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Results for “Genomic profiling”

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PubMedDate not supplied

Genomics and phenotypic profiles in dementia: implications for pharmacological treatment.

Constitutive genomics are probably determinant for the onset of dementia in conjunction with cerebrovascular and environmental factors. Furthermore, pharmacogenomic studies predict that the therapeutic response in Alzheimer's disease (AD) is genotype-specific, and that the expression of genes involved in the regulation of drug metabolism can influence efficacy and safety issues in pharmacotherapy. AD and dementia with a vascular component (DVC = VD + MXD) are the most prevalent forms of dementia. These clinical entities share many similarities, but they differ in major phenotypic and genotypic profiles, as revealed by structural and functional genomics studies. Comparative phenotypic studies have identified significant differences in 25% of more than 100 parametric variables, including anthropometry, cardiovascular function, aortic atherosclerosis, brain atrophy, blood pressure, blood biochemistry, hematology, thyroid function, folic acid and vitamin B(12) levels, brain hemodynamics and lymphocyte markers. The phenotypic profile of patients with DVC differs from that of AD patients in the following: (a) anthropometric values, (b) cardiovascular function, (c) blood pressure, (d) lipid metabolism, (e) uric acid levels, (f) peripheral calcium levels, (g) liver function (GOT, GPT, GGT), (h) alkaline phosphatase, (i) lactate dehydrogenase, (j) red and white blood cells, (k) regional brain atrophy (left temporal region, inter-hippocampal distance) and (l) brain blood flow velocity. Functional genomics studies incorporating APOE-related changes in biological markers extended the difference between AD and DVC up to 57%. Structural genomics studies with AD-related genes, including APP, MAPT, APOE, PS1, PS2, A2M, ACE, AGT, cFOS and PRNP genes, demonstrate different genetic profiles in AD and DVC, with an absolute genetic variation rate ranging from 30 to 80%, depending upon genes and genetic clusters. Single gene analysis identifies relative genetic variations ranging from 0 to 5%. The relative polymorphic variation in genetic clusters integrated by 2, 3 or 4 genes associated with AD ranges from 1 to 3%. The main phenotypic differences between AD and DVC are genotype-dependent, especially in AD, probably indicating that different genomic factors are essential for the expression of dementia symptoms that might be accelerated or induced by environmental and/or cerebrovascular factors.

Age Distribution↗
PubMed2004

Genome-wide expression profiling of a cardiac pressure overload model identifies major metabolic and signaling pathway responses.

Cardiac hypertrophy is a predictor of cardiovascular morbidity and mortality independent of other risk factors. Pressure overload induces the development of left ventricular hypertrophy (LVH) and left atrial enlargement (LAE) in the mammalian heart. To systematically investigate the transcriptional changes, which mediate these processes, we have performed a genome-wide transcriptional profiling of each of the four heart chambers from mice subjected to transverse aortic constriction (TAC). A major new finding of this analysis is that during enlargement the left atrium undergoes radical changes in gene transcription that may play a significant role in pathophysiology. Structural changes in the LA and LV are correlated with significant changes in the transcriptional profile of these chambers, with thousands of differentially expressed known and novel factors. Statistical analysis of the results identified Gene Ontology biological process groups with significant group-wide changes, including angiogenesis, energy pathways, fatty acid oxidation, oxidative phosphorylation, cytoskeletal and matrix reorganization, and G-protein coupled receptor (GPCR) signaling. To facilitate future research, a searchable annotated Internet database has been constructed that allows access to the expression data presented here. Further study of these genes and processes will lead to better understanding of pathways involved in the pathophysiology of the cardiac response to pressure overload.

Animals↗
PubMed1997

Genotype analysis of human blood isolates of Campylobacter jejuni in England and Wales.

Genomic profiles were obtained for 76 strains of Campylobacter jejuni isolated from bacteraemic patients in England and Wales over the period 1981-94. Genotyping was performed by restriction fragment length polymorphism (RFLP) analysis using a random cloned DNA probe, and by ribotyping with a PCR-generated C. jejuni 16S ribosomal DNA probe. Phenotypic characterization was achieved by heat-stable (HS) and heat-labile (HL) serogrouping, and Preston phagetyping and biotyping. The blood isolates were genomically heterogenous, with 24 RFLP/16S profiles occurring within the 76 strains. Forty-four percent of isolates belonged to one of three RFLP/16S genotypes, reflecting the patterns seen in faecal isolates, except that genotypes usually associated with the HS 1 antigen were uncommon. The two most prevalent genotypes, characteristic of HS 2 and HS 4 strains, showed similarity by cluster analysis. Further evidence was seen of associations between phenotypic and genotypic characters within some HS serogroups. Chromosomal profiling by RFLP analysis does not indicate that particular genotypes have a predisposition to invade the bloodstream.

Bacteremia↗
PubMed2026

Spatial multiomics in biomedical research: advances beyond transcriptomics.

Coordinated changes in gene expression, epigenetic regulation, protein and metabolic activities together drive disease progression and determine clinical outcomes. While spatially resolved transcriptomics has been widely adopted across biomedical fields, it offers an incomplete picture limited to transcriptomic levels. Here, we survey the latest developments in spatial multiomics technologies, with particular emphasis on platforms that extend beyond conventional transcriptomics and profile genomics, epigenomics, proteomics, or metabolomics within intact tissues. These approaches are rapidly becoming commercialized, and here we highlight major technical breakthroughs, enhanced sample compatibility, emerging applications, and computational tools for data analysis. This Review aims to equip researchers with a clear understanding of the current technological landscape and to accelerate the adoption of spatial multiomics methods in biomedical research.

Humans↗
PubMed2004

Chemical genomics: probing protein function using small molecules.

Chemical genomics is concerned with the effects of both genetic variation and chemical perturbation on the cellular effects of small molecules. Chemical genomics relies on selecting biological networks for study, such as those represented by different cell types or disease models, in order to build the desired specificity into the experimental design. The most relevant network property for such experiments is the global connectivity of all cellular proteins comprising the functional ensemble, as illustrated by case studies of the evolution of cyclooxygenase inhibitors and heat-shock protein modulators. Recent examples of chemical genomic profiling, particularly of different cell types, highlight the power of carefully planned experimental approaches in chemical genomics. These new approaches demonstrate the use of the genome to find new targets or new modes of biological interaction.

Animals↗
PubMed2005

Using genome-wide transcriptional profiling to elucidate small-molecule mechanism.

Transcriptional profiling with DNA microarrays can be used to measure the genome-wide transcriptional response to small molecules. Recent progress in the analysis of gene-expression data has relied on the generation of databases of profiles documenting the transcriptional effects of various compound treatments and genetic perturbations. A positive correlation between the transcriptional response induced by a novel small molecule and a database profile can provide insight into the molecule's mechanism. Transcriptional profiling can also be used to assess a small molecule's specificity for its target and to facilitate analysis of pathways downstream of the target.

Gene Expression Profiling↗
PubMed2006

Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes.

Mammals are unable to regenerate their heart after major cardiomyocyte loss caused by myocardial infarction. Human embryonic stem cells (hESCs) can give rise to functional cardiomyocytes and therefore have exciting potential as a source of cells for replacement therapy. Understanding the molecular regulation of cardiomyocyte differentiation from stem cells is crucial for the stepwise enhancement and scaling of cardiomyocyte production that will be necessary for transplantation therapy. Our novel hESC differentiation protocol is now efficient enough for meaningful genome-wide transcriptional profiling by microarray technology of hESCs, differentiating toward cardiomyocytes. Here, we have identified and validated time-dependent gene expression patterns and shown a reflection of early embryonic events; induction of genes of the primary mesoderm and endodermal lineages is followed by those of cardiac progenitor cells and fetal cardiomyocytes in consecutive waves of known and novel genes. Collectively, these results permit enhancement of stepwise differentiation and facilitate isolation and expansion of cardiac progenitor cells. Furthermore, these genes may provide new clinically relevant clues for identifying causes of congenital heart defects.

Cell Differentiation↗
PubMed2003

Pulmonary gene expression profiling of inhaled ricin.

Aerosol exposure to ricin causes irreversible pathological changes of the respiratory tract resulting in epithelial necrosis, pulmonary edema and ultimately death. The pulmonary genomic profile of BALB/c mice inhalationally exposed to a lethal dose of ricin was examined using cDNA arrays. The expression profile of 1178 mRNA species was determined for ricin-exposed lung tissue, in which 34 genes had statistically significant changes in gene expression. Transcripts identified by the assay included those that facilitate tissue healing (early growth response gene (egr)-1), regulate inflammation (interleukin (IL)-6, tristetraproline (ttp)), cell growth (c-myc, cytokine-inducible SH2-containing protein (cish)- 3), apoptosis (T-cell death associated protein (tdag)51, pim-1) and DNA repair (ephrin type A receptor 2 (ephA2)). Manipulation of these gene products may provide a means of limiting the severe lung damage occurring at the cellular level. Transcriptional activation of egr-1, cish-3, c-myc and thrombospondin (tsp)-1 was already apparent when pathological and physiological changes were observed in the lungs at 12 h postexposure. These genes may well serve as markers for ricin-induced pulmonary toxicity. Ongoing studies are evaluating this aspect of the array data and the potential of several genes for clinical intervention.

Administration, Inhalation↗
PubMed2004

Combination treatment of glioblastoma multiforme cell lines with the anti-malarial artesunate and the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774.

New drugs and combination modalities for otherwise non-responsive brain tumors are urgently required. The anti-malarial artesunate (ART) and the EGFR tyrosine kinase inhibitor OSI-774 reveal profound cytotoxic activity. The effectiveness of a combination treatment and the underlying molecular determinants of cellular response are unknown. In the present investigation, we studied ART and OSI-774 in glioblastoma multiforme (GBM) cell lines. Supra-additive inhibition of cell growth was observed in U-87MG.DeltaEGFR cells transduced with a deletion-mutant constitutively active EGFR gene, while additive effects were present in cells transduced with wild-type EGFR (U-87MG.WT-2N), kinase-deficient EGFR (U-87MG.DK-2N), mock vector controls (U-87MG.LUX), or non-transduced parental U-87MG cells. Among nine other non-transduced GBM cell lines, supra-additive effects were found in two cell lines (G-210GM, G-599GM), while ART and OSI-774 acted in an additive manner in the other seven cell lines (G-211GM, G-750GM, G-1163GM, G-1187GM, G-1265GM, G-1301GM, and G-1408GM). Sub-additive or antagonistic effects were not observed. Genomic gains and losses of genetic material in the non-transduced cell lines as assessed by comparative genomic hybridization were correlated with the IC(50) values for ART and OSI-774 and subsequently subjected to hierarchical cluster analysis and cluster image mapping. A genomic profile of imbalances was detected that predicted cellular response to ART and OSI-774. The genes located at the genomic imbalances of interest may serve as candidate resistance genes of GBM cells towards ART and OSI-774. In conclusion, the combination treatment of ART and OSI-774 resulted in an increased growth inhibition of GBM cell lines as compared to each drug alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2026

Molecular epidemiology and genomic characteristics of clinical Acinetobacter baumannii isolates from patients with hospital-acquired pneumonia in China, 2019-2020: a multicentre retrospective study.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a leading cause of hospital-acquired pneumonia (HAP) with high mortality. However, large-scale nationwide data of HAP-causing CRAB in China remain limited. METHODS: Here, we performed a nationwide multicentre retrospective study to characterise the molecular epidemiology and genomic features of 802 A. baumannii isolates from patients with HAP across 33 tertiary hospitals in China during 2019-2020. Antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS), phylogenetic and comparative genomic analysis were used to investigate molecular epidemiology of HAP-causing CRAB strain. Clinical comparative analyses were carried out on data from 500 patients with HAP stratified by distinct antimicrobial susceptibility and genomic profiles, and a Galleria mellonella infection model was utilised for in vivo virulence assessment. FINDINGS: The overall carbapenem resistance rate of A. baumannii was 82.0% (658/802), with marked regional variations. CRAB exhibited high resistance to conventional agents but remained largely susceptible to polymyxin, tigecycline, cefiderocol and sulbactam-durlobactam. Among enrolled patients, CRAB infection was linked to substantially higher mortality (39.0% vs. 17.5%), and multivariate analysis confirmed ICU admission and advanced age as independent risk factors for patients with CRAB infection. Molecular typing revealed STPas2 (96.2%) as the absolutely predominant type; STOxf208, STOxf195, STOxf540, and STOxf369 were the most prevalent Oxford sequence types with obvious geographic stratification and divergent comorbidity profiles among corresponding patients. A total of 654 CRAB isolates harboured carbapenemase genes, with blaOXA-23 dominating at 98.8%. Genomic analysis revealed lineage-specific features: STOxf208 carried more virulence genes, while STOxf540 harboured a broader antimicrobial resistance genes (ARGs). The STOxf208 clone mainly belonged to KL2 (62.1%) and KL7 (36.8%) serotypes, with KL2 strains possessing richer ARGs and virulence factors, and in vivo virulence assays further validated that KL2 strains possessed higher pathogenicity than KL7 strains. INTERPRETATION: This study demonstrates the extremely high prevalence and clonal dominance of CRAB in Chinese patients with HAP, providing critical evidence for clinical treatment, antimicrobial stewardship, and targeted infection control. FUNDING: National Key Research and Development Program of China (2024YFE0106200), National Natural Science Foundation of China (U22A20338, 82502763, W2621007), Zhejiang Provincial Natural Science Foundation of China (LQN25H190006), Zhejiang Provincial Postdoctoral Science Foundation (ZJ2025058).

Acinetobacter baumannii↗
PubMed2025

Whole-Genome Sequencing of 54 Dengchuan Cattle (Bos taurus) from Southwest China.

Domestic cattle (Bos taurus) play a significant role in human society as they provide abundant food resources and contribute to the development of agriculture and traditional culture. Dengchuan cattle, a local breed from Yunnan, Southwest China, are known for their high-quality milk and are at risk of extinction due to crossbreeding. To preserve the superior genetic resources of Dengchuan cattle, this study conducted whole-genome sequencing of 54 Dengchuan cattle using blood DNA samples, generating approximately 3.56 TB of clean data with an average sequencing depth of 32.78X. The sequencing data were aligned to the bovine reference genome (ARS-UCD2.0), achieving an average alignment rate of 99.85%. A total of 9,950,420 SNPs and 2,476,207 indels were detected using variant calling workflow. These data were utilized to characterize genomic profile of this unique cattle breed. The data generated in this study can be incorporated into the global cattle genomic diversity database, providing valuable information for comparative studies on cattle.

Animals↗
PubMed2002

Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster.

BACKGROUND: We characterized RNA transcript levels for the whole Drosophila genome during normal aging. We compared age-dependent profiles from animals aged under full-nutrient conditions with profiles obtained from animals maintained on a low-calorie medium to determine if caloric restriction slows the aging process. Specific biological functions impacted by caloric restriction were identified using the Gene Ontology annotation. We used the global patterns of expression profiles to test if particular genomic regions contribute differentially to changes in transcript profiles with age and if global disregulation of gene expression occurs during aging. RESULTS: Whole-genome transcript profiles contained a statistically powerful genetic signature of normal aging. Nearly 23% of the genome changed in transcript representation with age. Caloric restriction was accompanied by a slowing of the progression of normal, age-related changes in transcript levels. Many genes, including those associated with stress response and oogenesis, showed age-dependent transcript representation. Caloric restriction resulted in the downregulation of genes primarily involved in cell growth, metabolism, and reproduction. We found no evidence that age-dependent changes in transcription level were confined to genes localized to specific regions of the genome and found no support for widespread disregulation of gene expression with age. CONCLUSIONS: Aging is characterized by highly dynamic changes in the expression of many genes, which provides a powerful molecular description of the normal aging process. Caloric restriction extends life span by slowing down the rate of normal aging. Transcription levels of genes from a wide variety of biological functions and processes are impacted by age and dietary conditions.

Aging↗
PubMedDate not supplied

Application of molecular genetic methods in diagnostics and epidemiology of food-borne bacterial pathogens.

Salmonella enterica, Campylobacter and Yersinia species, Shiga toxin-producing Escherichia coli (STEC), Listeria monocytogenes and Clostridium perfringens are the bacterial pathogens constituting the greatest burden of food-borne disease in Finland. Several molecular genetic methods have been applied to diagnose, discriminate and survey these bacteria. PCR, PCR-RFLP and PFGE are the most widely and successfully used. However, these methods are unable to replace conventional and internationally standardised phenotyping. Electronic database libraries of the different genomic profiles will enable continuous surveillance of infections and detection of possible infection clusters at an early stage. Furthermore, whole-genome sequence data have opened up new insights into epidemiological surveillance. Laboratory-based surveillance performed in a timely manner and exploiting adequate methods, and co-operation at local, national and international levels are among the key elements in preventing food-borne diseases. This paper reviews different applications of molecular genetic methods for investigating enteric bacterial pathogens and gives examples of the methods successfully used in diagnostics and epidemiological studies in Finland.

Bacteria↗
PubMed2025

Paratyphoid fever and the genomics of Salmonella enterica serovar Paratyphi A in Taiwan.

BACKGROUND: Salmonella enterica serovar Paratyphi A (S. Paratyphi A) has emerged as a significant global health concern due to the progressive development of antimicrobial resistance and its broader geographic distribution. In Taiwan, paratyphoid fever was historically rare and predominantly associated with imported cases. Since 2022, however, a marked increase in domestically acquired infections has been observed, prompting investigations into their origin and likely route of introduction. METHODS: We analyzed surveillance data on 223 patients with paratyphoid fever reported in Taiwan between January 2001 and December 2024. Whole-genome sequencing and antimicrobial susceptibility testing were performed on 88 S. Paratyphi A isolates obtained from both imported and domestically acquired infections from 2007 to 2024. Phylogenetic analysis and genotyping were conducted to assess genetic relatedness and to trace potential sources of introduction by comparing them with global isolates. RESULTS: Although 55.2% of paratyphoid fever infections were imported, domestically acquired infections became predominant after 2022. Most isolates (76.1%) were resistant to nalidixic acid and nonsusceptible to ciprofloxacin due to gyrA mutations at codon 83 (S83F or S83Y). The majority of domestic isolates were classified as ST129 and paratype 2.4 and showed close genetic relatedness to strains from Indonesia. Of the 31 domestic isolates collected between 2022 and 2024, 30 clustered with Indonesian strains, and 28 exhibited nearly identical genomic profiles, which suggested a prolonged outbreak likely linked to a common external source, such as contaminated imported food. CONCLUSIONS: The genomic evidence suggests that the recent increase in domestically acquired S. Paratyphi A infections in Taiwan represents a prolonged outbreak rather than a sustained epidemiological shift. These infections were closely related to strains from Indonesia, suggesting a potential epidemiological link between the two countries in the transmission of paratyphoid fever. While 76.1% of isolates were nonsusceptible to ciprofloxacin due to gyrA mutations, susceptibility to traditional first-line agents remained high. The observed decline in case numbers in 2024 may indicate that the outbreak is subsiding. Genomic surveillance played a crucial role in tracing sources of infection and informing targeted public health responses.

Paratyphoid Fever↗
PubMed2005

New paradigms in cardiovascular medicine: emerging technologies and practices: perioperative genomics.

Considerable progress has been made in understanding the pathophysiology of perioperative stress responses and their impact on the cardiovascular system; however, researchers are just beginning to unravel genetic and molecular determinants that predispose to increased risk for postoperative cardiovascular adverse events. A new field, coined perioperative genomics, aims to apply functional genomic approaches to uncover the biological reasons why similar patients can have dramatically different clinical outcomes after surgery. For the perioperative physician, such findings may soon translate into prospective risk assessment incorporating genomic profiling of markers important in inflammatory, thrombotic, vascular, and neurologic responses to perioperative stress, with implications ranging from individualized additional pre-operative testing and physiological optimization, to perioperative decision-making, choice of monitoring strategies, and critical care resource utilization. We review current knowledge regarding genomic technologies in perioperative cardiovascular disease characterization and outcome prediction, as well as discuss future trends/challenges for translating integrated "omic" information into daily clinical management of the surgical patient.

Animals↗
PubMed2001

Gene program for cardiac cell survival induced by transient ischemia in conscious pigs.

Therapy for ischemic heart disease has been directed traditionally at limiting cell necrosis. We determined by genome profiling whether ischemic myocardium can trigger a genetic program promoting cardiac cell survival, which would be a novel and potentially equally important mechanism of salvage. Although cardiac genomics is usually performed in rodents, we used a swine model of ischemia/reperfusion followed by ventricular dysfunction (stunning), which more closely resembles clinical conditions. Gene expression profiles were compared by subtractive hybridization between ischemic and normal tissue of the same hearts. About one-third (23/74) of the nuclear-encoded genes that were up-regulated in ischemic myocardium participate in survival mechanisms (inhibition of apoptosis, cytoprotection, cell growth, and stimulation of translation). The specificity of this response was confirmed by Northern blot and quantitative PCR. Unexpectedly, this program also included genes not previously described in cardiomyocytes. Up-regulation of survival genes was more profound in subendocardium over subepicardium, reflecting that this response in stunned myocardium was proportional to the severity of the ischemic insult. Thus, in a swine model that recapitulates human heart disease, nonlethal ischemia activates a genomic program of cell survival that relates to the time course of myocardial stunning and differs transmurally in relation to ischemic stress, which induced the stunning. Understanding the genes up-regulated during myocardial stunning, including those not previously described in the heart, and developing strategies that activate this program may open new avenues for therapy in ischemic heart disease.

Animals↗
PubMed2005

Chromosome 5p aberrations are early events in lung cancer: implication of glial cell line-derived neurotrophic factor in disease progression.

Lung cancer is the most widely diagnosed malignancy in the world. Understanding early-stage disease will give insight into its pathogenesis. Despite the fact that pre-invasive lesions are challenging to isolate, and often yield insufficient DNA for the analysis of multiple loci, genomic profiling of such lesions will lead to the discovery of causal genetic alterations, which may be otherwise masked by the gross instability associated with tumors. In this study, we report the identification of multiple early genetic events on chromosome 5p in lung cancer progression. Using a high-resolution 5p-specific genomic array, which contains a tiling path of DNA segments for comparative genomic hybridization, nine novel minimal regions of loss and gain were discovered in bronchial carcinoma in situ (CIS) specimens. Within these regions we identified two candidate genes novel to lung cancer. The 0.27 Mbp region at 5p15.2 contains a single gene, Triple Functional Domain, which we determined to be differentially expressed in tumors. The 0.34 Mbp region at 5p13.2 contains Glial Cell Line-Derived Neurotrophic Factor (GDNF), which is a ligand for the RET oncogene product and is normally expressed during lung development (but absent in adult lung tissue). Our data showed not only that GDNF is overexpressed at the transcript level in squamous non-small-cell lung carcinoma, but also that the GDNF protein is present in early-stage lesions. Reactivation of the fetal lung expressed GDNF in early lesions and its amplification in CIS suggests an early role in tumorigenesis. These results highlight the value of examining the genomes of pre-invasive stages of cancer at tiling resolution.

Chromosome Deletion↗
PubMed2004

Genome-wide expression profile of steroid response in Saccharomyces cerevisiae.

The response of the yeast Saccharomyces cerevisiae to human steroid hormone progesterone was studied by genomic expression profiling. The transcription profile data revealed that steroid response was a global phenomenon wherein a host of genes were affected. For example, 163 genes were upregulated and 40 genes were downregulated, by at least more than twofold. The major categories of upregulated genes included protein destination (15%), metabolism (14%), transport facilitation (12%), cell growth, cell division, and DNA synthesis (8%), and transcription (7%), while metabolism (22%), transcription (11%), intracellular transport (10%), cell growth, cell division, and DNA synthesis (10%), energy (8%), cell rescue, defense, and cell death (6%), and protein synthesis (6%) encoding genes were downregulated. Notwithstanding the fact that yeast cells do not possess commonly occurring steroid response cascade similar to higher eukaryotes, our results demonstrate that a short-term exposure to progesterone results in differential regulation of predominantly stress responsive genes.

Gene Expression Profiling↗