the detection of molecular deviations from personalized metabolism, which are correlated to altered health conditions, and they are intended to provide a multi-disciplinary overview for researchers interested in adding multiomic analysis to their current efforts. This includes an introduction to mass spectrometry-based omics technologies, current state-of-the-art capabilities and their respective strengths and limitations for surveying molecular information. Furthermore, we describe how knowledge gained from these assessments can be applied to personalized medicine and diagnostic strategies.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/mo/d3mo00214d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140316073","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":"Genome-scale metabolic models in translational medicine: the current status and potential of machine learning in improving the effectiveness of the models","authors":"Beste Turanli, Gizem Gulfidan, Ozge Onluturk Aydogan, Ceyda Kula, Gurudeeban Selvaraj and Kazim Yalcin Arga","doi":"10.1039/D3MO00152K","DOIUrl":"10.1039/D3MO00152K","url":null,"abstract":"<p >The genome-scale metabolic model (GEM) has emerged as one of the leading modeling approaches for systems-level metabolic studies and has been widely explored for a broad range of organisms and applications. Owing to the development of genome sequencing technologies and available biochemical data, it is possible to reconstruct GEMs for model and non-model microorganisms as well as for multicellular organisms such as humans and animal models. GEMs will evolve in parallel with the availability of biological data, new mathematical modeling techniques and the development of automated GEM reconstruction tools. The use of high-quality, context-specific GEMs, a subset of the original GEM in which inactive reactions are removed while maintaining metabolic functions in the extracted model, for model organisms along with machine learning (ML) techniques could increase their applications and effectiveness in translational research in the near future. Here, we briefly review the current state of GEMs, discuss the potential contributions of ML approaches for more efficient and frequent application of these models in translational research, and explore the extension of GEMs to integrative cellular models.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139911187","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":"Pancreatic cancer environment: from patient-derived models to single-cell omics","authors":"Ao Gu, Jiatong Li, Shimei Qiu, Shenglin Hao, Zhu-Ying Yue, Shuyang Zhai, Meng-Yao Li and Yingbin Liu","doi":"10.1039/D3MO00250K","DOIUrl":"10.1039/D3MO00250K","url":null,"abstract":"<p >Pancreatic cancer (PC) is a highly malignant cancer characterized by poor prognosis, high heterogeneity, and intricate heterocellular systems. Selecting an appropriate experimental model for studying its progression and treatment is crucial. Patient-derived models provide a more accurate representation of tumor heterogeneity and complexity compared to cell line-derived models. This review initially presents relevant patient-derived models, including patient-derived xenografts (PDXs), patient-derived organoids (PDOs), and patient-derived explants (PDEs), which are essential for studying cell communication and pancreatic cancer progression. We have emphasized the utilization of these models in comprehending intricate intercellular communication, drug responsiveness, mechanisms underlying tumor growth, expediting drug discovery, and enabling personalized medical approaches. Additionally, we have comprehensively summarized single-cell analyses of these models to enhance comprehension of intercellular communication among tumor cells, drug response mechanisms, and individual patient sensitivities.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139766667","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}