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PubMed2026

Lipid metabolism is a key central, systemic and gut microbial feature of the decline in rat hippocampal function during middle age.

Middle age is emerging as a turning point in brain ageing, prognostic of future cognitive health and amenable to intervention. Metabolic and proteomic differences during this period are not yet fully understood and may potentially influence functions of the hippocampus, a brain area that regulates memory and anxiety. While the gut microbiota is implicated in brain ageing, the relationship between the gut microbiota, the metabolic state, and hippocampal proteome in middle age has not been investigated. We hypothesise that peripheral metabolic or protein features are associated with hippocampal vulnerability in middle age. Therefore, young adult and middle-aged rats were assessed for behavioural, proteomic, metabolic, and gut microbiota differences. Proteomic profiling of the hippocampus revealed differential expression of proteins indicative of altered synaptic signalling. Concurrently, adult hippocampal neurogenesis was decreased in middle age. Hippocampal microglia exhibited a lipid rich, inflammatory phenotype in middle age which correlated with poorer memory performance. CSF and serum proteomic and metabolomic analyses identified dysregulated lipid-related pathways potentially contributing to hippocampal vulnerability in middle age. Furthermore, 16S rRNA sequencing revealed reduced abundance of bacteria involved in lipid metabolism regulation. However, faecal microbiota transfer from young to middle aged rats was not sufficient to robustly improve hippocampus-dependent spatial memory. Together, these findings highlight dysfunctional lipid metabolism as a key feature of middle age that may contribute to decline in hippocampal function. Given that the scope for intervention is limited during older age, targeting biomarkers involved in metabolic and lipid homeostasis may be pivotal for the development of pharmacological or lifestyle-based interventions during middle age which could ultimately delay future cognitive ageing.

Animals↗
PubMed2026

Integrating multi-omics technologies to decipher microbiome functions.

Multi-omics approaches have revolutionized our understanding of microbial communities by enabling simultaneous interrogation of genomic, transcriptomic, proteomic, and metabolomic data. The systematic integration and analysis of these deep datasets help decipher the functional roles of microbiomes, providing critical insights into microbial activities, interactions, and dynamics across diverse environments. Biological complexity makes multi-omics analysis of a single, isolated organism demanding but highly informative, yet this complexity increases further when samples comprise hundreds to thousands of individual species. As microbiome research continues to expand into clinical, environmental, and engineered systems, standardized workflows, benchmarked datasets, and community-driven initiatives are essential to ensure reproducibility, standardization and interpretability. Establishing and disseminating best practices for experimental design, data processing, and integrative analyses will be critical for maximizing comparability and scientific rigor across studies. This perspective highlights recent advances in multi-omics microbiome research, outlines key obstacles in data integration and metadata harmonization, and proposes a collaborative roadmap for scalable, FAIR-compliant multi-omics investigations and potentially disruptive Artificial Intelligence (AI) advances comparable to those of AlphaFold in the field of microbiome science.

Multiomics↗
PubMedDate not supplied

Identification and mapping of protein-protein interactions by a combination of cross-linking, cleavage, and proteomics.

Protein-protein interactions are vital for almost all cellular functions, and many require the formation of multiprotein complexes. Identification of the macroscopic and microscopic protein interactions within these complexes is essential in understanding their mechanisms, both under physiologic as well as pathologic conditions. This review describes the current technology available to investigate interactions between proteins utilizing chemical cross-linking and site-directed cleavage reagents, outlining the necessary steps involved in identifying interacting proteins both in vitro and in vivo. Once interacting proteins are identified, more information about the architecture of the assemblies is necessary. Unique separation techniques coupled with cross-linking and mass spectrometry can now identify specific interaction sites and lead to the development of quaternary structural protein models. Furthermore, combination of these methods with proteomic approaches enables the identification and analysis of complex interactions in vivo. Finally, future directions in cross-linking methodologies are discussed.

Cross-Linking Reagents↗
PubMed2026

Proteomic analysis of cisplatin-induced spermatogenesis defects in mice.

BACKGROUND: Cisplatin is a crucial chemotherapeutic agent used for treating various cancers; however, its excessive use can cause irreversible damage to the reproductive system, and the protein expression profile of cisplatin-induced testicular injury remains unclear. METHODS: Male C57BL/6 mice were treated with cisplatin at various doses, and testes were collected for histological, immunofluorescence, and proteomic analyses. Germ cell loss and apoptosis were assessed using H&E staining, TUNEL assays, and immunofluorescence for LIN28A, SYCP3, MVH, and CDK1. Label-free quantitative proteomics identified differentially expressed proteins, which were analyzed for functional enrichment and protein-protein interactions. RESULTS: We observed that cisplatin treatment led to smaller testes, reduced sperm count, and a significant decrease in the number of spermatocytes and spermatids in mice. Label-free quantitative proteomic analysis revealed that cisplatin significantly reduced the expression of cyclin-dependent kinase 1 (CDK1), a key spermatogenesis regulator, in the testes. Reduction in CDK1 expression is correlated with spermatogenic arrest, particularly in spermatocytes. CONCLUSION: These findings highlight the critical role of CDK1 in cisplatin-induced spermatogenic dysfunction and provide new insights into fertility preservation strategies for patients with cancer undergoing chemotherapy.

Animals↗
PubMed2004

Membrane trafficking in plants: new discoveries and approaches.

The general organization and function of the endomembrane system is highly conserved in eukaryotic cells. In addition, increasing numbers of studies demonstrate that normal plant growth and development are dependent on specialized tissue and subcellular-specific components of the plant membrane trafficking machinery. New approaches, including chemical genomics and proteomics, will likely accelerate our understanding of the diverse functions of the plant endomembrane system.

Abscisic Acid↗
PubMed2005

Proteomic analysis using an unfinished bacterial genome: the effects of subminimum inhibitory concentrations of antibiotics on Mannheimia haemolytica virulence factor expression.

Here we identify, using nonelectrophoretic proteomics, effects of subminimum inhibitory concentrations (subMIC) of two antibiotic preparations, chlortetracycline (CTC), and chlortetracycline-sulfamethazine (CTC + SMZ), on protein expression in the bovine respiratory pathogen Mannheimia haemolytica. The M. haemolytica genome is currently in draft form, and annotation is incomplete. Relying on the principle of gene sequence conservation across species, we used annotated genomes from closely related species to identify, confirm, and functionally annotate 495 M. haemolytica proteins. To conduct quantitative comparative proteomics, we developed a protein quantitation method based on the cross correlation function of the SEQUEST algorithm. When M. haemolytica was cultivated in the presence of 1/4 MIC of CTC and CTC + SMZ, expression of proteins involved in energy production, nucleotide metabolism, translation, and the bacterial stress response (chaperones) were affected. The most notable subMIC effect was a significant decrease in the expression of leukotoxin A, which is an important M. haemolytica virulence factor. Reduction in leukotoxin expression could be one of the molecular mechanisms responsible for the efficacy of these antibiotics against bovine respiratory disease.

Algorithms↗
PubMed2005

Dissecting the Rickettsia prowazekii genome: genetic and proteomic approaches.

The obligate nature of Rickettsia prowazekii intracellular growth places severe restrictions on the analysis of rickettsial gene function and gene expression. Fortunately, this situation is improving as methods for the genetic manipulation and proteomic analysis of this fascinating human pathogen become available. In this paper, we review the current status of rickettsial genetics and the isolation of rickettsial mutants using a genetic approach. In addition, the examination of rickettsial gene expression through characterization of the rickettsial proteome will be described. This will include a description of a high-throughput, accurate mass approach that has identified 596 rickettsial proteins in a complex rickettsial protein sample.

Bacteriological Techniques↗
PubMed2003

[Physiology of immune response genes].

In addition to performing its major physiological function--a control of the immune response, the major gene complex: HLA system, also maintains a human genetic diversity. The latter provides optimal conditions for survival of human being as species. We submit modern data on genome and proteome mechanisms which are principal for maintenance of these functions.

Animals↗
PubMed2004

Recent advances in neuroproteomics and potential application to studies of drug addiction.

The rapidly growing field of proteomics seeks to track changes in protein expression function that underlie the growth and differentiation of individual cell types, both during normal development and during the onset and progression of disease. Recent years have seen great strides in mRNA expression analysis, and the development of new technologies for protein profiling. However, current methods are limited to analysis of the relative expression level of only a few hundred to perhaps 2000 proteins, well below the ability of DNA microarrays to potentially interrogate the mRNA expression of more than 25,000 genes. Proteomics faces a special challenge in studies of the nervous system, where cellular and sub-cellular architecture is among the most complex in the body. This article presents an overview of current proteomic profiling technologies, reviews the recent use of some of these approaches in studies of the nervous system, and discusses the potential application of neuroproteomics to studies of drug addiction.

Animals↗
PubMed2002

Proteomics based on high-efficiency capillary separations.

Identifying and quantifying in a high throughput manner the proteins expressed by cells, tissues or an organism provides the basis for understanding the functions of its constituents at a "systems" level. As a result, proteome analysis has increasingly become the focus of significant interest and research over the past decade. This is especially true following the recent stunning achievements in genomics analyses. However, unlike the static genome, the complexities and dynamism of the proteome present significant analytical challenges and demand highly efficient separations and detection technologies. A number of recent technological advancements have been in direct response to these challenges. Currently, strategically mated combinations of sophisticated separations techniques and advanced mass spectrometric detection represent the best approach to addressing the intricacies of the proteome. Liquid-phase separations, often within capillaries, are increasingly recognized as the best separations technique for this approach. In combination on-line with mass spectrometry, liquid-phase separations provide the improved analytical sensitivity, sample throughput, and quantitation capabilities necessitated by the multifaceted problems within proteomics analyses. This review focuses primarily on current high-efficiency capillary separations techniques, including both capillary liquid chromatography and capillary electrophoresis, applied to the analysis of complex proteomic samples. We emphasize developments at our laboratory and illustrate technical advances that attempt to review the role of separations within the broader context of a state-of-the-art integrated proteomics effort.

Chromatography, Liquid↗
PubMed2004

Emerging biomarker technologies.

New technology offers great potential for advances in cancer biomarker research. Here, we describe a number of new technologies and discuss their potential for use in molecular cancer epidemiology. The successful sequencing of the human genome has revealed several new insights, including the fact that the human genome consists of only 40,000 genes and is highly variable, with approximately 60,000 functional polymorphisms. High-throughput genomic technologies continue to facilitate the identification and analysis of mutations and polymorphisms in key genes and expand the spectrum of available genomic biomarkers. The next major challenge is the identification of novel proteins and understanding the structure, function and interaction of proteins and other molecules--information that cannot be obtained from genomics alone. Emerging technologies including arrays, proteomics and nanotechnology provide new platforms for high-throughput, highly sensitive, functional assays. These technologies will complement existing and emerging genomic technologies and result in the identification of new biomarkers of cancer risk. They will, however, require extensive validation in epidemiological studies.

Biomarkers↗
PubMed2004

Applying proteomics to signaling networks.

The information from genome sequencing provides a new framework for a systems-wide understanding of protein networks and cellular function. Whereas microarray technologies provide information about global gene expression within cells, complementary proteomic strategies monitor expression of proteins and their posttranslational modifications. Improved technologies that have emerged for comprehensive and high-throughput protein analysis yield novel insights into cell regulation.

Animals↗
PubMed2026

An overview of the use of proteomics and peptidomics to characterize alternative protein foods.

The global protein transition is accelerating the development of alternative protein foods, mainly derived from plants, insects, algae, fungi, and cellular agriculture. Ensuring the authenticity, safety, and nutritional adequacy of these emerging protein matrices requires molecular-level characterization beyond traditional compositional analyses. Proteomics and peptidomics have emerged as transformative analytical platforms capable of decoding the molecular signatures that define protein origin, structural integrity, digestibility, functionality, and health potential. The review comprehensively examines the application of proteomics, and peptidomics for profiling alternative protein foods. Further, the source authentication strategies based on species-specific protein and peptide biomarkers, detection of adulteration in complex matrices, and allergenicity assessment is discussed. Special attention is also given to nutritional proteomics with protein digestibility, gastrointestinal peptide release, and identification of bioactive sequences. SIGNIFICANCE: The importance of this review is that proteomics and peptidomics are becoming central in the management of the fast-growing environment of alternative protein foods, such as plant-based, insect, algal, fungal, and cultured meat products. It provides an explanation of the application of mass spectrometry-based processes to decode molecular signatures defining the origin of proteins, their structural integrity, digestibility, allergenicity, and bioactive properties, and thus directly contribute to safety, nutritional analysis, and authenticity of the product. Presentation of the article includes the integration of the knowledge of traditional muscle foods with alternative systems of proteins, where validated protein and peptide biomarkers are used in authentication, fraud detection, and allergy risk assessment in a wide variety of matrices. It also indicates the role of nutritional proteomics and peptidomics in informing the formulation strategy to promote digestibility and release of health-promoting peptides. In general, this review will guide scientists, the food industry, and regulatory bodies to use modern proteomic technologies in quality assurance, and decision-making, for the advancementof sustainable protein-based foods.

Proteomics↗
PubMed2002

Linkage and linkage disequilibrium mapping of ERP and EEG phenotypes.

Linkage analyses of highly heritable electrophysiological phenotypes (EEG, ERP) that can potentially identify individuals at risk for alcoholism were performed on a large sample of families with a high density of alcohol dependence as part of the Collaborative Study on the Genetics of Alcoholism (COGA); these genetic findings are summarized. Quantitative trait loci (QTLs) were identified for several ERP characteristics (P300, N100, N400) and for the beta frequencies of the EEG where we report linkage and linkage disequilibrium at a GABA(A) receptor gene on chromosome 4. Genetic analyses of ERPs suggest that several regions of the human genome contain genetic loci related to the generation of N100, N400 and P300, which are possible candidate loci underlying the functional organization of human neuroelectric activity. The advent of genomics and proteomics and a fuller understanding of gene regulation, will open new horizons on the critical electrical events so essential for human brain function.

Adolescent↗
PubMed2003

PCAS--a precomputed proteome annotation database resource.

BACKGROUND: Many model proteomes or "complete" sets of proteins of given organisms are now publicly available. Much effort has been invested in computational annotation of those "draft" proteomes. Motif or domain based algorithms play a pivotal role in functional classification of proteins. Employing most available computational algorithms, mainly motif or domain recognition algorithms, we set up to develop an online proteome annotation system with integrated proteome annotation data to complement existing resources. RESULTS: We report here the development of PCAS (ProteinCentric Annotation System) as an online resource of pre-computed proteome annotation data. We applied most available motif or domain databases and their analysis methods, including hmmpfam search of HMMs in Pfam, SMART and TIGRFAM, RPS-PSIBLAST search of PSSMs in CDD, pfscan of PROSITE patterns and profiles, as well as PSI-BLAST search of SUPERFAMILY PSSMs. In addition, signal peptide and TM are predicted using SignalP and TMHMM respectively. We mapped SUPERFAMILY and COGs to InterPro, so the motif or domain databases are integrated through InterPro. PCAS displays table summaries of pre-computed data and a graphical presentation of motifs or domains relative to the protein. As of now, PCAS contains human IPI, mouse IPI, and rat IPI, A. thaliana, C. elegans, D. melanogaster, S. cerevisiae, and S. pombe proteome.PCAS is available at http://pak.cbi.pku.edu.cn/proteome/gca.php CONCLUSION: PCAS gives better annotation coverage for model proteomes by employing a wider collection of available algorithms. Besides presenting the most confident annotation data, PCAS also allows customized query so users can inspect statistically less significant boundary information as well. Therefore, besides providing general annotation information, PCAS could be used as a discovery platform. We plan to update PCAS twice a year. We will upgrade PCAS when new proteome annotation algorithms identified.

Algorithms↗
PubMed2006

Computational identification of beta-barrel outer-membrane proteins in Mycobacterium tuberculosis predicted proteomes as putative vaccine candidates.

Mycobacterial porins and other beta-barrel outer-membrane proteins are represented by the structure of Mycobacterium smegmatis porin MspA. On the basis of existing knowledge of beta-barrel outer-membrane proteins, several state of the art prediction methods, as well as a new in-house program (PROB) were employed for the systematic exploration of Mycobacterium tuberculosis predicted proteomes for potential beta-barrel structures. PROB allowed parameter optimization while functioning with an adaptive algorithm for the detection of outer-membrane beta-barrel proteins in highly divergent proteomes. As a result of the predictions, 114 proteins in total were predicted to be beta-barrel structures; of these, 40 were PE-PPE proteins, 8 Mce proteins, 24 hypothetical, 11 probable membrane proteins, 10 transporters, 4 lipoproteins, and 14 classified as other. The congruence among three of the predictors, PROB, TMB-Hunt, and BOMP, was low with only three proteins (MT0318, MT0356, and MT2423) predicted by the three. Overall, 79 new proteins for which no previous experimental work has been performed are reported. At least 10 of these have high potential of being not only surface-exposed but also served as putative vaccine candidates as determined by in silico predictions of CD4T cell MHC-II restricted epitopes.

Algorithms↗
PubMed2002

Functional protein microarrays.

Microarrays of immobilized functional proteins have the potential to increase dramatically the throughput of proteomic analysis. Micro-immunoassays, in which biological samples are exposed to arrays of immobilized antibodies, can be used for protein expression profiling. In addition, protein function can be elucidated by performing binding and enzymatic assays on arrays of biologically active proteins.

Animals↗
PubMed2005

The role of proteomics in investigating psychiatric disorders.

Proteomics is the study of protein expression and function on a genome-wide scale and its application in psychiatric research is relatively new. As protein expression is the mediator of genetic vulnerabilities, it is critical that this area is explored further to increase our understanding of psychiatric disease and reveal potential new treatments.

Brain↗