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1.
Sci Rep ; 14(1): 10105, 2024 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698020

RESUMEN

Colorectal cancer (CRC) is one of the top five most common and life-threatening malignancies worldwide. Most CRC develops from advanced colorectal adenoma (ACA), a precancerous stage, through the adenoma-carcinoma sequence. However, its underlying mechanisms, including how the tumor microenvironment changes, remain elusive. Therefore, we conducted an integrative analysis comparing RNA-seq data collected from 40 ACA patients who visited Dongguk University Ilsan Hospital with normal adjacent colons and tumor samples from 18 CRC patients collected from a public database. Differential expression analysis identified 21 and 79 sequentially up- or down-regulated genes across the continuum, respectively. The functional centrality of the continuum genes was assessed through network analysis, identifying 11 up- and 13 down-regulated hub-genes. Subsequently, we validated the prognostic effects of hub-genes using the Kaplan-Meier survival analysis. To estimate the immunological transition of the adenoma-carcinoma sequence, single-cell deconvolution and immune repertoire analyses were conducted. Significant composition changes for innate immunity cells and decreased plasma B-cells with immunoglobulin diversity were observed, along with distinctive immunoglobulin recombination patterns. Taken together, we believe our findings suggest underlying transcriptional and immunological changes during the adenoma-carcinoma sequence, contributing to the further development of pre-diagnostic markers for CRC.


Asunto(s)
Adenoma , Neoplasias Colorrectales , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Adenoma/genética , Adenoma/inmunología , Adenoma/patología , República de Corea , Biología Computacional/métodos , Masculino , Femenino , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Pronóstico , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/genética , Estimación de Kaplan-Meier , Perfilación de la Expresión Génica
2.
Hum Genomics ; 18(1): 34, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38566255

RESUMEN

BACKGROUND: Male-pattern baldness (MPB) is the most common cause of hair loss in men. It can be categorized into three types: type 2 (T2), type 3 (T3), and type 4 (T4), with type 1 (T1) being considered normal. Although various MPB-associated genetic variants have been suggested, a comprehensive study for linking these variants to gene expression regulation has not been performed to the best of our knowledge. RESULTS: In this study, we prioritized MPB-related tissue panels using tissue-specific enrichment analysis and utilized single-tissue panels from genotype-tissue expression version 8, as well as cross-tissue panels from context-specific genetics. Through a transcriptome-wide association study and colocalization analysis, we identified 52, 75, and 144 MPB associations for T2, T3, and T4, respectively. To assess the causality of MPB genes, we performed a conditional and joint analysis, which revealed 10, 11, and 54 putative causality genes for T2, T3, and T4, respectively. Finally, we conducted drug repositioning and identified potential drug candidates that are connected to MPB-associated genes. CONCLUSIONS: Overall, through an integrative analysis of gene expression and genotype data, we have identified robust MPB susceptibility genes that may help uncover the underlying molecular mechanisms and the novel drug candidates that may alleviate MPB.


Asunto(s)
Alopecia , Transcriptoma , Humanos , Masculino , Transcriptoma/genética , Alopecia/genética , Alopecia/metabolismo , Genotipo , Pronóstico , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad
3.
Arthritis Res Ther ; 26(1): 47, 2024 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-38336809

RESUMEN

BACKGROUND: Juvenile idiopathic arthritis (JIA) is one of the most prevalent rheumatic disorders in children and is classified as an autoimmune disease (AID). While a robust genetic contribution to JIA etiology has been established, the exact pathogenesis remains unclear. METHODS: To prioritize biologically interpretable susceptibility genes and proteins for JIA, we conducted transcriptome-wide and proteome-wide association studies (TWAS/PWAS). Then, to understand the genetic architecture of JIA, we systematically analyzed single-nucleotide polymorphism (SNP)-based heritability, a signature of natural selection, and polygenicity. Next, we conducted HLA typing using multi-ethnicity RNA sequencing data. Additionally, we examined the T cell receptor (TCR) repertoire at a single-cell level to explore the potential links between immunity and JIA risk. RESULTS: We have identified 19 TWAS genes and two PWAS proteins associated with JIA risks. Furthermore, we observe that the heritability and cell type enrichment analysis of JIA are enriched in T lymphocytes and HLA regions and that JIA shows higher polygenicity compared to other AIDs. In multi-ancestry HLA typing, B*45:01 is more prevalent in African JIA patients than in European JIA patients, whereas DQA1*01:01, DQA1*03:01, and DRB1*04:01 exhibit a higher frequency in European JIA patients. Using single-cell immune repertoire analysis, we identify clonally expanded T cell subpopulations in JIA patients, including CXCL13+BHLHE40+ TH cells which are significantly associated with JIA risks. CONCLUSION: Our findings shed new light on the pathogenesis of JIA and provide a strong foundation for future mechanistic studies aimed at uncovering the molecular drivers of JIA.


Asunto(s)
Artritis Juvenil , Niño , Humanos , Artritis Juvenil/genética , Predisposición Genética a la Enfermedad/genética , Proteínas/genética , Alelos
4.
Comput Biol Med ; 167: 107685, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37976829

RESUMEN

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by airflow limitation and chronic inflammation of the lungs that is a leading cause of death worldwide. Since the complete pathological mechanisms at the single-cell level are not fully understood yet, an integrative approach to characterizing the single-cell-resolution landscape of COPD is required. To identify the cell types and mechanisms associated with the development of COPD, we conducted a meta-analysis using three single-cell RNA-sequencing datasets of COPD. Among the 154,011 cells from 16 COPD patients and 18 healthy subjects, 17 distinct cell types were observed. Of the 17 cell types, monocytes, mast cells, and alveolar type 2 cells (AT2 cells) were found to be etiologically implicated in COPD based on genetic and transcriptomic features. The most transcriptomically diversified states of the three etiological cell types showed significant enrichment in immune/inflammatory responses (monocytes and mast cells) and/or mitochondrial dysfunction (monocytes and AT2 cells). We then identified three chemical candidates that may potentially induce COPD by modulating gene expression patterns in the three etiological cell types. Overall, our study suggests the single-cell level mechanisms underlying the pathogenesis of COPD and may provide information on toxic compounds that could be potential risk factors for COPD.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Transcriptoma , Humanos , Transcriptoma/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , Pulmón , Factores de Riesgo , ARN
5.
Int J Mol Sci ; 24(14)2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37511476

RESUMEN

Psoriasis is a chronic inflammatory skin disease characterized by cutaneous eruptions and pruritus. Because the genetic backgrounds of psoriasis are only partially revealed, an integrative and rigorous study is necessary. We conducted a transcriptome-wide association study (TWAS) with the new Genotype-Tissue Expression version 8 reference panels, including some tissue and multi-tissue panels that were not used previously. We performed tissue-specific heritability analyses on genome-wide association study data to prioritize the tissue panels for TWAS analysis. TWAS and colocalization (COLOC) analyses were performed with eight tissues from the single-tissue panels and the multi-tissue panels of context-specific genetics (CONTENT) to increase tissue specificity and statistical power. From TWAS, we identified the significant associations of 101 genes in the single-tissue panels and 64 genes in the multi-tissue panels, of which 26 genes were replicated in the COLOC. Functional annotation and network analyses identified that the genes were associated with psoriasis and/or immune responses. We also suggested drug candidates that interact with jointly significant genes through a conditional and joint analysis. Together, our findings may contribute to revealing the underlying genetic mechanisms and provide new insights into treatments for psoriasis.


Asunto(s)
Psoriasis , Transcriptoma , Humanos , Estudio de Asociación del Genoma Completo , Perfilación de la Expresión Génica , Especificidad de Órganos , Psoriasis/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple
6.
Front Mol Neurosci ; 15: 996698, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36245924

RESUMEN

Cerebral adrenoleukodystrophy (cALD) is a rare neurodegenerative disease characterized by inflammatory demyelination in the central nervous system. Another neurodegenerative disease with a high prevalence, Alzheimer's disease (AD), shares many common features with cALD such as cognitive impairment and the alleviation of symptoms by erucic acid. We investigated cALD and AD in parallel to study the shared pathological pathways between a rare disease and a more common disease. The approach may expand the biological understandings and reveal novel therapeutic targets. Gene set enrichment analysis (GSEA) and weighted gene correlation network analysis (WGCNA) were conducted to identify both the resemblance in gene expression patterns and genes that are pathologically relevant in the two diseases. Within differentially expressed genes (DEGs), GSEA identified 266 common genes with similar up- or down-regulation patterns in cALD and AD. Among the interconnected genes in AD data, two gene sets containing 1,486 genes preserved in cALD data were selected by WGCNA that may significantly affect the development and progression of cALD. WGCNA results filtered by functional correlation via protein-protein interaction analysis overlapping with GSEA revealed four genes (annexin A5, beta-2-microglobulin, CD44 molecule, and fibroblast growth factor 2) that showed robust associations with the pathogeneses of cALD and AD, where they were highly involved in inflammation, apoptosis, and the mitogen-activated protein kinase pathway. This study provided an integrated strategy to provide new insights into a rare disease with scant publicly available data (cALD) using a more prevalent disorder with some pathological association (AD), which suggests novel druggable targets and drug candidates.

7.
Front Microbiol ; 13: 971503, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36090084

RESUMEN

Antimicrobial peptides (AMPs) show promises as valuable compounds for developing therapeutic agents to control the worldwide health threat posed by the increasing prevalence of antibiotic-resistant bacteria. Animal venom can be a useful source for screening AMPs due to its various bioactive components. Here, the deep learning model was developed to predict species-specific antimicrobial activity. To overcome the data deficiency, a multi-task learning method was implemented, achieving F1 scores of 0.818, 0.696, 0.814, 0.787, and 0.719 for Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, respectively. Peptides PA-Full and PA-Win were identified from the model using different inputs of full and partial sequences, broadening the application of transcriptome data of the spider Pardosa astrigera. Two peptides exhibited strong antimicrobial activity against all five strains along with cytocompatibility. Our approach enables excavating AMPs with high potency, which can be expanded into the fields of biology to address data insufficiency.

8.
PLoS One ; 17(9): e0274879, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36174000

RESUMEN

Uterine fibroid is one of the most prevalent benign tumors in women, with high socioeconomic costs. Although genome-wide association studies (GWAS) have identified several loci associated with uterine fibroid risks, they could not successfully interpret the biological effects of genomic variants at the gene expression levels. To prioritize uterine fibroid susceptibility genes that are biologically interpretable, we conducted a transcriptome-wide association study (TWAS) by integrating GWAS data of uterine fibroid and expression quantitative loci data. We identified nine significant TWAS genes including two novel genes, RP11-282O18.3 and KBTBD7, which may be causal genes for uterine fibroid. We conducted functional enrichment network analyses using the TWAS results to investigate the biological pathways in which the overall TWAS genes were involved. The results demonstrated the immune system process to be a key pathway in uterine fibroid pathogenesis. Finally, we carried out chemical-gene interaction analyses using the TWAS results and the comparative toxicogenomics database to determine the potential risk chemicals for uterine fibroid. We identified five toxic chemicals that were significantly associated with uterine fibroid TWAS genes, suggesting that they may be implicated in the pathogenesis of uterine fibroid. In this study, we performed an integrative analysis covering the broad application of bioinformatics approaches. Our study may provide a deeper understanding of uterine fibroid etiologies and informative notifications about potential risk chemicals for uterine fibroid.


Asunto(s)
Leiomioma , Transcriptoma , Femenino , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Leiomioma/genética , Toxicogenética
9.
IEEE J Biomed Health Inform ; 26(12): 6150-6160, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36070258

RESUMEN

Ion channels, which can be modulated by peptides, are promising drug targets for neurological, metabolic, and cardiovascular disorders. Because it is expensive and labor-intensive to experimentally screen ion channel-modulating peptides (IMPs), in-silico approaches can serve as excellent alternatives. In this study, we present PrIMP, prediction models for screening IMPs that can target sodium, potassium, and calcium ion channels, as well as nicotine acetylcholine receptors (nAChRs). To overcome the data insufficiency of the IMPs, we utilized two types of knowledge transfer approaches: multi-task learning (MTL) and transfer learning (TL). MTL enabled model training for four target tasks simultaneously with hard parameter sharing, thereby increasing model generalization. TL transferred knowledge of pre-trained model weights from antimicrobial peptide data, which was a much larger, naturally-occurring functional peptide dataset that could potentially improve the model performance. MTL and TL successfully improved the prediction performance of prediction models. In addition, a hybrid approach by implementing deep learning along with traditional machine learning was utilized, with additional performance improvements. PrIMP achieved F1 scores of 0.924 (sodium ion channel), 0.937 (potassium ion channel), 0.898 (calcium ion channel), and 0.931 (nAChRs). The pre-processed dataset and proposed model are available at https://github.com/bzlee-bio/PrIMP.


Asunto(s)
Canales Iónicos , Aprendizaje Automático , Humanos , Péptidos
10.
iScience ; 25(7): 104475, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35789852

RESUMEN

Silver nanomaterials have potent antibacterial properties that are the foundation for their wide commercial use as well as for concerns about their unintended environmental impact. The nanoparticles themselves are relatively biologically inert but they can undergo oxidative dissolution yielding toxic silver ions. A quantitative relationship between silver material structure and dissolution, and thus antimicrobial activity, has yet to be established. Here, this dissolution process and associated biological activity is characterized using uniform nanoparticles with variable dimension, shape, and surface chemistry. From this, a phenomenological model emerges that quantitatively relates material structure to both silver dissolution and microbial toxicity. Shape has the most profound influence on antibacterial activity, and surprisingly, surface coatings the least. These results illustrate how material structure may be optimized for antimicrobial properties and suggest strategies for minimizing silver nanoparticle effects on microbes.

11.
Artículo en Inglés | MEDLINE | ID: mdl-35699986

RESUMEN

Three chitinolytic, Gram-negative, light pink, capsule-forming, rod-shaped bacterial strains with gliding motion (MYSH2T, MJ1aT and dk17T) were isolated from seashells, soil and foxtail, respectively. Phylogenetic analysis of the 16S rRNA gene sequences and concatenated alignment of 92 core genes indicated that strains MYSH2T, MJ1aT and dk17T were novel species of the genus Mucilaginibacter and exhibited a high 16S rRNA sequence similarity (i.e. more than 97.2 %) among each other. These novel strains contained summed feature 3 (C16:1 ω7c and/or C16:1 ω6), iso-C15:0 and MK-7 as the predominant fatty acids and menaquinone. According to the CAZys coding gene of KAAS, MYSH2T and MJ1aT were interpreted as strains containing both GH18 and 19 family coding genes, except for dk17T, which shows only GH19 family genes. These strains likely degrade chitin to chitobiose or directly to N-acetyl-d-glucosamine, which may enhance their chitinolytic capacity, thus making these stains potentially useful for industrial chitin degradation. Based on distinct morphological, physiological, chemotaxonomic and phylogenetic differences from their closest phylogenetic neighbours, we propose that strains MYSH2T, MJ1aT and dk17T represent three novel species in the genus Mucilaginibacter, for which the names Mucilaginibacter conchicola sp. nov. (=KACC 19716T=JCM 32787T), Mucilaginibacter achroorhodeus sp. nov. (=KACC 19906T=NBRC 113667T) and Mucilaginibacter pallidiroseus sp. nov. (=KACC 19907T=NBRC 113666T) are proposed. An emended description of the genus Mucilaginibacter is proposed.


Asunto(s)
Ácidos Grasos , Microbiología del Suelo , Técnicas de Tipificación Bacteriana , Bacteroidetes , Composición de Base , Quitina , ADN Bacteriano/genética , Ácidos Grasos/química , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
12.
Commun Biol ; 5(1): 615, 2022 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-35729261

RESUMEN

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, which significantly impact the quality of life. Transcriptome-wide association study (TWAS) was conducted to estimate both transcriptomic and genomic features of AD and detected significant associations between 31 expression quantitative loci and 25 genes. Our results replicated well-known genetic markers for AD, as well as 4 novel associated genes. Next, transcriptome meta-analysis was conducted with 5 studies retrieved from public databases and identified 5 additional novel susceptibility genes for AD. Applying the connectivity map to the results from TWAS and meta-analysis, robustly enriched perturbations were identified and their chemical or functional properties were analyzed. Here, we report the first research on integrative approaches for an AD, combining TWAS and transcriptome meta-analysis. Together, our findings could provide a comprehensive understanding of the pathophysiologic mechanisms of AD and suggest potential drug candidates as alternative treatment options.


Asunto(s)
Dermatitis Atópica , Transcriptoma , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/genética , Dermatitis Atópica/metabolismo , Reposicionamiento de Medicamentos , Estudio de Asociación del Genoma Completo/métodos , Humanos , Calidad de Vida
13.
Artículo en Inglés | MEDLINE | ID: mdl-35238736

RESUMEN

A Gram-negative, moderately halophilic bacterium, designated as strain Y3S6T, was isolated from a surface seawater sample collected from Dongangyoeng cave, Udo-myeon, Jeju-si, Jeju-do, Repulic of Korea. Cells of strain Y3S6T were aerobic, rod-shaped, non-sporulated, yellow, catalase- negative, oxidase-negative and motile with one polar flagellum. Growth of strain Y3S6T occurred at 15-40 °C (optimum: 25-30 °C), at pH 6.0-9.0 (optimum: pH 7.0) and in the presence of 0-13% NaCl (optimum: 1-6 %, w/v). The novel strain was able to produce carotenoids. Its chemotaxonomic and morphological characteristics were consistent with those of members of the genus Halomonas. Phylogenetic analysis of the 16S rRNA gene sequence revealed that strain Y3S6T formed a clade with Halomonas pellis L5T (98.97 %) and Halomonas saliphila LCB169T(98.90%). The average nucleotide identity and digital DNA-DNA hybridization values of strain Y3S6T with the most closely related strains for which whole genomes are publicly available were 82.3-85.2% and 62.8-66.1 %, respectively. The major fatty acids in strain Y3S6T were C16 : 0, C19 : 0 cyclo ω8c and summed feature 8 (composed of C18 : 1 ω7c and/or C18 : 1 ω6c), and the predominant quinone was Q-9. Its polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phosphoglycolipid, one unidentified phosphoaminoglycolipid and one unidentified phospholipid. The genomic DNA G+C content based on the draft genome sequence was 64.2 mol%. The results of physiological and biochemical tests and 16S rRNA sequence analysis clearly revealed that strain Y3S6T represents a novel species in the genus Halomonas, for which the name Halomonas antri sp. nov. has been proposed. The type strain is Y3S6T (=KACC 21536T=NBRC 114315=TBRC 15164T).


Asunto(s)
Halomonas , Técnicas de Tipificación Bacteriana , Composición de Base , Carotenoides , ADN Bacteriano/genética , Ácidos Grasos/química , Filogenia , ARN Ribosómico 16S/genética , Agua de Mar/microbiología , Análisis de Secuencia de ADN
14.
Chonnam Med J ; 58(1): 37-42, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35169558

RESUMEN

To investigate differences of tear neuromediators between subjects with and without dry eye (DE) depending on the ocular sensitivity. Thirty-one subjects with DE and 29 subjects without DE were recruited in this study. The eyes were stimulated by exposure to an irritating product applied to the periocular region. Both DE and non-DE subjects were divided into the high sensitivity and low sensitivity groups based on the degree of ocular sensitivity to ocular irritation. Baseline tear film break-up time (TBUT) and corneal staining score were examined, and tear samples were collected. The concentrations of the tear neuromediators, including nerve growth factor (NGF), serotonin, calcitonin gene-related peptide (CGRP), substance P, neuropeptide Y, and vasoactive intestinal peptide were measured using the enzyme-linked immune sorbent assay. The baseline neuromediator concentrations were compared between subjects with and without DE based on ocular sensitivity. In both DE and non-DE subjects, baseline TBUT was significantly lower in the high sensitivity group than in the low sensitivity group. In the high sensitivity group, baseline tear NGF levels were higher in subjects with DE than in those without DE. In the low sensitivity group, baseline levels of tear CGRP were lower in subjects with DE than in those without DE. Tear neuromediators associated with DE had differences in their concentrations depending on ocular sensitivity. In patients with DE, tear NGF levels increased with high ocular sensitivity to ocular irritation, whereas tear CGRP levels decreased with low ocular sensitivity.

15.
Int J Syst Evol Microbiol ; 71(12)2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34928203

RESUMEN

Two bacterial strains, designated MJB4T and SJ7T, were isolated from water samples collected from Jeongbang Falls on Jeju Island, Republic of Korea. Phylogenetic analysis of 16S rRNA gene sequences indicated that the two strains belonged to the genera Nocardioides and Hyunsoonleella, owing to their high similarities to Nocardioides jensenii DSM 29641T (97.5 %) and Hyunsoonleella rubra FA042 T (96.3 %), respectively. These values are much lower than the gold standard for bacterial species (98.7 %). The average nucleotide identity values between strains MJB4T, SJ7T and the reference strains, Nocardioides jensenii DSM 29641T, Nocardioides daejeonensis MJ31T and Hyunsoonleella flava T58T were 77.2, 75.9 and 75.4 %, respectively. Strains MJB4T and SJ7T and the type strains of the species involved in system incidence have average nucleotide identity and average amino acid threshold values of 60.1-82.6 % for the species boundary (95-96 %), which confirms that strains MJB4T and SJ7T represent two new species of genus Nocardioides and Hyunsoonleella, respectively. Based on phylogenetic and phenotypic data, strains MJB4T and SJ7T are considered to represent novel species of the genus Nocardioides and Hyunsoonleella, respectively, for which the names Nocardioides donggukensis sp. nov. (type strain MJB4T=KACC 21724T=NBRC 114402T) and Hyunsoonleella aquatilis sp. nov., (type strain SJ7T=KACC 21715T=NBRC 114486T) have been proposed.


Asunto(s)
Nocardioides , Filogenia , Microbiología del Agua , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Agua Dulce/microbiología , Nocardioides/clasificación , Nocardioides/aislamiento & purificación , ARN Ribosómico 16S/genética , República de Corea , Análisis de Secuencia de ADN
16.
Int J Mol Sci ; 22(22)2021 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-34830173

RESUMEN

As major components of spider venoms, neurotoxic peptides exhibit structural diversity, target specificity, and have great pharmaceutical potential. Deep learning may be an alternative to the laborious and time-consuming methods for identifying these peptides. However, the major hurdle in developing a deep learning model is the limited data on neurotoxic peptides. Here, we present a peptide data augmentation method that improves the recognition of neurotoxic peptides via a convolutional neural network model. The neurotoxic peptides were augmented with the known neurotoxic peptides from UniProt database, and the models were trained using a training set with or without the generated sequences to verify the augmented data. The model trained with the augmented dataset outperformed the one with the unaugmented dataset, achieving accuracy of 0.9953, precision of 0.9922, recall of 0.9984, and F1 score of 0.9953 in simulation dataset. From the set of all RNA transcripts of Callobius koreanus spider, we discovered neurotoxic peptides via the model, resulting in 275 putative peptides of which 252 novel sequences and only 23 sequences showing homology with the known peptides by Basic Local Alignment Search Tool. Among these 275 peptides, four were selected and shown to have neuromodulatory effects on the human neuroblastoma cell line SH-SY5Y. The augmentation method presented here may be applied to the identification of other functional peptides from biological resources with insufficient data.


Asunto(s)
Bases de Datos de Proteínas , Aprendizaje Profundo , Neurotoxinas , Péptidos , Venenos de Araña , Arañas , Animales , Neurotoxinas/química , Neurotoxinas/genética , Péptidos/química , Péptidos/genética , Venenos de Araña/química , Venenos de Araña/genética , Arañas/química , Arañas/genética
17.
Int J Mol Sci ; 22(2)2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33445803

RESUMEN

Systemic juvenile idiopathic arthritis (sJIA) is a rare subtype of juvenile idiopathic arthritis, whose clinical features are systemic fever and rash accompanied by painful joints and inflammation. Even though sJIA has been reported to be an autoinflammatory disorder, its exact pathogenesis remains unclear. In this study, we integrated a meta-analysis with a weighted gene co-expression network analysis (WGCNA) using 5 microarray datasets and an RNA sequencing dataset to understand the interconnection of susceptibility genes for sJIA. Using the integrative analysis, we identified a robust sJIA signature that consisted of 2 co-expressed gene sets comprising 103 up-regulated genes and 25 down-regulated genes in sJIA patients compared with healthy controls. Among the 128 sJIA signature genes, we identified an up-regulated cluster of 11 genes and a down-regulated cluster of 4 genes, which may play key roles in the pathogenesis of sJIA. We then detected 10 bioactive molecules targeting the significant gene clusters as potential novel drug candidates for sJIA using an in silico drug repositioning analysis. These findings suggest that the gene clusters may be potential genetic markers of sJIA and 10 drug candidates can contribute to the development of new therapeutic options for sJIA.


Asunto(s)
Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/genética , Marcadores Genéticos/genética , Transcriptoma/genética , Regulación hacia Abajo/genética , Descubrimiento de Drogas/métodos , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica/genética , Redes Reguladoras de Genes/genética , Humanos , Análisis por Micromatrices/métodos , Regulación hacia Arriba/genética
18.
Int J Syst Evol Microbiol ; 70(10): 5382-5388, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32877325

RESUMEN

A novel fibrillar matrix-producing, rod-shaped, red-orange, asporogenous, aerobic bacterium, designated DK36T, was isolated from roots of a rice plant in the Ilsan region near Dongguk University, South Korea. Cells of strain DK36T were Gram-stain-negative and motile by means of gliding. The temperature and pH ranges for growth were 7-35 °C (optimum: 30 °C) and pH 5-10 (optimum: pH 7.0). The strain did not require NaCl for growth but tolerated up to 8 % (w/v) NaCl. Phylogenetic anlaysis of the 16S rRNA gene sequence revealed that DK36T formed a monophyletic clade with Adhaeribacter aerophilus 6425 S-25T, Adhaeribacter aerolatus 6515 J-31T and Adhaeribacter swui 17mud1-7T with sequence similarities of 96.3, 95.5 and 95.2%, respectively. The average nucleotide identity and in silico DNA-DNA hybridization values of strain DK36T with the most closely related strains whose whole genomes are publicly available were 72.5-83.6% and 19-28 %, respectively. The strain showed the typical chemotaxonomic characteristics of the genus Adhaeribacter, with the presence of menaquinone MK-7 as the respiratory quinone, and C16 : 1ω5c, iso-C15 : 0 and summed feature 4 (composed of iso-C17 : 1 I/anteiso-C17 : 1 B) as the major fatty acids. The polar lipid profile consisted of phosphatidylethanolamine, one unidentified aminophosphoglycolipid, one unidentified phospholipid, two unidentified aminolipids and five unidentified polar lipids. The genomic DNA G+C content based on the draft genome sequence was 43.4 mol%. The results of physiological and biochemical tests and 16S rRNA gene sequence analysis clearly revealed that strain DK36T represents a novel species of the genus Adhaeribacter, for which the name Adhaeribacter rhizoryzae sp. nov. is proposed. The type strain is DK36T (=KACC 19902T=NBRC 113689T).


Asunto(s)
Bacteroidetes/clasificación , Oryza/microbiología , Filogenia , Rizosfera , Microbiología del Suelo , Técnicas de Tipificación Bacteriana , Bacteroidetes/aislamiento & purificación , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Fosfolípidos/química , Pigmentación , ARN Ribosómico 16S/genética , República de Corea , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química
19.
Genes Genomics ; 42(10): 1179-1188, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32804357

RESUMEN

BACKGROUND: There is now abundant information on genes involved in molluscan oogenesis and their associations with ovarian development. However, few studies have investigated the ovarian transcriptome of Pacific abalone (Haliotis discus hannai). OBJECTIVE: The objective of this study was to identify genes related to ovarian development and maturation in Pacific abalone utilizing RNA-sequencing (RNA-seq) and to verify the genes most relevant to different stages of maturation. METHODS: RNA samples from the ovarian tissues of sexually immature and mature abalone were used to construct cDNA libraries, which were paired-end sequenced on an Illumina HiSeq 2500 platform. Reads from individual samples (unigenes) were aligned to reference transcriptome databases for identification of differentially expressed genes (DEGs) between immature and mature ovarian libraries. Reverse transcription-quantitative polymerase chain reaction was used to verify the RNA-seq data. RESULTS: A total of 8779 unigenes were obtained from the ovaries of immature and mature abalone, with a total length of 3323,279 bp and an average length of 379 bp per gene. Gene ontology analysis assigned 5860 unigenes to biological processes, 855 to cellular components, and 1352 to molecular functions. Overall, 470 DEGs were identified, including 213 and 257 genes down-regulated and up-regulated in mature abalone, respectively. Among these, 13 relevant transcripts, including VTG1 and FZD7, were significantly highly expressed in the ovaries of mature abalone (p < 0.05, fold change > 2). CONCLUSION: This H. discus hannai ovary transcriptome provides molecular targets to better understand ovarian development, oogenesis, and sexual maturation, and to enhance Pacific abalone production.


Asunto(s)
Gastrópodos/genética , Ovario/crecimiento & desarrollo , ARN/genética , Transcriptoma/genética , Animales , Femenino , Gastrópodos/crecimiento & desarrollo , Biblioteca de Genes , Ontología de Genes , Ovario/metabolismo , Análisis de Secuencia de ARN , Maduración Sexual/genética
20.
Antibiotics (Basel) ; 9(7)2020 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-32707636

RESUMEN

The prevalence of antibiotic-resistant bacteria has become an immediate threat to public health. Antimicrobial peptides are attracting attention as a new source of antibiotics due to their ability to prevent drug-resistances with fewer side effects. Spider venom is composed of various bioactive substances with multiple functionalities such as antimicrobial and anti-inflammatory effects. Here, RNA sequencing was conducted on the venom gland of the spider Pardosa astrigera, and a potential toxin peptide with antibacterial properties was selected via homology and in silico analysis. A novel toxin, Lycotoxin-Pa4a, inhibited both gram-negative and gram-positive bacteria by disrupting the outer and bacterial cytoplasmic membrane. Moreover, the peptide downregulated the expression of pro-inflammatory mediators while upregulating the level of anti-inflammatory cytokine by inactivating mitogen-activated protein kinase signaling in a lipopolysaccharide-stimulated murine macrophage cell line. In this research, we identified a novel peptide toxin, Lycotoxin-pa4a, with antibacterial and anti-inflammatory properties, suggesting its potential for the development of a new antibiotics, as well as offering insights into the utilization of biological resources.

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