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Japanese Journal of Clinical Oncology Aug 2022Tumors with a high number of mutations in the genome, or tumor mutational burden, are presumed to be more likely to respond to immune checkpoint inhibitors. However, the...
BACKGROUND
Tumors with a high number of mutations in the genome, or tumor mutational burden, are presumed to be more likely to respond to immune checkpoint inhibitors. However, the optimal method to calculate tumor mutational burden using comprehensive genomic profiling assays is unknown.
METHODS
Todai OncoPanel is a dual panel of a deoxyribonucleic acid panel and a ribonucleic acid panel. Todai OncoPanel deoxyribonucleic acid panel version 6 is an improvement over version 3 with increased number of targeted genes and limited targeting of intronic regions. We calculated tumor mutational burden measured by Todai OncoPanel deoxyribonucleic acid panel versions 3 and 6 using three different calculation methods: all mutations within the targeted region (target tumor mutational burden), all mutations within the coding region (all coding tumor mutational burden) and non-synonymous mutations (non-synonymous coding tumor mutational burden). We then compared them with whole exosome sequencing tumor mutational burden. In addition, 16 lung cancer patients whose samples were analyzed using Todai OncoPanel deoxyribonucleic acid version 3 were treated with anti-PD-1 or PD-L1 antibody monotherapy.
RESULTS
When compared with whole exosome sequencing tumor mutational burden as the standard, tumor mutational burden measured by Todai OncoPanel deoxyribonucleic acid version 3 resulted in accuracy of 71% for all three calculation methods. In version 6, accuracy was 96% for target tumor mutational burden and all coding tumor mutational burden and 91% for non-synonymous coding tumor mutational burden. Patients with either partial response or stable disease had higher non-synonymous coding tumor mutational burden (6.7/Mb vs. 1.6/Mb, P = 0.02) and higher PD-L1 expression (40% vs. 3%, P = 0.01) and a trend toward higher target tumor mutational burden (9.2/Mb vs. 2.4/Mb, P = 0.09) compared with patients with progressive disease.
CONCLUSIONS
Increase in targeted gene number and limiting intronic regions improved tumor mutational burden measurement by Todai OncoPanel when compared with whole exosome sequencing tumor mutational burden. Target tumor mutational burden may be the method of choice to measure tumor mutational burden.
Topics: B7-H1 Antigen; Biomarkers, Tumor; DNA; Genomics; Humans; Lung Neoplasms; Mutation; Tumor Burden
PubMed: 35482395
DOI: 10.1093/jjco/hyac063 -
Fa Yi Xue Za Zhi Dec 2022In criminal investigations, postmortem interval (PMI) is important information to be inferred in homicide investigations, as well as the focus and the difficulty in... (Review)
Review
In criminal investigations, postmortem interval (PMI) is important information to be inferred in homicide investigations, as well as the focus and the difficulty in forensic pathology research. Because the DNA content in different tissues is relatively constant and shows changes regularly with the extension of PMI, it has become a research hotspot of PMI estimation. This paper reviews the recent progress of PMI estimation technologies including DNA-based single cell gel electrophoresis, image analysis, flow cytometry, real-time fluorescence quantitative PCR and high-throughput sequencing, hoping to provide references for forensic medicine practice and scientific research.
Topics: Humans; Postmortem Changes; Autopsy; DNA; Forensic Medicine; Forensic Pathology
PubMed: 36914391
DOI: 10.12116/j.issn.1004-5619.2022.420601 -
Journal of Materials Chemistry. B Mar 2020Deoxyribonucleic acid (DNA) nanotechnology is a relevant research field of nano-biotechnology, which has developed rapidly in recent years. Researchers have studied DNA... (Review)
Review
Deoxyribonucleic acid (DNA) nanotechnology is a relevant research field of nano-biotechnology, which has developed rapidly in recent years. Researchers have studied DNA far more than they have studied its genetic characteristics, and now it has evolved into the field of nanomedical materials. A variety of articles based on DNA nanostructures can be obtained by rational design and controllable preparation. In particular, intelligent DNA-based hydrogel materials have attracted significant attention as an essential representative of macro DNA materials. They have shown a wide range of applications, especially in the field of biomedical applications. DNA-based hydrogels have many unique and fascinating properties, such as, excellent biocompatibility, biodegradability, basic programmability, catalytic activities, therapeutic potential, and molecular recognition and bonds. The intelligent DNA hydrogel will undergo abrupt changes in the stimulation of temperature, pH value, ionic strength, and solvent composition. These factors can also be used for applications in intelligent materials that play an essential role in biomedical sciences. To date, intelligent DNA hydrogels have been reported for many applications, including controlled drug delivery, targeted gene therapy, cancer therapy, biosensors, protein production, and 3D cell cultures. However, the large-scale production of intelligent DNA hydrogels has not yet been realized, and the synergistic multifunctional integration has not been explored. This review summarizes the current state of DNA nanostructures, especially the intelligent DNA-based hydrogel materials, and focuses on design and engineering for bio-responsive use and proposes some reasonable prospects for the future development of intelligent DNA-based hydrogel materials.
Topics: Biocompatible Materials; Biomedical Research; DNA; Hydrogels; Particle Size; Smart Materials; Surface Properties
PubMed: 32073097
DOI: 10.1039/c9tb02716e -
Molecules (Basel, Switzerland) May 2023Precise control of the structure of metallic nanomaterials is critical for the advancement of nanobiotechnology. As DNA (deoxyribonucleic acid) can readily modify... (Review)
Review
Precise control of the structure of metallic nanomaterials is critical for the advancement of nanobiotechnology. As DNA (deoxyribonucleic acid) can readily modify various moieties, such as sulfhydryl, carboxyl, and amino groups, using DNA as a directing ligand to modulate the morphology of nanomaterials is a promising strategy. In this review, we focus on the use of DNA as a template to control the morphology of metallic nanoparticles and their biomedical applications, discuss the use of DNA for the metallization of gold and silver, explore the factors that influence the process, and outline its biomedical applications. This review aims to provide valuable insights into the DNA-guided growth of nanomaterials. The challenges and future directions are also discussed.
Topics: Nanostructures; Gold; Silver; DNA
PubMed: 37175332
DOI: 10.3390/molecules28093922 -
Accounts of Chemical Research Aug 2022Facing increasing demand for precision medicine, materials chemistry systems for bioanalysis with accurate molecular design, controllable structure, and adjustable...
Facing increasing demand for precision medicine, materials chemistry systems for bioanalysis with accurate molecular design, controllable structure, and adjustable biological activity are required. As a genetic biomacromolecule, deoxyribonucleic acid (DNA) is created via precise, efficient, and mild processes in life systems and can in turn precisely regulate life activities. From the perspective of materials chemistry, DNA possesses the characteristics of sequence programmability and can be endowed with customized functions by the rational design of sequences. In recent years, DNA has been considered to be a potential biomaterial for analysis and has been applied in the fields of bioseparation, biosensing, and detection imaging. To further improve the precision of bioanalysis, the supramolecular assembly of DNA on micro/nanointerfaces is an effective strategy to concentrate functional DNA modules, and thus the functions of DNA molecules for bioanalysis can be enriched and enhanced. Moreover, the new modes of DNA supramolecular assembly on micro/nanointerfaces enable the integration of DNA with the introduced components, breaking the restriction of limited functions of DNA materials and achieving more precise regulation and manipulation in bioanalysis. In this Account, we summarize our recent work on DNA supramolecular assembly on micro/nanointerfaces for bioanalysis from two main aspects. In the first part, we describe DNA supramolecular assembly on the interfaces of microscale living cells. The synthesis strategy of DNA is based on rolling-circle amplification (RCA), which generates ultralong DNA strands according to circular DNA templates. The templates can be designed with complementary sequences of functional modules such as aptamers, which allow DNA to specifically bind with cellular interfaces and achieve efficient cell separation. In the second part, we describe DNA supramolecular assembly on the interfaces of nanoscale particles. DNA sequences are designed with functional modules such as targeting, drug loading, and gene expression and then are assembled on interfaces of particles including upconversion nanoparticles (UCNPs), gold nanoparticles (AuNPs), and magnetic nanoparticle (MNPs). The integration of DNA with these functional particles achieves cell manipulation, targeted tumor imaging, and cellular regulation. The processes of interfacial assembly are well controlled, and the functions of the obtained bioanalytical materials can be flexibly regulated. We envision that the work on DNA supramolecular assembly on micro/nanointerfaces will be a typical paradigm for the construction of more bioanalytical materials, which we hope will facilitate the development of precision medicine.
Topics: Biocompatible Materials; DNA; Gold; Metal Nanoparticles
PubMed: 35839123
DOI: 10.1021/acs.accounts.2c00170 -
International Journal of Clinical... 2023Endometriosis, which is a common disease affecting approximately 10% of women of reproductive age, usually causes dysmenorrhea and infertility, thus seriously harming...
OBJECTIVE
Endometriosis, which is a common disease affecting approximately 10% of women of reproductive age, usually causes dysmenorrhea and infertility, thus seriously harming the patients' physical and mental health. However, there is a mean delay of 6.7 years between the onset of the symptoms and the surgical diagnosis of endometriosis. There is an increasing amount of evidence that suggests that epigenetic aberrations, including deoxyribonucleic acid (DNA) methylation, play a definite role in the pathogenesis of endometriosis. This study aimed to explore the noninvasive or minimally invasive biomarkers of this disease.
MATERIALS AND METHODS
Six patients with surgically confirmed ovarian endometriosis and six patients who received IUD implantation for contraception without endometriosis were recruited in the East Hospital of Tongji University in 2018. The genome methylation profiling of the eutopic and ectopic endometrium of ovarian endometriosis patients and normal endometrial specimens from healthy women was determined using a methylation microarray test. The test screened methylation-differentiated 5'-C-phosphate-G-3' (CpG) sites and then located the target genes affected by these sites following sequence alignment. Then, an additional 22 patients and 26 healthy controls were enrolled to further verify the difference in the selected genes between endometriosis patients and healthy women. The differential DNA methylation of the selected genes was validated via direct bisulfite sequencing and analysis of their messenger ribonucleic acid (mRNA) levels using quantitative reverse transcription polymerase chain reaction (qRT-PCR).
RESULTS
Fifteen differentially methylated CpG sites were found among the patients and healthy women, and five CpG sites were mapped to the introns of the human leukocyte antigen-C (HLA-C) gene; these were highly polymorphic between different HLA-C alleles and were HLA-C07 specific. The results indicated that the HLA-C07 carrier patients exhibited significantly higher DNA methylation levels at the intron VII of HLA-C compared to the HLA-C07 carrier healthy controls. High HLA-C07 mRNA levels were also observed using qRT-PCR with HLA-C07-specific primers, which indicated that the hypermethylation of CpG in intron VII might suppress a silencer that regulates HLA-C07 expressions.
CONCLUSION
Deoxyribonucleic acid hypermethylation in the intron VII of the HLA-C07 gene appears to regulate the expression of HLA-C07. The aberrant DNA methylation in this region was positively correlated with the occurrence of endometriosis.
Topics: Humans; Female; DNA Methylation; Endometriosis; Introns; HLA-C Antigens; RNA, Messenger; DNA
PubMed: 36974156
DOI: 10.1155/2023/2291156 -
Biomolecules Oct 2022Neutrophil extracellular traps (NETs) are net-like complexes expelled from neutrophils, composing cell-free deoxyribonucleic acid (DNA), histones, and neutrophil granule... (Review)
Review
Neutrophil extracellular traps (NETs) are net-like complexes expelled from neutrophils, composing cell-free deoxyribonucleic acid (DNA), histones, and neutrophil granule proteins. Besides capturing and eliminating pathogens, NETs also exacerbate the inflammatory response associated with various diseases, including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Currently, there are growing reports about NETs involved in the pathogenesis of ocular diseases. This review primarily focuses on the pathogenesis of NETs in the ophthalmology field, highlighting their importance in serving as potential targets for the therapy of ocular diseases.
Topics: Extracellular Traps; Histones; Neutrophils; DNA; Cell-Free Nucleic Acids
PubMed: 36291649
DOI: 10.3390/biom12101440 -
Advanced Materials (Deerfield Beach,... Sep 2023Controversy over artwork's authenticity is ongoing despite numerous technologies for copyright protection. Artists should build their own ways to protect the authority,...
Controversy over artwork's authenticity is ongoing despite numerous technologies for copyright protection. Artists should build their own ways to protect the authority, but these are still open to piracy. Here, a platform is proposed for developing anticounterfeiting labels based on physical unclonable functions (PUFs), in an artist-friendly manner, brushstrokes. Deoxyribonucleic acid (DNA), which is natural, biocompatible, and eco-friendly, can be applied as a paint that shows entropy-driven buckling instability of the liquid crystal phase. Brushed and wholly dried DNA exhibits line-shaped zig-zag textures with inherent randomness as a source of the PUF, and its primary performance and reliability are systematically examined. This breakthrough enables the utilization of these drawings in a wider range of applications.
Topics: Reproducibility of Results; Entropy; Liquid Crystals; DNA
PubMed: 37145961
DOI: 10.1002/adma.202302135 -
Fertility and Sterility Jun 2021
Topics: Aneuploidy; DNA; Genetic Testing; Humans; Mitochondrial Diseases; Preimplantation Diagnosis
PubMed: 33795137
DOI: 10.1016/j.fertnstert.2021.03.006 -
Analytical Chemistry Dec 2020Specificity of DNA polymerization plays a critical role in DNA replication and storage of genetic information. Likewise, biotechnological applications, such as nucleic...
Specificity of DNA polymerization plays a critical role in DNA replication and storage of genetic information. Likewise, biotechnological applications, such as nucleic acid detection, DNA amplification, and gene cloning, require high specificity in DNA synthesis catalyzed by DNA polymerases. However, errors in DNA polymerization (such as mis-incorporation and mis-priming) can significantly jeopardize the specificity. Herein, we report our discovery that the specificity of DNA enzymatic synthesis can be substantially enhanced (up to 100-fold higher) by attenuating DNA polymerase kinetics via the phosphorothioate dNTPs. This specificity enhancement allows convenient and sensitive nucleic acid detection, polymerization, PCR, and gene cloning with complex systems (such as human cDNA and genomic DNA). Further, we found that the specificity enhancement offered higher sensitivity (up to 50-fold better) for detecting nucleic acids, such as COVID-19 viral RNAs. Our findings have revealed a simple and convenient strategy for facilitating specificity and sensitivity of nucleic acid detection, amplification, and gene cloning.
Topics: DNA; DNA Nucleotidyltransferases; Humans; Polymerase Chain Reaction; Polymerization; RNA, Viral; SARS-CoV-2
PubMed: 33236629
DOI: 10.1021/acs.analchem.0c03223