ABSTRACT
During the last decade, the generation and accumulation of petabase-scale high-throughput sequencing data have resulted in great challenges, including access to human data, as well as transfer, storage, and sharing of enormous amounts of data. To promote data-driven biological research, the Korean government announced that all biological data generated from government-funded research projects should be deposited at the Korea BioData Station (K-BDS), which consists of multiple databases for individual data types. Here, we introduce the Korean Nucleotide Archive (KoNA), a repository of nucleotide sequence data. As of July 2022, the Korean Read Archive in KoNA has collected over 477 TB of raw next-generation sequencing data from national genome projects. To ensure data quality and prepare for international alignment, a standard operating procedure was adopted, which is similar to that of the International Nucleotide Sequence Database Collaboration. The standard operating procedure includes quality control processes for submitted data and metadata using an automated pipeline, followed by manual examination. To ensure fast and stable data transfer, a high-speed transmission system called GBox is used in KoNA. Furthermore, the data uploaded to or downloaded from KoNA through GBox can be readily processed using a cloud computing service called Bio-Express. This seamless coupling of KoNA, GBox, and Bio-Express enhances the data experience, including submission, access, and analysis of raw nucleotide sequences. KoNA not only satisfies the unmet needs for a national sequence repository in Korea but also provides datasets to researchers globally and contributes to advances in genomics. The KoNA is available at https://www.kobic.re.kr/kona/.
Subject(s)
Databases, Nucleic Acid , Republic of Korea , Humans , High-Throughput Nucleotide Sequencing/methodsABSTRACT
BACKGROUND: Detecting structural variations (SVs) at the population level using next-generation sequencing (NGS) requires substantial computational resources and processing time. Here, we compared the performances of 11 SV callers: Delly, Manta, GridSS, Wham, Sniffles, Lumpy, SvABA, Canvas, CNVnator, MELT, and INSurVeyor. These SV callers have been recently published and have been widely employed for processing massive whole-genome sequencing datasets. We evaluated the accuracy, sequence depth, running time, and memory usage of the SV callers. RESULTS: Notably, several callers exhibited better calling performance for deletions than for duplications, inversions, and insertions. Among the SV callers, Manta identified deletion SVs with better performance and efficient computing resources, and both Manta and MELT demonstrated relatively good precision regarding calling insertions. We confirmed that the copy number variation callers, Canvas and CNVnator, exhibited better performance in identifying long duplications as they employ the read-depth approach. Finally, we also verified the genotypes inferred from each SV caller using a phased long-read assembly dataset, and Manta showed the highest concordance in terms of the deletions and insertions. CONCLUSIONS: Our findings provide a comprehensive understanding of the accuracy and computational efficiency of SV callers, thereby facilitating integrative analysis of SV profiles in diverse large-scale genomic datasets.
Subject(s)
DNA Copy Number Variations , Genomics , Humans , Whole Genome Sequencing , High-Throughput Nucleotide Sequencing , Sequence Analysis, DNA , Genome, Human , Genomic Structural VariationABSTRACT
Ferroptosis, a type of cell death induced by lipid peroxidation, has emerged as a novel anti-cancer strategy. Cancer cells frequently acquire resistance to ferroptosis. However, the underlying mechanisms are poorly understood. To address this issue, we conducted a thorough investigation of the genomic and transcriptomic data derived from hundreds of human cancer cell lines and primary tissue samples, with a particular focus on non-small cell lung carcinoma (NSCLC). It was observed that mutations in Kelch-like ECH-associated protein 1 (KEAP1) and subsequent nuclear factor erythroid 2-related factor 2 (NRF2, also known as NFE2L2) activation are strongly associated with ferroptosis resistance in NSCLC. Additionally, AIFM2 gene, which encodes ferroptosis suppressor protein 1 (FSP1), was identified as the gene most significantly correlated with ferroptosis resistance, followed by multiple NRF2 targets. We found that inhibition of NRF2 alone was not sufficient to reduce FSP1 protein levels and promote ferroptosis, whereas FSP1 inhibition effectively sensitized KEAP1-mutant NSCLC cells to ferroptosis. Furthermore, we found that combined inhibition of FSP1 and NRF2 induced ferroptosis more intensely. Our findings imply that FSP1 is a crucial suppressor of ferroptosis whose expression is partially dependent on NRF2 and that synergistically targeting both FSP1 and NRF2 may be a promising strategy for overcoming ferroptosis resistance in cancer.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Ferroptosis , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Ferroptosis/genetics , Kelch-Like ECH-Associated Protein 1/genetics , Lung Neoplasms/genetics , NF-E2-Related Factor 2/geneticsABSTRACT
Aberrant DNA methylation plays a pivotal role in the onset and progression of colorectal cancer (CRC), a disease with high incidence and mortality rates in Korea. Several CRC-associated diagnostic and prognostic methylation markers have been identified; however, due to a lack of comprehensive clinical and methylome data, these markers have not been validated in the Korean population. Therefore, in this study, we aimed to obtain the CRC methylation profile using 172 tumors and 128 adjacent normal colon tissues of Korean patients with CRC. Based on the comparative methylome analysis, we found that hypermethylated positions in the tumor were predominantly concentrated in CpG islands and promoter regions, whereas hypomethylated positions were largely found in the open-sea region, notably distant from the CpG islands. In addition, we stratified patients by applying the CpG island methylator phenotype (CIMP) to the tumor methylome data. This stratification validated previous clinicopathological implications, as tumors with high CIMP signatures were significantly correlated with the proximal colon, higher prevalence of microsatellite instability status, and MLH1 promoter methylation. In conclusion, our extensive methylome analysis and the accompanying dataset offers valuable insights into the utilization of CRC-associated methylation markers in Korean patients, potentially improving CRC diagnosis and prognosis. Furthermore, this study serves as a solid foundation for further investigations into personalized and ethnicity-specific CRC treatments. [BMB Reports 2023; 56(10): 569-574].
Subject(s)
Colorectal Neoplasms , DNA Methylation , Humans , DNA Methylation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , CpG Islands/genetics , Republic of Korea , PhenotypeABSTRACT
A wave of new technologies has created opportunities for the cost-effective generation of high-throughput profiles of biological systems, foreshadowing a "data-driven science" era. The large variety of data available from biological research is also a rich resource that can be used for innovative endeavors. However, we are facing considerable challenges in big data deposition, integration, and translation due to the complexity of biological data and its production at unprecedented exponential rates. To address these problems, in 2020, the Korean government officially announced a national strategy to collect and manage the biological data produced through national R&D fund allocations and provide the collected data to researchers. To this end, the Korea Bioinformation Center (KOBIC) developed a new biological data repository, the Korea BioData Station (K-BDS), for sharing data from individual researchers and research programs to create a data-driven biological study environment. The K-BDS is dedicated to providing free open access to a suite of featured data resources in support of worldwide activities in both academia and industry.
ABSTRACT
Sodium metal batteries have been emerging as promising candidates for post-Li battery systems owing to the natural abundance, low costs, and high energy density of Na metal. However, exploiting an Na metal anode is accompanied by uncontrolled Na electrodeposition, particularly concerning dendrite growth, hampering practical Na metal battery applications. Herein, we propose sodiophilic gel polymer electrolytes with a porosity-gradient Janus structure to alleviate Na dendrite growth. Tethering only 1.1 mol % sodiophilic poly(ethylene glycol) to poly(vinylidene fluoride-co-hexafluoropropylene) suppresses Na dendrites by regulating homogeneous Na+ distribution, which relies on molecular-level coordination between Na+ and the sodiophilic functional groups. By exploiting the porosity-gradient Janus structure, we have demonstrated that regular porosity and well-defined morphology of polymer electrolytes, particularly at the Na/electrolyte interface, significantly impact dendrite growth. This study provides new insights into the rational design of Na dendrite-suppressing polymer electrolytes, primarily focusing on the ion-regulating ability achieved by surface engineering.
ABSTRACT
The enhancement of the structural stability of conversion-based metal sulfides at high current densities remains a major challenge in realizing the practical application of sodium-ion batteries (SIBs). The instability of metal sulfides is caused by the large volume variation and sluggish reaction kinetics upon sodiation/desodiation. To overcome this, herein, a heterostructured nanocube anode composed of CuS/FeS2 embedded in nitrogen-doped carbon (CuS/FeS2 @NC) is synthesized. Size- and shape-controlled porous carbon nanocubes containing metallic nanoparticles are synthesized by the two-step pyrolysis of a bimetallic Prussian blue analog (PBA) precursor. The simple sulfurization-induced formation of highly conductive CuS along with FeS2 facilitates sodium-ion diffusion and enhances the redox reversibility upon cycling. The mesoporous carbon structure provides excellent electrolyte impregnation, efficient charge transport pathways, and good volume expansion buffering. The CuS/FeS2 @NC nanocube anode exhibits excellent sodium storage characteristics including high desodiation capacity (608 mAh g-1 at 0.2 A g-1 ), remarkable long-term cycle life (99.1% capacity retention after 300 cycles at 5 A g-1 ), and good rate capability up to 5 A g-1 . The simple, facile synthetic route combined with the rational design of bimetallic PBA nanostructures can be widely utilized in the development of conversion-based metal sulfides and other high-capacity anode materials for high-performance SIBs.
ABSTRACT
Molybedenum disulfide (MoS2) is regarded as a promising anode material for next-generation sodium-ion batteries (SIBs) owing to its high theoretical capacity. However, its low conductivity, large volume changes, and undesirable phase transformation hinder its practical applications. In this study, we synthesize a hierarchically designed core-shell heterostructure based on nitrogen-doped MoS2/C and silicon oxycarbide (SiOC) (N-MoS2/C@SiOC) via the facile pyrolysis of a suspension of an N-MoS2/polyfurfural precursor in silicone oil. The in situ nitrogen doping in a two-dimensional MoS2 structure with carbon incorporation leads to the enlargement of the interlayer spacing and enhancement of the electronic conductivity and mechanical stability, which allows the facile, highly reversible insertion and extraction of sodium ions upon cycling. Further, the nanoscale SiOC shell with surface capacitive reactivity provides a conductive pathway, preventing unfavorable side reactions at the electrode/electrolyte interface and acting as a structure-reinforcing buffer against severe volume expansion issues. As a result, the N-MoS2/C@SiOC composite exhibits high reversible capacity (540.7 mAh g-1), high-capacity retention (>100% after 200 cycles), and excellent rate capability up to 10 A g-1. The simple hierarchical core-shell design strategy developed in this study allows for the fabrication of high-performance metal sulfide anodes as well as other high-capacity anode materials for energy storage applications.
ABSTRACT
The development of solid electrolytes (SEs) is a promising pathway to improve the energy density and safety of conventional Li-ion batteries. Several lithium chloride SEs, Li3MCl6 (M = Y, Er, In, and Sc), have gained popularity due to their high ionic conductivity, wide electrochemical window, and good chemical stability. This study systematically investigated 17 Li3MCl6 SEs to identify novel and promising lithium chloride SEs. Calculation results revealed that 12 Li3MCl6 (M = Bi, Dy, Er, Ho, In, Lu, Sc, Sm, Tb, Tl, Tm, and Y) were stable phase with a wide electrochemical stability window and excellent chemical stability against cathode materials and moisture. Li-ion transport properties were examined using bond valence site energy (BVSE) and ab initio molecular dynamics (AIMD) calculation. Li3MCl6 showed the lower migration energy barrier in monoclinic structures, while orthorhombic and trigonal structures exhibited higher energy barriers due to the sluggish diffusion along the two-dimensional path based on the BVSE model. AIMD results confirmed the slower ion migration along the 2D path, exhibiting lower ionic diffusivity and higher activation energy in orthorhombic and trigonal structures. For the further increase of ionic conductivity in monoclinic structures, Li-ion vacancy was formed by the substitution of M3+ with Zr4+. Zr-substituted phase (Li2.5M0.5Zr0.5Cl6, M = In, Sc) exhibited up to a fourfold increase in ionic conductivity. This finding suggested that the optimization of Li vacancy in the Li3MCl6 SEs could lead to superionic Li3MCl6 SEs.
ABSTRACT
Fusion genes represent an important class of biomarkers and therapeutic targets in cancer. ChimerDB is a comprehensive database of fusion genes encompassing analysis of deep sequencing data (ChimerSeq) and text mining of publications (ChimerPub) with extensive manual annotations (ChimerKB). In this update, we present all three modules substantially enhanced by incorporating the recent flood of deep sequencing data and related publications. ChimerSeq now covers all 10 565 patients in the TCGA project, with compilation of computational results from two reliable programs of STAR-Fusion and FusionScan with several public resources. In sum, ChimerSeq includes 65 945 fusion candidates, 21 106 of which were predicted by multiple programs (ChimerSeq-Plus). ChimerPub has been upgraded by applying a deep learning method for text mining followed by extensive manual curation, which yielded 1257 fusion genes including 777 cases with experimental supports (ChimerPub-Plus). ChimerKB includes 1597 fusion genes with publication support, experimental evidences and breakpoint information. Importantly, we implemented several new features to aid estimation of functional significance, including the fusion structure viewer with domain information, gene expression plot of fusion positive versus negative patients and a STRING network viewer. The user interface also was greatly enhanced by applying responsive web design. ChimerDB 4.0 is available at http://www.kobic.re.kr/chimerdb/.
Subject(s)
Biomarkers, Tumor/genetics , Computational Biology , Data Management , Databases, Genetic , Neoplasms/genetics , Data Mining , Humans , Neoplasms/therapy , Software , User-Computer InterfaceABSTRACT
We report proteogenomic analysis of diffuse gastric cancers (GCs) in young populations. Phosphoproteome data elucidated signaling pathways associated with somatic mutations based on mutation-phosphorylation correlations. Moreover, correlations between mRNA and protein abundances provided potential oncogenes and tumor suppressors associated with patient survival. Furthermore, integrated clustering of mRNA, protein, phosphorylation, and N-glycosylation data identified four subtypes of diffuse GCs. Distinguishing these subtypes was possible by proteomic data. Four subtypes were associated with proliferation, immune response, metabolism, and invasion, respectively; and associations of the subtypes with immune- and invasion-related pathways were identified mainly by phosphorylation and N-glycosylation data. Therefore, our proteogenomic analysis provides additional information beyond genomic analyses, which can improve understanding of cancer biology and patient stratification in diffuse GCs.
Subject(s)
Gene Regulatory Networks , Mutation , Proteogenomics/methods , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Age of Onset , Female , Glycosylation , Humans , Male , Phosphorylation , Protein Interaction Maps , Survival Analysis , Exome Sequencing/methodsABSTRACT
The surface of a 5 V class LiNi0.5Mn1.5O4 particle is modified with poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymer by utilizing the hydrophobic characteristics of the 3,4-ethylenedioxythiophene (EDOT) monomer and the tail group of cetyl trimethyl ammonium bromide (CTAB) surfactants, in addition to the electrostatic attraction between cationic CTAB surfactant and cathode materials with a negative ζ potential in aqueous solution. With this novel concept, we design and prepare a uniform EDOT monomer layer on the cathode materials, and chemical polymerization of the EDOT coating layer is then carried out to achieve PEDOT-coated cathode materials via a simple one-pot preparation process. This uniform conducting polymer layer provides notable improvement in the power characteristics of electrodes, and stable electrochemical performance can be obtained especially at severe operating conditions such as the fully charged state and elevated temperatures owing to the successful suppression of the side reaction between the oxide particle and the electrolyte as well as the suppression of Mn dissolution from the oxide material.
ABSTRACT
BACKGROUND: Increasing affordability of next-generation sequencing (NGS) has created an opportunity for realizing genomically-informed personalized cancer therapy as a path to precision oncology. However, the complex nature of genomic information presents a huge challenge for clinicians in interpreting the patient's genomic alterations and selecting the optimum approved or investigational therapy. An elaborate and practical information system is urgently needed to support clinical decision as well as to test clinical hypotheses quickly. RESULTS: Here, we present an integrated clinical and genomic information system (CGIS) based on NGS data analyses. Major components include modules for handling clinical data, NGS data processing, variant annotation and prioritization, drug-target-pathway analysis, and population cohort explorer. We built a comprehensive knowledgebase of genes, variants, drugs by collecting annotated information from public and in-house resources. Structured reports for molecular pathology are generated using standardized terminology in order to help clinicians interpret genomic variants and utilize them for targeted cancer therapy. We also implemented many features useful for testing hypotheses to develop prognostic markers from mutation and gene expression data. CONCLUSIONS: Our CGIS software is an attempt to provide useful information for both clinicians and scientists who want to explore genomic information for precision oncology.
Subject(s)
Genomics , Neoplasms/genetics , Precision Medicine/methods , Gene Expression Profiling , Humans , Molecular Sequence Annotation , Neoplasms/pathology , Signal TransductionABSTRACT
Phosphorus-rich CuP2 and its carbon composites have been investigated as an anode material for lithium-ion batteries. Through a facile, low-cost mechanochemical reaction, microsized composites composed of active CuP2 particles uniformly embedded in the carbon matrix have been successfully synthesized. Combined structural and electrochemical characterizations show that phosphorus-rich CuP2 undergoes irreversible reaction with lithium, giving metal-rich Cu3P and amorphous phosphorus at the end of the first cycle. Both Cu3P and phosphorus are reversibly formed in subsequent cycles, contributing to a high reversible capacity of >1000 mA h g-1. By controlling the carbon content, the electrochemical reversibility and stability of CuP2 are greatly improved. The carbon composite demonstrates a remarkable lithium-storage capability in terms of a stable capacity of >720 mA h g-1 over 100 cycles at 200 mA g-1, a high initial Coulombic efficiency of â¼83%, and a good rate capability with a capacity of >637 mA h g-1 at 1.6 A g-1. The performance improvement is mainly associated with the formation of the conductive carbon network that offers high conductivity and fast reaction kinetics, as well as enhanced structural stability of CuP2 anode.
ABSTRACT
The structural stability and electrical performance of SiO2 grown on SiC via direct plasma-assisted oxidation were investigated. To investigate the changes in the electronic structure and electrical characteristics caused by the interfacial reaction between the SiO2 film (thickness ~5 nm) and SiC, X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), density functional theory (DFT) calculations, and electrical measurements were performed. The SiO2 films grown via direct plasma-assisted oxidation at room temperature for 300s exhibited significantly decreased concentrations of silicon oxycarbides (SiOxCy) in the transition layer compared to that of conventionally grown (i.e., thermally grown) SiO2 films. Moreover, the plasma-assisted SiO2 films exhibited enhanced electrical characteristics, such as reduced frequency dispersion, hysteresis, and interface trap density (Dit ≈ 1011 cm-2 · eV-1). In particular, stress induced leakage current (SILC) characteristics showed that the generation of defect states can be dramatically suppressed in metal oxide semiconductor (MOS) structures with plasma-assisted oxide layer due to the formation of stable Si-O bonds and the reduced concentrations of SiOxCy species defect states in the transition layer. That is, energetically stable interfacial states of high quality SiO2 on SiC can be obtained by the controlling the formation of SiOxCy through the highly reactive direct plasma-assisted oxidation process.
ABSTRACT
A chemically bonded CuP2/C hybrid synthesized using a one-step mechanochemical reaction has been evaluated as an anode in sodium-ion batteries. Due to the synergistic effects of the formation of a strong P-O-C bond and the stable nanoscale conducting framework, it exhibits a high capacity with superior cyclability and rate performance.
ABSTRACT
CTLA4 and CD28 are co-regulatory receptors with opposite roles in T-cell signaling. By RNA sequencing, we identified a fusion between the two genes from partial gene duplication in a case of angioimmunoblastic T-cell lymphoma. The fusion gene, which codes for the extracellular domain of CTLA4 and the cytoplasmic region of CD28, is likely capable of transforming inhibitory signals into stimulatory signals for T-cell activation. Ectopic expression of the fusion transcript in Jurkat and H9 cells resulted in enhanced proliferation and AKT and ERK phosphorylation, indicating activation of downstream oncogenic pathways. To estimate the frequency of this gene fusion in mature T-cell lymphomas, we examined 115 T-cell lymphoma samples of diverse subtypes using reverse transcriptase polymerase chain reaction analysis and Sanger sequencing. We identified the fusion in 26 of 45 cases of angioimmunoblastic T-cell lymphomas (58%), nine of 39 peripheral T-cell lymphomas, not otherwise specified (23%), and nine of 31 extranodal NK/T cell lymphomas (29%). We further investigated the mutation status of 70 lymphoma-associated genes using ultra-deep targeted resequencing for 74 mature T-cell lymphoma samples. The mutational landscape we obtained suggests that T-cell lymphoma results from diverse combinations of multiple gene mutations. The CTLA4-CD28 gene fusion is likely a major contributor to the pathogenesis of T-cell lymphomas and represents a potential target for anti-CTLA4 cancer immunotherapy.
Subject(s)
CD28 Antigens/genetics , CTLA-4 Antigen/genetics , Lymphoma, T-Cell/genetics , Lymphoma, T-Cell/pathology , Oncogene Proteins, Fusion/genetics , Cell Line, Tumor , Cell Proliferation , Computational Biology/methods , Cytokines/metabolism , Gene Dosage , Gene Expression Profiling , Gene Order , Genetic Association Studies , High-Throughput Nucleotide Sequencing , Humans , Lymphoma, T-Cell/metabolism , Mutation , Phenotype , Reproducibility of ResultsABSTRACT
A Zn-based nanocomposite has been prepared through a facile, low-cost high-energy mechanochemical process and employed as an anode material for lithium-ion batteries. Structural characterization reveals that the micrometer-sized Zn-TiC-C nanocomposite is composed of Zn nanocrystals uniformly dispersed in a multifunctional TiC and conductive carbon matrix with a tap density of 1.3 g cm(-3). The Zn-TiC-C nanocomposite exhibits high reversible volumetric capacity (468 mA h cm(-3)), excellent cyclability over 800 cycles (79.2% retention), and good rate performance up to 12.5C (75% of its capacity at 0.25C rate). The enhanced electrochemical performance is mainly due to the presence of the well-mixed TiC+C matrix that plays an important role in providing high conductivity as well as mechanical buffer that mitigates the huge volume expansion and contraction during prolonged cycling. In addition, it prevents the particle growth by uniformly dispersing nanosized Zn within itself during cycling, maintaining high utilization (â¼100%) and fast reaction kinetics of Zn anode.
ABSTRACT
In proteogenomic analysis, construction of a compact, customized database from mRNA-seq data and a sensitive search of both reference and customized databases are essential to accurately determine protein abundances and structural variations at the protein level. However, these tasks have not been systematically explored, but rather performed in an ad-hoc fashion. Here, we present an effective method for constructing a compact database containing comprehensive sequences of sample-specific variants--single nucleotide variants, insertions/deletions, and stop-codon mutations derived from Exome-seq and RNA-seq data. It, however, occupies less space by storing variant peptides, not variant proteins. We also present an efficient search method for both customized and reference databases. The separate searches of the two databases increase the search time, and a unified search is less sensitive to identify variant peptides due to the smaller size of the customized database, compared to the reference database, in the target-decoy setting. Our method searches the unified database once, but performs target-decoy validations separately. Experimental results show that our approach is as fast as the unified search and as sensitive as the separate searches. Our customized database includes mutation information in the headers of variant peptides, thereby facilitating the inspection of peptide-spectrum matches.
Subject(s)
Peptides/metabolism , Proteins/metabolism , Proteomics/methods , Databases, Protein , Mutation , Peptides/genetics , Proteins/genetics , Stomach Neoplasms/metabolismABSTRACT
The molecular mechanisms underlying angioimmunoblastic T cell lymphoma (AITL), a common type of mature T cell lymphoma of poor prognosis, are largely unknown. Here we report a frequent somatic mutation in RHOA (encoding p.Gly17Val) using exome and transcriptome sequencing of samples from individuals with AITL. Further examination of the RHOA mutation encoding p.Gly17Val in 239 lymphoma samples showed that the mutation was specific to T cell lymphoma and was absent from B cell lymphoma. We demonstrate that the RHOA mutation encoding p.Gly17Val, which was found in 53.3% (24 of 45) of the AITL cases examined, is oncogenic in nature using multiple molecular assays. Molecular modeling and docking simulations provided a structural basis for the loss of GTPase activity in the RHOA Gly17Val mutant. Our experimental data and modeling results suggest that the RHOA mutation encoding p.Gly17Val is a driver mutation in AITL. On the basis of these data and through integrated pathway analysis, we build a comprehensive signaling network for AITL oncogenesis.