Biology subjects

Kim, M.-S.

Publications and source records attributed to Kim, M.-S..

30 records · Page 2Linked to original sources

bioRxiv2020

Combined analysis of the time-resolved transcriptome and proteome of the pathogenicity-activated plant pathogen Xanthomonas oryzae pv. oryzae

Xanthomonas oryzae pv. oryzae (Xoo) is a plant pathogen responsible for causing bacterial blight in rice. The immediate alterations in Xoo upon initial contact with rice are essential for pathogenesis. We studied time-resolved genome-wide gene expression in pathogenicity-activated Xoo cells at the transcriptome and proteome levels. The early response genes of Xoo include genes related to cell motility, inorganic ion transport, and effectors. The alteration of gene expression is initiated as early as few minutes after the initial interaction and changes with time. The time-resolved comparison of the transcriptome and proteome shows the differences between transcriptional and translational expression peaks in many genes, although the overall expression pattern of mRNAs and proteins is conserved. The discrepancy suggests an important role of translational regulation in Xoo at the early stages of pathogenesis. The gene expression analysis using time-resolved transcriptome and proteome provides unprecedented valuable information regarding Xoo pathogenesis.

plant biology↗

bioRxiv2020

Purging of deleterious mutations during domestication in the predominant selfing crop soybean

As a predominant plant protein and oil source for both food and feed, soybean is unique in that both domesticated and wild types are predominantly selfing. Here we present a genome-wide variation map of 781 soybean accessions that include 418 domesticated (Glycine max) and 345 wild (Glycine soja) accessions and 18 of their natural hybrids. We identified 10.5 million single nucleotide polymorphisms and 5.7 million small indels that contribute to within- and between-population variations. We describe improved detection of domestication-selective sweeps and drastic reduction of overall deleterious alleles in domesticated soybean relative to wild soybean in contrast to the cost of domestication hypothesis. This resource enables the marker density of existing data sets to be increased to improve the resolution of association studies.

genomics↗

bioRxiv2019

Genome resequencing, improvement of variant calling, and population genomic analyses provide insights into the seedlessness in the genus Vitis

The seedlessness of grape derived from stenospermocarpy is one of the most prized traits of table or raisin grapes. It is controlled by a complex genetic system containing one major dominant gene and multiple minor recessive genes. Here, we collected dense variation data from high-depth resequencing data of seeded, seedless, and wild relative grape genomes sequenced to > 37x mean depth. Variant calls were made using a modified variant calling pipeline that was suitable for highly diverse interspecific grape accessions. The modified pipeline enabled us to call several million more variants than the commonly recommended pipeline. The quality was validated by Sanger sequencing data and subsequently supported by the genetic population structure and the phylogenetic tree constructed using the obtained variation data, results of which were generally consistent with known pedigree and taxonomic classifications. Variation data enabled us to confirm a major dominant gene and identify minor recessive loci for seedlessness. Incidentally, we found that grape cultivar Rizamat contains an ancestral chromosomal region of the major gene in Sultanina, a predominant seedlessness donor cultivar. Furthermore, we predicted new candidate causal genes including Vitvi01g00455, Vitvi08g01528, and Vitvi18g01237 associated with the minor seedless-regulating loci, which showed high homology with genes that regulate seed development in Arabidopsis. This study provides fundamental insights relevant to variant calling from genome resequencing data of diverse interspecific hybrid germplasms such as grape and will accelerate future efforts aimed at crop improvement.

genetics↗

bioRxiv2019

Structure-function analyses of a keratin heterotypic complex identify specific keratin regions involved in intermediate filament assembly

Intermediate filaments (IFs) provide vital mechanical support in a broad array of cell types. Interference with this role causes cell fragility and accounts for a large number of human diseases. Gaining an understanding IF structure is paramount to understanding their function and designing therapeutic agents for relevant diseases. Here, we report the 2.6 [A] resolution crystal structure of a complex of interacting 2B domains of keratin 5 (K5) and K14. K5 and K14 form a long-range, left-handle coiled coil, with participating -helices aligned in parallel and in register. Follow-up mutagenesis revealed that specific contacts between interacting 2B domains play a crucial role during 10-nm IF assembly, likely at the step of octamer-octamer association. The resulting structural model represents the first atomic-resolution visualization of 2B-2B interactions consistent with the A22 dimer alignment and provide insight into the defects introduced by mutations in IF genes associated with human skin diseases.

biochemistry↗

bioRxiv2019

Construction of High-Resolution RAD-Seq Based Linkage Map, Anchoring Reference Genome, and QTL Mapping of the Sex Chromosome in the Marine Medaka Oryzias melastigma

Medaka (Oryzias spp.) is an important fish species in ecotoxicology and considered as a model species due to its biological features including small body size and short generation time. Since Japanese medaka Oryzias latipes is a freshwater species with access to an excellent genome resources, the marine medaka Oryzias melastigma is also applicable for marine ecotoxicology. In genome era, a high-density genetic linkage map is a very useful resource in genomic research, providing a means for comparative genomic analysis and verification of de novo genome assembly. In this study, we developed a high-density genetic linkage map for O. melastigma using restriction-site associated DNA sequencing (RAD-seq). The genetic map consisted of 24 linkage groups with 2,481 RAD-tag markers. The total map length was 1,784 cM with an average marker space of 0.72 cM. The genetic map was integrated with the reference-assisted chromosome assembly (RACA) of O. melastigma, which anchored 90.7% of the assembled sequence onto the linkage map. The values of complete Benchmarking Universal Single-Copy Orthologs (BUSCO) were similar to RACA assembly but N50 (23.74 Mb; total genome length 779.4 Mb; gap 5.29%) increased to 29.99 Mb (total genome length 778.7 Mb; gap 5.2%). Using MapQTL analysis with a single nucleotide polymorphism markers, we identified a major quantitative trait locus for sex traits on the Om10. The integration of the genetic map with the reference genome of marine medaka will serve as a good resource for studies in molecular toxicology, genomics, CRISPR/Cas9, and epigenetics.

bioinformatics↗

bioRxiv2019

On the prediction of protein abundance from RNA

BackgroundProfiling of mRNA expression is an important method to identify biomarkers but complicated by limited correlations between mRNA expression and protein abundance. We hypothesised that these correlations could be improved by mathematical models based on measuring splice variants and time delay in protein translation. MethodsWe characterised time-series of primary human naive CD4+ T cells during early T-helper type 1 differentiation with RNA-sequencing and mass-spectrometry proteomics. We then performed computational time-series analysis in this system and in two other key human and murine immune cell types. Linear mathematical mixed time-delayed splice variant models were used to predict protein abundances, and the models were validated using out-of-sample predictions. Lastly, we re-analysed RNA-Seq datasets to evaluate biomarker discovery in five T-cell associated diseases, validating the findings for multiple sclerosis (MS) and asthma. ResultsThe new models demonstrated median correlations of mRNA-to-protein abundance of 0.79-0.94, significantly out-performing models not including the usage of multiple splice variants and time-delays, as shown in cross-validation tests. Our mathematical models provided more differentially expressed proteins between patients and controls in all five diseases. Moreover, analysis of these proteins in asthma and MS supported their relevance. One marker, sCD27, was clinically validated in MS using two independent cohorts, for treatment response and prognosis. ConclusionOur splice variant and time-delay models substantially improved the prediction of protein abundance from mRNA data in three immune cell-types. The models provided valuable biomarker candidates, which were validated in clinical studies of MS and asthma. We propose that our strategy is generally applicable for biomarker discovery.

bioinformatics↗

bioRxiv2019

An event-related potential study of decision making and feedback utilization in female college students who binge drink

This study investigated the ability to use feedback for decision making in female college students who binge drink (BD) using the Iowa Gambling Task (IGT) and event-related potentials (ERPs). Twenty-seven binge drinkers and 23 non-binge drinkers (non-BD) were identified based on scores on the Korean version of the Alcohol Use Disorder Test and the Alcohol Use Questionnaire. The IGT consists of four cards, including two cards that result in a net loss, with large immediate gains but greater losses in the long term, and two cards that result in a net gain, with small immediate gains but reduced losses in the long term. Participants were required to choose one card at a time to maximize profit until the end of the task while avoiding losses. The BD group showed a significantly lower total net score than the non-BD group, indicating that the BD group chose more disadvantageous cards. The BD group showed significantly smaller {Delta}FRN amplitudes (difference in amplitudes of feedback-related negativity [FRN] between gain and loss feedback) except in P3. Additionally, {Delta}FRN amplitudes in the fronto-central area were positively correlated with the total net score and net scores for sectors 4 and 5. Thus, total net scores and later performance on the IGT increased as {Delta}FRN amplitudes from the fronto-central area increased. FRN is known to reflect early feedback evaluation employing a bottom-up mechanism, whereas P3 is known to reflect late feedback processing and allocation of attentional resources using a top-down mechanism. These results indicate that college students who binge drink have deficits in early evaluation of positive or negative feedback and that this deficit may be related to decision making deficits.

neuroscience↗

bioRxiv2018

TGFam-Finder: An optimal solution for target-gene family annotation in eukaryotic genomes

Whole genome annotation errors that omit essential protein-coding genes hinder further research. We developed Target Gene Family Finder (TGFam-Finder), an optimal tool for structural annotation of protein-coding genes containing target domain(s) of interest in eukaryotic genomes. Large-scale re-annotation of 100 publicly available eukaryotic genomes led to the discovery of essential genes that were missed in previous annotations. An average of 117 (346%) and 148 (45%) additional FAR1 and NLR genes were newly identified in 50 plant genomes. Furthermore, 117 (47%) additional C2H2 zinc finger genes were detected in 50 animal genomes including human and mouse. Accuracy of the newly annotated genes was validated by RT-PCR and cDNA sequencing in human, mouse and rice. In the human genome, 26 newly annotated genes were identical with known functional genes. TGFam-Finder along with the new gene models provide an optimized platform for unbiased functional and comparative genomics and comprehensive evolutionary study in eukaryotes.

bioinformatics↗

bioRxiv2018

Genetic Diversity Patterns and Domestication Origin of Soybean

Understanding diversity and evolution of a crop is an essential step to implement a strategy to expand its germplasm base for crop improvement research. Samples intensively collected from Korea, which is a small but central region in the distribution geography of soybean, were genotyped to provide sufficient data to underpin genome-wide population genetic questions. After removing natural hybrids and duplicated or redundant accessions, we obtained a non-redundant set comprising 1,957 domesticated and 1,079 wild accessions to perform population structure analyses. Our analysis demonstrates that while wild soybean germplasm will require additional sampling from diverse indigenous areas to expand the germplasm base, the current domesticated soybean germplasm is saturated in terms of genetic diversity. We then showed that our genome-wide polymorphism map enabled us to detect genetic loci underling flower color, seed-coat color, and domestication syndrome. A representative soybean set consisting of 194 accessions were divided into one domesticated subpopulation and four wild subpopulations that could be traced back to their geographic collection areas. Population genomics analyses suggested that the monophyletic group of domesticated soybeans was originated in eastern Japan. The results were further substantiated by a phylogenetic tree constructed from domestication-associated single nucleotide polymorphisms identified in this study.

plant biology↗

bioRxiv2017

Prometheus: omics portals for interkingdom comparative genomic analyses

Functional analyses of genes are crucial for unveiling biological responses, for genetic engineering, and for developing new medicines. However, functional analyses have largely been restricted to model organisms, representing a major hurdle for functional studies and industrial applications. To resolve this, comparative genome analyses can be used to provide clues to gene functions as well as their evolutionary history. To this end, we present Prometheus (http://prometheus.kobic.re.kr),web-based omics portal that contains more than 17,215 sequences from prokaryotic and eukaryotic genomes. This portal supports interkingdom comparative analyses via a domain architecture-based gene identification system, Gene Search, and users can easily and rapidly identify single or entire gene sets in specific pathways. Bioinformatics tools for further analyses are provided in Prometheus or through BioExpress, a cloud-based bioinformatics analysis platform. Prometheus suggests a new paradigm for comparative analyses with large amounts of genomic information.

bioinformatics↗

bioRxiv2017

Towards the human cellular microRNAome

microRNAs are short RNAs that serve as master regulators of gene expression and are essential components of normal development as well as modulators of disease. MicroRNAs generally act cell autonomously and thus their localization to specific cell types is needed to guide our understanding of microRNA activity. Current tissue-level data has caused considerable confusion and comprehensive cell-level data does not yet exist. Here we establish the landscape of human cell-specific microRNA expression. This project evaluated 8 billion small RNA-seq reads from 46 primary cell types, 42 cancer or immortalized cell lines, and 26 tissues. It identified both specific and ubiquitous patterns of expression that strongly correlate with adjacent super-enhancer activity. Analysis of unaligned RNA reads uncovered 207 unknown minor strand (passenger) microRNAs of known microRNA loci and 2,632 novel putative microRNA loci. Although cancer cell lines generally recapitulated the expression patterns of matched primary cells, their isomiR sequence families exhibited increased disorder suggesting Drosha and Dicer-dependent microRNA processing variability. Cell-specific patterns of microRNA expression were used to deconvolute variable cellular composition of adipose tissue samples highlighting one use of this cell-specific microRNA expression data. Characterization of cellular microRNA expression across a wide variety of cell types provides a new understanding of this critical regulatory RNA species.

genomics↗

bioRxiv2017

Multiple reference genome sequences of hot pepper reveal the massive evolution of plant disease resistance genes by retroduplication

Transposable elements (TEs) provide major evolutionary forces leading to new genome structure and species diversification. However, the role of TEs in the expansion of disease resistance gene families has been unexplored in plants. Here, we report high-quality de novo genomes for two peppers (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum). Dynamic genome rearrangements involving translocations among chromosome 3, 5 and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs exhibited great abundance across the angiosperms, with most cases lineage-specific and thus recent events. Our study revealed that retroduplication has played key roles in the emergence of new disease-resistance genes in plants.

plant biology↗