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At least 865 records · Page 48Linked to original sources
PubMed2025

Stress-induced altered expression of hippocampal nuclear and mitochondrial encoded genes in rats and cross-species genetic associations reveal molecular links to depression.

BACKGROUND: Mitochondria play a pivotal role in energy production, and their dysfunction not only hampers cells' ability to meet energy requirements but also contributes to the impairment of neural plasticity, a critical feature of depressive disorders. In this study, mitochondrial cross-omics analysis was carried out in the hippocampus of restraint rats to understand the role of mitochondria in depression pathophysiology. METHODS: The expression profiles of hippocampal mitochondrial and nuclear-encoded genes in mitochondrial fractions from restraint and handled control rats were obtained using high-throughput RNA sequencing. Weighted gene co-expression network analysis (WGCNA) was used to identify the gene co-expression and pathways associated with the restraint phenotype. Mutual Information Network algorithm tools Arance, CLR, and MRNET were additionally used to screen the functional modules and hub genes and their similarity with the WGCNA-based network analysis. Finally, cross-species homology followed by gene association analysis was conducted to obtain SNPs and haplotypes related to depression phenotype. RESULTS: A significant proportion of mitochondrial and nuclear-encoded genes showed differential regulation in the hippocampus of restraint rats. WGCNA and Mutual Information Network analysis yielded distinct functional modules significantly related to restraint phenotype. Further network analysis revealed distinct co-expression patterns associated with differentially expressed genes associated with these modules. Cross-species analysis showed 39 significantly associated SNPs with the depression phenotype, where the most significant SNP, rs10899570, was located within the TENM4 gene. Further, rs1573529 and rs10899570 were distributed into the linkage disequilibrium block where SNPs were highly correlated. Subsequent haplotype analysis showed that rs1573529 and rs10899570 were significantly associated with depressive behavior. CONCLUSIONS: The study demonstrates a significant impact of restraint stress on mitochondrial functions and genetic association, suggesting their critical role in depression pathophysiology.

Animals↗
PubMed2025

Roles of microbial interactions in determining the establishment and function of synthetic consortium inoculants for soil applications.

Synthetic microbial consortium inoculants are emerging nature-based solutions for promoting sustainable agriculture and mitigating environmental challenges. However, despite promising results in simpler lab-scale trials, many inoculants fail to establish or perform satisfactorily in field conditions. One most critical yet least understood factor influencing inoculant effectiveness is the complex microbial interactions, both within consortium inoculants ("within-community" interactions) and between consortium inoculants and native soil communities ("cross-community" interactions). Here, we first discuss major negative and positive "within-community" interactions and highlight the importance to design consortium inoculants with positive interactions for improved stability and functionality. We then examine the bidirectional "cross-community" interactions once introducing consortium inoculants to soils. Soil native communities often create strong resistance to the invasion of inoculants. We discuss major drivers controlling the invasibility of native communities and various strategies increasing the invasiveness of consortium inoculants. We then discuss how consortium inoculants can reshape native communities, with implications for long-term ecosystem resilience and functioning. We propose future research efforts including advancing strategies for harnessing natural species from relatively untapped soil reservoirs and using high-throughput interaction profiling with multi-omics and computational tools to build compatible synthetic consortia with desirable functions; leveraging positive interactions and prebiotics to facilitate inoculant establishment; and assessing fully soil functional resilience over longer terms, including recognizing the importance of rare keystone taxa. By integrating with ecological theory, this review provides a comprehensive insight into microbial interactions to advance the design, application, and monitoring of synthetic consortium inoculants for enhancing soil health and ecosystem sustainability.

establishment↗
PubMed2003

Nutritional genomics: implications for companion animals.

This is an exciting time for biological scientists as the "omics" era continues to evolve and shape the way science is understood and conducted. As genome sequencing of the human comes to a close, other mammals are in line to be sequenced. Along with pigs and cows, dogs are now on the high priority list for sequencing, and cats may soon follow suit. Until sequence data are available, genetic maps may be used to reveal important physical characteristics of a genome. Genome mapping is important in identifying gene placement, but gives little information regarding function. Therefore, functional genomics, including the global analysis of RNA and protein expression, protein localization and protein-protein interactions will emerge as important areas of study. The major use of the dog and cat genome maps hitherto has been for the study of human and veterinary medicine. These powerful resources also can be applied to the field of nutritional genomics and proteomics, enhancing our understanding of metabolism and optimizing companion animal nutritional and health status. Genomics has begun to be applied to nutritional research, but issues specifically relevant to companion animals have not been elucidated thus far. The study of genomics and proteomics will be crucial in areas such as nutrient requirement determination, disease prevention and treatment, functional ingredient testing and others. Nutritional genomics and proteomics will definitely play a vital role in the future of pet foods.

Animal Nutritional Physiological Phenomena↗
PubMed2026

Translating Flood-Tolerance Biology into Breeding: A 5D Framework for Next-Generation Rice Varieties.

Flooding is among the most devastating abiotic stresses limiting rice productivity. Although SUB1A introgression conferred submergence tolerance in several mega-varieties, this single-gene approach is insufficient for the diverse flood types-flash floods, stagnant floods, anaerobic germination, and deepwater inundation-progressively intensifying with climate change. Here, we review the physiological mechanisms and genetic architecture underlying tolerance to each flood type, emphasizing the dual role of reactive oxygen species (ROS) in signalling and damage, the management of elemental toxicities (Fe2+, Mn2+) under altered soil redox, and lessons from wetland species and lowland rice. We then examine why marker-assisted selection has failed for polygenic, multi-stress tolerance and identify persistent breeding bottlenecks. Building on this biological foundation, we outline an integrated 5D framework (Demand, Discovery, Design, Development, Deployment) that links gene-bank diversity, multi-omics discovery, predictive breeding and on-farm validation through continuous feedback. We discuss how connected breeding, the transition-from-trait-to-environment (TTE) strategy, and speed breeding can accelerate genetic gain, and we close with research priorities centred on the biology of multi-flood tolerance to develop climate-resilient rice.

5D breeding framework↗
PubMed2004

Post-genomics approaches for the elucidation of plant adaptive mechanisms to sulphur deficiency.

With the genome sequence of Arabidopsis and rice now available, plant science has stepped forward into a new phase. Post-genomics studies such as transcriptomics, proteomics, and metabolomics will bring about a breakthrough for the functional elucidation of genes and for an understanding of a whole process of living cells. Concerning studies of sulphur (S) metabolism, several reports have recently been published describing the transcript profiles of S-starved Arabidopsis. In this review, these -omics studies that have revealed the network linking several pathways related to jasmonic acid (JA), oxidative stress response, auxin, and flavonoid to S metabolic pathway are summarized.

Adaptation, Physiological↗
PubMed2005

MRS: a fast and compact retrieval system for biological data.

The biological data explosion of the 'omics' era requires fast access to many data types in rapidly growing data banks. The MRS server allows for very rapid queries in a large number of flat-file data banks, such as EMBL, UniProt, OMIM, dbEST, PDB, KEGG, etc. This server combines a fast and reliable backend with a very user-friendly implementation of all the commonly used information retrieval facilities. The MRS server is freely accessible at http://mrs.cmbi.ru.nl/. Moreover, the MRS software is freely available at http://mrs.cmbi.ru.nl/download/ for those interested in making their own data banks available via a web-based server.

Databases, Genetic↗
PubMed2005

Expansion of the BioCyc collection of pathway/genome databases to 160 genomes.

The BioCyc database collection is a set of 160 pathway/genome databases (PGDBs) for most eukaryotic and prokaryotic species whose genomes have been completely sequenced to date. Each PGDB in the BioCyc collection describes the genome and predicted metabolic network of a single organism, inferred from the MetaCyc database, which is a reference source on metabolic pathways from multiple organisms. In addition, each bacterial PGDB includes predicted operons for the corresponding species. The BioCyc collection provides a unique resource for computational systems biology, namely global and comparative analyses of genomes and metabolic networks, and a supplement to the BioCyc resource of curated PGDBs. The Omics viewer available through the BioCyc website allows scientists to visualize combinations of gene expression, proteomics and metabolomics data on the metabolic maps of these organisms. This paper discusses the computational methodology by which the BioCyc collection has been expanded, and presents an aggregate analysis of the collection that includes the range of number of pathways present in these organisms, and the most frequently observed pathways. We seek scientists to adopt and curate individual PGDBs within the BioCyc collection. Only by harnessing the expertise of many scientists we can hope to produce biological databases, which accurately reflect the depth and breadth of knowledge that the biomedical research community is producing.

Animals↗
PubMed2007

CYCLONET--an integrated database on cell cycle regulation and carcinogenesis.

Computational modelling of mammalian cell cycle regulation is a challenging task, which requires comprehensive knowledge on many interrelated processes in the cell. We have developed a web-based integrated database on cell cycle regulation in mammals in normal and pathological states (Cyclonet database). It integrates data obtained by 'omics' sciences and chemoinformatics on the basis of systems biology approach. Cyclonet is a specialized resource, which enables researchers working in the field of anticancer drug discovery to analyze the wealth of currently available information in a systematic way. Cyclonet contains information on relevant genes and molecules; diagrams and models of cell cycle regulation and results of their simulation; microarray data on cell cycle and on various types of cancer, information on drug targets and their ligands, as well as extensive bibliography on modelling of cell cycle and cancer-related gene expression data. The Cyclonet database is also accessible through the BioUML workbench, which allows flexible querying, analyzing and editing the data by means of visual modelling. Cyclonet aims to predict promising anticancer targets and their agents by application of Prediction of Activity Spectra for Substances. The Cyclonet database is available at http://cyclonet.biouml.org.

Animals↗
PubMed2026

Proportionality-based association metrics in count compositional data.

Compositional data comprise vectors that describe the constituent parts of a whole. Data arising from various -omics platforms such as 16S and RNA sequencing are compositional in nature. In this kind of data, correlations between features on raw counts have no meaningful interpretation. Metrics of proportionality were formulated to address this problem. However, an inherent bias arises when these metrics are calculated empirically on count-based measures due to variability in read depths. We quantify the bias introduced by empirically calculating proportionality-based association metrics in count data. Additionally, we propose a means of estimating these metrics within a logit-normal multinomial model in pursuit of more accurate estimates. The model-based estimates are shown to outperform empirical estimates in simulated data and are applied to a mouse embryonic stem cell single-cell sequencing dataset, as well as a pediatric-onset multiple sclerosis metagenomic dataset.

Animals↗
PubMed2023

GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data.

BACKGROUND: Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data. METHODS: We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T-cells, NK-cells, microglia, tumor associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal progenitor-like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recurrent tumors, to determine which deconvolution approach performed best. RESULTS: Marker-based deconvolution using GBM-tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis. CONCLUSIONS: GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.

Humans↗
PubMed2025

Global lncRNA expression profiles in medulloblastoma reveal crucial lncRNA-oncogene interactions in Sonic hedgehog and Group 4.

BACKGROUND: Advances in multi-omic studies have improved medulloblastoma (MB) characterization, yet novel molecular biomarkers are needed to refine tumor biology and therapeutic strategies. Current profiling mainly targets the protein-coding genome, while the potential of noncoding regions remains unexplored. This study aims to identify long noncoding RNAs (lncRNAs), emerging as crucial regulators in MB, as potential key biomarkers specific to molecular group, enhancing understanding of MB's genomic landscape. METHODS: RNA-seq data from 54 Spanish MB patients (C1) and 207 public samples (C2) were analyzed to profile lncRNAs. Expression and Weighted Gene Coexpression Network (WGCNA) analyses were performed to identify lncRNA-oncogene interactions. Group-specific interactions were examined to infer their role in MB pathogenesis and highlight potential lncRNA involvement in disease mechanisms. RESULTS: LncRNA expression profiles identified 4 clusters corresponding to the MB molecular groups, confirming their potential as biomarkers. Expression and WGCNA analyses revealed group-specific lncRNAs for Sonic hedgehog (SHH), Group 3 (Gr3), and Group 4 (Gr4) MB. Lnc-SMARCA2 was exclusively upregulated in SHH MB, and associated with ATOH1 and PDLIM3, key cilium regulators of this group's cell of origin. In Gr4 MB, MGC32805 and LOC107986446 were upregulated and linked to SNCAIP, potentially influencing PRDM6 activation via enhancer hijacking. Additionally, a 5-lncRNA signature linked to phototransduction was exclusive to Gr3, offering insights into its lineage switch and molecular regulation. CONCLUSIONS: Lnc-SMARCA2 and, MGC32805 and LOC107986446, are exclusively deregulated in SHH and Gr4 MB, respectively, and directly associated with group-specific MB oncogenes, representing promising novel biomarkers and therapeutic targets in MB.

cancer biomarkers↗
PubMed2026

Genome assembly and subgenomic interactions in Brassica napus additional lines with an alien B05 chromosome from B. juncea.

Alien chromosome addition lines hold significant value for breeding and genetic research. However, the genetic interaction between the recipient genome(s) and the alien chromosomes remain largely unclear. Here, we analyzed the genomic composition and gene expression of two purple-leaved B. napus alien addition lines carrying chromosome B05 from B. juncea: the monosomic line ZYCB3 (MAAL, 2n = 39, AACC + 1B05) and the disomic line ZY52 (DAAL, 2n = 40, AACC + 2B05). We assembled a chromosome-level genome of the DAAL ZY52 disomic line and characterized its genomic variation and chromosome introgression patterns. In addition to chromosome B05, multiple introgressed fragments derived from the donor B. juncea line ZYJC were identified, revealing extensive genome remodeling during distant hybridization and backcross breeding. We then used multi-omics approaches to explore chromosomal interactions and the regulation of anthocyanin biosynthesis. Notably, the addition of chromosome B05 was associated with stronger repression of homoeologous genes on C-subgenome chromosomes than on A-subgenome chromosomes. In ZY52, homoeologous genes on chromosome C01 showed reduced expression, whereas in the ZYCB3 monosomic line reduced expression was observed on both C01 and C02. Comparative transcriptomic and metabolomic analyses further showed that highly expressed anthocyanin biosynthesis genes (ABGs) on chromosome B05contributed to anthocyanin accumulation and the purple-leaf phenotype in both addition lines. Overall, this study provides new insights into interchromosomal interactions, genome remodeling, and phenotypic variation in alien addition lines.

Journal Article↗
PubMed2003

The future of regulatory toxicology: impact of the biotechnology revolution.

The molecular biology revolution and the advent of genomic and proteomic technologies are facilitating rapid advances in our understanding of the molecular details of cell and tissue function. These advances have the potential to transform toxicological and clinical practice, and are likely to lead to the supplementation or replacement of traditional biomarkers of cellular integrity, cell and tissue homeostasis, and morphological alterations that result from cell damage or death. New technologies that permit simultaneous monitoring of many hundreds, or thousands, of macro- and small molecules ("-omics" technologies) promise to allow functional monitoring of multiple (or perhaps all) key cellular pathways simultaneously. Elucidation of cellular responses to molecular damage, including evolutionarily conserved inducible molecular defense systems, suggests the possibility of new biomarkers based on molecular responses to functional perturbations and cellular damage. Our improved understanding of the molecular basis of various pathologies suggests that monitoring specific molecular responses may provide improved prediction of human outcomes. Responses that can be monitored directly in the human should provide "bridging biomarkers" that may eliminate much of the current uncertainty in extrapolating from laboratory models to human outcome. Another aspect of genomics is our enhanced ability to associate DNA sequence variations with biological outcomes and individual sensitivity. The human genome sequence has revealed that sequence variations are very common, and may be an important determinant of variation in biological outcomes. The impending availability of a complete human haplotype map linked to standard genetic markers greatly facilitates identification of genetic variations that convey sensitivity or resistance to chemical exposures. Genetic approaches have already linked a large number of genetic variants (polymorphisms) with human diseases and adverse reactions from exposure to drugs or toxicants, suggesting an important role in sensitivity to drugs and environmental agents, disease susceptibilities, and therapeutic responses. As these opportunities are transformed into reality, regulatory toxicological practice is likely to be shaped in the future by the combination of conventional pathology, toxicology, molecular genetics, biochemistry, cell biology, and computational bio-informatics-resulting in the broad application of molecular approaches to monitoring functional disturbances.

Animals↗
PubMed2005

Prediction of 2-year carcinogenicity study results for pharmaceutical products: how are we doing?

Some have proposed that 2-year carcinogenicity studies may not be necessary if the material is a direct-acting DNA mutagen, induces liver enzymes, causes hyperplasia or toxicity in particular organs, causes cell proliferation, is cytotoxic, causes hormonal perturbations, or if one has QSAR analyses or 'omics information. Safety pharmacology data, pharmacologic activity, metabolism data, and results of 13-week dose ranging studies (with organ weight data, clinical chemistry data, hematologic data, clinical signs and histopathologic findings) were compared with results of 2-year carcinogenicity studies reviewed by the Center for Drug Evaluation and Research (CDER)/FDA. The experience with the ICH genetic toxicology battery and alternative carcinogenicity models was also reviewed. It appears that the information available from short-term studies is not currently sufficient to accurately and reliably predict the outcome of long-term carcinogenicity studies.

Animals↗
PubMed2005

Systems biology for cancer.

PURPOSE OF REVIEW: Significant insight can be gained into complex biologic mechanisms of cancer via a combined computational and experimental systems biology approach. This review highlights some of the major systems biology efforts that were applied to cancer in the past year. RECENT FINDINGS: Two main approaches to computational systems biology are discussed: mechanistic dynamical simulations and inferential data mining. Significant developments have occurred in both areas. For example, mechanistic simulations of the EGFR pathway are promoting understanding of cancer, and Bayesian inference approaches allow for the reconstruction of regulatory networks. In addition, the article reports on advancements in experimental systems biology for determining protein-protein interactions and quantifying protein expression to generate the necessary data for computational modeling and inferential data mining. Emerging approaches will further improve the ability to bridge the gap between in vitro systems and in vivo human biology. Technologies paving the way include in vitro models that better reflect in vivo tumors, microfabricated devices of human physiology, and improved animal models. SUMMARY: An important challenge facing the field is how better to translate in vitro discoveries to the clinic. Computational systems biology approaches that use omic data to predict biology along with novel experimental systems that better represent human in vivo biology will prove useful in bridging this gap. Although still early, the potential application of systems biology and the future evolution of the field will significantly affect understanding of cancer disease mechanisms and the ability to devise effective therapeutics.

Computational Biology↗
PubMed2005

Biomarkers for toxicodynamic monitoring of immunosuppressants: NMR-based quantitative metabonomics of the blood.

Metabonomics is the latest "omics" science and provides metabolic endpoints of drug toxicity, drug efficacy, and pathophysiology. With high-resolution 'H-NMR (nuclear magnetic resonance)spectroscopy on body fluids (eg, urine, blood samples) used in combination with statistical tools, metabolic biomarkers of drug toxicity can be distinguished and validated. For 2 decades, immuno-suppressant cyclosporine (CsA) has been used in transplantation medicine as a potent calcineurin inhibitor with well-known nephrotoxic side effects. The combination of CsA with novel macrolide immunosuppressants-sirolimus (SRL) or everolimus (RAD)-has proved to have a beneficial synergistic immunosuppressive effect but may also possess an increased nephrotoxic potential. 1H-NMR spectroscopy was performed on the blood from CsA-, SRL-, and RAD (alone and in combination)-treated rats to predict metabolic toxicity and to identify and quantify specific metabolic biomarkers. After 6 days of treatment with 10 mg/kg CsA, a significant increase in blood glucose, hydroxybutyrate, creatine+creatinine, trimethylamine-N-oxide (TMAO), and cholesterol as well as a decrease in total glutathione concentrations were observed. SRL (3 mg/kg) enhanced the magnitude of CsA metabolic changes (enhanced toxicity),whereas combination with RAD (3 mg/kg) partly curtailed them. Together with pharmacokinetic studies, quantitative NMR-based metabonomics represents a powerful tool for pharmacokinetic-pharmacodynamic-toxicodynamic evaluation in drug research.

Animals↗
PubMed2006

Proteomic methods in nutrition.

PURPOSE OF REVIEW: Proteomics, the comprehensive analysis of a protein complement in a cell, tissue or biological fluid at a given time, is a key player in the family of -omic disciplines, which encompass genomics (gene analysis), transcriptomics (gene expression analysis) and metabolomics (metabolite profiling). This review summarizes the state of the art of proteomics technology and puts it into perspective for food-related research. Learning from proteomic experiences in the pharmaceutical context, this article may help to translate proteomics into nutrition and health. RECENT FINDINGS: Mass spectrometric technology has progressed enormously with regard to mass accuracy, resolution and peptide sequencing power. Likewise, upstream separation, depletion and enrichment techniques now allow us to deal with the large complexity and wide dynamic range of proteomic samples more efficiently. Consequently, proteomic studies now provide a broader, but still far from complete, coverage of a given proteome. SUMMARY: Proteomics adapted and applied to the context of nutrition and health has the potential to deliver biomarkers for health and comfort, reveal early indicators of disease disposition, assist in differentiating dietary responders from non-responders, and, last but not least, discover bioactive, beneficial food components.

Biomarkers↗
PubMed2025

EP300-mediated lactylation leads to ulcerative colitis via CD86-positive plasmacytoid dendritic cells: A Mendelian randomization and mediation analysis.

This study explores the potential mechanism between lactylation and ulcerative colitis (UC) using two-sample Mendelian randomization and multi-omics analysis. This study employed expression quantitative trait loci and protein quantitative trait loci as exposures, with UC from the Finnish database as the outcome, to conduct Mendelian randomization analysis on lactylation-related target genes, aiming to investigate the causal relationships between these exposures and the outcome. Sensitivity and pleiotropy tests, combined with colocalization analysis, are performed to identify the best target genes and ensure the robustness of the results. Finally, immune cells are included for mediation analysis between lactylation and UC to explore potential mechanisms of action. Through Mendelian randomization analysis combined with sensitivity and pleiotropy tests, 2 lactylation target genes were found to have a significant causal relationship with UC. Subsequent colocalization analysis confirmed EP300 as a potential gene target. After including immune cells in the mediation analysis, it was discovered that there is a potential mechanism involving EP300, CD86+ plasmacytoid dendritic cells (pDCs), and UC. There is a significant causal relationship between lactylation and UC. Furthermore, the lactylation-modified gene EP300 may lead to UC occurrence by regulating CD86+ pDCs.

Humans↗