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PubMed2005

Proteomics in nutrition and health.

Proteomics, the comprehensive analysis of a protein complement in a cell, tissue or biological fluid at a given time, has been enabled by quantum leaps in mass spectrometric technology, which allowed identification of large, involatile biomolecules. Over the last two decades, this discipline evolved from the sole delivery of protein identities to a platform, which reveals clues to function through e.g. characterisation of protein modifications and interactions as well as through quantitative proteomics, i.e. the global comparison of protein amounts between two defined biological states. Proteomics is an integral part and key player in the family of -omic disciplines as there are genomics (gene analysis), transcriptomics (gene expression analysis) and metabolomics (metabolite profiling). Considering the complexity, dynamics and protein concentration range of any given proteome, proteomics is the most challenging -omic discipline and requires the most sophisticated analysis pipeline. Proteomics represents an established technology in the pharmaceutical industry mainly for biomarker and drug target discovery. The potential of proteomics for research in the food industry is increasingly being recognised and the employment of proteomic approaches to nutrition and health issues is now emerging. This review summarizes (i) major technological achievements in mass spectrometry and proteomics, (ii) deliverables of proteomics in the context of nutrition and health, and (iii) applications of proteomics, and -- if appropriate -- transcriptomics to the research fields of digestive health, obesity and diabetes, immunity and allergy, probiotics, milk, and food preference.

Complex Mixtures↗
PubMed2004

Towards a comprehensive understanding of Bacillus subtilis cell physiology by physiological proteomics.

Using Bacillus subtilis as a model system for functional genomics, this review will provide insights how proteomics can be used to bring the virtual life of genes to the real life of proteins. Physiological proteomics will generate a new and broad understanding of cellular physiology because the majority of proteins synthesized in the cell can be visualized. From a physiological point of view two major proteome fractions can be distinguished: proteomes of growing cells and proteomes of nongrowing cells. In the main analytical window almost 50% of the vegetative proteome expressed in growing cells of B. subtilis were identified. This proteomic view of growing cells can be employed for analyzing the regulation of entire metabolic pathways and thus opens the chance for a comprehensive understanding of metabolism and growth processes of bacteria. Proteomics, on the other hand, is also a useful tool for analyzing the adaptational network of nongrowing cells that consists of several partially overlapping regulation groups induced by stress/starvation stimuli. Furthermore, proteomic signatures for environmental stimuli can not only be applied to predict the physiological state of cells, but also offer various industrial applications from fermentation monitoring up to the analysis of the mode of action of drugs. Even if DNA array technologies currently provide a better overview of the gene expression profile than proteome approaches, the latter address biological problems in which they can not be replaced by mRNA profiling procedures. This proteomics of the second generation is a powerful tool for analyzing global control of protein stability, the protein interaction network, protein secretion or post-translational modifications of proteins on the way towards the elucidation of the mystery of life.

Bacillus subtilis↗
PubMed2006

Expression analysis of the AtMLO gene family encoding plant-specific seven-transmembrane domain proteins.

The Arabidopsis (Arabidopsis thaliana) genome contains 15 genes encoding protein homologs of the barley mildew resistance locus o (MLO) protein biochemically shown to have a seven-transmembrane domain topology and localize to the plasma membrane. Towards elucidating the functions of MLOs, the largest family of seven-transmembrane domain proteins specific to plants, we comprehensively determined AtMLO gene expression patterns by a combination of experimental and in silico studies. Experimentation comprised analyses of transgenic Arabidopsis lines bearing promoter::Beta-glucuronidase (GUS) transcriptional fusions as well as semi-quantitative determination of transcripts by reverse transcription coupled to polymerase chain reaction (RT-PCR). These results were combined with information extracted from public gene profiling databases, and compared to the expression patterns of genes encoding the heterotrimeric G-protein subunits. We found that each AtMLO gene has a unique expression pattern and is regulated differently by a variety of biotic and/or abiotic stimuli, suggesting that AtMLO proteins function in diverse developmental and response processes. The expression of several phylogenetically closely-related AtMLO genes showed similar or overlapping tissue specificity and analogous responsiveness to external stimuli, suggesting functional redundancy, co-function, or antagonistic function(s).

Arabidopsis Proteins↗
PubMed2026

Histone deacetylases: From acetylation homeostasis to oncogenic and neurodegenerative disorders.

Histone deacetylases (HDACs) are central regulators of acetylation homeostasis, governing chromatin architecture, transcriptional dynamics, and diverse cellular processes through reversible lysine deacetylation. Dysregulation of HDAC activity disrupts epigenetic balance and is strongly implicated in oncogenic transformation and the progression of neurodegenerative disorders. This chapter provides a comprehensive overview of HDAC biology with a particular emphasis on experimental and analytical methodologies used to investigate their function. We describe the structural and functional diversity of HDAC classes and their roles in multiprotein complexes that regulate gene expression and cellular signaling. A major focus is placed on screening-compatible and mechanistic assays, including fluorometric, colorimetric, radiometric, fluorescence polarization, TR-FRET, AlphaScreen/AlphaLISA, and differential scanning fluorimetry approaches for quantitative measurement of enzymatic activity and inhibitor profiling. In addition, advanced methodologies such as mass spectrometry-based acetylome analysis, chromatin immunoprecipitation sequencing (ChIP-seq), recombinant enzyme assays, and cell-based reporter systems are discussed in the context of functional genomics and drug discovery. The integration of high-throughput screening, structural biology, and multi-omics strategies is highlighted as essential for dissecting HDAC-mediated regulatory networks. Collectively, this chapter serves as a methodological framework for studying HDAC function and developing targeted epigenetic therapies in cancer and neurodegenerative diseases.

Histone Deacetylases↗
PubMed2026

Genome-wide characterization of the TGF-β superfamily identifies bmp15, gdf9, and gsdf as sex-biased candidate regulators of gonadal differentiation in the synchronous hermaphrodite Plectropomus leopardus.

The transforming growth factor-β (TGF-β) superfamily plays conserved roles in vertebrate reproduction and gonadal sex differentiation. However, its genomic repertoire and sex-biased expression patterns remain unclear in the leopard coral grouper (Plectropomus leopardus), a species with synchronous hermaphroditism. Here, we performed a genome-wide identification of the TGF-β superfamily, identifying 42 genes from the chromosome-level genome. Phylogenetic and synteny analyses indicated that segmental duplication under purifying selection contributed to family expansion. Expression profiling across multiple tissues and four gonadal developmental stages (undifferentiated, 120 dph; early differentiated, 15 months; mature testis, 3 years; mature ovary, 3 years) identified eight gonad-enriched genes, among which bmp15 and gdf9 exhibited pronounced female-biased expression, with transcripts localized exclusively to the oocyte cytoplasm, particularly in stage II-III oocytes. In contrast, gsdf showed male-biased expression and was localized in spermatogenic cells of the testis. These reciprocal expression patterns indicate that bmp15/gdf9 and gsdf are candidate factors associated with gonadal sex differentiation. Our study provides the first comprehensive characterization of the TGF-β superfamily in P. leopardus and highlights bmp15, gdf9, and gsdf as candidate sex-differentiation factors in this hermaphroditic species.

Animals↗
PubMed2005

Hematopathology approaches to diagnosis and prognosis of indolent B-cell lymphomas.

The advent of new technologies has contributed to improvements in the diagnosis and classification of the non-Hodgkin lymphomas (NHL). Use of a more extensive test menu of paraffin active monoclonal antibodies for immunohistochemistry, molecular cytogenetic studies including standard cytogenetics, multi-color fluorescence in-situ hybridization (FISH), polymerase chain reaction and locus-specific FISH, as well as developments in high-resolution techniques including microarray gene expression profiling and array comparative genomic hybridization (CGH) allow more accurate diagnosis and precise definition of biomarkers of value in risk stratification. The identification of disease-specific gene lists resulting from expression profiling provides a number of potential protein targets that can be validated using immunohistochemistry. We will highlight how improvements in our understanding of lymphoma biology rapidly facilitate the development of new diagnostic reagents that could be used to alter clinical practice. These changing trends allow the development of new diagnostic strategies used to render accurate sub-classification of entities within the category of indolent B-cell lymphomas, including their distinction from related but more aggressive disorders, such as mantle cell lymphoma. A comprehensive understanding of the biology of these distinct lymphoid tumors will allow us to identify novel disease-related genes and should facilitate the development of improved diagnostics, outcome prediction, and personalized approaches to treatment.

Cell Transformation, Neoplastic↗
PubMed2026

Isolation and Characterization of a Naturally Occurring Brevundimonas vesicularis Strain Exhibiting High Phytoene Accumulation.

Phytoene, a colorless precursor of carotenoids, has attracted increasing attention because of its favorable bioavailability, antioxidant activity, and potential applications in functional foods, nutraceuticals, and animal nutrition. However, its industrial utilization remains limited by low natural abundance and the dependence of current production strategies on genetic engineering or metabolic pathway manipulation. In this study, we identified and characterized a naturally occurring Brevundimonas vesicularis strain (Bv-xms2024) exhibiting pronounced phytoene accumulation without genetic modification. The strain was comprehensively characterized using morphological, biochemical, molecular, genomic, metabolomic, and transcriptional analyses. Quantitative LC-MS/MS analysis demonstrated that Bv-xms2024 accumulated phytoene to 420.42 ± 98.11 μg/g dry biomass after 96 h of cultivation, substantially exceeding the levels of downstream carotenoids, including β-carotene and astaxanthin. Optimization of cultivation parameters identified 25 °C, pH 7.0, and 96 h as the optimal conditions for phytoene accumulation, while serial passaging confirmed stable production over 20 generations. Genome annotation identified the carotenoid biosynthetic gene repertoire, while RT-qPCR analysis revealed a temporal shift from early upregulation of crtE and crtB to later upregulation of downstream pathway genes, consistent with the observed phytoene-dominant carotenoid profile. Short-term tolerance evaluations in mice and chickens revealed no observable adverse effects under the tested conditions. Collectively, these findings identify Bv-xms2024 as a promising natural microbial resource for phytoene production and provide a basis for further process development and strain-level safety evaluation.

Brevundimonas vesicularis↗
PubMed2006

Erasure of methylation imprint at the promoter and CTCF-binding site upstream of H19 in human testicular germ cell tumors of adolescents indicate their fetal germ cell origin.

Genome-wide epigenetic modification plays a crucial role in regulating genome functions at critical stages of development. In particular, DNA methylation is known to be reprogrammed on a genome-wide level in germ cells and in preimplantation embryos, although it is relatively stable in somatic cells. In this reprogramming process, the genome becomes demethylated, and methylated de novo during later stages of development. Reprogramming of DNA methylation in male germ cells has not been fully investigated. Testicular germ cell tumors (TGCTs) possess a pluripotential nature and display protean histology from germ cells to embryonal and somatic cell differentiation. These properties make TGCT a unique model for studying germ cell development and gametogenesis in respect of DNA reprogramming. In order to obtain an insight into the epigenetic dynamics of TGCTs, we conducted a comprehensive analysis of differential methylated regions (DMRs) on H19 and IGF2 in TGCTs compared with testicular malignant lymphomas. In the present study, we show that methylation imprint at the promoter and CTCF-binding site upstream of H19 was completely erased in both seiminomatous and non-seminomatous TGCTs, whereas differential methylation was observed in testicular lymphomas. The erasure of methylation imprint was also observed in TGCTs with malignant transformation. We found biallelic unmethylation at the promoter and the CTCF-binding site upstream of H19 is required, but not sufficient for the biallelic expression of H19 in TGCTs. These data suggest that factors other than methylation contribute to transcriptional regulation of imprinted genes in TGCTs. The present data have shown that TGCTs carry distinctive epigenetic profiles at the core-imprinting domain of H19/IGF2 from other neoplasms of somatic cell origin. The data also suggest that both seminomatous and non-seminomatous TGCTs carry methylation profiles similar to fetal germ cells, but not adult germ cells, indicating the origin of TGCTs as fetal germ cells.

Adolescent↗
PubMed2002

Identification and characterisation of novel mammalian homologues of Drosophila polyhomeoticpermits new insights into relationships between members of the polyhomeotic family.

We have identified and characterised novel members of the mammalian polyhomeotic gene family, comprising a third human homologue, PHC3, and its mouse counterpart, Phc3. The two new genes have essentially the same genomic organisation, with 15 exons specifying proteins of 983 (PHC3) or 981 (Phc3) amino acids, with an overall sequence identity of 93%. Northern blot hybridisations have identified a single large transcript in a variety of adult mouse tissues and in situ hybridisation analyses indicate apparently ubiquitous expression during early human and mouse development. Exhaustive database screening suggests a maximum of three polyhomeotic homologues in humans and in mice and, for completeness, we have also derived the full-length coding sequence of the PHC2 gene (formerly called EDR2). The availability of full-length coding sequences for PHC2, PHC3 and Phc3 completes the profile of human and mouse polyhomeotic homologues and has enabled comprehensive comparative analyses of the human, mouse and Drosophilapolyhomeotic proteins. The mammalian paralogues are located on three different chromosomes and pairwise comparisons of their protein products typically show about 34% amino acid sequence identity, except for some highly conserved domains for which we present consensus mammalian sequences. The data indicate that the novel PHC3 and Phc3 proteins are significantly more closely related to PHC2/Phc2 than either is to PHC1/Phc1 and reveal two hitherto unknown but highly conserved N-terminal domains that are shared by the PHC2/Phc2 and PHC3/Phc3 proteins but that are poorly conserved or absent in other polyhomeotic family members.

Amino Acid Sequence↗
PubMed2003

End-sequence profiling: sequence-based analysis of aberrant genomes.

Genome rearrangements are important in evolution, cancer, and other diseases. Precise mapping of the rearrangements is essential for identification of the involved genes, and many techniques have been developed for this purpose. We show here that end-sequence profiling (ESP) is particularly well suited to this purpose. ESP is accomplished by constructing a bacterial artificial chromosome (BAC) library from a test genome, measuring BAC end sequences, and mapping end-sequence pairs onto the normal genome sequence. Plots of BAC end-sequences density identify copy number abnormalities at high resolution. BACs spanning structural aberrations have end pairs that map abnormally far apart on the normal genome sequence. These pairs can then be sequenced to determine the involved genes and breakpoint sequences. ESP analysis of the breast cancer cell line MCF-7 demonstrated its utility for analysis of complex genomes. End sequencing of approximately 8,000 clones (0.37-fold haploid genome clonal coverage) produced a comprehensive genome copy number map of the MCF-7 genome at better than 300-kb resolution and identified 381 genome breakpoints, a subset of which was verified by fluorescence in situ hybridization mapping and sequencing.

Animals↗
PubMed2026

Dissecting the shared genetic architecture between migraine subtypes and cardiovascular diseases: a multi-layered genomic analysis.

BACKGROUND: Epidemiological studies have linked migraine to an increased risk of cardiovascular disease (CVD); however, the shared genetic basis and putative causal relationships between migraine subtypes and cardiovascular traits remain poorly understood. METHODS: Leveraging large-scale GWAS summary statistics for migraine phenotypes (overall migraine, migraine with aura [MA], and migraine without aura [MO]) from FinnGen R12, along with seven cardiovascular diseases from publicly available consortia, we conducted a multi-layered genetic analysis. This integrative framework encompassed genetic correlation [linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL)], cross-trait meta-analysis (CPASSOC and PLACO), Bayesian colocalization, summary-data-based Mendelian randomization (SMR) using GTEx v8 eQTL data, and bidirectional two-sample Mendelian randomization (MR). RESULTS: Significant genetic correlations were identified between migraine and multiple cardiovascular traits, with hypertension and coronary artery disease (CAD) showing the most robust associations. MA exhibited broader genetic overlap with cardiovascular diseases than MO, including a notably stronger correlation with ischemic stroke, whereas MO demonstrated a stronger correlation with hypertension. Cross-trait meta-analysis identified 160 pleiotropic loci across 17 of 21 trait pairs. Colocalization analysis confirmed 32 loci harboring shared causal variants, mapped to 13 candidate genes, of which 7 (PHACTR1, LRP1, SOX7, ABO, FHOD3, MEI1, XKR6) were further validated by SMR as exhibiting tissue-specific regulatory effects. Among these, PHACTR1 displayed the broadest pleiotropic profile across migraine phenotypes and vascular diseases. After MR-PRESSO outlier removal, bidirectional MR identified 10 MR-supported associations, two of which (genetic liability to hypertension on overall migraine, and CAD on MA) survived Bonferroni correction, all free of detectable horizontal pleiotropy. Genetic liability to hypertension was associated with increased migraine risk (OR = 1.90, 95% CI 1.25-2.90, P = 2.64 × 10⁻³), atherosclerotic diseases showed subtype-specific effects (inverse for MO, positive for MA), and, in the reverse direction, migraine was associated with increased ischemic stroke risk. CONCLUSIONS: This study provides a comprehensive and systematic characterization of the shared genetic architecture between migraine subtypes and cardiovascular diseases. By identifying pleiotropic genes and bidirectional putative causal relationships with subtype-specific patterns, our findings carry implications for the development of targeted therapeutics and subtype-specific cardiovascular risk stratification.

Humans↗
PubMed2026

Identification of aquaporin (AQP) genes in the noble scallop Chlamys nobilis and characterization of their expression under low-temperature stress.

Aquaporins (AQPs) are transmembrane channel proteins essential for water homeostasis and cellular stress responses. In marine bivalves, their roles in cold tolerance remain poorly understood despite frequent winter mortality events in aquaculture. Here, we identified nine AQP genes in the genome of the economically important noble scallop Chlamys nobilis. Phylogenetic analysis revealed strong conservation with other bivalve AQPs, and structural features, including conserved NPA motifs and ar/R selectivity filters, support their canonical water/glycerol transport functions. Tissue-specific expression profiling showed predominant enrichment in osmoregulatory tissues (gills, intestine) and gonads. Under both chronic and acute low-temperature stress from 23 °C to 9 °C, most CnAQP genes exhibited transient upregulation followed by suppression. Notably, CnAQP4 displayed sustained upregulation, implicating it as a key mediator of long-term cold adaptation. Promoter analysis further revealed abundant cis-elements linked to growth and development as well as immune regulation. Our findings provide the first comprehensive characterization of the AQP family in C. nobilis, highlighting its critical role in maintaining cellular integrity during cold stress and offering molecular targets for selective breeding of cold-tolerant scallop strains.

Animals↗
PubMed2004

The utility of DNA microarrays for characterizing genotoxicity.

Microarrays provide an unprecedented opportunity for comprehensive concurrent analysis of thousands of genes. The global analysis of the response of genes to a toxic insult (toxicogenomics), as opposed to the historical method of examining a few select genes, provides a more complete picture of toxicologically significant events. Here we examine the utility of microarrays for providing mechanistic insights into the response of cells to DNA damage. Our data indicate that the value of the technology is in its potential to provide mechanistic insight into the mode of action of a genotoxic compound. Array-based expression profiling may be useful for differentiating compounds that interact directly with DNA from those compounds that are genotoxic via a secondary mechanism. As such, genomic microarrays may serve as a valuable alternative methodology that helps discriminate between these two classes of compounds. Key words: biomarkers, gene expression profile, genetic toxicology, mechanism of action, toxicogenomics.

Animals↗
PubMed2003

deCODE genetics, Inc.

deCODE genetics, Inc. has compiled the world's most comprehensive collection of population data on genealogy, genotypes and phenotypes. This combination of resources provides an effective system for identifying key genes linked to common diseases and to the regulation of drug response. deCODE has successfully mapped genes in over 25 common complex diseases and isolated genes in eight of these. The methodology used to map these genes is based upon the company's genealogical database of the Icelandic population, which enables deCODE scientists to efficiently conduct population- and genome-wide linkage studies to identify key genetic factors involved in phenotypes ranging from diseases to drug response. In its growing pharmacogenomics program, deCODE has combined this linkage approach with high-throughput expression profiling to develop accurate tests that can predict individual responsiveness to virtually any drug of interest. deCODE is applying its unrivaled discovery capabilities to bring to market new drugs, DNA-based diagnostic products and pharmacogenomic tests. The company believes that such tests will play a crucial role in delivering personalized medicine - contributing to the development of more effective means of diagnosing and treating disease by matching each patient with the most suitable drug.

Chromosome Mapping↗
PubMed2026

Exposome influences: a multi-omics perspective on the combined toxic effects of pharmaceuticals and personal care products in Alzheimer's disease.

According to WHO data, approximately 57 million people worldwide were affected by dementia in 2021, with prevalence projected to rise. Alzheimer's disease (AD), responsible for 60%-80% of dementia cases, continues to be a leading cause of mortality, with current treatments offering limited efficacy and disease-modifying therapies lacking widespread adoption or conclusive safety evidence, shifting the focus toward prevention and risk modification. Risk factors for AD include both non-modifiable elements, such as age, genetics, and gender, and modifiable factors, like environmental pollution, health status, and diet. While age remains the primary non-modifiable risk factor, early-onset dementia represents only up to 9% of cases. Addressing modifiable factors is essential, as it could prevent or delay almost half of dementia cases, with interventions-such as increased physical activity, smoking cessation, alcohol limitation, and overall health management-being significantly associated with a reduced risk. In this context, the exposome approach offers a comprehensive, integrative framework in which both modifiable and non-modifiable risk factors interact to influence individual susceptibility. Within the neural exposome, chronic low-dose exposure to xenobiotics-such as industrial chemicals, pesticides, metals, pharmaceuticals and personal care products (PPCPs), and air pollutants-may induce neurodegeneration via mechanisms including oxidative stress, neuroinflammation, proteinopathies, and epigenetic modifications, although establishing causality remains challenging. Integration of genomics, transcriptomics, proteomics, metabolomics, and lipidomics, combined with artificial intelligence (AI) techniques such as machine learning (ML) and deep learning (DL), provides promising avenues for biomarker discovery, enhanced preventive strategies, early non-invasive diagnosis, and therapeutic target identification by integrating multi-layered biological data with exposure profiles. This review highlights emerging AD risk factors-including PPCPs-underscoring complex, multifactorial nature of AD and exposome, and the requirement for an interdisciplinary research approach, while also addressing several critical research gaps and methodological limitations.

Alzheimer’s disease↗
PubMed2002

Global gene expression analysis of developing neocortex using SAGE.

The mammalian brain is estimated to contain about a hundred billion neurons, making it the most complex biological structure on earth. Trying to understand the assembly and function of this elaborate organ is a formidable task. Yet the information to build a brain is encoded by no more than a subset of the 80,000 genes present in the genome, a more manageable number. This review describes the use of SAGE technology (Serial Analysis of Gene Expression) to decode the genetic repertoire of genes that are differentially expressed in time and in space during development of the neocortex, the part of the mammalian brain responsible for complex traits. We demonstrate that SAGE is not only powerful for generating comprehensive molecular portraits from the developing cortex but can also assist in discovering new genes.

Animals↗
PubMed2001

Serial analysis of gene expression in chronic hepatitis C and hepatocellular carcinoma.

Hepatitis C virus (HCV) causes chronic hepatitis C (CH-C) and is epidemiologically linked with the occurrence of hepatocellular carcinoma (HCC). To elucidate the comprehensive gene expression profiles of CH-C and HCC, serial analysis of gene expression (SAGE) libraries were made from CH-C and HCC tissues of a patient, and compared with a reported SAGE library of a normal liver (NL). Scatter plots of the distribution of tags from the HCC library exhibited the existence of many differentially expressed genes compared with those from the CH-C and NL libraries. Up-regulation of IFN-gamma inducible genes and oxidative stress-inducible genes were identified in both the CH-C and HCC libraries, and some unpublished new genes were specifically up- or down-regulated in the HCC library. This genome-wide scanning study discloses the molecular portraits of CH-C and HCC, and provides novel candidate genes that should help clarify the mechanism of hepatocarcinogenesis in the chronically HCV-infected liver.

Base Sequence↗
PubMed2024

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species and strain level diversity and evolution.

Species of the Bacteroidales order are among the most abundant and stable bacterial members of the human gut microbiome with diverse impacts on human health. While Bacteroidales strains and species are genomically and functionally diverse, order-wide comparative analyses are lacking. We cultured and sequenced the genomes of 408 Bacteroidales isolates from healthy human donors representing nine genera and 35 species and performed comparative genomic, gene-specific, mobile gene, and metabolomic analyses. Families, genera, and species could be grouped based on many distinctive features. However, we also show extensive DNA transfer between diverse families, allowing for shared traits and strain evolution. Inter- and intra-specific diversity is also apparent in the metabolomic profiling studies. This highly characterized and diverse Bacteroidales culture collection with strain-resolved genomic and metabolomic analyses can serve as a resource to facilitate informed selection of strains for microbiome reconstitution.

Preprint↗