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  1. Article ; Online: Deep autoregressive generative models capture the intrinsics embedded in T-cell receptor repertoires.

    Jiang, Yuepeng / Li, Shuai Cheng

    Briefings in bioinformatics

    2023  Volume 24, Issue 2

    Abstract: T-cell receptors (TCRs) play an essential role in the adaptive immune system. Probabilistic models for TCR repertoires can help decipher the underlying complex sequence patterns and provide novel insights into understanding the adaptive immune system. In ...

    Abstract T-cell receptors (TCRs) play an essential role in the adaptive immune system. Probabilistic models for TCR repertoires can help decipher the underlying complex sequence patterns and provide novel insights into understanding the adaptive immune system. In this work, we develop TCRpeg, a deep autoregressive generative model to unravel the sequence patterns of TCR repertoires. TCRpeg largely outperforms state-of-the-art methods in estimating the probability distribution of a TCR repertoire, boosting the average accuracy from 0.672 to 0.906 measured by the Pearson correlation coefficient. Furthermore, with promising performance in probability inference, TCRpeg improves on a range of TCR-related tasks: profiling TCR repertoire probabilistically, classifying antigen-specific TCRs, validating previously discovered TCR motifs, generating novel TCRs and augmenting TCR data. Our results and analysis highlight the flexibility and capacity of TCRpeg to extract TCR sequence information, providing a novel approach for deciphering complex immunogenomic repertoires.
    MeSH term(s) Receptors, Antigen, T-Cell/genetics ; Models, Statistical
    Chemical Substances Receptors, Antigen, T-Cell
    Language English
    Publishing date 2023-02-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2068142-2
    ISSN 1477-4054 ; 1467-5463
    ISSN (online) 1477-4054
    ISSN 1467-5463
    DOI 10.1093/bib/bbad038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: TEINet: a deep learning framework for prediction of TCR-epitope binding specificity.

    Jiang, Yuepeng / Huo, Miaozhe / Cheng Li, Shuai

    Briefings in bioinformatics

    2023  Volume 24, Issue 2

    Abstract: The adaptive immune response to foreign antigens is initiated by T-cell receptor (TCR) recognition on the antigens. Recent experimental advances have enabled the generation of a large amount of TCR data and their cognate antigenic targets, allowing ... ...

    Abstract The adaptive immune response to foreign antigens is initiated by T-cell receptor (TCR) recognition on the antigens. Recent experimental advances have enabled the generation of a large amount of TCR data and their cognate antigenic targets, allowing machine learning models to predict the binding specificity of TCRs. In this work, we present TEINet, a deep learning framework that utilizes transfer learning to address this prediction problem. TEINet employs two separately pretrained encoders to transform TCR and epitope sequences into numerical vectors, which are subsequently fed into a fully connected neural network to predict their binding specificities. A major challenge for binding specificity prediction is the lack of a unified approach to sampling negative data. Here, we first assess the current negative sampling approaches comprehensively and suggest that the Unified Epitope is the most suitable one. Subsequently, we compare TEINet with three baseline methods and observe that TEINet achieves an average AUROC of 0.760, which outperforms baseline methods by 6.4-26%. Furthermore, we investigate the impacts of the pretraining step and notice that excessive pretraining may lower its transferability to the final prediction task. Our results and analysis show that TEINet can make an accurate prediction using only the TCR sequence (CDR3$\beta $) and the epitope sequence, providing novel insights to understand the interactions between TCRs and epitopes.
    MeSH term(s) Deep Learning ; Epitopes, T-Lymphocyte ; Receptors, Antigen, T-Cell ; Protein Binding
    Chemical Substances Epitopes, T-Lymphocyte ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2023-03-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2068142-2
    ISSN 1477-4054 ; 1467-5463
    ISSN (online) 1477-4054
    ISSN 1467-5463
    DOI 10.1093/bib/bbad086
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A Retrospective Review on Dysregulated Autophagy in Polycystic Ovary Syndrome: From Pathogenesis to Therapeutic Strategies.

    Zhao, Yan / Zhao, Xiaoxuan / Jiang, Tianyue / Xi, Hongyan / Jiang, Yuepeng / Feng, Xiaoling

    Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme

    2024  

    Abstract: The main purpose of this article is to explore the relationship between autophagy and the pathological mechanism of PCOS, and to find potential therapeutic methods that can alleviate the pathological mechanism of PCOS by targeting autophagy. Relevant ... ...

    Abstract The main purpose of this article is to explore the relationship between autophagy and the pathological mechanism of PCOS, and to find potential therapeutic methods that can alleviate the pathological mechanism of PCOS by targeting autophagy. Relevant literatures were searched in the following databases, including: PubMed, MEDLINE, Web of Science, Scopus. The search terms were "autophagy", "PCOS", "polycystic ovary syndrome", "ovulation", "hyperandrogenemia", "insulin resistance", "inflammatory state", "circadian rhythm" and "treatment", which were combined according to the retrieval methods of different databases. Through analysis, we uncovered that abnormal levels of autophagy were closely related to abnormal ovulation, insulin resistance, hyperandrogenemia, and low-grade inflammation in patients with PCOS. Lifestyle intervention, melatonin, vitamin D, and probiotics, etc. were able to improve the pathological mechanism of PCOS via targeting autophagy. In conclusion, autophagy disorder is a key pathological mechanism in PCOS and is also a potential target for drug development and design.
    Language English
    Publishing date 2024-04-02
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 80125-2
    ISSN 1439-4286 ; 0018-5043
    ISSN (online) 1439-4286
    ISSN 0018-5043
    DOI 10.1055/a-2280-7130
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Exploring Pyroptosis-related Signature Genes and Potential Drugs in Ulcerative Colitis by Transcriptome Data and Animal Experimental Validation.

    Zhao, Yang / Ma, Yiming / Pei, Jianing / Zhao, Xiaoxuan / Jiang, Yuepeng / Liu, Qingsheng

    Inflammation

    2024  

    Abstract: Ulcerative colitis (UC) is an idiopathic, relapsing inflammatory disorder of the colonic mucosa. Pyroptosis contributes significantly to UC. However, the molecular mechanisms of UC remain unexplained. Herein, using transcriptome data and animal ... ...

    Abstract Ulcerative colitis (UC) is an idiopathic, relapsing inflammatory disorder of the colonic mucosa. Pyroptosis contributes significantly to UC. However, the molecular mechanisms of UC remain unexplained. Herein, using transcriptome data and animal experimental validation, we sought to explore pyroptosis-related molecular mechanisms, signature genes, and potential drugs in UC. Gene profiles (GSE48959, GSE59071, GSE53306, and GSE94648) were selected from the Gene Expression Omnibus (GEO) database, which contained samples derived from patients with active and inactive UC, as well as health controls. Gene Set Enrichment Analysis (GSEA), Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on microarrays to unravel the association between UC and pyroptosis. Then, differential expressed genes (DEGs) and pyroptosis-related DEGs were obtained by differential expression analyses and the public database. Subsequently, pyroptosis-related DEGs and their association with the immune infiltration landscape were analyzed using the CIBERSORT method. Besides, potential signature genes were selected by machine learning (ML) algorithms, and then validated by testing datasets which included samples of colonic mucosal tissue and peripheral blood. More importantly, the potential drug was screened based on this. And these signature genes and the drug effect were finally observed in the animal experiment. GSEA and KEGG enrichment analyses on key module genes derived from WGCNA revealed a close association between UC and pyroptosis. Then, a total of 20 pyroptosis-related DEGs of UC and 27 pyroptosis-related DEGs of active UC were screened. Next, 6 candidate genes (ZBP1, AIM2, IL1β, CASP1, TLR4, CASP11) in UC and 2 candidate genes (TLR4, CASP11) in active UC were respectively identified using the binary logistic regression (BLR), least absolute shrinkage and selection operator (LASSO), random forest (RF) analysis and artificial neural network (ANN), and these genes also showed high diagnostic specificity for UC in testing sets. Specially, TLR4 was elevated in UC and further elevated in active UC. The results of the drug screen revealed that six compounds (quercetin, cyclosporine, resveratrol, cisplatin, paclitaxel, rosiglitazone) could target TLR4, among which the effect of quercetin on intestinal pathology, pyroptosis and the expression of TLR4 in UC and active UC was further determined by the murine model. These findings demonstrated that pyroptosis may promote UC, and especially contributes to the activation of UC. Pyroptosis-related DEGs offer new ideas for the diagnosis of UC. Besides, quercetin was verified as an effective treatment for pyroptosis and intestinal inflammation. This study might enhance our comprehension on the pathogenic mechanism and diagnosis of UC and offer a treatment option for UC.
    Language English
    Publishing date 2024-04-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 434408-x
    ISSN 1573-2576 ; 0360-3997
    ISSN (online) 1573-2576
    ISSN 0360-3997
    DOI 10.1007/s10753-024-02025-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Intercellular communication involving macrophages at the maternal-fetal interface may be a pivotal mechanism of URSA: a novel discovery from transcriptomic data.

    Zhao, Xiaoxuan / Jiang, Yuepeng / Luo, Shiling / Zhao, Yang / Zhao, Hongli

    Frontiers in endocrinology

    2023  Volume 14, Page(s) 973930

    Abstract: Unexplained recurrent spontaneous abortion (URSA) is a severe challenge to reproductive females worldwide, and its etiology and pathogenesis have not yet been fully clarified. Abnormal intercellular communication between macrophages (Mφ) and decidual ... ...

    Abstract Unexplained recurrent spontaneous abortion (URSA) is a severe challenge to reproductive females worldwide, and its etiology and pathogenesis have not yet been fully clarified. Abnormal intercellular communication between macrophages (Mφ) and decidual stromal cells (DSCs) or trophoblasts has been supposed to be the key to URSA. However, the exact molecular mechanisms in the crosstalk are not yet well understood. This study aimed to explore the potential molecule mechanism that may be involved in the communication between Mφ and DSC or trophoblast cells and determine their diagnostic characteristics by using the integrated research strategy of bioinformatics analysis, machine learning and experiments. First, microarrays of decidual tissue (GSE26787, GSE165004) and placenta tissue (GSE22490) in patients with URSA, as well as microarrays involving induced decidualization (GSE94644) and macrophage polarization
    MeSH term(s) Pregnancy ; Female ; Humans ; Transcriptome ; Abortion, Habitual ; Gene Expression Profiling ; Cell Communication/genetics ; Macrophages/metabolism
    Language English
    Publishing date 2023-05-17
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2023.973930
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Deciphering the endometrial immune landscape of RIF during the window of implantation from cellular senescence by integrated bioinformatics analysis and machine learning.

    Zhao, Xiaoxuan / Zhao, Yang / Jiang, Yuepeng / Zhang, Qin

    Frontiers in immunology

    2022  Volume 13, Page(s) 952708

    Abstract: Recurrent implantation failure (RIF) is an extremely thorny issue ... ...

    Abstract Recurrent implantation failure (RIF) is an extremely thorny issue in
    MeSH term(s) Cellular Senescence/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; Computational Biology ; Endometrium/metabolism ; Female ; HLA Antigens/metabolism ; Humans ; Machine Learning ; Oncogene Proteins ; Poly-ADP-Ribose Binding Proteins/metabolism ; Protein Serine-Threonine Kinases
    Chemical Substances Chromosomal Proteins, Non-Histone ; DEK protein, human ; HLA Antigens ; Oncogene Proteins ; Poly-ADP-Ribose Binding Proteins ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2022-09-05
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.952708
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Demystifying the landscape of endometrial immune microenvironment in luteal-phase from cuprotosis: Implications for the mechanism and treatment of RPL.

    Zhao, Xiaoxuan / Wang, Sihui / Du, Tingting / Jiang, Yuepeng / Zhao, Yang / Ma, Yiming / Shen, Dan / Shen, Yi / Ma, Jing

    Gene

    2024  Volume 903, Page(s) 148191

    Abstract: Background: Adaptive changes in the endometrial immune microenvironment during the luteal phase are essential for pregnancy, and their abnormalities are associated with recurrent pregnancy loss (RPL). Nevertheless, the specific mechanism is still ... ...

    Abstract Background: Adaptive changes in the endometrial immune microenvironment during the luteal phase are essential for pregnancy, and their abnormalities are associated with recurrent pregnancy loss (RPL). Nevertheless, the specific mechanism is still unknown. Cuprotosis, an innovatively discovered type of programmed cell death, provides us with a pioneering perspective to decipher the landscape of luteal-phase endometrial immune microenvironment in RPL. This study aimed to analyze the immune landscape of luteal-phase endometrial microenvironment in RPL and explore the association of cuprotosis with it through integrative bioinformatics analysis.
    Methods: The microarrays involving the luteal phase endometrial tissue of RPL were obtained from the GEO database. Differentially expressed genes (DEGs) of RPL were screened and key modules were detected by WGCNA. GO, KEGG, and GSEA immune enrichment analyses were performed on the DEGs in the most relevant modules to RPL. Then, the endometrial immune microenvironment landscape of RPL was analyzed, including immune infiltration analysis and correlation analysis between immune cells or immune functions. The interaction of cuprotosis-related genes (CRGs), the expression level between groups, the immune localization and their correlation with immune cells and immune function were analyzed. LASSO regression and Nomogram evaluated the diagnostic value of immune-related CRGS in RPL. Functional enrichment analysis was performed on the RPL signature CRGs. And RPL samples were grouped according to the expression of 7 RPL signature CRGs through unsupervised clustering analysis. After that, we analyzed the expression level of CRGs and immune infiltration, as well as performed immune function enrichment analysis in subtypes. In addition, we also screened potential drugs that might act on CRGs to improve the pathological mechanism of RPL.
    Results: In this study, we uncovered that DEGs and genes in key modules derived from weighted gene co-expression network analysis (WGCNA) were involved in immune regulation. And the immune infiltration landscape of RPL was significantly different from healthy controls. Furthermore, six hub genes were screened from CRGs based on Cytohubba, and their expression profilings were verified in RPL and normal mouse samples. Besides, seven CRGs closely associated with the immune regulation of RPL were identified by Spearman correlation analysis, including SLC31A1, LIAS, DLD, DLAT, DBT, ATP7B, and ATP7A, named as immune-related CRGs. Furthermore, three subgroups clustered according to these seven genes showed significant differences in immune landscape, suggesting a remarkable effect of CRGs on immune regulation. Last but not least, we analyzed the regulation network of transcription factors, miRNAs, and CRGs, and screened potential compounds for the treatment of RPL by targeting CRGs.
    Conclusions: The abnormal endometrial immune microenvironment in the luteal phase was associated with the pathomechanism of RPL, and cuprotosis was closely involved in the immune microenvironment in the luteal phase endometrium of RPL. Collectively, this study revealed the potential contribution of CRGs to the pathogenesis of RPL, providing a novel breakthroughs in insights into the pathogenesis, diagnosis, and treatment of RPL.
    MeSH term(s) Female ; Pregnancy ; Animals ; Mice ; Luteal Phase ; Apoptosis ; Cluster Analysis ; Computational Biology ; Endometrium
    Language English
    Publishing date 2024-01-20
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2024.148191
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Baicalin ameliorates deficient decidualization in URSA by regulating mitochondrial fission induced necroptosis.

    Zhao, Xiaoxuan / Zhao, Ying / Yang, Qujia / Ma, Jing / Zhao, Yang / Wang, Suxia / Jiang, Yuepeng / Zhang, Qin

    Biochimica et biophysica acta. Molecular cell research

    2024  Volume 1871, Issue 3, Page(s) 119675

    Abstract: Unexplained recurrent spontaneous abortion (URSA) is a common complication of pregnancy that affects the health of pregnant women. Deficient endometrial decidualization has been associated with URSA. However, the underlying mechanism is poorly understood. ...

    Abstract Unexplained recurrent spontaneous abortion (URSA) is a common complication of pregnancy that affects the health of pregnant women. Deficient endometrial decidualization has been associated with URSA. However, the underlying mechanism is poorly understood. This study aims to explore the mechanisms of mitochondrial fission induced necroptosis in deficient decidualization in URSA, and explore the regulation of baicalin on this mechanism. Initially, decidual tissues were collected from patients with URSA and health controls. Subsequently, in vitro induced decidualization model of Telomerase-Immortalized Human Endometrial Stromal Cells (T-hESCs) was constructed. Additionally, murine models of URSA (CBA/J × DBA/2) and normal pregnancy (CBA/J × BALB/c) were established, respectively. The level of decidualization, necroptosis, and mitochondrial fission of decidual tissues from clinical samples were detected. The function of mitochondrial fission on necroptosis during decidualization in T-hESCs was assessed by enhancing or inhibiting mitochondrial fission or necroptosis. Finally, CBA/J × DBA/2 pregnant mice were administrated with different doses of baicalin or saline, and the expression of mitochondrial fission, necroptosis, and decidualization markers were verified. The results of the study demonstrated a significant decrease in decidualization markers in the decidual tissues of URSA patients (P < 0.05), along with an increase in the incidence of cell necroptosis (P < 0.05) and hyperactive mitochondrial fission (P < 0.05). In vitro experiments, LPS was induced to trigger necroptosis of T-hESCs during induced decidualization, and decidualization markers IGFBP1 and PRL were subsequently decreased (P < 0.05). Besides, the mitochondrial fission agonist Tyrphostin A9 was found to promote the level of necroptosis (P < 0.05) and induced deficient decidualization (P < 0.05), which could be rescued by mitochondrial fission inhibitor Mdivi-1 and necroptosis inhibitor Nec-1 (P < 0.05). In addition, baicalin was shown to reduce hyperactive mitochondrial fission (P < 0.05), necroptosis (P < 0.05) and ameliorate deficient decidualization in vitro and in URSA murine models (P < 0.05). Collectively, baicalin shows potential in ameliorating deficient decidualization in URSA by inhibiting mitochondrial fission-triggered necroptosis.
    MeSH term(s) Pregnancy ; Humans ; Female ; Animals ; Mice ; Mice, Inbred CBA ; Mice, Inbred DBA ; Abortion, Spontaneous ; Mitochondrial Dynamics ; Necroptosis ; Flavonoids
    Chemical Substances baicalin (347Q89U4M5) ; Flavonoids
    Language English
    Publishing date 2024-01-18
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamcr.2024.119675
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: [No title information]

    Zhao, Yan / Zhao, Xiaoxuan / Jiang, Tianyue / Xi, Hongyan / Jiang, Yuepeng / Feng, Xiaoling

    Hormone and Metabolic Research

    2024  

    Abstract: The main purpose of this article is to explore the relationship between autophagy and the pathological mechanism of PCOS, and to find potential therapeutic methods that can alleviate the pathological mechanism of ... ...

    Abstract The main purpose of this article is to explore the relationship between autophagy and the pathological mechanism of PCOS, and to find potential therapeutic methods that can alleviate the pathological mechanism of PCOS by targeting autophagy. Relevant literatures were searched in the following databases, including: PubMed, MEDLINE, Web of Science, Scopus. The search terms were “autophagy”, “PCOS”, “polycystic ovary syndrome”, “ovulation”, “hyperandrogenemia”, “insulin resistance”, “inflammatory state”, “circadian rhythm” and “treatment”, which were combined according to the retrieval methods of different databases. Through analysis, we uncovered that abnormal levels of autophagy were closely related to abnormal ovulation, insulin resistance, hyperandrogenemia, and low-grade inflammation in patients with PCOS. Lifestyle intervention, melatonin, vitamin D, and probiotics, etc. were able to improve the pathological mechanism of PCOS via targeting autophagy. In conclusion, autophagy disorder is a key pathological mechanism in PCOS and is also a potential target for drug development and design.
    Keywords polycystic ovary syndrome ;  adrenal ; autophagy ; pathogenesis ; therapeutic strategies ; retrospective review
    Language English
    Publishing date 2024-04-02
    Publisher Georg Thieme Verlag
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 80125-2
    ISSN 1439-4286 ; 0018-5043
    ISSN (online) 1439-4286
    ISSN 0018-5043
    DOI 10.1055/a-2280-7130
    Database Thieme publisher's database

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  10. Book ; Online: VITS-Based Singing Voice Conversion Leveraging Whisper and multi-scale F0 Modeling

    Ning, Ziqian / Jiang, Yuepeng / Wang, Zhichao / Zhang, Bin / Xie, Lei

    2023  

    Abstract: This paper introduces the T23 team's system submitted to the Singing Voice Conversion Challenge 2023. Following the recognition-synthesis framework, our singing conversion model is based on VITS, incorporating four key modules: a prior encoder, a ... ...

    Abstract This paper introduces the T23 team's system submitted to the Singing Voice Conversion Challenge 2023. Following the recognition-synthesis framework, our singing conversion model is based on VITS, incorporating four key modules: a prior encoder, a posterior encoder, a decoder, and a parallel bank of transposed convolutions (PBTC) module. We particularly leverage Whisper, a powerful pre-trained ASR model, to extract bottleneck features (BNF) as the input of the prior encoder. Before BNF extraction, we perform pitch perturbation to the source signal to remove speaker timbre, which effectively avoids the leakage of the source speaker timbre to the target. Moreover, the PBTC module extracts multi-scale F0 as the auxiliary input to the prior encoder, thereby capturing better pitch variations of singing. We design a three-stage training strategy to better adapt the base model to the target speaker with limited target speaker data. Official challenge results show that our system has superior performance in naturalness, ranking 1st and 2nd respectively in Task 1 and 2. Further ablation justifies the effectiveness of our system design.
    Keywords Electrical Engineering and Systems Science - Audio and Speech Processing
    Subject code 006
    Publishing date 2023-10-04
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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