Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Comprehensive genomic profiling”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources
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. 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, metabolomic, and horizontal gene transfer analyses. Families, genera, and species could be grouped based on many distinctive features. We also observed extensive DNA transfer between diverse families, allowing for shared traits and strain evolution. Inter- and intra-species diversity is also apparent in the metabolomic profiling studies. This highly characterized and diverse Bacteroidales culture collection with strain-resolved genomic and metabolomic analyses represents a valuable resource to facilitate informed selection of strains for microbiome reconstitution.

Humans↗
PubMed2002

Gene expression in inherited breast cancer.

Large proportions of hereditary breast cancers are due to mutations in the two breast cancer susceptibility genes BRCA1 and BRCA2. Considerable effort has gone into studying the function(s) of these tumor suppressor genes, both in attempts to better understand why individuals with these inherited mutations acquire breast (and ovarian) cancer and to potentially develop better treatment strategies. The advent of tools such as cDNA microarrays has enabled researchers to study global gene expression patterns in, for example, primary tumors, thus providing more comprehensive overviews of tumor development and progression. Our recent study (Hedenfalk et al., 2001) strongly supports the principle that genomic approaches to classification of hereditary breast cancers are possible, and that further studies will likely identify the most significant genes that discriminate between subgroups and may influence prognosis and treatment. A large number of hereditary breast cancer cases cannot be accounted for by mutations in these two genes and are believed to be due to as yet unidentified breast cancer predisposition genes (BRCAx). Subclassification of these non-BRCA1/2 breast cancers using cDNA microarray-based gene expression profiling, followed by linkage analysis and/or investigation of genomic alterations, may help in the recognition of novel breast cancer predisposition loci. To summarize, gene expression-based analysis of hereditary breast cancer can potentially be used for classification purposes, as well as to expand upon our knowledge of differences between different forms of hereditary breast cancer. Initial studies indicate that a patient's genotype does in fact leave an identifiable trace on her/his cancer's gene expression profile.

BRCA1 Protein↗
PubMed2000

Comprehensive gene expression profile of the adult human renal cortex: analysis by cDNA array hybridization.

BACKGROUND: Profiling of gene expression in healthy and diseased renal tissue is important for elucidating the pathogenesis of renal diseases. Comprehensive information about the genes expressed in renal tissue is unavailable. The recently developed cDNA array hybridization methodology allows simultaneous monitoring of thousands of genes expressed renal tissue. METHODS: Complex [alpha-33P]-labeled cDNA probes were prepared from histopathologically uninvolved remnants of nine renal tissues obtained by nephrectomy. Each probe was hybridized to a high-density array of 18,326 paired target genes. The radioactive hybridization signals by phosphorimager screens were quantitated by special software. Bioinformatics from public genomic databases were used to assign a chromosomal location of each expressed transcript and gene function. Cluster analysis was used to arrange genes according to the similarity in pattern of gene expression. RESULTS: A total of 7563 different gene transcripts was detected in the nine tissue samples. Approximately 870 of these genes were full-length mRNA human transcripts (HT), and the remaining 6693 were expressed sequence tags (ESTs). The full-length transcripts were classified by function of the gene product and were listed with information of their chromosomal positions. To allow a comparison between gene expression in clinical and experimental studies, the mouse genes with known similar function to the human counterpart were included in the bioinformatics analysis. Cluster analysis of 502 full-length genes that are expressed in four or more renal tissues revealed more than 110 genes that are highly expressed in all the renal specimens. CONCLUSIONS: The presented data constitute a comprehensive preliminary transcriptional map of the adult human renal cortex. The information may serve as a resource for speeding up the discovery of genes underlying human renal disease. The integrated listing of the full-length expressed human and mouse genes is available through e-mail (Abdalla_Rifai@Brown.edu).

Adult↗
PubMed2004

Genetic relatedness among Campylobacter jejuni serotyped isolates of diverse origin as determined by numerical analysis of amplified fragment length polymorphism (AFLP) profiles.

AIMS: To use amplified fragment length polymorphism (AFLP) analysis to evaluate the genetic relatedness among 254 Campylobacter jejuni reference and field strains of diverse origin representing all defined 'Penner' serotypes for this species. METHODS AND RESULTS: Field strains (n = 207) from human diarrhoea and diverse animal and environmental sources were collected mainly through a National surveillance programme in Denmark and serotyped by use of the established 'Penner' scheme. Genetic relationships among these isolates, and the archetypal serotype reference strains, were assessed by numerical analysis of AFLP profiles derived from genomic DNA. Extensive genetic diversity was seen among the strains examined; however, 43 groups of isolates were identified at the 92% similarity (S-) level. Thirteen groups contained isolates from a single host, possibly representing genotypes of 'low risk' to human health. The remaining 30 groups contained isolates from humans, chickens and associated food products, cattle, sheep, turkeys, ostriches and/or dogs. Strains assigned to serotypes 2, 6/7, 11 and 12 formed major clusters at the 77.6% S-level. Most other serotypes did not form homogeneous clusters. CONCLUSIONS: High-resolution genotyping applied to strains from a comprehensive range of sources provides evidence for multiple sources of sporadic C. jejuni infection. The results suggest that public health protection measures should be directed at all foods of animal origin. SIGNIFICANCE AND IMPACT OF THE STUDY: The genetic relatedness among all 'Penner' serotypes of C. jejuni is assessed by AFLP analysis. In addition, further evidence of epidemic and host-specific clones of C. jejuni is provided.

Campylobacter Infections↗
PubMed2003

Genome-wide gene expression analysis of prostate carcinoma.

Advances in our knowledge of the molecular basis of prostate cancer have the potential to improve patient care and outcome. The investigative pace has recently been dramatically enhanced by the availability of the complete human genome sequence and the development of high-throughput technology for comprehensive genetic analysis. The application of genomic scale analysis to the study of prostate cancer has resulted in significant successes, including methods of more precise diagnosis and identification of potential prognostic markers and therapeutic targets. It is clear that these novel technologies and approaches provide many opportunities for biologists and clinicians; however, there are many challenges in moving these discoveries forward.

Androgen Antagonists↗
PubMed1998

Statistical features of human exons and their flanking regions.

To facilitate gene finding and for the investigation of human molecular genetics on a genome scale, we present a comprehensive survey on various statistical features of human exons. We first show that human exons with flanking genomic DNA sequences can be classified into 12 mutually exclusive categories. This classification could serve as a standard for future studies so that direct comparisons of results can be made. A database for eight categories (related to human genes in which coding regions are split by introns) was built from GenBank release 87.0 and analyzed by a number of methods to characterize statistical features of these sequences that may serve as controls or regulatory signals for gene expression. The statistical information compiled includes profiles of signals for transcription, splicing and translation, various compositional statistics and size distributions. Further analyses reveal novel correlations and constraints among different splicing features across an internal exon that are consistent with the Exon Definition model. This information is fundamental for a quantitative view of human gene organization, and should be invaluable for individual scientists to design human molecular genetics experiments.

Adenine↗
PubMed2026

Malignant epithelial states drive immune dysfunction in ampulla of Vater carcinoma.

BACKGROUND: Ampulla of Vater (AoV) carcinoma is a rare malignancy arising at the junction of intestinal and pancreatobiliary epithelium. Its heterogeneous clinical behavior and histological diversity have hindered therapeutic advances, and the cellular basis of this heterogeneity remains unclear. We aimed to construct a single-cell transcriptomic atlas of AoV carcinoma, with a focus on identifying epithelial subtypes and their interactions with the tumor microenvironment (TME). METHODS: We performed single-cell RNA sequencing on eight primary AoV tumors and four matched normal tissues. Comprehensive clustering and transcriptomic analyses identified cell-type composition, epithelial heterogeneity, and tumor-immune interactions. Findings were validated using deconvolution of bulk RNA-seq data from 62 AoV carcinoma patients. Results Malignant epithelial cells were categorized into four distinct subtypes: Int-Wnt, PB-KRAS, Int-Hypoxia, and Cycling stage. PB-KRAS cells exhibited stem-like transcriptional programs and high genomic instability. Deconvolution analysis of bulk RNA-seq data from the independent AoV cohort revealed that enrichment of the PB-KRAS subtype correlated with tumor recurrence and poor survival. Our immune profiling analysis discovered a significant association between PB-KRAS subtype and GZMK+ CD8+ T cells, which are in a pre-dysfunctional state, alongside SPP1+ macrophages exhibiting immunosuppressive traits. Spatial transcriptome data further supports the immunosuppressive natures of TME around PB-KRAS subtype malignant epithelial cells in AoV carcinoma. CONCLUSIONS: Our study presents a single-cell atlas of AoV carcinoma, highlighting the molecular diversity of malignant epithelium and its association with the immune microenvironment. The PB-KRAS subtype emerges as a stem-like, immunosuppressive tumor state associated with poor prognosis, providing insights for future therapeutic targeting.

Ampulla of Vater carcinoma↗
PubMed2003

Mining meiosis and gametogenesis with DNA microarrays.

Gametogenesis is a key developmental process that involves complex transcriptional regulation of numerous genes including many that are conserved between unicellular eukaryotes and mammals. Recent expression-profiling experiments using microarrays have provided insight into the co-ordinated transcription of several hundred genes during mitotic growth and meiotic development in budding and fission yeast. Furthermore, microarray-based studies have identified numerous loci that are regulated during the cell cycle or expressed in a germ-cell specific manner in eukaryotic model systems like Caenorhabditis elegans, Mus musculus as well as Homo sapiens. The unprecedented amount of information produced by post-genome biology has spawned novel approaches to organizing biological knowledge using currently available information technology. This review outlines experiments that contribute to an emerging comprehensive picture of the molecular machinery governing sexual reproduction in eukaryotes.

Animals↗
PubMed2004

Maximizing the efficacy of SAGE analysis identifies novel transcripts in Arabidopsis.

The efficacy of using Serial Analysis of Gene Expression (SAGE) to analyze the transcriptome of the model dicotyledonous plant Arabidopsis was assessed. We describe an iterative tag-to-gene matching process that exploits the availability of the whole genome sequence of Arabidopsis. The expression patterns of 98% of the annotated Arabidopsis genes could theoretically be evaluated through SAGE and using an iterative matching process 79% could be identified by a tag found at a unique site in the genome. A total of 145,170 reliable experimental tags from two Arabidopsis leaf tissue SAGE libraries were analyzed, of which 29,632 were distinct. The majority (93%) of the 12,988 experimental tags observed greater than once could be matched within the Arabidopsis genome. However, only 78% were matched to a single locus within the genome, reflecting the complexities associated with working in a highly duplicated genome. In addition to a comprehensive assessment of gene expression in Arabidopsis leaf tissue, we describe evidence of transcription from pseudo-genes as well as evidence of alternative mRNA processing and anti-sense transcription. This collection of experimental SAGE tags could be exploited to assist in the on-going annotation of the Arabidopsis genome.

Antisense Elements (Genetics)↗
PubMed2025

Molecular Characterization and Epidemiology of Human Noroviruses in the Sverdlovsk Region, Russian Federation.

Human noroviruses (HuNoVs) stand as the primary cause of acute viral gastroenteritis outbreaks worldwide, particularly impacting children under the age of five. In Russia, reports of norovirus gastroenteritis have surged, especially in the post-COVID-19 era starting in 2022, with elevated infection rates reported into 2024. These viruses exhibit significant mutational variability, leading to the emergence of recombinant strains that can evade immune responses. A comprehensive examination of the complete genome is crucial for understanding the evolution of norovirus genes and for predicting potential outbreaks. This research focuses on analyzing the genotypic composition of HuNoVs circulating in the Sverdlovsk region during 2024, using Sanger sequencing and next-generation sequencing (NGS). Biological samples were collected (n = 384) from patients diagnosed with norovirus infection within the region. Bioinformatics analysis targeted the nucleotide sequences of the ORF1/ORF2 fragment and the assembly of complete genomes for the GII.4 and GII.7 genotypes. In total, 220 HuNoVs were characterized, representing 57.3% of the collected samples. The main capsid variants forming the predominant genotypic profile included GII.4 (n = 88, 40%), GII.7 (n = 86, 39%), and GII.17 (n = 14, 6%). Using NGS, we successfully assembled 8 out of 10 complete genomes for noroviruses GII.4[P16] and GII.7[P7]. Non-synonymous substitutions appeared at amino acid sites corresponding to the subdomains of VP1 in these strains. This molecular-genetic analysis provides contemporary insights into the genotypic composition, circulation patterns, and evolutionary dynamics associated with the dominant genovariants GII.4[P16] and GII.7[P7].

Norovirus↗
PubMed1996

[Genetic screening of head-neck carcinomas using comparative genomic hybridization (CGH)].

BACKGROUND: Comparative Genomic Hybridization (CGH) is a novel cytogenetic method that allows the comprehensive analysis of a tumor genome for DNA gains and losses. METHODS: CGH was performed on genomic DNA extracted from 14 primary head and neck squamous cell carcinomas. Equal amounts of biotin-labeled tumor DNA and digoxigenin-labeled normal reference DNA were hybridized to normal metaphase chromosomes. The tumor DNA was visualized with fluorescein (FITC) and the normal DNA with rhodamine (TRITC) and detected in a fluorescence microscope. The signal intensities of the different fluorochromes were quantitated as gray levels along the single chromosomes. The over-and underrepresented DNA segments were quantified by computation of FITC/TRITC ratio images and average ratio profiles. RESULTS: Consensus deletion regions were most frequently observed on chromosome arms 3p (14 cases), 9p (11), 13q (10), 18q (10), 5q (9), 4q (9), 4p (7), 11q (7), 6q (6), 8p (6), and 11p (6). Copy number increases were identified for chromosomes 3q (11), 16p (9), 17q (9), 19p (8), 19q (7), 22 (7), 1p (6), 8q (6), 9q (6), and 20q (6). Particularly, the 3q isochromosome formation (3p loss/3q amplification), found in 10 cases, was a basic alteration. In addition, 11 tumors showed a 11 q13 amplification. CONCLUSION: CGH analysis allows the identification of recurrent genetic alterations in head and neck squamous cell carcinomas that will be associated with specific tumor phenotypes like metastatic behavior and prognosis.

Adult↗
PubMed2002

Generation of kidney transcriptomes using serial analysis of gene expression.

Chronic renal disease initiation and progression remain incompletely understood. Genomewide expression monitoring should clarify the mechanisms which cause progressive renal disease by determining how clusters of genes coordinately change their activity. Serial analysis of gene expression (SAGE) is a technique of expression profiling which permits simultaneous and quantitative analysis of 9- to 13-bp sequence tags that correspond to unique mRNAs. Key principles of the technique are use of PCR in a manner to minimize distortion and serial concatenation of tags which facilitates sequencing and permits identification of many expressed genes in a single cDNA molecule. Tags are extracted from many concatenated sequences, counted using software, and identified by comparison with existing gene databases. In aggregate, gene expression profiles generated from a tag library comprise a transcriptome which represents a comprehensive and quantitative profile of genes expressed at the time of analysis. These global snapshots of gene expression patterns can better define basic cell biology and provide insights into disease pathogenesis by simultaneously determining the net consequences of gene-gene and gene-environment interactions on expression of thousands of genes. Rather than applying a priori assumptions (i.e., hypothesis testing), transcriptome analysis is hypothesis generating and requires no prior knowledge of gene expression. SAGE kidney transcriptomes, from normal animals and animals with progressive kidney disease, are being produced and can be analyzed for novel pathogenetic mechanisms. The use of SAGE and other genomic and proteomic tools should result in a better understanding of kidney disease pathogenesis and in identification of new therapeutic targets.

Animals↗
PubMed2004

Genotyping and genetic diversity of Arcobacter butzleri by amplified fragment length polymorphism (AFLP) analysis.

AIMS: To investigate the potential of amplified fragment length polymorphism (AFLP) profiling for genotyping Arcobacter butzleri and to obtain further data on the genetic diversity of this organism. METHODS AND RESULTS: Seventy-three isolates of Danish, British, Turkish, Swedish, Nigerian and North American origin from human infections, chickens, turkeys, ducks, sheep and poultry abbatoir effluent were studied by use of a protocol that involved stringent PCR amplification of fragments derived from digestion of genomic DNA with restriction enzymes BglII and Csp6I. The mean similarity value of duplicate profiles of 10 isolates was 91.15%, indicating the method to be reproducible. Numerical analysis of all 73 isolates distinguished 51 subtypes at the 91% similarity level, of which 39 comprised single strains. The remaining 34 isolates were distributed among 12 subtypes, each of which contained strains homogeneous with respect to their respective source of isolation. However, contemporaneous strains from the same source could also be distinguished. CONCLUSIONS: AFLP profiling is an effective method for typing the genetically diverse organism A. butzleri. SIGNIFICANCE AND IMPACT OF THE STUDY: The study represents a comprehensive analysis of the genetic diversity of A. butzleri by use of isolates from six countries spanning three continents and also shows that several distinct A. butzleri genotypes may be found in a given environment. AFLP profiling appears to have considerable potential for molecular epidemiological studies of this ubiquitous emerging pathogen that is implicated as a causative agent of both human and animal disease.

Abattoirs↗
PubMed2026

Spindle Cell Predominant Anaplastic Pleomorphic Xanthoastrocytoma (WHO Grade 3) With Focal Piloid Features: A Rare Case Study With Comprehensive Molecular Profiling.

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor of the central nervous system. The typical form demonstrates relatively low-grade histologic features, whereas an anaplastic variant shows more aggressive behavior, including increased mitotic activity and necrotic changes. These tumors are often associated with alterations involving key growth signaling pathways and cell cycle regulatory genes, with molecular features that may resemble those seen in other high-grade astrocytic neoplasms. We describe an unusual example of an anaplastic pleomorphic xanthoastrocytoma showing focal piloid differentiation. The patient presented with acute neurologic symptoms, and imaging demonstrated a large, enhancing, well-circumscribed cerebral lesion with limited surrounding edema. Histologic evaluation revealed a highly cellular astrocytic neoplasm composed of spindle-shaped cells with marked pleomorphism, including scattered multinucleated forms, brisk mitotic activity, and necrotic areas. At the periphery, regions with elongated bipolar glial cells and occasional cytoplasmic inclusions suggestive of piloid morphology were identified. Molecular analysis demonstrated an activating alteration in the mitogen-activated protein kinase (MAPK) pathway along with additional genomic abnormalities, while mutations commonly associated with diffuse gliomas were not detected. The presence of piloid features within an otherwise anaplastic tumor is rare and may be relevant to the relatively favorable outcome observed during extended follow-up.

anaplastic↗
PubMed2026

Pan-genome characterization of the maize 4CL gene family and its dynamic responses to abiotic stress.

1.Pan-genome analysis across 26 maize inbred lines identified 13 Zm4CL genes (nine core and four near-core) classified into three evolutionary clades.2.Structural variations (SVs) are significantly associated with the expression and altered conserved protein domains of key Zm4CL genes.3.Zm4CL genes exhibit distinct tissue-specific expression patterns and dynamic enzymatic and transcriptional responses to stresses, particularly cold and drought.4-Coumarate:CoA ligase (4CL) is a key enzyme in the phenylpropanoid pathway and plays important roles in plant growth, development, and responses to environmental stresses. However, a comprehensive pan-genome analysis of the 4CL gene family in maize is still lacking. In this study, 13 Zm4CL genes were identified from a maize pan-genome comprising 26 diverse inbred lines, including nine core genes and four near-core genes. Phylogenetic analysis classified these genes into three evolutionary clades, while Ka/Ks analysis indicated that most members have been maintained under purifying selection, although several genes exhibited greater evolutionary divergence and relatively relaxed evolutionary constraints. Structural variation (SV) analysis revealed significant associations between SVs and the expression of Zm4CL2 and Zm4CL3, while sequence comparisons suggested that SVs were also associated with alterations in conserved protein domains in some genotypes. Transcriptome analyses revealed distinct tissue-specific expression patterns and diverse transcriptional responses to abiotic and biotic stresses. Enzyme activity assays showed that cold stress significantly increased 4CL activity at 12 h, whereas heat, salt, and alkali stresses caused an initial decrease followed by recovery, while drought had no significant effect. Time-course RT-qPCR further validated dynamic expression changes of representative Zm4CL genes under cold and drought stresses. Overall, this study provides a comprehensive pan-genome framework for understanding the evolutionary conservation, regulatory diversification, and stress-responsive characteristics of the maize Zm4CL gene family, providing valuable resources for future functional studies and the genetic improvement of stress tolerance in maize.

Zea mays↗
PubMed2026

Big data in multiple sclerosis.

PURPOSE OF REVIEW: This review summarizes recent key advancements in multiple sclerosis (MS) achieved through the utilization of big data from diverse sources and advanced analytical techniques. RECENT FINDINGS: Real-world evidence (RWE) derived from MS big data has significantly enhanced treatment strategies, redefined the concept of disease progression, refined prognostic models, and facilitated personalized medicine. RWE has highlighted the long-term benefits of early intensive treatment compared to escalation strategies, the unfavorable risk profile associated with treatment de-escalation and the importance of managing treatments during pregnancy. Additionally, it has revealed similarities and differences in the effectiveness and safety of specific high-efficacy therapies, as well as key predictors for switching treatments. RWE has also emphasized the central role of progression independent of relapse activity as a significant driver of disability and predictor of unfavorable long-term outcomes in both adult and pediatric onset MS. A data-driven approach utilizing artificial intelligence and big data has established a comprehensive framework for understanding the disease's evolution. Multimodal big data frameworks - encompassing clinical data, MRI, genomics, biomarkers, and app-based metrics - have demonstrated their ability to enhance diagnostic performance and risk stratification in MS. SUMMARY: Big data approaches are transforming MS research and clinical practice by providing stronger RWE to guide therapeutic decision-making, refining models of disease progression, and developing more precise prognostic tools.

Humans↗
PubMed2005

Gene expression analysis of peripheral blood leukocytes from discordant sib-pairs with schizophrenia and bipolar disorder reveals points of convergence between genetic and functional genomic approaches.

We performed global RNA transcript analysis and comprehensive gene group analysis of peripheral blood leukocyte (PBL) RNA from two groups of matched sib-pairs that were discordant for either schizophrenia (n = 33 sib-pairs) or bipolar disorder (n = 5 sib-pairs). The pairs chosen for these analyses were selected from families with known patterns of genetic linkage (5q for schizophrenia and 6q for bipolar disorder). At the single gene level, we obtained lists of the transcripts with the most significant changes in expression and from these lists determined those with the highest degree of predictive power for classifying subjects according to diagnosis in these samples. At the gene group level, we comprehensively analyzed pairwise expression changes of more than 4,000 functional groups and cytogenetic locations, and present a novel method of displaying these data that we term "cytogenomic" mapping. Verification of selected changes in expression was performed using quantitative real-time RT-PCR. Our results provide compelling evidence for the utility of analyzing PBL RNA for changes in expression in neuropsychiatric disorders.

Adult↗
PubMed2002

Identification of 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive genes in mouse liver by serial analysis of gene expression.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic environmental pollutants that causes various biological effects on mammals. To identify the genes involved in hepatotoxicity and hepatocarcinogenesis induced by TCDD, we have conducted here serial analysis of gene expression of mouse liver 7 days after treatment with a single oral dose of 20 microg TCDD/kg body weight. We have sequenced total of 113,067 tags, including 56,420 tags and 56,647 tags from normal liver and TCDD-treated liver library, respectively. Statistical analysis showed that TCDD significantly altered 346 transcripts (p < 0.05) including 94 ESTs. The genes regulated by TCDD were not only the genes encoding drug metabolizing enzymes and stress response genes but also a wide variety of genes encoding cytoskeleton related proteins, signal transduction, and plasma proteins. This comprehensive gene expression analysis would provide novel genes that may help to clarify the mechanism of TCDD effects on mammalian liver, and also give a new approach for prevention and treatment.

Animals↗