DNA Conformational Changes Research Articles

Landscaping DNA binding potential of piperine derivatives by computational and biophysical methods

Piperine, the alkaloid from Black pepper, is known for its wide range of pharmacological effects. The DNA binding activity of piperine was reported earlier. In this work, we explore the DNA duplex binding properties of four piperine derivatives, piperonal, piperonyl alcohol, piperonylic acid, and piperic acid using biophysical and computational techniques. Various spectroscopic and calorimetric techniques were employed for the experimental analysis. We employed UV − vis absorption and fluorescence spectroscopy to verify the binding of piperine to calf thymus DNA (ctDNA). The energetics of this interaction were analysed using isothermal titration calorimetry (ITC). Conformational changes in DNA resulting from ligand interactions were investigated using circular dichroism spectroscopy. All these experimental results consistently demonstrate that the piperine derivatives exhibit stronger binding affinity to DNA than piperine. Computational analyses, utilizing molecular docking and dynamics, revealed similar results to experimental studies, indicating that the compounds bind to the minor groove of DNA like piperine, primarily through van der Waals interactions. Both in vitro and in silico investigations demonstrated the strong DNA binding potential of the examined piperine derivatives. This study is the first to report on the comparative interaction between these piperine derivatives and a DNA duplex.

Computational Simulation and Biophysical Study on Cerium Chloride-Induced B-to-Z Transition in (CG) n DNA.

Rare earth elements have been shown to trigger the B-to-Z DNA transition in diverse self-assembled branched DNA architectures. Herein, we investigated the influence of cerium chloride on the conformational changes of DNA sequences containing repeated cytosine-guanine (CG)6-12 or guanine-cytosine (GC)6-12 sequences. The CD results show that (CG)6-12 repeats were susceptible to the formation of Z-DNA at low concentrations of CeCl3. On the other hand, (GC)6-12 is unable to undergo B-Z DNA transition and instead exhibits condensation with a similar amount of CeCl3. The CD signature was found to be different and unique in both alternate repeats during the interaction with CeCl3. The sequence-specific effects on the B-Z transition are based on the order of nucleotides in DNA. With the addition of EDTA, the Z-form of DNA is reverted to the native B-form. Further, we have reported the positive zeta potential of CeCl3-induced Z-DNA in contrast to the negative zeta potential of B-DNA. The differential zeta-potential value during the B-Z transition is complementary to the conformational changes of DNA. The molecular simulation study also supports the sequence-specific conformational change between the B- and Z-forms of DNA molecules. This newly described reversible topological and sequence-dependent transition is crucial for understanding the structural and biological roles of Z-DNA in response to CeCl3.

I-Motif DNA Based Fluorescent Ratiometric Microneedle Sensing Patch for Sensitive Response of Small pH Variations in Interstitial Fluid.

Detection of slight pH changes in skin interstitial fluid (ISF) is crucial yet challenging for studying pathological processes and understanding personal health conditions. In this work, we construct an i-motif DNA based fluorescent ratiometric microneedle sensing patch (IFR-pH MN patch) strategy that enables minimally invasive, high-resolution, and sensitive transdermal monitoring of small pH variations in ISF. The IFR-pH MN patch with advanced integration of both ISF sampling and pH sensing was fabricated from the cross-linking of gelatin methacryloyl and methacrylated hyaluronic acid, wrapping with pH-sensitive hairpin-containing i-motif DNA based fluorescent ratiometric probes in the matrix. Because it is mechanically robust for skin penetration and has high swelling ability, the IFR-pH MN patch could be quickly extracted as sufficient liquid from agarose gel (∼56.4 μL in 10 min). Benefiting from conformation changes of the hairpin-containing i-motif DNA under pH variation and ratiometric fluorescence signal readout, the IFR-pH MN patch could quantitate pH over a small range between pH 6.2 and 6.9 with an accuracy of 0.2 pH units in the mimic skin model. Furthermore, in vivo testing on wound and tumor mouse models indicated the ability of the biocompatible IFR-pH MN patch to penetrate the skin for obtaining transdermal pH values, demonstrating the potential applications in monitoring and intervention of pathological states.

Single-molecule dynamic structural biology with vertically arranged DNA on a fluorescence microscope.

The intricate interplay between DNA and proteins is key for biological functions such as DNA replication, transcription and repair. Dynamic nanoscale observations of DNA structural features are necessary for understanding these interactions. Here we introduce graphene energy transfer with vertical nucleic acids (GETvNA), a method to investigate DNA-protein interactions that exploits the vertical orientation adopted by double-stranded DNA on graphene. This approach enables the dynamic study of DNA conformational changes via energy transfer from a probe dye to graphene, achieving spatial resolution down to the Ångström scale at subsecond temporal resolution. We measured DNA bending induced by adenine tracts, bulges, abasic sites and the binding of endonuclease IV. In addition, we observed the translocation of the O6-alkylguanine DNA alkyltransferase on DNA, reaching single base-pair resolution and detecting preferential binding to adenine tracts. This method promises widespread use for dynamical studies of nucleic acids and nucleic acid-protein interactions with resolution so far reserved for traditional structural biology techniques.

Enhancing DNA Translocation Performance and Conformational Changes in Quartz Nanopipettes by Ionic Liquid Modification

Enhancing DNA Translocation Performance and Conformational Changes in Quartz Nanopipettes by Ionic Liquid Modification

Conformational Changes in DNA and Protein Biomolecules in Pathogenesis of Ischemic Stroke.

Conformational changes in DNA and protein biomolecules were studied in ischemic stroke (IS) cases varying severity by Raman spectroscopy. The conformational structure of hematoporphyrin was found to change in IS patients, leading to a higher (I1355/I1550)/(I1375/I1580) ratio (hemoglobin affinity of for ligands) and an increase in I1375/I1172 (a change in pyrrole conformation). Changes in genomic DNA spectra were observed at frequencies caused by stretching vibrations of primary amines (3400 cm-1), secondary amines and hydroxyls involved in hydrogen bonding (3100 cm-1), and CH2 groups of sugar phosphates (2900 cm-1) and vibrations of vibrational bonds between nitrogenous bases and sugars (1400 cm-1). The significant changes observed in genomic DNA and hemoglobin spectra were assumed to indicate conformational rearrangements of the molecules in IS. Severe IS was associated with maximum changes in DNA and hemoglobin spectra.

An Insight into the Mechanism of DNA Cleavage by DNA Endonuclease from the Hyperthermophilic Archaeon Pyrococcus furiosus.

Hyperthermophilic archaea such as Pyrococcus furiosus survive under very aggressive environmental conditions by occupying niches inaccessible to representatives of other domains of life. The ability to survive such severe living conditions must be ensured by extraordinarily efficient mechanisms of DNA processing, including repair. Therefore, in this study, we compared kinetics of conformational changes of DNA Endonuclease Q from P. furiosus during its interaction with various DNA substrates containing an analog of an apurinic/apyrimidinic site (F-site), hypoxanthine, uracil, 5,6-dihydrouracil, the α-anomer of adenosine, or 1,N6-ethenoadenosine. Our examination of DNA cleavage activity and fluorescence time courses characterizing conformational changes of the dye-labeled DNA substrates during the interaction with EndoQ revealed that the enzyme induces multiple conformational changes of DNA in the course of binding. Moreover, the obtained data suggested that the formation of the enzyme-substrate complex can proceed through dissimilar kinetic pathways, resulting in different types of DNA conformational changes, which probably allow the enzyme to perform its biological function at an extreme temperature.

Integrative transcriptomic profiling of ncRNAs and mRNAs in developing mouse lens.

In recent years, burgeoning research has underscored the pivotal role of non-coding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein-protein interaction networks, mRNA-lncRNA co-expression networks, and circRNA-microRNA-mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field.

Skipping events impose repeated binding attempts: profound kinetic implications of protein-DNA conformational changes.

The kinetics of protein-DNA recognition, along with its thermodynamic properties, including affinity and specificity, play a central role in shaping biological function. Protein-DNA recognition kinetics are characterized by two key elements: the time taken to locate the target site amid various nonspecific alternatives; and the kinetics involved in the recognition process, which may necessitate overcoming an energetic barrier. In this study, we developed a coarse-grained (CG) model to investigate interactions between a transcription factor called the sex-determining region Y (SRY) protein and DNA, in order to probe how DNA conformational changes affect SRY-DNA recognition and binding kinetics. We find that, not only does a requirement for such a conformational DNA transition correspond to a higher energetic barrier for binding and therefore slower kinetics, it may further impede the recognition kinetics by increasing unsuccessful binding events (skipping events) where the protein partially binds its DNA target site but fails to form the specific protein-DNA complex. Such skipping events impose the need for additional cycles protein search of nonspecific DNA sites, thus significantly extending the overall recognition time. Our results highlight a trade-off between the speed with which the protein scans nonspecific DNA and the rate at which the protein recognizes its specific target site. Finally, we examine molecular approaches potentially adopted by natural systems to enhance protein-DNA recognition despite its intrinsically slow kinetics.

Macromolecules with predominant β-pleated sheet proteins in extracellular vesicles released from Raphanus sativus L. var. caudatus Alef microgreens induce DNA damage-mediated apoptosis in HCT116 colon cancer cells

Plant-derived bioactive macromolecules (i.e., proteins, lipids, and nucleic acids) were prepared as extracellular vesicles (EVs). Plant-derived EVs are gaining pharmaceutical research interest because of their bioactive components and delivery properties. The spherical nanosized EVs derived from Raphanus sativus L. var. caudatus Alef microgreens previously showed antiproliferative activity in HCT116 colon cancer cells from macromolecular compositions (predominantly proteins). To understand the mechanism of action, the biological activity studies, i.e., antiproliferation, cellular biochemical changes, DNA conformational changes, DNA damage, apoptotic nuclear morphological changes, apoptosis induction, and apoptotic pathways, were determined by neutral red uptake assay, synchrotron radiation-based Fourier transform infrared microspectroscopy, circular dichroism spectroscopy, comet assay, 4′,6-diamidino-2-phenylindole (DAPI) staining, flow cytometry, and caspase activity assay, respectively. EVs inhibited HCT116 cell growth in concentration- and time-dependent manners, with a half-maximal inhibitory concentration of 675.4 ± 33.8 μg/ml at 48 h and a selectivity index of 1.5 ± 0.076. HCT116 treated with EVs mainly changed the cellular biochemical compositions in the nucleic acids and carbohydrates region. The DNA damage caused no changes in DNA conformation. The apoptotic nuclear morphological changes were associated with the increased apoptotic cell population. The apoptotic cell death was induced by both extrinsic and intrinsic pathways. EVs have potential as antiproliferative bioparticles.

Assessment of the electrostatic binding of ferrocenylmethyl-nitroaniline derivatives to DNA: A combined experimental and theoretical study

The present study investigates the electrostatic binding interactions between ferrocenylmethylnitroaniline derivatives and DNA using a combination of experimental and theoretical approaches. The objective is to elucidate the binding mechanisms and evaluate the potential of these derivatives as DNA-targeting agents. Experimental techniques, including cyclic voltammetry (CV) and UV–Vis spectroscopy (UV–Vis), were employed to assess the binding affinity and conformational changes in DNA upon interaction with the derivatives. Our findings reveal that the ferrocenylmethylnitroaniline derivatives exhibit strong electrostatic interactions with DNA, as confirmed by the negative formal potential shift observed in CV. The binding constants and free binding energies obtained from the docking simulation were found to be consistent with those obtained from CV and UV–Vis spectral analysis. Furthermore, the binding site size was determined from the voltametric data. Complementary theoretical calculations such as geometry optimization, MEP analysis, Mulliken charge distribution, and HOMO-LUMO surface were performed by DFT approach (B3LYP/aug-cc-pVTZ/6-311++G (d,p)) to gain insights into the structural data, active regions, and chemical reactivity of derivatives. Molecular docking simulation verifies that electrostatic attraction plays a fundamental role in the interaction of Fc2N, Fc3N, and Fc4N with DNA. The molecular dynamics simulations elucidated the stability of DNA-ligand complexes formed with Fc2N, Fc3N, and Fc4N compounds. Analysis of root mean square deviation (RMSD) and radius of gyration (Rg) indicated stable binding and maintained compactness of DNA structures, underscoring the robustness of these interactions for potential therapeutic applications.Top of Form

Synergistic effects and competitive relationships between DOC and DOX as acting on DNA molecules: Studied with confocal Raman spectroscopy and molecular docking technology

Docetaxel (DOC) is one of the second-generation antineoplastic drugs of the taxanes family with excellent antitumor activity. However, the mechanism of DOC inducing tumor cell apoptosis and treating cancer diseases, especially its interaction with DNA in the nucleus, and its adjuvant or combined Doxorubicin (DOX) acting on DNA molecules are unclear. In this study, the interaction mechanism between DOC and DNA, as well as the synergistic effects and competitive relationships among DOC and DOX when they simultaneously interact with DNA molecules were studied by laser confocal Raman spectroscopy combined with UV–visible absorption spectroscopy and molecular docking technology. The spectroscopic results showed that the binding constant of DOC to DNA is 5.25 × 103 M−1, the binding modes of DOC and DNA are non-classical intercalation and electrostatic binding, and the DNA-DOC complex has good stability. When DOC or DOX interacts with DNA alone, both of them can bind with bases and phosphate backbone of DNA, and also lead to DNA conformation changes; when DOC and DOX interact with DNA at the same time, the orders of interaction not only affect their binding sites with DNA, but also cause changes in the surrounding environment of the binding sites. In addition, the molecular docking results further verified that DOC and DOX have synergy and competition when they interact with DNA molecules simultaneously. The docking energies of DNA-DOC and DNA-DOX indicate the important role of van der Waals forces and hydrogen bonds. This study has practical significance for the design and development of antitumor drugs with less toxic based on the taxanes family and the combination with other drugs for the treatment of cancer.

An ATP-free packaging of T4 DNA

Packaging of viral DNA into a capsid with liquid crystalline density is a crucial step in viral reproduction. DNA packaging with an adenosine triphosphate (ATP)-fueled molecular motor is an established viral DNA packaging mechanism system. On the other hand, DNA is compacted by the conformational change attributable to multivalent cations exclusively at valences higher than three. The conformational change of DNA was not considered as a mechanism of DNA packaging of viruses. Here, T4 DNA, ejected from a capsid in the ambient concentration of phosphate corresponding to the intra-cell concentration, is packaged into the capsid when the phosphate concentration decreases to the extra-cell concentration in coexistence with divalent cations, that is, Ca2+ and Mg2+. The compaction and packaging processes coincide with the conformational change of DNA. Divalent cations can compact T4 DNA when the counter anion is phosphate. The DNA-packaged and re-generated virions showed equivalent infective ability with the original populations. Fluorescent microscopy distinguished the conformational changes of DNA between compact forms and coil forms. Packaged or unpackaged DNA was confirmed enzymatically. Plaque-forming unit (Pfu) was used as the measure of infectious ability of virions. The concentration of ATP was measured by the luminometric method. The packaging process was proceeded in picomolar or lower concentration of ATP. This series of procedures may constitute a new ATP-free or low-ATP approach to packaging viral DNA with DNA conformational change underpinning the process. The results from this study may disclose an undiscovered facet of T4 life cycle.

Long-term, non-invasive FTIR detection of low-dose ionizing radiation exposure

Non-invasive methods of detecting radiation exposure show promise to improve upon current approaches to biological dosimetry in ease, speed, and accuracy. Here we developed a pipeline that employs Fourier transform infrared (FTIR) spectroscopy in the mid-infrared spectrum to identify a signature of low dose ionizing radiation exposure in mouse ear pinnae over time. Mice exposed to 0.1 to 2 Gy total body irradiation were repeatedly measured by FTIR at the stratum corneum of the ear pinnae. We found significant discriminative power for all doses and time-points out to 90 days after exposure. Classification accuracy was maximized when testing 14 days after exposure (specificity > 0.9 with a sensitivity threshold of 0.9) and dropped by roughly 30% sensitivity at 90 days. Infrared frequencies point towards biological changes in DNA conformation, lipid oxidation and accumulation and shifts in protein secondary structure. Since only hundreds of samples were used to learn the highly discriminative signature, developing human-relevant diagnostic capabilities is likely feasible and this non-invasive procedure points toward rapid, non-invasive, and reagent-free biodosimetry applications at population scales.

Involvement of Histone Acetyltransferase 1 (HAT1) in the Spermatogenesis of Non-Condensed Nuclear Sperm in Chinese Mitten Crab, Eriocheir sinensis.

Chinese mitten crab, Eriocheir sinensis, is a decapod crustacean with a special, non-condensated nucleus in the sperm. Studies have shown that the nuclear compact state of male germ cells during the spermatogenesis is closely related to histone modification. To explore the possible role of histone acetyltransferase 1 (HAT1) in the chromatin organization during the E. sinensis spermatogenesis, we took the testis tissues of both adult and juvenile crabs as the materials of study and analyzed the biological functions of HAT1 by whole transcriptome sequencing and bioinformatics, then further analyzed the expression and distribution of HAT1 using the methods of RT-qRCR, western blotting, and immunofluorescence location. The results showed that HAT1 is an alkaline-unstable hydrophilic protein. Itwaspredictedtointeractwith a variety of histones and chromosome assembly proteins, including Asf1b, Chaf1b, and Hist1h3f, and is involved in many biological functions pertaining to chromatin dynamics such as chromatin organization, DNAdependent nucleosome assembly, DNA conformational changes, and so on. HAT1 was up-regulated in the adult testes compared to the juvenile (n = 3, P < 0.05). HAT1 was mainly located in the nuclei of male germ cells of E. sinensis. As spermatogenesis proceeded, the expression of HAT1 decreased and evendisappearedinthenuclei (n = 3, P < 0.05). HAT1 is an important player in histone acetylation, which facilitates chromatin alteration in a three-dimensional conformation. The expression of HAT1 in different male germ cells might indicate the chromatin dynamics at the diversity stages of spermatogenesis. The high expression of HAT1 at the early stages of E. sinensis spermatogenesis hints the active involvement in chromatin organization, while its progressively reduced expression accompanied by the progression of spermatogenesis suggests a relatively gradual stabilization and stereotyping of chromatin. As for the disappearance of HAT1 in mature sperm with non-condensed nuclei, the reduction in histones targeted by HAT1 or histone acetylation may be an important initiator.

Dynamic Insights into DNA Conformational Changes and the Impact of Magnesium Ions on Topoisomerase IA Enzymes: A Molecular Dynamics Simulation Study

Molecular dynamics simulations were employed to scrutinize the conformational changes in DNA strands and elucidate the influence of magnesium ions on Topoisomerase IA enzymes. Through the computation of Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), hydrogen bond distances, dihedral angles, and Solvated Accessible Surface Area (SASA), we meticulously examined the structural dynamics. The results reveal intricate patterns of DNA strand alterations, showcasing the profound role of magnesium ions in modulating the behavior of Topoisomerase IA enzymes. This study contributes essential insights into the molecular mechanisms governing DNA conformational changes, offering a foundation for further understanding the biochemical intricacies of Topoisomerase IA enzyme function.

DNA conformational change embrace ultraviolet photolysis: A dual-mode sensing platform for electrochemical and fluorescent signaling

We developed a dual-mode biosensor that utilizes DNA conformational changes and ultraviolet photolysis for electrochemical (EC) and fluorescence (FL) detection. In this study, a stem-loop-structured carcinoembryonic antigen (CEA) aptamer was modified on an Au electrode, and this aptamer contained a redox-labeled methylene blue (MB), short-chain DNA with a 6-carboxylic fluorescein (FAM) and a PC linker that can be cleaved by ultraviolet light. Subsequently, CEA and CEA antibody-modified upconversion nanoparticle bioconjugates (CEA-Ab@UCNPs) were added. In the presence of CEA, Ab@UCNPs can bind CEA and push the MB which was originally close to the electrode surface, away from the electrode surface, resulting in a reduced redox current. Under irradiation with a 980 nm laser, the UCNPs emit ultraviolet light, leading to photocleavage of the PC linker and the release of FAM for FL sensing. Under optimal conditions, the EC and FL modes showed good responses to CEA within 0.01–50 ng/mL and 0.1–80 ng/mL, respectively.

Mononuclear copper(II) complexes with polypyridyl ligands: synthesis, characterization, DNA interactions/cleavages and in vitro cytotoxicity towards human cancer cells.

DNA being the necessary element in cell regeneration, controlled cellular apoptosis via DNA binding/cleaving is considered an approach to combat cancer cells. The widely prescribed metallodrug cisplatin has shown interactions with the guanine-N7 center, and a plethora of complexes are continually developed to enhance crosslinking properties as well as covalent and non-covalent interactions. Two pentadentate ligands, L1 (1-(6-(1H-benzo[d]imidazol-2-yl)pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine) and L2 (1-(6-(1-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine), were synthesized together with their respective copper(II) complexes [1](ClO4)2 and [2](ClO4)2, which crystallized in a trigonal bipyramidal fashion. Different analytical and spectroscopic methods confirmed their formation, and their redox behaviour was also examined. The interactions of salmon sperm DNA (ss-DNA) with these two complexes were explored using absorbance spectroscopy, and they both exhibited a binding affinity (Kb) of ∼104 M-1. Fluorescence quenching experiments with ethidium bromide (EB)-bound DNA (EB-DNA) were also performed, and Stern-Volmer constant (KSV) values of 6.93 × 103 and 2.34 × 104 M-1 for [1](ClO4)2 and [2](ClO4)2, respectively, were obtained. Furthermore, DNA conformational changes due to the interactions of both complexes were validated via circular dichroism. We also assessed the DNA cleavage property of these complexes, which resulted in the linearization of circular plasmid DNA. This finding was supported by studying the growth of MDA-MB-231 breast cancer cells upon treatment with both Cu(II) complexes; IC50 values of 5.34 ± 1.02 μM and 0.83 ± 0.18 μM were obtained for [1](ClO4)2 and [2](ClO4)2, respectively. This validates their affinity towards DNA, and these insights can be further utilized for non-platinum based economical metallodrug development based on first row transition metals.

Validation of a Proteomic-Based Prognostic Model for Breast Cancer and Immunological Analysis.

Breast cancer (BC) has emerged as an extremely destructive malignancy, causing significant harm to female patients and society at large. Proteomic research holds great promise for early diagnosis and treatment of diseases, and the integration of proteomics with genomics can offer valuable assistance in the early diagnosis, treatment, and improved prognosis of BC patients. In this study, we downloaded breast cancer protein expression data from The Cancer Genome Atlas (TCGA) and combined proteomics with genomics to construct a proteomic-based prognostic model for BC. This model consists of nine proteins (HEREGULIN, IDO, PEA15, MERIT40_pS29, CIITA, AKT2, CD171 DVL3, and CABL9). The accuracy of the model in predicting the survival prognosis of BC patients was further validated through risk curve analysis, survival curve analysis, and independent prognostic analysis. We further confirmed the impact of differential expression of these nine key proteins on overall survival in BC patients, and the differential expression of the key proteins and their encoding genes was validated using immunohistochemical staining. Enrichment analysis revealed functional associations primarily related to PPAR signaling pathway, steroid hormone metabolism, chemokine signaling pathway, DNA conformation changes, immunoglobulin production, and immunoglobulin complex in the high- and low-risk groups. Immune infiltration analysis revealed differential expression of immune cells between the high- and low-risk groups, providing a theoretical basis for subsequent immunotherapy. The model constructed in this study can predict the survival of BC patients, and the identified key proteins may serve as biomarkers to aid in the early diagnosis of BC. Enrichment analysis and immune infiltration analysis provide a necessary theoretical basis for further exploration of the molecular mechanisms and subsequent immunotherapy.

4mC-CGRU: Identification of N4-Methylcytosine (4mC) sites using convolution gated recurrent unit in Rosaceae genome

An epigenetic modification is DNA N4-methylcytosine (4mC) that affects several biological functions without altering the DNA nucleotides, including DNA conformation, cell development, replication, stability, and DNA structural changes. To prevent restriction enzyme from damaging self-DNA, 4mC performs a critical role in restriction–modification functions. Existing studies mainly focused on finding hand-crafted features to identify 4mC locations, but these methods are inefficient due to high time consuming and high costs. In our research work, we propose a 4mC-CGRU which is a deep learning-based computational model with a standard encoding method to identify the 4mC sites from DNA sequences that learned autonomous feature selection in the Rosaceae genome, particularly in Rosa chinensis (R. chinensis) and Fragaria vesca (F. vesca). The proposed model consists of a convolutional neural network (CNN) and a gated recurrent unit network (GRU)-based model for identifying 4mC sites from Fragaria vesca and Rosa chinensis in the genomes. The CNN model extracts useful features from the datasets and the GRU classifies the DNA sequences. Thus, our approach can automatically extract important features to detect relative sites from DNA sequence. The performance analysis shows that the proposed model consistently outperforms over the state-of-the-art works in detecting 4mC sites.