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  • Oxford University Press (OUP)  (6)
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  • Oxford University Press (OUP)  (6)
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  • 1
    Online Resource
    Online Resource
    Potential therapeutic targets for sarcopenia identified by Mendelian randomisation
    Oxford University Press (OUP) ; 2023
    In:  Age and Ageing Vol. 52, No. 2 ( 2023-02-01)
    Details
    In: Age and Ageing, Oxford University Press (OUP), Vol. 52, No. 2 ( 2023-02-01)
    Abstract: Identifying sarcopenia’s causally associated plasma proteins would provide potential therapeutic targets. Methods We screened out sarcopenia-related proteins with genome-wide association studies (GWAS) summary data and cis-protein loci genetic instruments. Summary data of sarcopenia were obtained from a GWAS of 256,523 Europeans aged 60 years and over. The causal effects of the proteins were investigated by cis-Mendelian Randomisation (MR) and multiverse sensitivity analysis. We also explored the robust proteins’ causal associations with appendicular lean mass (ALM) and surveyed their druggability and clinical development activities. Results In sum, 60 proteins from plasma proteome analysis studies and 12 from other studies were enrolled for MR analysis. In the whole population, four proteins (HPT, AT1B2, ISLR2 and TNF12) showed causal associations with the risk of sarcopenia according to the European Working Group on Sarcopenia in Older People (EWGSOP) criterion. In the female population, AT1B2 and TNFSF12 revealed causal associations with sarcopenia risk according to the EWGSOP criterion; HGF revealed a negative association according to the National Institutes of Health criterion. All of them were druggable, and the inhibitors of TNF12 and HGF were evaluated in clinical trials for other diseases. TNF12 also revealed a negative causal association with ALM, whereas HGF was positively causally associated with ALM. Conclusions Five druggable plasma proteins revealed causal associations with sarcopenia in the whole or female populations. TNF12 and HGF were the targets of therapeutic agents evaluated in clinical trials, and they were also causally associated with ALM. Our study suggested the potential mechanisms and therapeutic targets for sarcopenia.
    Type of Medium: Online Resource
    ISSN: 0002-0729 , 1468-2834
    URL: Article
    DOI: 10.1093/ageing/afad024
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2065766-3
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  • 2
    Online Resource
    Online Resource
    Multiple-statistical genome-wide association analysis and genomic prediction of fruit aroma and agronomic traits in peaches
    Oxford University Press (OUP) ; 2023
    In:  Horticulture Research Vol. 10, No. 7 ( 2023-07-04)
    Details
    In: Horticulture Research, Oxford University Press (OUP), Vol. 10, No. 7 ( 2023-07-04)
    Abstract: ‘Chinese Cling’ is an important founder in peach breeding history due to the pleasant flavor. Genome-wide association studies (GWAS) combined with genomic selection are promising tools in fruit tree breeding, as there is a considerable time lapse between crossing and release of a cultivar. In this study, 242 peaches from Shanghai germplasm were genotyped with 145 456 single-nucleotide polymorphisms (SNPs). The six agronomic traits of fruit flesh color, fruit shape, fruit hairiness, flower type, pollen sterility, and soluble solids content, along with 14 key volatile odor compounds (VOCs), were recorded for multiple-statistical GWAS. Except the reported candidate genes, six novel genes were identified as associated with these traits. Thirty-nine significant SNPs were associated with eight VOCs. The putative candidate genes were confirmed for VOCs by RNA-seq, including three genes in the biosynthesis pathway found to be associated with linalool, soluble solids content, and cis-3-hexenyl acetate. Multiple-trait genomic prediction enhanced the predictive ability for γ-decalactone to 0.7415 compared with the single-trait model value of 0.1017. One PTS1-SSR marker was designed to predict the linalool content, and the favorable genotype 187/187 was confirmed, mainly existing in the ‘Shanghai Shuimi’ landrace. Overall, our findings will be helpful in determining peach accessions with the ideal phenotype and show the potential of multiple-trait genomic prediction to improve accuracy for highly correlated genetic traits. The diagnostic marker will be valuable for the breeder to bridge the gap between quantitative trait loci and marker-assisted selection for developing strong-aroma cultivars.
    Type of Medium: Online Resource
    ISSN: 2052-7276
    URL: Article
    DOI: 10.1093/hr/uhad117
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2781828-7
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  • 3
    Online Resource
    Online Resource
    ASDB: a resource for probing protein functions with small molecules
    Oxford University Press (OUP) ; 2016
    In:  Bioinformatics Vol. 32, No. 11 ( 2016-06-01), p. 1752-1754
    Details
    In: Bioinformatics, Oxford University Press (OUP), Vol. 32, No. 11 ( 2016-06-01), p. 1752-1754
    Abstract: Summary: Identifying chemical probes or seeking scaffolds for a specific biological target is important for protein function studies. Therefore, we create the Annotated Scaffold Database (ASDB), a computer-readable and systematic target-annotated scaffold database, to serve such needs. The scaffolds in ASDB were derived from public databases including ChEMBL, DrugBank and TCMSP, with a scaffold-based classification approach. Each scaffold was assigned with an InChIKey as its unique identifier, energy-minimized 3D conformations, and other calculated properties. A scaffold is also associated with drugs, natural products, drug targets and medical indications. The database can be retrieved through text or structure query tools. ASDB collects 333 601 scaffolds, which are associated with 4368 targets. The scaffolds consist of 3032 scaffolds derived from drugs and 5163 scaffolds derived from natural products. For given scaffolds, scaffold-target networks can be generated from the database to demonstrate the relations of scaffolds and targets. Availability and implementation: ASDB is freely available at http://www.rcdd.org.cn/asdb/with the major web browsers. Contact:  junxu@biochemomes.com or xujun9@mail.sysu.edu.cn Supplementary information:  Supplementary data are available at Bioinformatics online.
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    URL: Article
    DOI: 10.1093/bioinformatics/btw055
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    eccDNA-pipe: an integrated pipeline for identification, analysis and visualization of extrachromosomal circular DNA from high-throughput sequencing data
    Oxford University Press (OUP) ; 2024
    In:  Briefings in Bioinformatics Vol. 25, No. 2 ( 2024-01-22)
    Details
    In: Briefings in Bioinformatics, Oxford University Press (OUP), Vol. 25, No. 2 ( 2024-01-22)
    Abstract: Extrachromosomal circular DNA (eccDNA) is currently attracting considerable attention from researchers due to its significant impact on tumor biogenesis. High-throughput sequencing (HTS) methods for eccDNA identification are continually evolving. However, an efficient pipeline for the integrative and comprehensive analysis of eccDNA obtained from HTS data is still lacking. Here, we introduce eccDNA-pipe, an accessible software package that offers a user-friendly pipeline for conducting eccDNA analysis starting from raw sequencing data. This dataset includes data from various sequencing techniques such as whole-genome sequencing (WGS), Circle-seq and Circulome-seq, obtained through short-read sequencing or long-read sequencing. eccDNA-pipe presents a comprehensive solution for both upstream and downstream analysis, encompassing quality control and eccDNA identification in upstream analysis and downstream tasks such as eccDNA length distribution analysis, differential analysis of genes enriched with eccDNA and visualization of eccDNA structures. Notably, eccDNA-pipe automatically generates high-quality publication-ready plots. In summary, eccDNA-pipe provides a comprehensive and user-friendly pipeline for customized analysis of eccDNA research.
    Type of Medium: Online Resource
    ISSN: 1467-5463 , 1477-4054
    URL: Article
    DOI: 10.1093/bib/bbae034
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2036055-1
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    MIX-TPI: a flexible prediction framework for TCR–pMHC interactions based on multimodal representations
    Oxford University Press (OUP) ; 2023
    In:  Bioinformatics Vol. 39, No. 8 ( 2023-08-01)
    Details
    In: Bioinformatics, Oxford University Press (OUP), Vol. 39, No. 8 ( 2023-08-01)
    Abstract: The interactions between T-cell receptors (TCR) and peptide-major histocompatibility complex (pMHC) are essential for the adaptive immune system. However, identifying these interactions can be challenging due to the limited availability of experimental data, sequence data heterogeneity, and high experimental validation costs. Results To address this issue, we develop a novel computational framework, named MIX-TPI, to predict TCR–pMHC interactions using amino acid sequences and physicochemical properties. Based on convolutional neural networks, MIX-TPI incorporates sequence-based and physicochemical-based extractors to refine the representations of TCR–pMHC interactions. Each modality is projected into modality-invariant and modality-specific representations to capture the uniformity and diversities between different features. A self-attention fusion layer is then adopted to form the classification module. Experimental results demonstrate the effectiveness of MIX-TPI in comparison with other state-of-the-art methods. MIX-TPI also shows good generalization capability on mutual exclusive evaluation datasets and a paired TCR dataset. Availability and implementation The source code of MIX-TPI and the test data are available at: https://github.com/Wolverinerine/MIX-TPI.
    Type of Medium: Online Resource
    ISSN: 1367-4811
    URL: Article
    DOI: 10.1093/bioinformatics/btad475
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1468345-3
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  • 6
    Online Resource
    Online Resource
    MDA5 expression is associated with TGF-β-induced fibrosis: potential mechanism of interstitial lung disease in anti-MDA5 dermatomyositis
    Oxford University Press (OUP) ; 2022
    In:  Rheumatology Vol. 62, No. 1 ( 2022-12-23), p. 373-383
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. 1 ( 2022-12-23), p. 373-383
    Abstract: This study aimed to investigate the high-resolution CT (HRCT) characteristics of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5 DM-ILD), and to clarify the underlying mechanisms of the clinical phenomenon. Methods Clinical data and HRCT patterns were compared between anti-MDA5 DM-ILD (n = 32) and antisynthetase syndrome-associated ILD (ASS-ILD) (n = 29). RNA sequencing of whole-blood samples from the two groups, and in vitro experiments using human embryonic lung fibroblasts (HELFs) were conducted to explore the potential mechanisms of the clinical findings. Results The anti-MDA5 DM-ILD subset had a significantly higher incidence of rapidly progressive ILD (RPILD) than ASS-ILD (65.6% vs 37.9%; P = 0.031). The relative percentage of the lung fibrosis HRCT pattern was significantly lower in the anti-MDA5 DM-ILD group, especially the RPILD subgroup (P = 0.013 and 0.003, respectively). RNA sequencing detected the upregulated genes including interferon-induced helicase C domain 1 (encoding MDA5), and a trend towards downregulated expression of TGF-β signalling components in anti-MDA5 DM-ILD. In vitro culture of HELFs revealed that upregulated expression of MDA5 in HELFs was correlated with the downregulated expression of alpha smooth muscle actin, connective tissue growth factor, collagen I and collagen III by suppressing the TGF-β signalling pathway. Conclusions Anti-MDA5 DM-ILD patients have significantly less lung fibrosis and elevated MDA5 expression. The upregulated expression of MDA5 has relations with the suppression of the pro-fibrotic function of fibroblasts via the TGF-β signalling pathway, which may partially explain the mechanism of the clinical phenomenon.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/keac234
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474143-X
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