Molecular omics最新文献

{"title":"Proteomic and metabolic profiling reveals molecular phenotype associated with chemotrophic growth of Rubrivivax benzoatilyticus JA2 on l-tryptophan†","authors":"Shabbir Ahmad, Mujahid Mohammed, Lakshmi Prasuna Mekala, Sasikala Chintalapati and Ramana Chintalapati","doi":"10.1039/D4MO00170B","DOIUrl":"10.1039/D4MO00170B","url":null,"abstract":"<p > <em>Rubrivivax benzoatilyticus</em> strain JA2 is an anoxygenic phototrophic bacterium, able to grow under different growth modes. Particularly under chemotrophic conditions, it produces novel Trp-melanin, anthocyanin-like, and pyomelanin pigments. However, the underlying molecular adaptations of strain JA2 that lead to the formation of novel metabolites under chemotrophic conditions remain unexplored. The present study used iTRAQ-based global proteomic and metabolite profiling to unravel the biochemical processes operating under the <small>L</small>-tryptophan-fed chemotrophic state. Exometabolite profiling of <small>L</small>-tryptophan fed chemotrophic cultures revealed production of diverse indolic metabolites, many of which are hydroxyindole derivatives, along with unique pigmented metabolites. Proteomic profiling revealed a global shift in the proteome and detected 2411 proteins, corresponding to 61.8% proteins expressed. Proteins related to signalling, transcription-coupled translation, stress, membrane transport, and metabolism were highly differentially regulated. Extensive rewiring of amino acid, fatty acid, lipid, and energy metabolism was observed under <small>L</small>-tyrptophan fed chemotrophic conditions. Moreover, energy conservation and cell protection strategies such as efflux pumps involved in the efflux of aromatic compounds were activated. The study demonstrated a correlation between some of the detected indole derivatives and the up-regulation of proteins associated with <small>L</small>-tryptophan catabolism, indicating a possible role of aromatic mono/dioxygenases in the formation of hydroxyindole derivatives and pigments under chemotrophic conditions. The overall study revealed metabolic flexibility in utilizing aromatic compounds and molecular adaptations of strain JA2 under the chemotrophic state.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 1","pages":" 51-68"},"PeriodicalIF":3.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740007","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":"Influence of sex, age, ethnicity/race, and body mass index on the cerumen volatilome using two data analysis approaches: binary and semiquantitative†","authors":"João Marcos G. Barbosa, Lurian Caetano David, Camilla Gabriela de Oliveira, Anselmo Elcana de Oliveira and Nelson R. Antoniosi Filho","doi":"10.1039/D4MO00071D","DOIUrl":"10.1039/D4MO00071D","url":null,"abstract":"<p >Human cerumen analysis is an innovative and non-invasive trend in diagnosing diseases. Recently, new cerumen volatile-based methods using binary (volatile presence/absence) and semiquantitative (volatile intensity) data approaches have shown great potential in detecting biomarkers for cancer, chronic and rare diseases, and xenobiotic exposures. However, to date, the impacts of demographic factors such as body mass index (BMI), sex, age, and ethnicity/race in cerumen data have not been widely described, which can hamper interpretation in biomarker discovery investigations. This study examined the effects of such factors in cerumen, defining the baseline volatile organic metabolites (VOMs) across different physiological groups. Cerumen samples from seventy volunteers were analyzed using headspace/gas chromatography–mass spectrometry (HS/GC–MS) and multivariate statistical analysis using binary and semiquantitative data approaches. In the binary data approach, several VOMs exhibited patterns of high occurrence in some specific demographic groups. However, no pattern of discrimination that could be attributed to demographic factors was observed. In the semiquantitative approach, the relative abundance of cerumen VOMs was more impacted by sex and BMI than age and ethnicity/race. In summary, we describe how cerumen VOM occurrence and abundance are affected by patient phenotype, which can pave the way for more personalized medicine in future cerumen volatile-based methods.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 10","pages":" 666-677"},"PeriodicalIF":3.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569320","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":"GRL–PUL: predicting microbe–drug association based on graph representation learning and positive unlabeled learning","authors":"Jinqing Liang, Yuping Sun and Jie Ling","doi":"10.1039/D4MO00117F","DOIUrl":"10.1039/D4MO00117F","url":null,"abstract":"<p >Extensive research has confirmed the widespread presence of microorganisms in the human body and their crucial impact on human health, with drugs being an effective method of regulation. Hence it is essential to identify potential microbe–drug associations (MDAs). Owing to the limitations of wet experiments, such as high costs and long durations, computational methods for binary classification tasks have become valuable alternatives for traditional experimental approaches. Since validated negative MDAs are absent in existing datasets, most methods randomly sample negatives from unlabeled data, which evidently leads to false negative issues. In this manuscript, we propose a novel model based on graph representation learning and positive-unlabeled learning (GRL–PUL), to infer potential MDAs. Firstly, we screen reliable negative samples by applying weighted matrix factorization and the PU-bagging strategy on the known microbe–drug bipartite network. Then, we combine muti-model attributes and constructed a microbe–drug heterogeneous network. After that, graph attention auto-encoder module, an encoder combining graph convolutional networks and graph attention networks, is introduced to extract informative embeddings based on the microbe–drug heterogeneous network. Lastly, we adopt a modified random forest as the final classifier. Comparison experiments with five baseline models on three benchmark datasets show that our model surpasses other methods in terms of the AUC, AUPR, ACC, F1-score and MCC. Moreover, several case studies show that GRL–PUL could capably predict latent MDAs. Notably, we further verify the effectiveness of a reliable negative sample selection module by migrating it to other state-of-the-art models, and the experimental results demonstrate its ability to substantially improve their prediction performance.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 1","pages":" 38-50"},"PeriodicalIF":3.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624751","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":"Investigation of the motif activity of transcription regulators in pancreatic β-like cell subpopulations differentiated from human induced pluripotent stem cells†","authors":"Eric Leclerc, Mikhail Pachkov, Lisa Morisseau, Fumiya Tokito, Cecile Legallais, Rachid Jellali, Masaki Nishikawa, Amar Abderrahmani and Yasuyuki Sakai","doi":"10.1039/D4MO00082J","DOIUrl":"10.1039/D4MO00082J","url":null,"abstract":"<p >Pancreatic β-cells are composed of different subtypes that play a key role in the control of insulin secretion and thereby control glucose homeostasis. <em>In vitro</em> differentiation of human induced pluripotent stem cells (hiPSCs) into 3D spheroids leads to the generation of β-cell subtypes and thus to the development of islet-like structures. Using this cutting-edge cell model, the aim of the study was to decipher the signaling signature that underlines β-cell subtypes, with a focus on the search for the activity of motifs of important transcription regulators (TRs). The investigation was performed using data from previous single-cell sequencing analysis introduced into the integrated system for motif activity response analysis (ISMARA) of transcription regulators. We extracted the matrix of important TRs activated in the β-cell subpopulation and bi-hormonal-like β-cells. Based on these TRs and their targets, we built specific regulatory networks for main cell subpopulations. Our data confirmed the transcriptomic heterogeneity of the β-cell subtype lineage and suggested a mechanism that could account for the differentiation of β-cell subtypes during pancreas development. We do believe that our findings could be instrumental for understanding the mechanisms that affect the balance of β-cell subtypes, leading to impaired insulin secretion in type 2 diabetes.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 10","pages":" 654-665"},"PeriodicalIF":3.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569321","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":"Sustained hypoxia but not intermittent hypoxia induces HIF-1α transcriptional response in human aortic endothelial cells†","authors":"Rengul Cetin-Atalay, Angelo Y. Meliton, Yufeng Tian, Kaitlyn A. Sun, Parker S. Woods, Kun Woo D. Shin, Takugo Cho, Alex Gileles-Hillel, Robert B Hamanaka and Gökhan M. Mutlu","doi":"10.1039/D4MO00142G","DOIUrl":"10.1039/D4MO00142G","url":null,"abstract":"<p >Obstructive sleep apnea (OSA) is characterized by intermittent hypoxic environments at the cellular level and is an independent risk factor for the development of cardiovascular disease. Endothelial cell (EC) dysfunction precedes the development of cardiovascular disease; however, the mechanisms by which ECs respond to these intermittent hypoxic events are poorly understood. To better understand EC responses to hypoxia, we examined the effects of sustained hypoxia (SH) and intermittent hypoxia (IH) on the activation of HIF-1α in ECs. While SH stabilized HIF-1α and led to its nuclear localization, IH did not activate HIF-1α and the expression of its target genes. Using RNA-sequencing, we evaluated transcriptional responses of ECs to hypoxia. SH induced the expression of HIF-1α and hypoxia response genes, while IH affected cell-cycle regulation genes. A cytoscape protein–protein interaction network for EC response to hypoxia was created with differentially expressed genes. The network comprises cell-cycle regulation, inflammatory signaling <em>via</em> NF-κB and response to VEGF stimulus subnetworks on which SH and IH had distinct activities. As OSA is associated with elevated catecholamines, we investigated the effect of epinephrine on the EC response to SH and IH. Transcriptomic responses under IH and epinephrine revealed protein–protein interaction networks emphasizing distinct subnetworks, including cytokine-mediated TNFα signaling <em>via</em> NF-κB, Wnt/LRP/DKK signaling and cell cycle regulation. This study reveals differential transcriptomic responses under SH and IH characterised by HIF-1α transcriptional response induced only by SH, but not by IH. The study also features the potential molecular events that may occur at the vascular level in OSA.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 1","pages":" 19-31"},"PeriodicalIF":3.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605334","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":"MobiChIP: a compatible library construction method of single-cell ChIP-seq based droplets†","authors":"Xianhong Yu, Guantao Zheng, Liting Xu, Weiyi Guo, Guodong Chen, Yiling Zhu, Tingting Li, Mingming Rao, Linyan Wang, Rong Cong and Hao Pei","doi":"10.1039/D4MO00111G","DOIUrl":"10.1039/D4MO00111G","url":null,"abstract":"<p >To illustrate epigenetic heterogeneity, versatile tools of single-cell ChIP-seq (scChIP-seq) are essential for both convenience and accuracy. We developed MobiChIP, a compatible ChIP-seq library construction method based on current sequencing platforms for single-cell applications. MobiChIP efficiently captures fragments from tagmented nuclei across various species and allows sample mixing from different tissues or species. This strategy offers robust nucleosome amplification and flexible sequencing without customized primers. MobiChIP reveals regulatory landscapes of chromatin with active (H3K27ac) and repressive (H3K27me3) histone modification in peripheral blood mononuclear cells (PBMCs) and accurately identifies epigenetic repression of the <em>Hox</em> gene cluster, outperforming ATAC-seq. Meanwhile, we also integrated scChIP-seq with scRNA-seq to further illustrate cellular genetic and epigenetic heterogeneity.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 1","pages":" 32-37"},"PeriodicalIF":3.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605332","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":"Lipidomics in forensic science: a comprehensive review of applications in drugs, alcohol, latent fingermarks, fire debris, and seafood authentication","authors":"Pingyang Liu, Zhanfang Liu, Hong Zhou, Jun Zhu, Zhenwen Sun, Guannan Zhang and Yao Liu","doi":"10.1039/D4MO00124A","DOIUrl":"10.1039/D4MO00124A","url":null,"abstract":"<p >Forensic science, an interdisciplinary field encompassing the collection, examination, and presentation of evidence in legal proceedings, has recently embraced lipidomics as a valuable tool. Lipidomics, a subfield of metabolomics, specializes in the analysis of lipid structures and functions, offering insights into biological processes that can aid forensic investigations. While not a substitute for DNA analysis in personal identification, lipidomics complements this technique by focusing on small biological molecules, with distinct sample requirements. This review comprehensively explores the current applications of lipidomics in forensic science. The review commences with an introduction to the concept and historical background of lipidomics, subsequently delving into its utilization in diverse areas such as drug analysis, ethyl alcohol and substitute assessment, latent fingermark detection, fire debris analysis, and seafood authentication. By showcasing the various biological materials and methods employed, this review underscores the potential of lipidomics as a powerful adjunct in forensic investigations.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 10","pages":" 618-629"},"PeriodicalIF":3.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470722","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":"Size exclusion chromatography based proteomic and degradomic profiling of inflammasome-activated, murine bone marrow-derived dendritic cells highlights complex retention and release of cleavage products†","authors":"Daniel Vogele, Svenja Wöhrle, Benedikt S. Saller, Klemens Fröhlich, Bálint András Barta, Miguel Cosenza-Contreras, Olaf Groß and Oliver Schilling","doi":"10.1039/D4MO00163J","DOIUrl":"10.1039/D4MO00163J","url":null,"abstract":"<p >Coupling size exclusion chromatography (SEC) with mass spectrometry-based proteomics enables investigating protein complexes, with degradomic profiling providing deeper insights into complex-associated proteolytic processing and retaining of cleavage products. This study aims to map protein complex formation upon inflammasome activation in bone marrow-derived dendritic cells (BMDCs) from gasdermin D-deficient mice, focusing on proteolytic enzymes and truncated proteins in higher molecular weight complexes. Cultured BMDCs were primed with LPS and subsequently treated with nigericin or Val-boroPro (VbP). SEC-fractionated proteins were TMT-labelled and analyzed <em>via</em> liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified 6862 proteins and 70 802 peptides, including 14 714 semi-tryptic peptides indicating elevated endogenous proteolytic processing. The sequence motif of numerous cleavage sites maps to caspase-like activity. Inflammasome activation was corroborated by elevated levels of apoptosis-associated speck-like protein containing a CARD (ASC) in higher molecular weight (MW) fractions and increased IL-1β levels in low MW fractions upon nigericin or VbP treatment. The majority of truncated cleavage products remained within their corresponding, higher MW protein complexes while caspase-specific cleavage products of Rho-associated protein kinase 1, gelsolin, and AP-2 complex subunit alpha-2 dissociated to lower MW fractions. SEC profiles identified 174 proteases, with cell surface proteases forming high MW complexes, including ADAMs and DPP4 but not MMP14. VbP treatment led to the accumulation of ISG15 in low MW fractions while RNA polymerase II coactivator p15 shifted to higher MW fractions. This study demonstrates that SEC-coupled proteomics and degradomic profiling offer unique insights into protein complex dynamics and proteolytic processes upon inflammasome activation.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 9","pages":" 595-610"},"PeriodicalIF":3.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392001","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":"Comprehensive untargeted lipidomic profiling of third generation lentiviral vectors and packaging cells†","authors":"Joshua A. Roberts, Elena Godbout, Jocelyn A. Menard, Christopher N. Boddy, Jean-Simon Diallo and Jeffrey C. Smith","doi":"10.1039/D4MO00052H","DOIUrl":"10.1039/D4MO00052H","url":null,"abstract":"<p >Lentiviral vectors (LV) are emerging tools for genetic therapies and novel cancer treatments. While effective, LV-based therapies have extremely large costs associated with their manufacturing and delivery. LV technology descends from human immunodeficiency virus (HIV), whose lipid envelope has been previously measured and shown to have a direct impact on its transduction efficiency. We developed a rapid, robust, and sensitive untargeted lipidomics pipeline to analyze novel LV biotherapeutic products and demonstrate its utility on HEK 293T packaging cells and concentrated culture media containing LV. The impact of 48 hours of LV production on the lipidome of HEK 293T cells was measured and compared to the expression of vesicular stomatitis virus G protein (VSV G) over the same timeframe. 151 lipids were identified in HEK 293T packaging cells, 84 of which had fold changes with FDR-corrected <em>P</em> &lt; 0.05 compared to HEK 293T treated with media. It was found that fold changes with FDR-adjusted <em>P &lt;</em> 0.05 after VSV G expression and LV production were highly correlated (<em>R</em><small>²</small> = 0.89). Concentrating LV in culture media led to the identification of 102 lipids, half of which were determined to be unique LV virion lipids after subtracting the media lipidome. Our approach can be readily used to study the lipid dynamics of large-scale LV production and be rapidly translated into targeted methods to quantify individual lipid components or applied to other viral vector platforms.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 10","pages":" 642-653"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392000","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":"Systemic analysis of lipid metabolism from individuals to multi-organism systems†","authors":"Samuel Furse, Carlos Martel, David F. Willer, Daniel Stabler, Denise S. Fernandez-Twinn, Jennifer Scott, Ryan Patterson-Cross, Adam J. Watkins, Samuel Virtue, Thomas A. K. Prescott, Ellen Baker, Jennifer Chennells, Antonio Vidal-Puig, Susan E. Ozanne, Geoffrey C. Kite, Milada Vítová, Davide Chiarugi, John Moncur, Albert Koulman, Geraldine A. Wright, Stuart G. Snowden and Philip C. Stevenson","doi":"10.1039/D4MO00083H","DOIUrl":"10.1039/D4MO00083H","url":null,"abstract":"<p >Lipid metabolism is recognised as being central to growth, disease and health. Lipids, therefore, have an important place in current research on globally significant topics such as food security and biodiversity loss. However, answering questions in these important fields of research requires not only identification and measurement of lipids in a wider variety of sample types than ever before, but also hypothesis-driven analysis of the resulting ‘big data’. We present a novel pipeline that can collect data from a wide range of biological sample types, taking 1 000 000 lipid measurements per 384 well plate, and analyse the data systemically. We provide evidence of the power of the tool through proof-of-principle studies using edible fish (mackerel, bream, seabass) and colonies of <em>Bombus terrestris</em>. Bee colonies were found to be more like mini-ecosystems and there was evidence for considerable changes in lipid metabolism in bees through key developmental stages. This is the first report of either high throughput LCMS lipidomics or systemic analysis in individuals, colonies and ecosystems. This novel approach provides new opportunities to analyse metabolic systems at different scales at a level of detail not previously feasible, to answer research questions about societally important topics.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 9","pages":" 570-583"},"PeriodicalIF":3.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154634","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}