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PubMed2026

Fatty Acid Biosynthesis Inhibitors─Fabimycin and Triclosan─Trigger Distinct Resistance Mutations in FabI and Potently Kill Gram-Negative Pathogens.

In an effort to develop efficacious antibacterials that engage targets for which there is no preexisting resistance, inhibition of the enoyl-acyl carrier protein reductase FabI has shown promise, with triclosan and fabimycin as representative members of the two major drug classes that show activity against important bacterial pathogens. Here, we use a morbidostat and whole-genome sequencing approach to comprehensively evaluate the resistance profiles that arise in pathogenic bacteria in response to these FabI inhibitors. When assessed against E. coli, fabimycin and triclosan were found to induce primarily nonoverlapping resistance profiles, leading to minimal cross-resistance between the two compounds. Furthermore, in vivo evaluation of the prominent resistant mutants indicates poor fitness, with the fittest mutant still susceptible to fabimycin. Collectively, these results suggest the combination use of two antibiotics that engage different positions on the same target as a means to kill pathogenic bacteria and limit resistance.

Triclosan↗

PubMed2002

Application of metabolomics to plant genotype discrimination using statistics and machine learning.

MOTIVATION: Metabolomics is a post genomic technology which seeks to provide a comprehensive profile of all the metabolites present in a biological sample. This complements the mRNA profiles provided by microarrays, and the protein profiles provided by proteomics. To test the power of metabolome analysis we selected the problem of discrimating between related genotypes of Arabidopsis. Specifically, the problem tackled was to discrimate between two background genotypes (Col0 and C24) and, more significantly, the offspring produced by the crossbreeding of these two lines, the progeny (whose genotypes would differ only in their maternally inherited mitichondia and chloroplasts). OVERVIEW: A gas chromotography--mass spectrometry (GCMS) profiling protocol was used to identify 433 metabolites in the samples. The metabolomic profiles were compared using descriptive statistics which indicated that key primary metabolites vary more than other metabolites. We then applied neural networks to discriminate between the genotypes. This showed clearly that the two background lines can be discrimated between each other and their progeny, and indicated that the two progeny lines can also be discriminated. We applied Euclidean hierarchical and Principal Component Analysis (PCA) to help understand the basis of genotype discrimination. PCA indicated that malic acid and citrate are the two most important metabolites for discriminating between the background lines, and glucose and fructose are two most important metabolites for discriminating between the crosses. These results are consistant with genotype differences in mitochondia and chloroplasts.

Algorithms↗

PubMed2006

Advancement in characterization of genomic alterations for improved diagnosis, treatment and prognostics in cancer.

Most human cancers are characterized by genetic instabilities. These instabilities manifest themselves as a series of genetic alterations, including discrete mutations and chromosomal aberrations. With the human genome deciphered, high-throughput technologies are rapidly advancing the field to generate genome-wide gene expression and mutation profiles that are highly correlative of biologic and disease phenotypes. While recent advancement in comprehensive genomic characterization presents an unprecedented opportunity for advancing the treatment of cancer, there are still many challenges that need to be overcome before we can fully utilize genomic markers and targets for cancer prediction, diagnostics, treatment and prognostics. This review describes recent advances in comprehensive genomic characterization at the DNA level, and considers some of the challenges that remain for defining the precise genomic portrait of tumors. Potential solutions that may help overcome these challenges are also offered.

Animals↗

PubMed2006

Epigenetic instability and chromosomal instability in hepatocellular carcinoma.

The aim of this study was to clarify the association between the epigenetic instability phenotype and the chromosomal instability phenotype in primary hepatocellular carcinoma (HCC). Sixty primary HCC tumors were examined. Methylation status for nine CpG islands (the p16, COX2, GSTP1, RASSF1A, E-cadherin, and APC gene promoters, and the MINT 1, 25, and 31 clones) was evaluated by methylation-specific polymerase chain reaction. Chromosomal structural alterations of these 60 HCC tumors were characterized in our previous study by using whole genomic array-based comparative genomic hybridization. We found that the epigenetic instability phenotype and the chromosomal instability phenotype are not mutually exclusive in hepatocarcinogenesis and that they do not show a simple cause-and-effect relationship. Hepatitis virus infection in the background liver was significantly associated with these instability phenotypes. Furthermore, we identified an epigenetic instability-dependent HCC that shows frequent epigenetic aberrations without chromosomal instability. It was noteworthy that epigenetic instability-positive and -negative HCCs displayed distinctive combinations of chromosomal structural alterations. In summary, by combined analyses of genetic and epigenetic aberration profiles in HCC, we obtained a comprehensive view of genomic alterations in hepatocarcinogenesis. Our results have clinical relevance because epigenetic instability-dependent HCCs may respond well to methylation inhibitory therapies.

Adult↗

PubMed2003

Microarray expression profiling: capturing a genome-wide portrait of the transcriptome.

The bacterial transcriptome is a dynamic entity that reflects the organism's immediate, ongoing and genome-wide response to its environment. Microarray expression profiling provides a comprehensive portrait of the transcriptional world enabling us to view the organism as a 'system' that is more than the sum of its parts. The vigilance of microorganisms to environmental change, the alacrity of the transcriptional response, the short half-life of bacterial mRNA and the genome-scale nature of the investigation collectively explain the power of this method. These same features pose the most significant experimental design and execution issues which, unless surmounted, predictably generate a distorted image of the transcriptome. Conversely, the expression profile of a properly conceived and conducted microarray experiment can be used for hypothesis testing: disclosure of the metabolic and biosynthetic pathways that underlie adaptation of the organism to chang-ing conditions of growth; the identification of co-ordinately regulated genes; the regulatory circuits and signal transduction systems that mediate the adaptive response; and temporal features of developmental programmes. The study of bacterial pathogenesis by microarray expression profiling poses special challenges and opportunities. Although the technical hurdles are many, obtaining expression profiles of an organism growing in tissue will probably reveal strategies for growth and survival in the host's microenvironment. Identifying these colonization strategies and their cognate expression patterns involves a 'deconstruction' process that combines bioinformatics analysis and in vitro DNA array experimentation.

Bacteria↗

PubMed2004

Tissue microarrays.

The identification of disease-related genes is a major focus of modern biomedical research. Recent techniques, including array-based platforms for molecular profiling of disease tissues such as DNA arrays for expression profiling or matrix comparative genomic hybridization, allow for the comprehensive screening of the whole genome in a single experiment. Consequently, thousands of candidate genes have already been identified that may be linked to disease development and progression, and the process of lead discovery continues unimpeded. The evaluation of the clinical value of such leads is challenging because thousands of well-characterized tissue specimens must be analyzed. Tissue microarray (TMA) technology enables high-throughput tissue analyses to keep pace with the rapid process of lead discovery. With this technique, up to 1000 minute tissue samples are brought into an array format and analyzed simultaneously. The TMA technology is a fast, cost-effective, and statistically powerful method that will substantially facilitate translational research.

Animals↗

PubMed2026

MULTIPREVENT: Integrated screening for smoking-related multimorbidity using low-dose chest computed tomography.

OBJECTIVES: Tobacco consumption, combined with individual genetic predispositions, contributes to an age-dependent risk not only for lung cancer but also for other non-communicable diseases (NCDs) such as cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), osteoporosis, and diabetes. The MULTIPREVENT project aims to validate whether low-dose computed tomography (LDCT) of the chest, combined with simple biomarkers, functional tests, and genomic profiling, can serve as an effective tool for comprehensive health assessment and risk prediction of multimorbidity in adults. STUDY DESIGN: The study is based on a prospective epidemiological design involving 3000 participants from the MOLTEST-BIS lung cancer screening cohort (2016-2018). These participants, aged 50-79 years (during MOLTEST-BIS) and with a smoking history of at least 30 pack-years, will undergo two follow-up assessments in 2025-2027 and 2030-2032. METHODS: Each follow-up includes LDCT, spirometry, standardized blood pressure measurement, anthropometric evaluation, biomarker assessment (lipid profile, lipoprotein(a), glycated haemoglobin), and health-related questionnaires. Genetic profiling will be performed using the Illumina Infinium Global Screening Arrays approach to identify inherited predispositions to major NCDs. All data, clinical, imaging (including radiomics), molecular, and genetic, will be integrated through machine learning algorithms to develop AI-based risk prediction models. RESULTS: The MULTIPREVENT study is expected to generate a wide range of scientific, clinical, and infrastructural results that will serve as a foundation for future public health initiatives in integrated prevention. CONCLUSIONS: By linking imaging and biochemical markers, genetic susceptibility, and clinical parameters within a longitudinal design, MULTIPREVENT will establish data-driven, AI-supported prevention strategies aimed at reducing morbidity and mortality among adults exposed to tobacco. The project will also serve as a model for population-based multimorbidity prevention programs.

Humans↗

PubMed2025

Study Protocol for HeartMagic: A Prospective Observational Cohort Characterizing Subtypes of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure (HF) is a life-threatening syndrome with significant morbidity and mortality. Although evidence-based drug treatments have effectively reduced morbidity and mortality in HF with reduced ejection fraction (EF), few therapies have been demonstrated to improve outcomes in HF with preserved EF. This may be caused by the existence of several HF with preserved EF subtypes that each need different treatments. There is therefore an unmet need for a comprehensive approach to subtype patients with HF with preserved EF. This protocol details the approach employed in the HeartMagic (Heart Failure Studied With a Machine Learning, Genomics, and Imaging Combination) study to address this gap. METHODS: This prospective multicenter observational cohort study will include 500 consecutive patients with HF with preserved EF at 2 Swiss university hospitals, along with 50 age-matched patients with HF with reduced EF and 50 healthy controls. In addition to routine clinical workup, participants undergo genomic, transcriptomic, and metabolomic analyses, and the anatomy, composition, and function of the heart are quantified by comprehensive echocardiography and magnetic resonance imaging. Quantitative magnetic resonance imaging is also applied to characterize the kidney. The primary outcome is a composite of 1-year cardiovascular mortality or rehospitalization. Machine learning-based multimodal clustering will be employed to identify distinct HF with preserved EF subtypes. Statistical analysis will include group comparisons, survival analysis, and integrative multimodal clustering combining clinical, imaging, ECG, genomic, transcriptomic, and metabolomic data to identify and validate HF with preserved EF subtypes. CONCLUSIONS: The integration of comprehensive magnetic resonance imaging with extensive genomic and metabolomic profiling in this study will result in an unprecedented panoramic view of HF with preserved EF and help distinguish functional subgroups, which may provide a basis for personalized therapies.

Aged↗

PubMedDate not supplied

Regulation of microtubule, apoptosis, and cell cycle-related genes by taxotere in prostate cancer cells analyzed by microarray.

Taxotere showed antitumor activity against solid tumors including prostate cancer. However, the molecular mechanism(s) of action of Taxotere has not been fully elucidated. In order to establish such molecular mechanism(s) in both hormone-insensitive (PC3) and hormone-sensitive (LNCaP) prostate cancer cells, comprehensive gene expression profiles were obtained by Affymetrix Human Genome U133A Array. The RNA from the cells treated with 2 nM Taxotere was subjected to microarray analysis. We found that a total of 166, 365, and 1785 genes showed greater than two-fold change in PC3 cells after 6, 36, and 72 hours of treatment, respectively compared to 57, 823, and 964 genes in LNCaP cells. The expression of tubulin was decreased, whereas the expression of microtubule-associated proteins was increased in Taxotere-treated prostate cancer cells, confirming the microtubule-targeting effect of Taxotere. Clustering analysis showed downregulation of some genes for cell proliferation and cell cycle. In contrast, Taxotere upregulated some genes that are related to induction of apoptosis and cell cycle arrest. From these results, we conclude that Taxotere caused alterations of a large number of genes, many of which may contribute to the molecular mechanism(s) by which Taxotere affects prostate cancer cells. Further molecular studies are needed in order to determine the cause and effect relationships between these genes altered by Taxotere. Nevertheless, our results could be further exploited for devising strategies to optimize therapeutic effects of Taxotere for the treatment of prostate cancer.

Antineoplastic Agents, Phytogenic↗

PubMed2000

High-fidelity mRNA amplification for gene profiling.

The completion of the Human Genome Project has made possible the comprehensive analysis of gene expression, and cDNA microarrays are now being employed for expression analysis in cancer cell lines or excised surgical specimens. However, broader application of cDNA microarrays is limited by the amount of RNA required: 50-200 microg of total RNA (T-RNA) and 2-5 microg poly(A) RNA. To broaden the use of cDNA microarrays, some methods aiming at intensifying fluorescence signal have resulted in modest improvement. Methods devoted to amplifying starting poly(A) RNA or cDNA show promise, in that detection can be increased by orders of magnitude. However, despite the common use of these amplification procedures, no systematic assessment of their limits and biases has been documented. We devised a procedure that optimizes amplification of low-abundance RNA samples by combining antisense RNA (aRNA) amplification with a template-switching effect (Clonetech, Palo Alto, CA). The fidelity of aRNA amplified from 1:10,000 to 1:100,000 of commonly used input RNA was comparable to expression profiles observed with conventional poly(A) RNA- or T-RNA-based arrays.

Gene Amplification↗

PubMed2006

Gene expression profiling in the discovery, optimization and development of novel drugs: one universal screening platform.

With recent advances in robotics and high-content screening and analysis methods, transcriptional profiling can now be utilized as a comprehensive forward chemical genomics platform for drug discovery, lead selection and lead optimization. It can be used to define the state of a cell on the basis of gene networks, and to search for drugs that can shift cellular states in a manner predicted at the genome level to be therapeutically beneficial. The treatment of cells with compounds produces transcriptional 'fingerprints' that reveal mechanism-of-action, and enable discrimination between individual compounds based on drug behaviors important to all phases of drug discovery and development.

Animals↗

PubMed2026

The current and future perspective of ChickenGTEx project and its applications in precision breeding.

The Chicken Genotype-Tissue Expression (ChickenGTEx) project was established to systematically characterize the regulatory landscape of the chicken genome and to accelerate the translation of functional genomics into precision breeding. By integrating whole-genome sequencing with multi-tissue transcriptomic profiling, ChickenGTEx provides a comprehensive atlas of gene expression regulation across diverse tissues and physiological systems. Current findings demonstrate that complex production traits are governed by coordinated regulatory networks rather than isolated loci, with substantial contributions from tissue-specific gene expression, structural variation, and genotype-by-sex interactions. Sex-dependent regulatory effects further refine the genetic architecture of metabolic, immune, and reproductive traits, highlighting the importance of incorporating sex as a biological variable in genomic analyses. Application of integrative omics frameworks within elite layer populations has revealed multilayer regulatory mechanisms underlying extended laying performance, feed efficiency, metabolic health, and eggshell quality. By partitioning phenotypic variance into genetic, regulatory, and host-microbiome components, these approaches move beyond association-based mapping toward causal inference and biological interpretation. Importantly, validated regulatory loci identified through ChickenGTEx and related analyses provide actionable markers for genomic selection and rational targets for precision genome modification. Looking forward, continued expansion of regulatory atlases, incorporation of single-cell and longitudinal data in diverse environmental conditions, and integration of functional annotation into breeding pipelines will further enhance prediction accuracy and sustainable genetic improvement. The ChickenGTEx project thus represents a foundational platform bridging functional genomics and practical poultry breeding.

Animals↗

PubMed2027

Teratoma Formation and Genomic Profiling Using Multi-Omics Approaches.

Teratoma formation is the gold standard assay for evaluating the developmental pluripotency of human and mouse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Following subcutaneous injection into immunodeficient mice, pluripotent stem cells spontaneously differentiate into derivatives representing all three embryonic germ layers-ectoderm, mesoderm, and endoderm. Beyond serving as a functional assay for pluripotency, teratomas provide a unique three-dimensional model system for studying early human development and lineage specification in vivo. This chapter describes comprehensive protocols for teratoma formation in immunodeficient mice, tissue processing for multiple downstream genomic applications, and multi-omics profiling approaches. We detail methods for embryonic stem cell culture, teratoma generation via subcutaneous injection, tissue dissection and processing for chromatin immunoprecipitation followed by sequencing (ChIP-Seq), RNA sequencing (RNA-Seq), single-cell multiome profiling combining chromatin accessibility (ATAC-Seq) and gene expression (scRNA-Seq), and histological analysis using hematoxylin and eosin (H&E) staining. Additionally, we provide bioinformatics workflows for analyzing the resulting genomic datasets to characterize the epigenetic and transcriptional landscapes of teratoma-derived tissues. These methods enable comprehensive molecular characterization of developmental processes and provide valuable resources for stem cell biologists studying pluripotency, differentiation, and early embryonic development.

Teratoma↗

PubMed2006

Gene expression profiling analysis in nephrology: towards molecular definition of renal disease.

The increase in progressive kidney disease, resulting in a constantly rising prevalence of endstage renal disease (ESRD), urgently warrants the development of more effective strategies to diagnose, prevent, and intervene in renal disease. Histological information obtained by renal biopsies (RBx) is a cornerstone of the current management of kidney disease. Renal tissue can provide critical information on the disease process not available by nontissue-based approaches. However, insight gained by conventional histopathology remains limited and additional strategies to define renal disease on a molecular level are required. The sequencing of the human genome, together with recent advances in genome-wide profiling techniques, has provided the framework for a comprehensive analysis of renal disease-associated transcriptional programs. In this review, strategies to apply these technological advances towards the analysis of RBx will be described, with special emphasis on their potential impact on clinical management, but also on their inherent limitations. Finally, an outlook towards the emerging proteomic studies of renal disease will be given.

Antigens, CD20↗

PubMed2026

Probability of Mitochondrial DNA heteroplasmy in different tissues from European populations.

Mitochondrial DNA (mtDNA) heteroplasmy complicates genetic analyses due to its variability across individuals and tissues. We analyzed over 400 Spanish blood samples and integrated published Massively Parallel Sequencing (MPS) data from ten additional European tissues. Heteroplasmy was tissue-specific, with skeletal muscle, kidney, and liver showing the highest levels, while the intestines, skin, and cerebellum had the lowest. Blood uniquely displayed more heteroplasmies in coding than non-coding regions. Several conserved positions not previously described as hotspots showed high frequencies. These results establish the first comprehensive tissue-specific heteroplasmic profile of the complete mitochondrial genome in a European population, improving the interpretation of mtDNA variation in forensic and biomedical contexts.

Humans↗

PubMed2002

Metabolomics and microarrays for improved understanding of phenotypic characteristics controlled by both genomics and environmental constraints.

Advances in our understanding of functional genomics are best addressed by integrative studies that include measurements of mRNA, proteins, and low molecular weight metabolites over time and varied conditions. Bioinformatics can then be used to relate this data to the genome. Current technology allows for comprehensive and rapid mRNA expression profiling and mass spectrophotometric measurement of low molecular weight intermediates and metabolic products. In prokaryotic organisms, this combination provides a potentially powerful tool for identifying gene function and regulatory networks even in the absence of a combined proteomic approach.

Carbon Radioisotopes↗

PubMed2001

Cell encapsulation technology as a therapeutic strategy for CNS malignancies.

Gene therapy using viral vectors has to date failed to reveal its definitive clinical usefulness. Cell encapsulation technology represents an alternative, nonviral approach for the delivery of biologically active compounds to tumors. This strategy involves the use of genetically engineered producer cells that secrete a protein with therapeutic potential. The cells are encapsulated in an immunoisolating material that makes them suitable for transplantation. The capsules, or bioreactors, permit the release of recombinant proteins that may assert their effects in the tumor microenvironment. During the last decades, there has been significant progress in the development of encapsulation technologies that comprise devices for both macro- and microencapsulation. The polysaccharide alginate is the most commonly used material for cell encapsulation and is well tolerated by various tissues. A wide spectrum of cells and tissues has been encapsulated and implanted, both in animals and humans, indicating the general applicability of this approach for both research and medical purposes, including CNS malignancies. Gliomas most frequently recur at the resection site. To provide local and sustained drug delivery, the bioreactors can be implanted in the brain parenchyma or in the ventricular system. The development of comprehensive analyses of geno- and phenotypic profiles of a tumor (genomics and proteomics) may provide new and important guidelines for choosing the optimal combination of bioreactors and recombinant proteins for therapeutic use.

Alginates↗

PubMed1999

Comprehensive evaluation of isoprenoid biosynthesis regulation in Saccharomyces cerevisiae utilizing the Genome Reporter Matrix.

Gene expression profiling is rapidly becoming a mainstay of functional genomic studies. However, there have been relatively few studies of how the data from expression profiles integrate with more classic approaches to examine gene expression. This study used gene expression profiling of a portion of the genome of Saccharomyces cerevisiae to explore the impact of blocks in the isoprenoid biosynthetic pathway on the expression of genes and the regulation of this pathway. Approximately 50% of the genes whose expression was altered by blocks in isoprenoid biosynthesis were genes previously known to participate in the pathway. In contrast to this simple correspondence, the regulatory patterns revealed by different blocks, and in particular by antifungal azoles, was complex in a manner not anticipated by earlier studies.

Base Sequence↗