Biomedical subjects

Yu Xue

Publications and source records attributed to Yu Xue.

At least 19 recordsLinked to original sources

PubMed2026

Discovery and validation of novel plasma protein biomarkers for severe tuberculosis patients.

OBJECTIVE: Severe tuberculosis (STB) imposes a substantial disease burden, yet reliable biomarkers for distinguishing STB from mild/moderate tuberculosis (MTB) remain scarce. This study aimed to identify and independently validate plasma protein biomarkers associated with tuberculosis severity. METHODS: In this multicenter prospective study, 298 adults with confirmed pulmonary tuberculosis were enrolled into screening (n = 128) and independent validation (n = 170) cohorts. Plasma samples were analysed using data-independent acquisition proteomics. Differentially expressed proteins were screened via Limma and four machine-learning algorithms, with candidate proteins measured by enzyme-linked immunosorbent assays. Receiver operating characteristic analysis assessed individual and combined diagnostic performance. RESULTS: STB patients were older and presented with lymphopenia, hypoalbuminemia, neutrophilia, and elevated lactate dehydrogenase. Among 166 differentially expressed proteins, HSPA5, HSP90B1, EEF1D, and SULT1A1 were selected for validation. In STB patients, HSPA5, HSP90B1, and EEF1D were upregulated, whereas SULT1A1 was downregulated. The four-protein panel achieved an AUC of 0.908 (95% CI 0.864-0.952), with 87.5% sensitivity and 83.8% specificity, modestly outperforming HSPA5 alone (AUC = 0.894). Functional enrichment implicated cholesterol metabolism, immune-inflammatory pathways, and endoplasmic reticulum stress. CONCLUSIONS: The four-protein panel effectively discriminated STB from MTB; however, its marginal improvement over HSPA5 alone suggests that an HSPA5-based assay may offer a simpler, more practical, and potentially cost-effective strategy for severity stratification.

Humans↗

PubMed2026

GCH1, identified by a ferroptosis-related prognostic model, contributes to progression and drug resistance of esophageal cancer.

OBJECTIVE: Esophageal cancer has a poor prognosis and limited treatment options. Ferroptosis, an iron-dependent cell death pathway, is a promising therapeutic target; however, its significance in esophageal cancer remains largely unexplored. Here, we investigated the prognostic significance of ferroptosis-related genes in esophageal cancer and identified a key functional regulator that may serve as a therapeutic target. METHODS: We analyzed ferroptosis-related gene expression profiles with The Cancer Genome Atlas-Esophageal Carcinoma (TCGA-ESCA) cohort and constructed a prognostic risk model using LASSO Cox regression analysis. Among the genes in this model, GTP cyclohydrolase 1 (GCH1) was selected for functional investigation, based on its established role in antioxidant defense. Subsequently, in vitro experiments were performed to assess the effects of GCH1 knockdown on cell proliferation, migration, clonogenicity, and ferroptosis-related biochemical indicators. The role of GCH1 in antitumor immunity was evaluated through co-culture of esophageal cancer cells with activated T cells, and drug sensitivity was assessed using cytotoxicity assays. RESULTS: A prognostic model consisting of nine ferroptosis-related genes (STC2, TRIB3, HMGB3, CXCL8, GCH1, PARP10, APOE, MTIM, and GPER1) with reliable risk stratification was constructed. The prognostic model could reflect the differences in drug responses and immune cell infiltration. GCH1 knockdown suppressed esophageal cancer cell proliferation, migration, and clonogenicity. Furthermore, GCH1 knockdown increased the intracellular levels of reactive oxygen species, lipid peroxidation, and ferrous iron (Fe2+). Co-culture assays demonstrated that GCH1 knockdown in tumor cells increased the production of granzyme B and interferon-γ by CD8+ T cells. Moreover, GCH1 silencing sensitized esophageal cancer cells to both sorafenib and cisplatin. CONCLUSIONS: This study established a ferroptosis-related prognostic model for esophageal cancer and identified GCH1 as a critical regulator that contributes to esophageal cancer progression and drug resistance. These findings suggest that targeting GCH1 may be a promising strategy to improve drug sensitivity and clinical outcomes in esophageal cancer.

Esophageal cancer↗

PubMed2026

Novel biallelic FSIP2 variants cause male infertility with multiple morphological abnormalities of sperm flagella in humans.

Biallelic variants in fibrous sheath-interacting protein 2 ( FSIP2 ) gene are a known cause of multiple morphological abnormalities of the sperm flagella (MMAF). This study aimed to identify novel FSIP2 variants and evaluate their impact on sperm ultrastructure and intracytoplasmic sperm injection (ICSI) outcomes. Whole-exome sequencing (WES) was employed to screen a cohort of 92 MMAF patients, with candidate variants validated via Sanger sequencing and third-generation sequencing. We identified one homozygous variant in a proband from a consanguineous family and two pairs of compound heterozygous variants in two unrelated, non-consanguineous families. Routine semen analysis demonstrated markedly reduced motility across all probands. Detailed morphological and ultrastructural assessments using Papanicolaou staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) demonstrated that approximately 80.0% of spermatozoa exhibited pathological elongation of the mitochondrial sheath in the midpiece. Furthermore, 50.0%-70.0% of spermatozoa displayed fibrous sheath dysplasia or loss in the principal piece. Immunofluorescence assays and Western blotting confirmed that FSIP2 protein localization was disrupted, and the expression of key axonemal assembly factors was dysregulated. Notably, successful pregnancies were achieved via ICSI in the partners of two probands. This study expands the mutational spectrum of FSIP2 in both consanguineous and non-consanguineous populations. Ultrastructural abnormalities, such as mitochondrial sheath elongation and fibrous sheath disassembly, highlight FSIP2 's critical role in flagellar assembly. Clinical results further support ICSI as an effective therapeutic intervention for affected individuals.

Humans↗

PubMed2006

Crystal structure of the PXR-T1317 complex provides a scaffold to examine the potential for receptor antagonism.

The human pregnane X receptor (PXR) recognizes a range of structurally and chemically distinct ligands and plays a key role in regulating the expression of protective gene products involved in the metabolism and excretion of potentially harmful compounds. The identification and development of PXR antagonists is desirable as a potential way to control the up-regulation of drug metabolism pathways during the therapeutic treatment of disease. We present the 2.8A resolution crystal structure of the PXR ligand binding domain (LBD) in complex with T0901317 (T1317), which is also an agonist of another member of the orphan class of the nuclear receptor superfamily, the liver X receptor (LXR). In spite of differences in the size and shape of the receptors' ligand binding pockets, key interactions with this ligand are conserved between human PXR and human LXR. Based on the PXR-T1317 structure, analogues of T1317 were generated with the goal of designing an PXR antagonist effective via the receptor's ligand binding pocket. We find that selectivity in activating PXR versus LXR was achieved; such compounds may be useful in addressing neurodegenerative diseases like Niemann-Pick C. We were not successful, however, in producing a PXR antagonist. Based on these observations, we conclude that the generation of PXR antagonists targeted to the ligand binding pocket may be difficult due to the promiscuity and structural conformability of this xenobiotic sensor.

Crystallization↗

PubMed2006

NBA-Palm: prediction of palmitoylation site implemented in Naïve Bayes algorithm.

BACKGROUND: Protein palmitoylation, an essential and reversible post-translational modification (PTM), has been implicated in cellular dynamics and plasticity. Although numerous experimental studies have been performed to explore the molecular mechanisms underlying palmitoylation processes, the intrinsic feature of substrate specificity has remained elusive. Thus, computational approaches for palmitoylation prediction are much desirable for further experimental design. RESULTS: In this work, we present NBA-Palm, a novel computational method based on Naïve Bayes algorithm for prediction of palmitoylation site. The training data is curated from scientific literature (PubMed) and includes 245 palmitoylated sites from 105 distinct proteins after redundancy elimination. The proper window length for a potential palmitoylated peptide is optimized as six. To evaluate the prediction performance of NBA-Palm, 3-fold cross-validation, 8-fold cross-validation and Jack-Knife validation have been carried out. Prediction accuracies reach 85.79% for 3-fold cross-validation, 86.72% for 8-fold cross-validation and 86.74% for Jack-Knife validation. Two more algorithms, RBF network and support vector machine (SVM), also have been employed and compared with NBA-Palm. CONCLUSION: Taken together, our analyses demonstrate that NBA-Palm is a useful computational program that provides insights for further experimentation. The accuracy of NBA-Palm is comparable with our previously described tool CSS-Palm. The NBA-Palm is freely accessible from: http://www.bioinfo.tsinghua.edu.cn/NBA-Palm.

Acyltransferases↗

PubMed2006

Prediction of Nepsilon-acetylation on internal lysines implemented in Bayesian Discriminant Method.

Protein acetylation is an important and reversible post-translational modification (PTM), and it governs a variety of cellular dynamics and plasticity. Experimental identification of acetylation sites is labor-intensive and often limited by the availability of reagents such as acetyl-specific antibodies and optimization of enzymatic reactions. Computational analyses may facilitate the identification of potential acetylation sites and provide insights into further experimentation. In this manuscript, we present a novel protein acetylation prediction program named PAIL, prediction of acetylation on internal lysines, implemented in a BDM (Bayesian Discriminant Method) algorithm. The accuracies of PAIL are 85.13%, 87.97%, and 89.21% at low, medium, and high thresholds, respectively. Both Jack-Knife validation and n-fold cross-validation have been performed to show that PAIL is accurate and robust. Taken together, we propose that PAIL is a novel predictor for identification of protein acetylation sites and may serve as an important tool to study the function of protein acetylation. PAIL has been implemented in PHP and is freely available on a web server at: http://bioinformatics.lcd-ustc.org/pail.

Acetylation↗

PubMed2006

Carvedilol restore cardiac calcium release channel structure and function in heart failure.

BACKGROUND: The ryanodine receptor (RyR2) on cardiac sarcoplasmic reticulum is the key calcium release channel required for excitation-contraction coupling. In failing hearts, the stoichiometry and function of the RyR2 macromolecular complex is altered. AIMS: In the present study, we used a well-characterized canine model of pacing-induced HF to show that Carvedilol both restores the normal stoichiometry of the RyR2 macromolecular complex and normalizes the function of the channel. METHODS: A rapid cardiac pacing regimen that results in severe HF was used. Animals were assigned to 1 of 4 groups: (1) normal without heart instrumentation (n=6), (2) HF (n=6), (3) HF treated with Carvedilol (n=6), and (4) normal without heart instrumentation plus Carvedilol (n=6). In groups 2 and 3, after baseline measurements had been obtained, rapid left ventricular (LV) pacing was initiated at 210 bpm for 3 weeks, followed by an additional week of pacing at 240 bpm with an external pacemaker. Carvedilol was begun 2 weeks after initiation of pacing and continued for 2 weeks. Carvedilol was begun 2 weeks after baseline measurement for the control dogs with heart instrumentation. SR membranes were prepared from canine ventricular tissue, protein concentration was measured by Bradford assay. RESULTS: Here, we show that systemic oral administration of Carvedilol reverses protein kinase A hyperphosphorylation of RyR2, restores the stoichiometry of the RyR2 macromolecular complex, and normalizes single-channel function in a canine model of heart failure. CONCLUSIONS: These results may, in part, explain the improved cardiac function observed in heart failure patients treated with Carvedilol.

Administration, Oral↗

PubMed2006

SUMOsp: a web server for sumoylation site prediction.

Systematic dissection of the sumoylation proteome is emerging as an appealing but challenging research topic because of the significant roles sumoylation plays in cellular dynamics and plasticity. Although several proteome-scale analyzes have been performed to delineate potential sumoylatable proteins, the bona fide sumoylation sites still remain to be identified. Previously, we carried out a genome-wide analysis of the SUMO substrates in human nucleus using the putative motif psi-K-X-E and evolutionary conservation. However, a highly specific predictor for in silico prediction of sumoylation sites in any individual organism is still urgently needed to guide experimental design. In this work, we present a computational system SUMOsp--SUMOylation Sites Prediction, based on a manually curated dataset, integrating the results of two methods, GPS and MotifX, which were originally designed for phosphorylation site prediction. SUMOsp offers at least as good prediction performance as the only available method, SUMOplot, on a very large test set. We expect that the prediction results of SUMOsp combined with experimental verifications will propel our understanding of sumoylation mechanisms to a new level. SUMOsp has been implemented on a freely accessible web server at: http://bioinformatics.lcd-ustc.org/sumosp/.

Algorithms↗

PubMed2006

MeMo: a web tool for prediction of protein methylation modifications.

Protein methylation is an important and reversible post-translational modification of proteins (PTMs), which governs cellular dynamics and plasticity. Experimental identification of the methylation site is labor-intensive and often limited by the availability of reagents, such as methyl-specific antibodies and optimization of enzymatic reaction. Computational analysis may facilitate the identification of potential methylation sites with ease and provide insight for further experimentation. Here we present a novel protein methylation prediction web server named MeMo, protein methylation modification prediction, implemented in Support Vector Machines (SVMs). Our present analysis is primarily focused on methylation on lysine and arginine, two major protein methylation sites. However, our computational platform can be easily extended into the analyses of other amino acids. The accuracies for prediction of protein methylation on lysine and arginine have reached 67.1 and 86.7%, respectively. Thus, the MeMo system is a novel tool for predicting protein methylation and may prove useful in the study of protein methylation function and dynamics. The MeMo web server is available at: http://www.bioinfo.tsinghua.edu.cn/~tigerchen/memo.html.

Arginine↗

PubMed2006

PPSP: prediction of PK-specific phosphorylation site with Bayesian decision theory.

BACKGROUND: As a reversible and dynamic post-translational modification (PTM) of proteins, phosphorylation plays essential regulatory roles in a broad spectrum of the biological processes. Although many studies have been contributed on the molecular mechanism of phosphorylation dynamics, the intrinsic feature of substrates specificity is still elusive and remains to be delineated. RESULTS: In this work, we present a novel, versatile and comprehensive program, PPSP (Prediction of PK-specific Phosphorylation site), deployed with approach of Bayesian decision theory (BDT). PPSP could predict the potential phosphorylation sites accurately for approximately 70 PK (Protein Kinase) groups. Compared with four existing tools Scansite, NetPhosK, KinasePhos and GPS, PPSP is more accurate and powerful than these tools. Moreover, PPSP also provides the prediction for many novel PKs, say, TRK, mTOR, SyK and MET/RON, etc. The accuracy of these novel PKs are also satisfying. CONCLUSION: Taken together, we propose that PPSP could be a potentially powerful tool for the experimentalists who are focusing on phosphorylation substrates with their PK-specific sites identification. Moreover, the BDT strategy could also be a ubiquitous approach for PTMs, such as sumoylation and ubiquitination, etc.

Amino Acid Sequence↗

PubMed2006

CSS-Palm: palmitoylation site prediction with a clustering and scoring strategy (CSS).

UNLABELLED: Palmitoylation is an important post-translational lipid modification of proteins. Unlike prenylation and myristoylation, palmitoylation is a reversible covalent modification, allowing for dynamic regulation of multiple complex cellular systems. However, in vivo or in vitro identification of palmitoylation sites is usually time-consuming and labor-intensive. So in silico predictions could help to narrow down the possible palmitoylation sites, which can be used to guide further experimental design. Previous studies suggested that there is no unique canonical motif for palmitoylation sites, so we hypothesize that the bona fide pattern might be compromised by heterogeneity of multiple structural determinants with different features. Based on this hypothesis, we partition the known palmitoylation sites into three clusters and score the similarity between the query peptide and the training ones based on BLOSUM62 matrix. We have implemented a computer program for palmitoylation site prediction, Clustering and Scoring Strategy for Palmitoylation Sites Prediction (CSS-Palm) system, and found that the program's prediction performance is encouraging with highly positive Jack-Knife validation results (sensitivity 82.16% and specificity 83.17% for cut-off score 2.6). Our analyses indicate that CSS-Palm could provide a powerful and effective tool to studies of palmitoylation sites. AVAILABILITY: CSS-Palm is implemented in PHP/PERL+MySQL and can be freely accessed at http://bioinformatics.lcd-ustc.org/css_palm/ CONTACT: yaoxb@ustc.edu.cn; xuyn@bmb.uga.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bionformatics online.

Algorithms↗

PubMed2005

GPS: a comprehensive www server for phosphorylation sites prediction.

Protein phosphorylation plays a fundamental role in most of the cellular regulatory pathways. Experimental identification of protein kinases' (PKs) substrates with their phosphorylation sites is labor-intensive and often limited by the availability and optimization of enzymatic reactions. Recently, large-scale analysis of the phosphoproteome by the mass spectrometry (MS) has become a popular approach. But experimentally, it is still difficult to distinguish the kinase-specific sites on the substrates. In this regard, the in silico prediction of phosphorylation sites with their specific kinases using protein's primary sequences may provide guidelines for further experimental consideration and interpretation of MS phosphoproteomic data. A variety of such tools exists over the Internet and provides the predictions for at most 30 PK subfamilies. We downloaded the verified phosphorylation sites from the public databases and curated the literature extensively for recently found phosphorylation sites. With the hypothesis that PKs in the same subfamily share similar consensus sequences/motifs/functional patterns on substrates, we clustered the 216 unique PKs in 71 PK groups, according to the BLAST results and protein annotations. Then, we applied the group-based phosphorylation scoring (GPS) method on the data set; here, we present a comprehensive PK-specific prediction server GPS, which could predict kinase-specific phosphorylation sites from protein primary sequences for 71 different PK groups. GPS has been implemented in PHP and is available on a www server at http://973-proteinweb.ustc.edu.cn/gps/gps_web/.

Animals↗

PubMed2005

A genome-wide analysis of sumoylation-related biological processes and functions in human nucleus.

Protein sumoylation is an important reversible post-translational modification of proteins in the nucleus, and it orchestrates a variety of the cellular processes. Genome-wide analysis of functional abundance and distribution of Small Ubiquitin-related MOdifier (SUMO) substrates may shed a light on how sumoylation is involved in nuclear biological processes and functions. Two interesting questions about sumoylation have emerged: (1) how many SUMO substrates exist in mammalian proteomes, such as human and mouse, (2) and what are their functions and how are they involved in a variety of biological processes? To address these two questions,we present an in silico genome-scale analysis for SUMO substrates in human. Based on the pattern recognition and phylogenetic conservation, we retrieved a list of 2683 potential SUMO substrates conserved in both human and mouse. Then, by functional enrichment analysis, we surveyed the over-represented GO terms and functional domains of them against the whole human proteome. Besides the consistence between our analyses and in vivo or in vitro work, the in silico predicted candidates also point to several potential roles of sumoylation, e.g., perception of sound. These potential SUMO substrates in human are of great value for further in vivo or in vitro experimental analysis.

Animals↗

PubMed2005

Effects of changing orders in the update rules on traffic flow.

Based on the Nagel-Schreckenberg (NaSch) model of traffic flow, we study the effects of the orders of the evolutive rule on traffic flow. It has been found from simulation that the cellular automaton (CA) traffic model is very sensitively dependent on the orders of the evolutive rule. Changing the evolutive steps of the NaSch model will result in two modified models, called the SDNaSch model and the noise-first model, with different fundamental diagrams and jamming states. We analyze the mechanism of these two different traffic models and corresponding traffic behaviors in detail and compare the two modified model with the NaSch model. It is concluded that the order arrangement of the stochastic delay and deterministic deceleration indeed has remarkable effects on traffic flow.

Journal Article↗

PubMed2005

Structural disorder in the complex of human pregnane X receptor and the macrolide antibiotic rifampicin.

The human nuclear xenobiotic receptor, pregnane X receptor (PXR), detects a variety of structurally distinct endogenous and xenobiotic compounds and controls expression of genes central to drug and cholesterol metabolism. The macrolide antibiotic rifampicin, a front-line treatment for tuberculosis, is an established PXR agonist and, at 823 Da, is one of the largest known ligands for the receptor. We present the 2.8 A crystal structure of the ligand-binding domain of human PXR in complex with rifampicin. We also use structural and mutagenesis data to examine the origins of the directed promiscuity exhibited by the PXRs across species. Three structurally flexible loops adjacent to the ligand-binding pocket of PXR are disordered in this crystal structure, including the 200-210 region that is part of a sequence insert novel to the promiscuous PXRs relative to other members of the nuclear receptor superfamily. The 4-methyl-1-piperazinyl ring of rifampicin, which would lie adjacent to the disordered protein regions, is also disordered and not observed in the structure. Taken together, our results indicate that one wall of the PXR ligand-binding cavity can remain flexible even when the receptor is in complex with an activating ligand. These observations highlight the key role that structural flexibility plays in PXR's promiscuous response to xenobiotics.

Animals↗

PubMed2005

Enhancing chaoticity of spatiotemporal chaos.

In some practical situations strong chaos is needed. This introduces the task of chaos control with enhancing chaoticity rather than suppressing chaoticity. In this paper a simple method of linear amplifications incorporating modulo operations is suggested to make spatiotemporal systems, which may be originally chaotic or nonchaotic, strongly chaotic. Specifically, this control can eliminate periodic windows, increase the values and the number of positive Lyapunov exponents, make the probability distributions of the output chaotic sequences more homogeneous, and reduce the correlations of chaotic outputs for different times and different space units. The applicability of the method to practical tasks, in particular to random number generators and secure communications, is briefly discussed.

Journal Article↗

PubMed2004

GPS: a novel group-based phosphorylation predicting and scoring method.

Protein phosphorylation is an important reversible post-translational modification of proteins, and it orchestrates a variety of cellular processes. Experimental identification of phosphorylation site is labor-intensive and often limited by the availability and optimization of enzymatic reaction. In silico prediction may facilitate the identification of potential phosphorylation sites with ease. Here we present a novel computational method named GPS: group-based phosphorylation site predicting and scoring platform. If two polypeptides differ by only two consecutive amino acids, in particular when the two different amino acids are a conserved pair, e.g., isoleucine (I) and valine (V), or serine (S) and threonine (T), we view these two polypeptides bearing similar 3D structures and biochemical properties. Based on this rationale, we formulated GPS that carries greater computational power with superior performance compared to two existing phosphorylation sites prediction systems, ScanSite 2.0 and PredPhospho. With database in public domain, GPS can predict substrate phosphorylation sites from 52 different protein kinase (PK) families while ScanSite 2.0 and PredPhospho offer at most 30 PK families. Using PKA as a model enzyme, we first compared prediction profiles from the GPS method with those from ScanSite 2.0 and PredPhospho. In addition, we chose an essential mitotic kinase Aurora-B as a model enzyme since ScanSite 2.0 and PredPhospho offer no prediction. However, GPS offers satisfactory sensitivity (94.44%) and specificity (97.14%). Finally, the accuracy of phosphorylation on MCAK predicted by GPS was validated by experimentation, in which six out of seven predicted potential phosphorylation sites on MCAK (Q91636) were experimentally verified. Taken together, we have generated a novel method to predict phosphorylation sites, which offers greater precision and computing power over ScanSite 2.0 and PredPhospho.

Algorithms↗

PubMed2004

[Advances on inhibin genes].

Inhibins are gonadal glycoprotein hormones belonging to the transforming growth factor-beta superfamily that act to suppress pituitary follicle-stimulating hormone synthesis and secretion. In this paper, we briefly introduced the cloning, structure, localization, polymorphism, expression, molecular regulation of inhibin-alpha(INHA), -betaA (INHBA) and -beta B (INHBB) subunit genes and their relationships with reproductive performance and cancer. The inhibin genes (INHA, INHBA and INHBB) had significant effect on litter size in sheep. The ovine INHA, INHBA and INHBB genes had been mapped to chromosomes 2q41-->q43, 4q26 and 2q31-->q33, respectively. The female mice carrying INHBB mutations suffered from distinct developmental and reproductive defects. The INHA gene was significantly associated with premature ovarian failure in women.

Animals↗