Xusheng Wang
A5100721481- Bioinformatics and Genomic Networks
- Advanced Proteomics Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Alzheimer's disease research and treatments
- Mass Spectrometry Techniques and Applications
- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Genetic Mapping and Diversity in Plants and Animals
- Mitochondrial Function and Pathology
- Genomics and Phylogenetic Studies
- Genetic Associations and Epidemiology
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Genetics and Neurodevelopmental Disorders
- GABA and Rice Research
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Isotope Analysis in Ecology
- Rice Cultivation and Yield Improvement
- Neuroinflammation and Neurodegeneration Mechanisms
- Molecular Biology Techniques and Applications
University of Tennessee Health Science Center
2008-2025
Sun Yat-sen University
2025
University of Tennessee at Knoxville
2025
St. Jude Children's Research Hospital
2014-2024
Institut thématique Génétique, génomique et bioinformatique
2024
University of North Dakota
2020-2024
South China University of Technology
2024
Changchun University
2023
South China Normal University
2020
Xi'an University of Technology
2019
Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource adult brain across 1866 individuals. The contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles many cell types; quantitative-trait loci (QTLs); further QTLs associated with chromatin, splicing, cell-type...
Deposition of insoluble protein aggregates is a hallmark neurodegenerative diseases. The universal presence β-amyloid and tau in Alzheimer’s disease (AD) has facilitated advancement the amyloid cascade hypotheses that have dominated AD pathogenesis research therapeutic development. However, underlying etiology remains to be fully elucidated. Here we report comprehensive study human brain-insoluble proteome by mass spectrometry. We identify 4,216 proteins, among which 36 proteins accumulate...
Gold-nanoparticles-based colorimetric assay is an attractive detection format, but limited by the tedious and ineffective posthybridization manipulations for genomic analysis. Here, we present a new design gene-sensing platform based on clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system. In this strategy, programmable recognition of DNA Cas12a/crRNA RNA Cas13a/crRNA with complementary target activates trans-ssDNA or -ssRNA cleavage. Target-induced ssRNA cleavage...
Based on amyloid cascade and tau hypotheses, protein biomarkers of different Aβ species in cerebrospinal fluid (CSF) blood/plasma/serum have been examined to correlate with brain pathology. Recently, unbiased proteomic profiling these human samples has initiated identify a large number novel AD biomarker candidates, but it is challenging define reliable candidates for subsequent large-scale validation. We present comprehensive strategy high confidence by integrating multiple proteomes AD,...
RNA splicing is highly prevalent in the brain and has strong links to neuropsychiatric disorders; yet, role of cell type-specific transcript-isoform diversity during human development not been systematically investigated. In this work, we leveraged single-molecule long-read sequencing deeply profile full-length transcriptome germinal zone cortical plate regions developing neocortex at tissue single-cell resolution. We identified 214,516 distinct isoforms, which 72.6% were novel (not...
Database search programs are essential tools for identifying peptides via mass spectrometry (MS) in shotgun proteomics. Simultaneously achieving high sensitivity and specificity during a database is crucial improving proteome coverage. Here we present JUMP, new hybrid program that generates amino acid tags ranks peptide spectrum matches (PSMs) by an integrated score from the pattern matching. In typical run of liquid chromatography coupled with high-resolution tandem MS, more than 95% MS/MS...
Phenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using large murine population segregating for ∼5 million sequence variants, and compare our results those extracted from matched analysis of gene variants cohort. For the mouse cohort, amassed deep broad open-access phenome consisting ∼4,500 metabolic, physiological, pharmacological behavioural traits, more than 90 independent expression...
Protein ubiquitination is an essential post-translational modification regulating neurodevelopment, synaptic plasticity, learning, and memory, its dysregulation contributes to the pathogenesis of neurological diseases. Here we report a systematic analysis ubiquitinated proteome (ubiquitome) in rat brain using newly developed monoclonal antibody that recognizes diglycine tag on lysine residues trypsinized peptides (K-GG peptides). Initial specificity showed can distinguish K-GG from linear GG...
Blood-based protein measurement is a routine practice for detecting biomarkers in human disease. Comprehensive profiling of blood/plasma/serum proteome challenge due to an extremely large dynamic range, as exemplified by small subset highly abundant proteins. Antibody-based depletion these proteins alleviates the problem but introduces experimental variations. We aimed establish method direct undepleted serum and apply toward biomarker discovery Alzheimer's disease (AD), AD most common form...
Isobaric labeling quantification by mass spectrometry (MS) has emerged as a powerful technology for multiplexed large-scale protein profiling, but measurement accuracy in complex mixtures is confounded the interference from coisolated ions, resulting ratio compression. Here we report that compression can be essentially resolved combination of pre-MS peptide fractionation, MS2-based detection, and post-MS computational correction. To recapitulate complexity biological samples, pooled tandem...
Cellular heterogeneity in the human brain obscures identification of robust cellular regulatory networks, which is necessary to understand function non-coding elements and impact genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons glia with transcriptomic enhancer profiles, characterize gene landscape two major cell classes brain. We then leverage cell-type-specific landscapes gain insight into etiology several disorders. find that Alzheimer's...
TREM2 is exclusively expressed by microglia in the brain and strongly linked to risk for Alzheimer’s disease (AD). As microglial responses modulated are central AD pathogenesis, enhancing signaling has been explored as an therapeutic strategy. However, effective window targeting unclear. Here, using microglia-specific inducible mouse models overexpressing human wild-type (TREM2-WT) or R47H variant (TREM2-R47H), we show that TREM2-WT expression reduces amyloid deposition neuritic dystrophy...
Molecular-glue degraders are small molecules that induce a specific interaction between an E3 ligase and target protein, resulting in the proteolysis. The discovery of molecular glue currently relies mostly on screening approaches. Here, we describe library cereblon (CRBN) ligands against panel patient-derived cancer cell lines, leading to SJ7095, potent degrader CK1α, IKZF1 IKZF3 proteins. Through structure-informed exploration structure activity relationship (SAR) around this molecule...
The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold increases contiguity 290-fold compared with its predecessor. Gene annotations are now more complete, improving mapping precision genomic, transcriptomic, proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains substrains using mRatBN7.2. defined...
Murine models of Alzheimer's disease (AD) are crucial for elucidating mechanisms but have limitations in fully representing AD molecular complexities. Here we present the comprehensive, age-dependent brain proteome and phosphoproteome across multiple mouse amyloidosis. We identified shared pathways by integrating with human metadata prioritized components multi-omics analysis. Collectively, two commonly used (5xFAD APP-KI) replicate 30% protein alterations; additional genetic incorporation...
What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized respect to biological function? In what ways do these functionally enigmatic differ from well-studied genes? To address two questions, we devised a computational approach that defines so-called ignoromes. As proof principle, extracted analyzed large subset brain. We find publications associated this set highly skewed—the top 5% absorb 70% the...
The development of high-resolution liquid chromatography (LC) is essential for improving the sensitivity and throughput mass spectrometry (MS)-based proteomics. Here we present systematic optimization a long gradient LC-MS/MS platform to enhance protein identification from complex mixture. employed an in-house fabricated, reverse-phase column (100 μm × 150 cm, 5 C18 beads) coupled Q Exactive MS. was capable achieving peak capacity ∼700 in 720 min 10-45% acetonitrile. optimal loading level ∼6...