[Pancreatic carcinoma--changes in the genetic profile. Description and characterization using Genome Project techniques].
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Cell Transformation, Neoplastic↗
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Results for “Genomic characterization”
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Genomic and functional characterization of ST11-KL64 hypervirulence-associated carbapenem-resistant Klebsiella pneumoniae co-harboring bla KPC-2 and bla NDM-13.
BACKGROUND: Hypervirulence-associated carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) is a major clinical and public health threat. However, ST11-KL64 hv-CRKP co-harboring bla KPC-2 and bla NDM-13 remains poorly characterized, particularly regarding genomic relatedness, plasmid dynamics, and attenuated virulence-associated phenotypes. METHODS: We retrospectively investigated clinical K. pneumoniae isolates collected at a tertiary hospital in Chengdu, China, between January and December 2024. Hypervirulence-associated markers were screened by PCR, followed by antimicrobial susceptibility testing and carbapenemase inhibitor enhancement assay to identify genotype-defined hv-CRKP. All isolates were subjected to molecular typing. ST11-KL64 isolates co-harboring bla KPC-2 and bla NDM-13 were subjected to Illumina sequencing, with the representative isolate K3 undergoing hybrid whole-genome sequencing and functional characterization. RESULTS: Among the 46 hvKP isolates recovered from 43 patients, 35 were identified as hv-CRKP, predominantly ST11-KL64. Three ST11-KL64 hv-CRKP isolates co-harbored bla KPC-2/bla NDM-13, and Illumina sequencing coupled with core-genome SNP (cgSNP) typing revealed minimal genetic variation. The expanded cgSNP analysis supported close relatedness between K3 and Beijing isolate K56649. K3 carried a pLVPK-like virulence plasmid, a bla KPC-2-bearing IncFII/IncR plasmid, and a bla NDM-13-bearing IncI1 plasmid. Relative to pK2044, K3 exhibited an rmpA-proximal ISKpn26-associated insertion and a complex alteration of the 5'-terminal coding region of rmpA. The bla NDM-13 plasmid was conjugatively transferred to Escherichia coli C600 with a mean conjugation frequency of 5.213 × 10-3 transconjugants per recipient cell and bla NDM-13 maintained high stability following approximately 100 generations of antibiotic-free passage, whereas bla KPC-2 was not detected under the tested conditions. Phenotypically, K3 showed a negative string test, low mucoviscosity, and attenuated virulence-associated phenotypes. CONCLUSION: Our results reveal that the three isolates formed a closely related local genomic cluster, among which K3 was closely related to the K56649 clone. In addition, K3 exhibited conjugative transfer capacity of the bla NDM-13-bearing IncI1 plasmid, and alterations at the rmpA locus accompanied by reduced rmpA transcript abundance were associated with low mucoviscosity.
IncI1 plasmid↗
A large-scale comparison of genomic sequences: one promising approach.
We introduce a novel, linguistic-like method of genome analysis. We propose a natural approach to characterizing genomic sequences based on occurrences of fixed length words from a predefined, sufficiently large set of words (strings over the alphabet [A, C, G, T]). A measure based on this approach is called compositional spectrum and is actually a histogram of imperfect word occurrences. Our results assert that the compositional spectrum is an overall characteristic of a long sequence i.e., a complete genome or an uninterrupted part of a chromosome. This attribute is manifested in the similarity of spectra obtained on different stretches of the same genome, and simultaneously in a broad range of dissimilarities between spectral representations of different genomes. High flexibility characterizes this approach due to imperfect matching and as a result sets of relatively long words can be considered. The proposed approach may have various applications in intra- and intergenomic sequence comparisons.
Algorithms↗
Identification and molecular characterization of a bovine G3 rotavirus which causes age-independent diarrhea in cattle.
G3 rotaviruses have been reported rarely in cattle, and none have been characterized. We report the first genomic characterization of a bovine G3 rotavirus, CP-1, which had been biologically characterized in vivo and shown to cause age-independent diarrhea. CP-1 was a G3 rotavirus as its VP7 had 92 to 96% deduced amino acid identity to those of G3 rotaviruses. However, initially, CP-1 was identified as a G10 rotavirus by RT-PCR even though the CP-1 VP7 had only 81 to 85% deduced amino acid identity to those of G10 rotaviruses. Rotavirus CP-1 was of P[5] specificity, a type common in cattle, and had a bovine NSP1 and NSP4. These results added another animal species to those in which G3 rotaviruses have been found, characterized a bovine rotavirus which caused age-independent diarrhea in calves, and raised the possibility that bovine G3 rotaviruses may be misdiagnosed as G10 rotaviruses.
Age Factors↗
Mobile genetic elements-driven partitions of mega-plasmids resistome in Salmonella Infantis.
Salmonella enterica serovar Infantis (S. Infantis) becomes the primary pathogen among the top Salmonella serotypes, contributing to numerous cases of foodborne illness annually in the United States. S. Infantis infection has spread rapidly worldwide, especially the clones with pESI-like plasmids. However, the underlying mechanisms regarding the transmission of S. Infantis, particularly mobile genetic elements (MGEs), mediated horizontal gene transfer, are limited. The objective of this study was to evaluate the relationship, if any, among MGEs, antibiotic-resistant genes (ARGs), and virulence factors (VFs) within S. Infantis via genomic analysis. A total of 91 S. Infantis complete genomes with high sequencing quality were selected for downstream bioinformatic analysis. The results showed that the majority of VFs were located in the bacterial chromosomes, while most ARGs were carried by S. Infantis mega-plasmids in an MGE-favored manner. Integrons and transposons were closely associated with certain ARGs, but prophages within mega-plasmids displayed a diverse ARG profile. Collectively, MGE-mediated horizontal gene transfer might lead to ARG acquisition by mega-plasmids, subsequently contributing to the resistome of S. Infantis. Our findings provide insights into the development of MGE-associated resistome in S. Infantis that could inform more effective prevention and intervention strategies to control this pathogen, further ensuring public health and safety.IMPORTANCEThe rapid emergence and transmission of antibiotic-resistant foodborne pathogens pose a significant risk to public health, necessitating the discovery of underlying mechanisms to control multidrug-resistant pathogens. Salmonella enterica serovar Infantis (S. Infantis) has become a pathogen of clinical and epidemiological relevance in recent years, ranking as the top prevalent serovar associated with foodborne illnesses and exhibiting resistance to several antibiotics. The current investigation of multidrug resistance (MDR) S. Infantis strains primarily emphasized the presence of mega-plasmids. However, the question of how mega-plasmids contribute to the transmission of antibiotic-resistant genes (ARG) is unaddressed. Utilizing the genomic characterization of S. Infantis complete genomes with high quality, our study revealed that the resistome of S. Infantis mega-plasmids-the primary ARG reservoirs of S. Infantis-followed a specific pattern of mobile genetic elements (MGEs). Monitoring the spread of MGE-carried ARGs within mega-plasmids should be considered in future surveillance.
Interspersed Repetitive Sequences↗
[Nutritional genomics: toward a personalized diet].
Nutrigenomics is the application of high-throughput genomics tools to the study of diet-gene interactions in order to identify dietetic components having beneficial or detrimental health effects. Nutrition becomes indeed one of the environmental factors influencing gene expression. We can consider nutrigenomics as a multidisciplinary science that comes after the human genome characterization and that put the genomic techniques besides the biochemical and epidemiological aspects, with the aim to understand the etiologic aspects of chronic diseases such as cancer, type 2 diabetes mellitus (T2DM), obesity, cardiovascular diseases (CVD), metabolic syndrome, etc. Nutrigenomics is linked to nutrigenetics, which studies the genetic basis of the different individual response to the same nutritional stimulus. This phenomenon arises from gene polymorphism. As a consequence genes are important in determining a function, but nutrition is able to modify the degree of gene expression. These are however theories only at an early stage, but a perspective in the change of dietetic intervention is emerging. A really personalized diet will be a diet considering the nutritional status, the nutritional needs based on age, body composition, work and physical activities, but also considering the genotype. The integration of all these information and in particular the ones arising from genomic, proteomic and metabolomic analyses will be useful to define the "nutritional phenotype".
Diet↗
The human ETS1 gene: genomic structure, promoter characterization and alternative splicing.
Genomic clones encompassing the human ETS1 gene were isolated and utilized to define its molecular organization. This gene consists of eight exons spanning over 60 kb. The 5' end of the human ETS1 gene was subcloned and characterized. S1 nuclease, primer extension and RNAase protection analyses of human mRNAs showed multiple transcription initiation sites. DNA sequence analysis indicated a high G + C content in the promoter region and the absence of either a 'TATA' box or a 'CAAT' box. Six consensus recognition sequences for the transcription factor SP1, two AP1 consensus sequences and one consensus AP2 recognition sequence were identified, as well as two GC elements with dyad symmetry. A palindromic region similar to the serum response element of the c-fos gene and two octamer consensus recognition sequences were located upstream of the promoter region. A series of promoter deletion constructs positioned upstream from the bacterial chloramphenicol acetyl transferase gene were transfected into HeLa cells and their functional promoter activity assayed. The deletion constructs identified the 5' boundary for maximum promoter activity at 486 bp upstream of the first initiation site and suggest possible positive and negative regulatory regions. Polymerase chain reaction analysis of ETS1 cDNA identified several amplified products, indicating alternative splicing. In addition to the presence of mRNA products lacking exon VII, products lacking exon IV, as well as ones lacking both exons IV and VII, were found.
Base Sequence↗
Evaluation of affymetrix severe acute respiratory syndrome resequencing GeneChips in characterization of the genomes of two strains of coronavirus infecting humans.
Severe acute respiratory syndrome (SARS) was discovered during a recent global outbreak of atypical pneumonia. A number of immunologic and molecular studies of the clinical samples led to the conclusion that a novel coronavirus (SARS-CoV) was associated with the outbreak. Later, a SARS resequencing GeneChip was developed by Affymetrix to characterize the complete genome of SARS-CoV on a single GeneChip. The present study was carried out to evaluate the performance of SARS resequencing GeneChips. Two human SARS-CoV strains (CDC#200301157 and Urbani) were resequenced by the SARS GeneChips. Five overlapping PCR amplicons were generated for each strain and hybridized with these GeneChips. The successfully hybridized GeneChips generated nucleotide sequences of nearly complete genomes for the two SARS-CoV strains with an average call rate of 94.6%. Multiple alignments of nucleotide sequences obtained from SARS GeneChips and conventional sequencing revealed full concordance. Furthermore, the GeneChip-based analysis revealed no additional polymorphic sites. The results of this study suggest that GeneChip-based genome characterization is fast and reproducible. Thus, SARS resequencing GeneChips may be employed as an alternate tool to obtain genome sequences of SARS-CoV strains pathogenic for humans in order to further understand the transmission dynamics of these viruses.
Genome, Viral↗
The transposable element landscape of the model legume Lotus japonicus.
The largest component of plant and animal genomes characterized to date is transposable elements (TEs). The availability of a significant amount of Lotus japonicus genome sequence has permitted for the first time a comprehensive study of the TE landscape in a legume species. Here we report the results of a combined computer-assisted and experimental analysis of the TEs in the 32.4 Mb of finished TAC clones. While computer-assisted analysis facilitated a determination of TE abundance and diversity, the availability of complete TAC sequences permitted identification of full-length TEs, which facilitated the design of tools for genomewide experimental analysis. In addition to containing all TE types found in previously characterized plant genomes, the TE component of L. japonicus contained several surprises. First, it is the second species (after Oryza sativa) found to be rich in Pack-MULEs, with >1000 elements that have captured and amplified gene fragments. In addition, we have identified what appears to be a legume-specific MULE family that was previously identified only in fungal species. Finally, the L. japonicus genome contains many hundreds, perhaps thousands of Sireviruses: Ty1/copia-like elements with an extra ORF. Significantly, several of the L. japonicus Sireviruses have recently amplified and may still be actively transposing.
Chromosome Mapping↗
An infrastructure for comparative genomics to functionally characterize genes and proteins.
Current genome projects are resulting in a flood of sequence data. The interpretation of these sequences is lagging, and optimized data analysis strategies need to be developed. Much can be learned from comparing different genomes, as genomes of distant organisms may still encode proteins with high sequence similarity. The order of genes (co linearity) in genomes may also be conserved to some extend. We have employed both these observations to create a multi-functional, computational analysis system (genomeSCOUT) which allows for rapid identification and functional characterization of genes and proteins through genome comparison. With a number of independent algorithms, information about different levels of protein homology (concerning e.g. paralogs, orthologs and clusters of orthologous groups, COGs) and gene order is collected and stored in several value added databases. These databases are then used for interactive comparison of genomes and subsequent analysis. The application is based on the well established data integration system SRS. This ensures (1) fast handling of large genomic data sets, (2) straightforward access to a multitude of biological databases, (3) unique linking functions between these databases, (4) highly efficient collection of information on genes and proteins, and 5. fully integrated and user friendly graphical representations of search results. This application can be used for projects as diverse as the correct annotation of genomes, the optimization of (micro) organisms for industrial production, or the identification of drug targets.
Computational Biology↗
Sensitive multistep clinical molecular screening of 180 unrelated individuals with retinoblastoma detects 36 novel mutations in the RB1 gene.
Retinoblastoma (RB) is a neoplasm of retinal origin caused by mutations in RB1, the retinoblastoma tumor suppressor gene. To facilitate genetics counseling and patient management, we adopted a multistep molecular screening assay for detecting RB1 mutations. This assay included DNA sequencing to identify mutations within coding exons and immediate flanking intronic regions, Southern blot analysis to characterize genomic rearrangements, and transcript analysis to characterize potential splicing mutations buried within introns. In a pilot investigation of 180 patients from North America, we identified germline RB1 mutations in 77 out of 85 bilateral RB patients (91%), 7 out of 10 familial unilateral (70%), and 6 out of 85 unilateral patients with no family history of RB (7%). Mutations included 36 novel alterations spanning the entire RB1 gene. Seven of these novel changes were missense or silent mutations. Sequence analysis predicted that, in five out of seven cases, the changes can cause aberrant splicing. This was confirmed by transcript analysis in four out of five cases. In addition, four intronic point mutations within nonconsensus sites activated cryptic splice sites. Without the transcript analysis, the significance of these 11 mutations would have remained undefined. In a separate investigation of a subset of unilateral RB tumors, we identified somatic biallelic RB1 gene inactivation in 34 out of 56 cases (61%) cases. In 14 tumors, only one of the two RB1 mutations could be detected, and in eight tumors, no mutations were detected. The absence of detectable RB1 mutations in eight bilateral cases and eight unilateral tumors suggests that alternative genetic mechanisms may underlie the development of RB in certain individuals.
DNA Mutational Analysis↗
Proteomic studies of human and other vertebrate muscle proteins.
This review summarizes results of some systemic studies of muscle proteins of humans and some other vertebrates. The studies, started after introduction of two-dimensional gel electrophoresis of O'Farrell, were significantly extended during development of proteomics, a special branch of functional genomics. Special attention is paid to analysis of characteristic features of strategy for practical realization of the systemic approach during three main stages of these studies: pre-genomic, genomic (with organizational registration of proteomics), and post-genomic characterized by active use of structural genomics data. Proteomic technologies play an important role in detection of changes in isoforms of various muscle proteins (myosins, troponins, etc.). These changes possibly reflecting tissue specificity of gene expression may underline functional state of muscle tissues under normal and pathological conditions, and such proteomic analysis is now used in various fields of medicine.
Animals↗
Characterization of Sepik and Entebbe bat viruses closely related to yellow fever virus.
Yellow fever virus has a special place in medical history as the first animal virus isolated and as the prototype virus in the genus Flavivirus, which contains many serious human pathogens. Only recently, its closely related viruses within the group were identified phylogenetically. In this study, we obtained complete or near complete genome sequences of two viruses most closely related to yellow fever virus: Sepik virus of Papua New Guinea and Entebbe bat virus of Africa. Based on full-genomic characterization and genomic traits among related viruses, we identified Sepik virus to be most closely related to yellow fever virus and analyzed the pattern of repeat and conserved sequence motifs in the 3'-noncoding region among the members of yellow fever virus cluster. We also discuss the geographic dispersal as a part of ecological traits of this lineage of flaviviruses.
Amino Acid Sequence↗
Holistic approaches for improvement of maize resistance against lodging stress: current status and future perspective.
Lodging is a major constraint in maize production, causing significant yield losses, reduced grain quality, and harvesting inefficiencies, thereby posing a serious challenge to global food security and climate-resilient agriculture. This review synthesizes current knowledge on the genetic, physiological, and agronomic determinants of maize lodging resistance and evaluates holistic strategies for improving tolerance to lodging stress. Recent advances in quantitative trait locus (QTL) mapping, genome-wide association studies (GWAS), functional gene characterization, genome editing, high-throughput phenotyping, and precision agronomy have provided powerful tools to enhance stalk biomechanics, root anchorage, and adaptive plant architecture. Integrating genomic discovery with advanced phenomics and optimized agronomic management offers a scalable framework for accelerating the development of high-yielding, lodging-resilient maize cultivars. However, critical gaps remain in understanding the genetic coordination between stalk strength and root system architecture, integrating multi-omics approaches to unravel regulatory networks, validating genome-editing interventions across diverse agro-ecologies, and developing environment-responsive predictive breeding models and cost-effective phenotyping tools, particularly for stress-prone regions. Addressing these challenges through coordinated multi-environment trials and integrative molecular-agronomic strategies will facilitate the translation of genomic discoveries into climate-resilient, high-performing maize cultivars. By consolidating molecular insights with applied breeding and management practices, this review provides a comprehensive framework that guides researchers in designing genome-informed and field-validated approaches to improve maize resistance to lodging stress and support sustainable crop production systems.
Zea mays↗
Environmental genomics: exploring ecological sequence space.
The ability to extract and characterize genomic DNA fragments from mixed microbial assemblages is providing novel insights into the ecology, evolution, and metabolism of uncultured microorganisms in nature.
Biodiversity↗
ASAP: amplification, sequencing & annotation of plastomes.
BACKGROUND: Availability of DNA sequence information is vital for pursuing structural, functional and comparative genomics studies in plastids. Traditionally, the first step in mining the valuable information within a chloroplast genome requires sequencing a chloroplast plasmid library or BAC clones. These activities involve complicated preparatory procedures like chloroplast DNA isolation or identification of the appropriate BAC clones to be sequenced. Rolling circle amplification (RCA) is being used currently to amplify the chloroplast genome from purified chloroplast DNA and the resulting products are sheared and cloned prior to sequencing. Herein we present a universal high-throughput, rapid PCR-based technique to amplify, sequence and assemble plastid genome sequence from diverse species in a short time and at reasonable cost from total plant DNA, using the large inverted repeat region from strawberry and peach as proof of concept. The method exploits the highly conserved coding regions or intergenic regions of plastid genes. Using an informatics approach, chloroplast DNA sequence information from 5 available eudicot plastomes was aligned to identify the most conserved regions. Cognate primer pairs were then designed to generate approximately 1 - 1.2 kb overlapping amplicons from the inverted repeat region in 14 diverse genera. RESULTS: 100% coverage of the inverted repeat region was obtained from Arabidopsis, tobacco, orange, strawberry, peach, lettuce, tomato and Amaranthus. Over 80% coverage was obtained from distant species, including Ginkgo, loblolly pine and Equisetum. Sequence from the inverted repeat region of strawberry and peach plastome was obtained, annotated and analyzed. Additionally, a polymorphic region identified from gel electrophoresis was sequenced from tomato and Amaranthus. Sequence analysis revealed large deletions in these species relative to tobacco plastome thus exhibiting the utility of this method for structural and comparative genomics studies. CONCLUSION: This simple, inexpensive method now allows immediate access to plastid sequence, increasing experimental throughput and serving generally as a universal platform for plastid genome characterization. The method applies well to whole genome studies and speeds assessment of variability across species, making it a useful tool in plastid structural genomics.
Base Sequence↗
Molecular characterization of a Spanish isolate of Mycobacterium malmoense.
We present the genomic characterization of a Spanish isolate of Mycobacterium malmoense. Identification and molecular characterization of the microorganism were performed using the technique of PCR-restriction fragment length polymorphism analysis (PRA) and sequencing of the 16S and the ITS spacer (16S-23S rDNA intergenic spacer region). It was seen that our isolate is very similar to the strain described in Sweden, but differs in the sequencing of the ITS from the isolate in Great Britain. Molecular techniques facilitate a rapid diagnosis and enable a better understanding of the epidemiology of this microorganism.
AIDS-Related Opportunistic Infections↗
Molecular determinants of antimicrobial resistance in Klebsiella pneumoniae isolates among geriatric patients in Chattogram, Bangladesh: a cross-sectional study.
Klebsiella pneumoniae (KPN) infections pose heightened risks in the geriatric population due to weakened immunity, prevalent comorbidities, potential exposure in long-term care settings, and increased likelihood of antibiotic resistance (ABR). The study focused on the prevalence and antibiotic resistance of KPN infections, the presence of ABR genes in KPN, and the genomic characterization of KPN obtained from geriatric patients in Chattogram. A total of 543 specimens were collected from four hospitals in Chattogram, along with demographic data from hospital records. Genomic DNA was extracted from multi-drug-resistant (MDR) KPN, and the presence of ABR genes, blaTEM-1, sul-1, aadB, blaNDM-1, blaSHV-11, and phoE was identified. To characterize the KPN genomes, two MDR KPN isolates were subjected to whole-genome sequencing (WGS), and the data were analyzed using bioinformatics tools to identify genomic determinants of ABR. KPN exhibited high resistance to ceftazidime (96%), cefuroxime (92%), and cefixime (83%), but sensitivity to colistin (79%) and amikacin (75%). MDR KPN was mostly detected in sputum (36%) and urine (27%) specimens, where the prevalence of ABR genes, blaTEM-1, sul1, aadB, blaNDM-1, and blaSHV-11 were 28.2%, 17%, 6.17%, 56%, and 48% of these strains, respectively. These genomes exhibited distinct profiles for sequence types, ST420 and ST277 in Kpn007 and Kpn016, respectively, and ABR genes (qnrS1, blaCTX-M-15, and blaSHV-27), virulence factors (ybt, iuc1, iro1), and contained both K (K20, K46) and O antigens (O1, O3b). MDR KPN in the geriatric population poses a serious health concern due to their increased vulnerability to infections and limited treatment options, requiring careful management.IMPORTANCEMultidrug resistance (MDR) and the hypervirulence nature of Klebsiella pneumoniae (KPN) in geriatric patients pose a critical health concern in nosocomial infections worldwide and result in high clinical complexity and mortality. The study investigated the factors for KPN infections and analyzed antimicrobial resistance profiles. More than 60% of Klebsiella pneumoniae isolates from geriatric patients were resistant to third- and fourth-generation cephalosporins, and most isolates carried blaNDM-1 and blaSHV-11 genes. Analyzing whole genomes of two KPNs, Kpn007 (ST277) was identified as a hypervirulent strain with aerobactin and yersinia siderophores, contributing to virulence, and Kpn016 (ST420) carried fluoroquinolone (qnrS1), ESBL (blaCTX-M-15 and blaSHV-27) resistance. Both genomes contained K antigens (K20 and K46) and O antigens (O1 and O3b).
Humans↗