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PubMed2025

A prognostic signature for lung adenocarcinoma in people who have never smoked.

Knowledge of tumor cell dynamics can inform prognosis and treatment yet is largely lacking for lung adenocarcinoma in people who have never smoked (NS-LUAD). With RNA-seq data from 684 NS-LUAD and validation in an independent dataset, we identified three subtypes with distinct phenotypic traits and cell compositions. Additional genomic and histological data further characterized the subtypes. 'Steady', marked by low proliferation, high alveolar cell fraction, moderate-to-well differentiation, and fewer driver genes' alterations, is linked to prolonged survival and low immune evasion. 'Proliferative' shows high proliferation markers, TP53 mutations, and gene fusions. 'Chaotic', with high epithelial-to-mesenchymal transition markers, has the worst prognosis even within stage I tumors. Lacking known molecular or histological characteristics, this aggressive subtype is solely identified by transcriptomic data. A 60-gene signature recapitulates the overall classification and strongly predicts survival even within subgroups based on tumor stage or known genomic features, emphasizing its potential for improving NS-LUAD prognostication in clinical settings.

Journal Article↗
PubMed2005

Adenovirus as an emerging pathogen in immunocompromised patients.

Adenoviruses are non-enveloped, lytic, DNA viruses capable of infecting most animal species. There are 51 different human adenovirus serotypes, which are grouped from A to F on the basis of genome size, composition, homology and organization. Pathogenicity varies according to group and type, but infections are generally well controlled by the host immune system in immunocompetent individuals. However, in the immunosuppressed, adenoviral infections are a frequent cause of morbidity and mortality. To date there is no effective therapy. Adoptive transfer of immune T cells offers a therapeutic option, but this strategy has been hindered by the lack of information on targets of protective cellular immunity, and by the immunological heterogeneity of the 51 human adenoviruses. Nevertheless, until such an approach is implemented, or an effective antiviral agent becomes commercially available, it is likely that adenovirus infections will continue to be responsible for a significant number of virus-associated deaths each year.

Adenoviridae↗
PubMed1999

Genetic analysis of Borrelia garinii OspA serotype 4 strains associated with neuroborreliosis: evidence for extensive genetic homogeneity.

Infection with Borrelia garinii outer surface protein (Osp) A serotype 4 strains has been correlated with the development of neuroborreliosis in Lyme borreliosis patients in Europe. OspA serotype 4 isolates have been recovered primarily from human cerebrospinal fluid, suggesting a tropism for this environment. Previous studies with monoclonal antibodies directed against OspA and OspC demonstrated that OspA serotype 4 strains are antigenically closely related. In view of the pronounced antigenic and genetic variability that has been noted in the Osps of other Borrelia isolates, we sought to determine if OspA serotype 4 strains represent a recently emerged clonal lineage of B. garinii. Toward this goal, a representative group of OspA serotype 4 strains was analyzed for traits that typically exhibit hypervariability among isolates that cause Lyme borreliosis. The following criteria were assessed: (i) ospC sequences, (ii) plasmid composition, (iii) genomic restriction fragment length polymorphism (RFLP) patterns, and (iv) the RFLP patterns of the upstream homology box (UHB) element which flanks members of the UHB gene family at their 5' end. Collectively, these analyses demonstrate genetic homogeneity, suggesting that OspA serotype 4 strains are a recently emerged clonal lineage with an apparent tropism for the central nervous system.

Antigens, Bacterial↗
PubMed1977

Purification and biochemical properties of Egtved viral RNA.

32P-labeled Egtved virus RNA was released from highly purified virus by phenol-SDS extraction. The single-stranded nature of the RNA was demonstrated by (1) its buoyant density of 1.69 g/cm3 in Cs2-SO4, (2) its susceptibility to digestion by pancreatic ribonuclease in either 1 X SSC or 0.01 X SSC (standard saline citrate), (3) its base composition (29.3% C, 23.6% A, 14.5% U. 32.6% G). This Egtved virus is different from the other rhabdoviruses since the base composition of its genomic RNA is lower in its composition of A + U. Such a result could have possible taxonomic implications concerning the orignin and evolution of Egtved Virus relative to the other known rhabdoviruses.

Adenine↗
PubMed2004

Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells.

Adenoviruses often cause lethal infections in immunocompromised individuals. Adoptive transfer of immune T cells offers a therapeutic option, but this strategy has been hindered by the paucity of information on molecular targets of cellular immunity and by the immunologic heterogeneity of the 51 human adenoviruses, which are grouped from A to F on the basis of genome size, composition, homology, and organization. Clonal analysis of the adenovirus-specific cytotoxic T lymphocyte (CTL) responses of seropositive individuals identified 5 novel CD8(+) T-cell epitopes, all located in conserved regions of the capsid protein hexon. Reactive T cells were cross-reactive between 2 to 4 groups, while no T cells specific for a single subgroup were detected. Thus, by exploiting these peptide targets, it is possible to prepare a T-cell population capable of reacting with most adenoviruses that cause disease in immunocompromised patients.

Adenoviridae↗
PubMed2005

T-cell immunotherapy for adenoviral infections of stem-cell transplant recipients.

Human adenoviruses are ubiquitous lytic DNA viruses that can be divided into 51 different serotypes, grouped from A to F on the basis of genome size, composition, homology, and organization. Adenovirus infections, although frequent, are rarely fatal in immunocompetent individuals, due to potent innate and adaptive immune responses. By contrast, adenoviruses are a significant cause of morbidity and mortality in immunosuppressed individuals, for whom there are limited treatment options. Since antiviral drugs have variable efficacy in the treatment of severe adenovirus disease, iatrogenic reconstitution with in vitro expanded virus-specific cytotoxic T lymphocytes (CTLs) is an attractive option for prophylaxis and treatment, particularly because the endogenous recovery of adenovirus-specific T cells has proved important in controlling infection in vivo. Thus, we have characterized human T-cell responses to adenovirus in vitro and explored the potential of adoptive T-cell immunotherapy as a prophylactic or therapeutic strategy for adenovirus infections posttransplant.

Adenoviridae Infections↗
PubMed2025

Breaking the reproducibility barrier with standardized protocols for plant-microbiome research.

Inter-laboratory replicability is crucial yet challenging in microbiome research. Leveraging microbiomes to promote soil health and plant growth requires understanding underlying molecular mechanisms using reproducible experimental systems. In a global collaborative effort involving five laboratories, we aimed to help advance reproducibility in microbiome studies by testing our ability to replicate synthetic community assembly experiments. Our study compared fabricated ecosystems constructed using two different synthetic bacterial communities, the model grass Brachypodium distachyon, and sterile EcoFAB 2.0 devices. All participating laboratories observed consistent inoculum-dependent changes in plant phenotype, root exudate composition, and final bacterial community structure, where Paraburkholderia sp. OAS925 could dramatically shift microbiome composition. Comparative genomics and exudate utilization linked the pH-dependent colonization ability of Paraburkholderia, which was further confirmed with motility assays. The study provides detailed protocols, benchmarking datasets, and best practices to help advance replicable science and inform future multi-laboratory reproducibility studies.

Plants↗
PubMed2006

Susceptibility genes for the side effect of antipsychotics on body weight and obesity.

Antipsychotic-induced body weight gain is becoming a major health concern since the increasing use of this medication in different mental disorders with a high prevalence in different populations. The percentage of patients gaining weight following antipsychotic medication can reach up to 80% according to the antipsychotic used, with around 30% developing obesity. The origins of this adverse effect of antipsychotics are probably multifactorial with the environment (food and exercise habits, medication) and the genetics coming into play. We have compiled the available genetic results on the antipsychotic-induced body weight gain and obesity. Candidate genes analysis showed that six genes have been associated with this adverse effect of antipsychotics. Among these, the associations with the serotonin receptor 2C and the leptin genes have been observed in more then one study. Thirteen other genes, mainly antipsychotic known receptors, have shown negative results. To find informative gene variations, we have also compared the effects of some polymorphisms of the serotonin receptor 2C and 2A in mental disorders, for antipsychotic therapeutic effect, for antipsychotic neuronal side effects, and for obesity. We have found results for six polymorphisms in each of the two genes. When association was observed for more then one phenotype, the same genotype or allele was generally involved identifying those sensitive to environmental pressures and to genetic background. Animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been evaluated for changes in obesity-related phenotypes. Seventeen out of the twenty-three antipsychotic receptors with transgenic models showed some effects on obesity-related phenotypes. Ten of these receptors have not been tested yet for antipsychotic-induced body weight gain, while the others have been tested only once with negative results, or is already associated to the effect such as the serotonin receptor 2C. Finally, pharmacogenomic approaches have allowed to detect more then 300 possible candidate genes for antipsychotic-induced body weight gain.

Animals↗
PubMed1987

The genome of anaplasma: DNA base composition and DNA/DNA hybridization.

The Tm value of DNA from Anaplasma centrale and Anaplasma marginale was found to be 87.1 degrees C and 89.3 degrees C, respectively. The G + C content, calculated from the Tm, was 45.1% for A. centrale and 48.5% for A. marginale. Identical hybridization patterns were obtained when the DNA from one species was hybridized to restriction endonuclease-digested DNA from the other species.

Anaplasma↗
PubMed2005

Entropic stabilization of proteins and its proteomic consequences.

Evolutionary traces of thermophilic adaptation are manifest, on the whole-genome level, in compositional biases toward certain types of amino acids. However, it is sometimes difficult to discern their causes without a clear understanding of underlying physical mechanisms of thermal stabilization of proteins. For example, it is well-known that hyperthermophiles feature a greater proportion of charged residues, but, surprisingly, the excess of positively charged residues is almost entirely due to lysines but not arginines in the majority of hyperthermophilic genomes. All-atom simulations show that lysines have a much greater number of accessible rotamers than arginines of similar degree of burial in folded states of proteins. This finding suggests that lysines would preferentially entropically stabilize the native state. Indeed, we show in computational experiments that arginine-to-lysine amino acid substitutions result in noticeable stabilization of proteins. We then hypothesize that if evolution uses this physical mechanism as a complement to electrostatic stabilization in its strategies of thermophilic adaptation, then hyperthermostable organisms would have much greater content of lysines in their proteomes than comparably sized and similarly charged arginines. Consistent with that, high-throughput comparative analysis of complete proteomes shows extremely strong bias toward arginine-to-lysine replacement in hyperthermophilic organisms and overall much greater content of lysines than arginines in hyperthermophiles. This finding cannot be explained by genomic GC compositional biases or by the universal trend of amino acid gain and loss in protein evolution. We discovered here a novel entropic mechanism of protein thermostability due to residual dynamics of rotamer isomerization in native state and demonstrated its immediate proteomic implications. Our study provides an example of how analysis of a fundamental physical mechanism of thermostability helps to resolve a puzzle in comparative genomics as to why amino acid compositions of hyperthermophilic proteomes are significantly biased toward lysines but not similarly charged arginines.

Aminopeptidases↗
PubMed1996

Base composition and gene distribution: critical patterns in mammalian genome organization.

Recent success in developing transcriptional maps of large genomic regions provide excellent opportunities for the investigation of mammalian genome organization. Detailed definition of organizational features will, in the short term, aid in prioritizing genomic sequencing efforts and in interpreting sequencing results and, in the long term, will surely provide insights into the structural, functional and evolutionary basis for the mammalian chromosome and chromosomal banding patterns. For such efforts, human chromosome 21 provides an excellent model system because the physical and clone maps are detailed, and several transcriptional mapping projects have provided large numbers of novel genes. It is, therefore, valuable at this point to examine these transcriptional mapping data and to compare them with the isochore model of the mammalian genome, which describes patterns in base composition and predicts gene distributions. Not only do compelling organizational patterns appear, but new questions about additional possible patterns in gene size, structure, conservation and transcription can be asked.

Animals↗
PubMed2002

Dinucleotide compositional analysis of Sinorhizobium meliloti using the genome signature: distinguishing chromosomes and plasmids.

The symbiotic N(2)-fixing alpha-proteobacterium Sinorhizobium meliloti has three replicons: a circular chromosome (3.7 Mb) and two smaller replicons, pSymA (1.4 Mb) and pSymB (1.7 Mb). Sequence analysis has revealed that an essential gene is carried on pSymB, which brings into question whether pSymB should be considered a chromosome or a plasmid. Based on the criterion that essential genes define a chromosome, several species have been shown to have multiple chromosomes. Many of these species are part of the alpha subdivision of the Proteobacteria family. Here, additional justification is presented for designating the pSymB replicon as a chromosome. It is shown that chromosomes within a species share a more similar dinucleotide composition, or genome signature, than plasmids do with the host chromosome(s). Dinucleotide signatures were determined for each of the S. meliloti replicons, and, consistent with the suggestion that pSymB is a chromosome, it is shown that the pSymB signature more closely resembles that of the S. meliloti chromosome, while the pSymA signature is typical of other alpha-proteobacterial plasmids.

Genome, Bacterial↗
PubMed2026

Nucleotide Combination Proportions Across Algae, Monocotyledons and Dicotyledons: Insights into Plant Genome Evolution.

Plant evolution started with unicellular algae, gradually evolving multicellularity and terrestrial colonization. These evolutionary events were accompanied by the interplay of chromosome polyploidization, rearrangement, gene loss, and point mutation. We counted the proportion of nucleotide combinations in the genome sequences of 64 sequenced plants, and analyzed the significant difference in these nucleotide combination proportions among algae, monocotyledons and dicotyledons. The correlation of highly significant different and no significant different nucleotide combinations was analyzed respectively. Nucleotide combinations and their reverse complementary sequence proportions were analyzed in different functional regions of the genome. These results reveal that some nucleotide combinations are subject to strict selection, and these combinations have a higher proportion in the CDS regions and lower proportion in the intergenic regions. Meanwhile, there are some nucleotide combinations that are under less selective pressure, and these combinations have a higher proportion in the intergenic regions and lower proportion in the CDS regions. Cluster analysis based on trinucleotide to octanucleotide combination proportions reveals that plant genome evolution is accompanied by clade-wide differentiation of genome-wide nucleotide composition patterns, in addition to well-documented chromosomal polyploidization, structural rearrangement and gene loss events. We analyzed the changes in the proportion of nucleotide combinations at the genome level in 64 sequenced plants, providing a new idea for studying genome evolution in the plant kingdom.

comparative genomics↗
PubMed1997

Bacterial features in the genome of Methanococcus jannaschii in terms of gene composition and biased base composition in ORFs and their surrounding regions.

As a result of genome projects, the complete nucleotide sequence of the entire genome of an archaeon, Methanococcus jannaschii, was recently determined as well as other complete sequences of bacterial and eucaryal genomes. When all the 1680 predicted protein-coding [corrected] genes of M. jannaschii were classified on the basis of sequence similarity, it was found that this archaeon had a chimeric set of 1016 bacterial-type, 471 eucaryal-type and 193 species- or archaebacteria-specific genes. However, most of the genes predicted to be involved in translation and transcription pathways including RNA genes were of the eucaryal-type with only a few exceptions such as 16S ribosomal RNA and some translation factor-like genes. This appeared curious since previous studies indicated that methanogens have bacterial features in gene organization and expression. To understand the apparent inconsistency between physiological observations and the result of the classification of genes for transcription and translation, we examined the structural relatedness of the genome of M. jannaschii to those of other species. In practice, we compared base compositional patterns in ORFs and their surrounding regions. This made it possible to reveal the relationships among the translation- and transcription-related structures in genomes. In this study, we conducted a statistical test called 'G-test' to evaluate the base biases around the boundaries of ORFs. We then found that M. jannaschii possesses more bacterial features in base biases than eucaryal ones, e.g. strong G biases at the positions corresponding to the Shine-Dalgarno site. This indicates that the few exceptional bacterial genes for translation, such as 16S ribosomal RNA and translation factor-like genes, play crucial roles in the translation pathway in M. jannaschii. The possibility that the genome structure in the last common ancestor of all present species was bacterial is discussed.

Base Composition↗
PubMed1994

Coleopterancidal delta-endotoxin and constructing its genomic library.

The composition of crystal proteins and plasmid patterns in five new coleopterancidal strains of Bacillus thuringiensis were investigated. Larvae of Plagiodera versicolora were chosen as a model insect in bioassay. Strain YM-03 had the highest toxicity. Plasmid patterns were detected by rapid agarose gel electrophoresis. It was demonstrated that plasmid patterns of five Bt strains were quite different. The partial amino acid sequences of the N-terminal of crystal protein from YM-03 were analyzed by amino acid analyzer. A genomic library of delta-endotoxin of YM-03 was constructed. The EcoRI fragments (20-30 kb) from the total DNA were ligated with the vector DNA of pLAFRI. Thirteen clones which contained both of pLAFRI and foreign DNA fragments were obtained from 17 recombined plasmids. The frequency of recombinant clones was 76%. Three positive clones, LE392 (pBYM2), LE392 (pBYM3) and LE392 (pBYM4) were detected from 1200 resistant clones by using a synthesized 18bp probe from a coleopterancidal delta-endotoxin gene. It was shown that LE392 (pBYM3) and LE392 (pBYM4) had the same EcoRI digestion patterns and that they all contained coleoptera-specific delta-endotoxin gene but showed a different level of expression.

Amino Acid Sequence↗
PubMed1975

Evidence for fidelity of chromatin reconstitution.

Several lines of evidence are presented which support the contention that chromatin may be dissociated, fractionated, and reconstituted without altering the compositional, structural, or transcriptional integrity of the genome. The similar compositions of native and reconstituted chromatins are suggested by the absence of significant differences in their protein/DNA ratios and in the polyacrylamide gel electrophoretic profiles of their histones and nonhistone chromosomal proteins. Criteria for fidelity of genome structure in reconstituted chromatin include binding of reporter molecules with specificity for the minor groove of DNA, binding of histones, number of sites available for addition of nucleotides, and circular dichroism spectra. When the transcriptional activities of native and reconstituted chromatins were compared under conditions where reinitiation is prohibited, significant changes were not observed. Taken together, the present results strongly suggest, but do not conclusively establish, fidelity of chromatin reconstitution.

Animals↗
PubMed2005

Codon utilization, DNA landscaping and fractal analysis in bacteriophage phi(adh).

The bacteriophage phi(adh) has a low G+C content and encodes its protein products using a restricted number of the codons, which it could theoretically use. Investigated were (i) the restricted codon usage by determining codon indices and codon distances for various genes and ORFs, (ii) distribution of purines and pyrimidines on the two strands of the double-stranded genome and within all genes and ORFs, and (iii) nucleotide positional bias within the genome. The genes and ORFs can be clustered into four groups, based on codon distance analysis. The genome landscape showed that the plus strand was more purine-rich than the negative one and that the only area of the genome where the landscape was located in the pyrimidine-rich region was at the start of the sequence which was also the only region of the genome where ORFs were found on the negative strand. The nucleotide composition of the genome, examined by fractal analysis showed little, if any, DNA positional bias, as opposed to overall compositional bias with a self-similarity profile. The ORFs showed a bias in favour of purines on the coding strand.

Amino Acids↗
PubMed2004

Correspondence regarding Bharanidharan et al., "Correlations between nucleotide frequencies and amino acid composition in 115 bacterial species".

Bharanidharan et al. [Biochem. Biophys. Res. Commun. 315 (2004) 1097-1103] claimed that the frequencies of most amino acids are determined by the dinucleotide composition of the genome. Here, regarding a methodological problem in their work, it is suggested that the standard deviations of amino acid frequencies should be determined to indicate how significant a certain deviation from the predicted frequency is. Furthermore, using a different method that is expected to be more reliable, we suggest that the dinucleotide composition cannot explain the observed frequencies of most amino acids, and the deviations of amino acid frequencies from what dinucleotide composition predicts are larger than to be expected by chance.

Amino Acids↗