Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Molecular Classification”

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 775 records · Page 43Linked to original sources
PubMed2006

Applying pattern recognition methods to analyze the molecular properties of a homologous series of nitrogen mustard agents.

The purpose of this research was to analyze the pharmacological properties of a homologous series of nitrogen mustard (N-mustard) agents formed after inserting 1 to 9 methylene groups (-CH2-) between 2 -N(CH2CH2Cl)2 groups. These compounds were shown to have significant correlations and associations in their properties after analysis by pattern recognition methods including hierarchical classification, cluster analysis, nonmetric multi-dimensional scaling (MDS), detrended correspondence analysis, K-means cluster analysis, discriminant analysis, and self-organizing tree algorithm (SOTA) analysis. Detrended correspondence analysis showed a linear-like association of the 9 homologs, and hierarchical classification showed that each homolog had great similarity to at least one other member of the series-as did cluster analysis using paired-group distance measure. Nonmetric multi-dimensional scaling was able to discriminate homologs 2 and 3 (by number of methylene groups) from homologs 4, 5, and 6 as a group, and from homologs 7, 8, and 9 as a group. Discriminant analysis, K-means cluster analysis, and hierarchical classification distinguished the high molecular weight homologs from low molecular weight homologs. As the number of methylene groups increased the aqueous solubility decreased, dermal permeation coefficient increased, Log P increased, molar volume increased, parachor increased, and index of refraction decreased. Application of pattern recognition methods discerned useful interrelationships within the homologous series that will determine specific and beneficial clinical applications for each homolog and methods of administration.

Antineoplastic Agents, Alkylating↗
PubMed2026

Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.

Small cell lung cancer is one of the most aggressive malignancies, characterized by rapid tumor growth, early metastatic spread and extremely poor survival. Although most patients initially respond to platinum-based chemotherapy, relapse is almost inevitable and treatment options at recurrence remain limited. The recent introduction of immune checkpoint inhibitors has provided only modest clinical benefit, largely due to the fact that these tumors are immunologically cold. These limitations highlight the urgent need to better understand the molecular features of small cell lung cancer in order to identify more effective therapeutic strategies. In this review, we summarize current knowledge of the molecular landscape of small cell lung cancer, with particular emphasis on transcriptome-based classifications that have identified four major molecular subtypes defined by distinct transcriptional regulators and gene expression programs. We discuss how these classifications have improved the biological understanding of the disease and stimulated efforts to develop subtype-specific therapeutic strategies. At the same time, we highlight important limitations of this framework, including the remarkable transcriptional plasticity of tumor cells, which allows dynamic transitions between subtypes and may contribute to therapeutic resistance. To address these challenges, we examine additional molecular features that may represent more stable vulnerabilities, including recurrent genomic alterations, such as the widespread loss of tumor suppressor genes or oncogene amplifications through extrachromosomal DNA. We also discuss emerging approaches aimed at identifying novel context-specific cancer dependencies, including genome-scale functional screens in vitro and in vivo and genetic restraint analyses. Finally, we consider the growing potential of liquid biopsy strategies, which exploit the high level of circulating tumor DNA in patients with this disease to detect clinically relevant genomic alterations and monitor tumor evolution. Overall, this review highlights both the opportunities and challenges associated with molecular stratification in small cell lung cancer. The integration of transcriptional classifications with genomic and functional approaches may help identify more robust therapeutic vulnerabilities and guide the development of more effective treatments for this highly aggressive disease.

Cancer vulnerabilities↗
PubMed2025

Biomarker identification through spatial proteomics for the characterization of indeterminate thyroid nodules.

PURPOSE: The identification of novel molecular biomarkers may assist in the characterization of indeterminate thyroid nodules, which pose significant diagnostic challenges. Here, we aimed to explore the potential of proteomic analyses to support biomarker discovery in challenging thyroid lesions. METHODS: Linear Discriminant Analysis (LDA) was applied to Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) data from 44 thyroid neoplasms to select the most impactful molecular features for the classification of different tumor histologies, as well as for the distinction between NRAS-mutant (mNRAS) and NRAS-wild-type (wtNRAS) tumors. Relevant peaks were subsequently identified through nanoscale liquid chromatography electrospray ionization tandem mass spectrometry (nLC-ESI-MS/MS). RESULTS: The LDA selected nine relevant molecular markers distinguishing noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) from other tumor histologies (balanced accuracy = 73%), as well as 19 relevant markers able to identify mNRAS cases (balanced accuracy = 84%). Nine differentially expressed proteins were putatively identified: among them, ATP-dependent RNA helicase DDX42 showed a similar distribution between NIFTPs and papillary thyroid carcinomas (PTCs) / follicular variant PTCs (FVPTCs), while the distribution of the Histone H4 signal was similar between NIFTPs and follicular adenomas (FAs). In addition, Protein disulfide-isomerase A1 and Complement C4-B were overexpressed in wtNRAS compared to mNRAS cases, regardless of histology. CONCLUSION: The LDA-selected features enable to distinguish NIFTPs from morphologically similar lesions and to discriminate between mNRAS and wtNRAS cases. The identified markers might complement genetic analyses and provide insights into the distinct pathogenic drivers behind the development of mNRAS compared to wtNRAS lesions.

Humans↗
PubMed2005

Genome evolution and biodiversity in teleost fish.

Teleost fish, which roughly make up half of the extant vertebrate species, exhibit an amazing level of biodiversity affecting their morphology, ecology and behaviour as well as many other aspects of their biology. This huge variability makes fish extremely attractive for the study of many biological questions, particularly of those related to evolution. New insights gained from different teleost species and sequencing projects have recently revealed several peculiar features of fish genomes that might have played a role in fish evolution and speciation. There is now substantial evidence that a round of tetraploidization/rediploidization has taken place during the early evolution of the ray-finned fish lineage, and that hundreds of duplicate pairs generated by this event have been maintained over hundreds of millions of years of evolution. Differential loss or subfunction partitioning of such gene duplicates might have been involved in the generation of fish variability. In contrast to mammalian genomes, teleost genomes also contain multiple families of active transposable elements, which might have played a role in speciation by affecting hybrid sterility and viability. Finally, the amazing diversity of sex determination systems and the plasticity of sex chromosomes observed in teleost might have been involved in both pre- and postmating reproductive isolation. Comparison of data generated by current and future genome projects as well as complementary studies in other species will allow one to approach the molecular and evolutionary mechanisms underlying genome diversity in fish, and will certainly significantly contribute to our understanding of gene evolution and function in humans and other vertebrates.

Animals↗
PubMed1995

Molecular characterization and identification of Saprolegnia by restriction analysis of genes coding for ribosomal RNA.

Restriction fragment length polymorphisms (RFLPs) in two regions of the ribosomal DNA (rDNA) repeat unit were examined in 33 strains representing 18 species of Saprolegnia. The Polymerase Chain Reaction (PCR) was used to separately amplify the 18S rDNA and the region spanning the two internal transcribed spacers (ITS) and the 5.8S ribosomal RNA gene. Amplified products were subjected to a battery of restriction endonucleases to generate various fingerprints. The internal transcribed spacer region exhibited more variability than the 18S rDNA and yielded distinctive profiles for most of the species examined. Most of the species showing 100% similarity for the 18S rDNA could be distinguished by 5.8S + ITS restriction polymorphisms except for S. hypogyna, S. delica, S. lapponica, and S. mixta. The rDNA data indicate that S. lapponica and S. lapponica and S. mixta are conspecific with S. ferax, whereas there is no support for the proposed synonymies of S. diclina with S. delica and of S. mixta with S. monoica. Results from cluster analysis of the two data sets were very consistent and tree topologies were the same, regardless of the clustering method used. A further examination of multiple strains in the S. diclina-S. parasitica complex showed that restriction profiles are conserved across different strains of S. parasitica originating from the U.K. and Japan. HhaI and BsaI restriction polymorphisms were observed in isolates from the U.S. and India. The endonuclease BstUI was diagnostic for S. parasitica, generating identical fingerprints for all stains regardless of host and geographic origin. Except for the atypical strain ATCC 36144, restriction patterns were also largely conserved in S. diclina. Correlation of the rDNA data with morphological and ultrastructural features showed that S. diclina and S. parasitica are not conspecific. Restriction polymorphisms in PCR-amplified rDNA provide a molecular basis for the classification of Saprolegnia and will be useful for the identification of strains that fail to produce antheridia and oogonia.

Base Sequence↗
PubMed2004

PL-I of Spisula solidissima, a highly elongated sperm-specific histone H1.

The major chromosomal protein of the mature sperm of the surf clam, Spisula solidissima, is a histone H1-related protamine-like (PL-I) protein of low electrophoretic mobility. We report here the complete sequence of two isoforms of its encoding genes. These genes encode a protein of 453 and 454 amino acids, respectively. The predicted mass of the larger isoforms (51,437 Da) was confirmed using electrospray ionization mass spectrometry. The amino-terminal tail of the S. solidissima PL-I is greatly elongated because of the presence of 39 tandem hexapeptide repeats of the motif (K/R)KRSAS with a few semiconservative amino acid substitutions. These repeats are very closely mirrored by their encoding DNA sequence, which indicates that an expansion because of sequence duplication most likely occurred. The C-terminal domain consists of a histone H1-related core with a predicted winged-helix tertiary structure, which is followed by an unstructured lysine-rich tail. This information provides additional molecular support for the classification and underlying evolution of sperm nuclear basic proteins in bivalve molluscs.

3' Untranslated Regions↗
PubMedDate not supplied

Defining phyla: evolutionary pathways to metazoan body plans.

Phyla are defined by two sets of criteria, one morphological and the other historical. Molecular evidence permits the grouping of animals into clades and suggests that some groups widely recognized as phyla are paraphyletic, while some may be polyphyletic; the phyletic status of crown phyla is tabulated. Four recent evolutionary scenarios for the origins of metazoan phyla and of supraphyletic clades are assessed in the light of a molecular phylogeny: the trochaea hypothesis of Nielsen; the clonal hypothesis of Dewel; the set-aside cell hypothesis of Davidson et al.; and a benthic hypothesis suggested by the fossil record. It is concluded that a benthic radiation of animals could have supplied the ancestral lineages of all but a few phyla, is consistent with molecular evidence, accords well with fossil evidence, and accounts for some of the difficulties in phylogenetic analyses of phyla based on morphological criteria.

Animal Population Groups↗
PubMed1999

A new clinical perspective of corneal dystrophies through molecular genetics.

In the past 2 years, significant advances have been made in the genetics of corneal dystrophies. Genetic heterogeneity (one disease condition caused by single mutations in any one of multiple genes) and phenotypic diversity (many disease conditions caused by mutations in a single gene) are common emerging themes. Genetic heterogeneity in Meesmann corneal dystrophy was established with the identification of two causative genes, keratins 3 and 12, that encode cytoskeletal proteins. Conversely, mutations in a single gene, keratoepithelin, were found to cause several distinct corneal dystrophies affecting the Bowman layer and the stroma. We present a novel preliminary classification of corneal dystrophies based on molecular etiology. This classification may be useful in understanding the pathogenesis of corneal dystrophies and in developing new strategies to treat these dystrophies.

Cornea↗
PubMed2001

A multivariate insight into the in vitro antitumour screen database of the National Cancer Institute: classification of compounds, similarities among cell lines and the influence of molecular targets.

A multivariate insight into the in vitro antitumour screen database of the NCI by means of the SIMCA package allows to propose hypotheses on the mechanism of action of novel anticancer compounds. As an example, the application of multivariate analysis to the NCI standard database provided clues to the classification of drugs whose mechanism is either unknown or controversial. Moreover, the influence of intrinsic biochemical cell line properties (molecular targets) on the sensitivity to drug treatment could be evaluated simultaneously for classes of compounds which act by the same mechanism. Interestingly, the present approach can also provide a correlation between the molecular targets and the therapeutical fingerprint of novel active compounds thus suggesting specific biochemical studies for the investigation of new mechanisms of drug action and resistance. The statistical approach reported here represents a valuable tool for handling theenormous data sets deriving from recent genome-wide investigations of gene expression in the NCI cell lines.

Antineoplastic Agents↗
PubMedDate not supplied

Evolutionary origin of eukaryotic cells.

This article reviews literature on the transition from rudimentary prokaryotic life to eukaryotes. An overview of the differences between these organisms and theories of eukaryogenesis are reviewed. Various methods of investigating the transformation from prokaryotes to eukaryotes are elaborated, including the fossil, the molecular and living records, and examples are given. Lastly, the recent molecular studies and the impact on phylogenetic classification for the tree of life, based on molecular evolution, are discussed.

Archaea↗
PubMed2001

Molecular taxonomy of the genus Chlorobium.

This review summarizes molecular studies on the taxonomy of the genus Chlorobium. Furthermore, we try to introduce a comprehensive view of how joining traditional phenotypic-based taxonomy with the current molecular approaches leads to a more natural classification. Moreover, we introduce the current insights that molecular techniques have brought to the detection and identification of nonisolated Chlorobium strains in their environments.

Chlorobi↗
PubMed2006

[Advances in molecular biology of extended-spectrum beta-lactamase].

Extended-spectrum beta-lactamases (ESBLs), mediated by plasmids, can hydrolyze and cause resistance to penicillins, broad spectrum-cephalosporins, and monobactams. Most ESBLs are derived from the widespread broad-spectrum beta-lactamases TEM-1 and SHV-1. There are also other families of ESBLs, including CTX-M and OXA-type enzymes as well as novel unrelated beta-lactamases. This article reviews recent advances in the classification, characteristics, and other molecular biological aspects of ESBLs.

Molecular Biology↗
PubMedDate not supplied

Feature selection for descriptor based classification models. 1. Theory and GA-SEC algorithm.

The paper describes different aspects of classification models based on molecular data sets with the focus on feature selection methods. Especially model quality and avoiding a high variance on unseen data (overfitting) will be discussed with respect to the feature selection problem. We present several standard approaches and modifications of our Genetic Algorithm based on the Shannon Entropy Cliques (GA-SEC) algorithm and the extension for classification problems using boosting.

Journal Article↗
PubMed2000

Useful prognostic panel markers to express the biological tumor status in resected lung adenocarcinomas.

BACKGROUND: Tumor stage and its histological subtype remain the most important predictors of clinical behavior in current pulmonary practice of lung cancer. However, many investigators agree that these parameters are not sufficient to predict which tumor will recur, even after radical curative surgery. Therefore, it is necessary to evaluate the significance of other morphological, biological and molecular parameters beyond TNM classification. METHODS: Pathological specimens were collected from 45 patients after resection for stage IA (five), stage IB (10), stage IIB (10), stage IIIA (14) and stage IV (six) lung adenocarcinomas. A panel of two morphological (proportion of stroma within the tumor and degree of tumor differentiation), two biological [DNA ploidy and argyrophilic nucleolar organizer region (AgNOR)] and three molecular (immunohistochemical expression of Ki-67, p53 and bcl-2) markers was chosen for analysis of the primary tumor. Life Tables for Survival were used to analyze the individual impact of each variable on survival. Cox proportional hazards model analysis was used to construct an independent tumor status model for cancer recurrence and death. Chi-squared analyses were used to determine the statistically significant relationship among all the variables present in the study. RESULTS: Multivariate analysis demonstrated statistically significant risk for the following markers: AgNOR, p53 and bcl-2, controlled for stages and surgical resection. CONCLUSIONS: The immunohistochemical expression of p53 and bcl-2 oncogenes and the expression of AgNOR cell proliferation index are critical values in the progression of lung adenocarcinomas. They can express the biological tumor status and indicate a more accurate prognosis.

Adenocarcinoma↗
PubMed1979

Clinical relevance of different electrophoretic methods for the analysis of urinary proteins.

Three electrophoretic techniques are usually available in the clinical laboratories for the qualitative investigation of urinary protein patterns: 1) acetate cellulose, 2) immuno-electrophoresis; and 3) SDS-polyacrylamide gel electrophoresis. Proteinuria (the excretion of proteins in excess of 150 mg/day or 100 microgram/min) usually signifies either increased permeability of the glomerular-capillary membrane of diminished tubular reabsorption. Since glomerular disease is associated with an increased clearance of albumin and higher molecular weight proteins, whereas tubular damage is associated with the predominant excretion of proteins of lower molecular weight than albumin, it seems logical to establish a classification of proteinuria according to the molecular weight of its constituents. One can thus basically distinguish 5 types of proteinurias: 1) physiological; 2) tubular; 3) selective glomerular; 4) non selective glomerular; and 5) mixed proteinurias. Additionally one must distinguish "myeloma proteinurias" where monoclonal complete or incomplete gamma-globulins are found in the urine. Clinically it may be useful to determine the qualitatively normal or pathologic character of a quantitatively normal proteinuria, especially in the following conditions: 1) for early diagnosis of nephropathy in patients, such as diabetics, which are particularly prone to suffer from renal complications; 2) to confirm the clinical cure or to predict the recurrence of renal diseases; and 3) in such situations as orthostatic, or myeloma proteinuria, or any elevation of the urinary protein output of unknown etiology.

Clinical Laboratory Techniques↗
PubMed2006

Diversification of Neoaves: integration of molecular sequence data and fossils.

Patterns of diversification and timing of evolution within Neoaves, which includes almost 95% of all bird species, are virtually unknown. On the other hand, molecular data consistently indicate a Cretaceous origin of many neoavian lineages and the fossil record seems to support an Early Tertiary diversification. Here, we present the first well-resolved molecular phylogeny for Neoaves, together with divergence time estimates calibrated with a large number of stratigraphically and phylogenetically well-documented fossils. Our study defines several well-supported clades within Neoaves. The calibration results suggest that Neoaves, after an initial split from Galloanseres in Mid-Cretaceous, diversified around or soon after the K/T boundary. Our results thus do not contradict palaeontological data and show that there is no solid molecular evidence for an extensive pre-Tertiary radiation of Neoaves.

Animals↗
PubMed1996

Molecular mechanisms of action of bacterial exotoxins.

Toxins are one of the inventive strategies that bacteria have developed in order to survive. As virulence factors, they play a major role in the pathogenesis of infectious diseases. Recent discoveries have once more highlighted the effectiveness of these precisely adjusted bacterial weapons. Furthermore, toxins have become an invaluable tool in the investigation of fundamental cell processes, including regulation of cellular functions by various G proteins, cytoskeletal dynamics and neural transmission. In this review, the bacterial toxins are presented in a rational classification based on the molecular mechanisms of action.

Animals↗
PubMed1999

Genetic susceptibility to neurodevelopmental disorders.

A large body of evidence suggests that genetic factors influence liability to many common neurodevelopmental disorders. Examples include Tourette syndrome, attention-deficit hyperactivity disorder, autism, and dyslexia. Characterization of the genetic component of susceptibility to these conditions at a molecular level should improve classification, elucidate fundamental neurobiologic mechanisms of disease, and suggest novel approaches to treatment. Susceptibility loci for complex traits could be identified by detecting linkage to a well-mapped genetic marker or by detecting association with a putative high-risk allele at a candidate locus. This article reviews the principles underlying these complementary approaches, and notes recent progress in specific conditions. As the molecular epidemiology of susceptibility to common neurodevelopmental disorders emerges, it might be increasingly possible to identify "high-risk" and "low-risk" genotypes. Clinicians should understand the nature of this kind of information in order to appreciate its power as well as its limitations.

Attention Deficit Disorder with Hyperactivity↗