Xusheng Wang

Fudan University · Academy for Engineering and Technology

Sample-wise deconvolution methods have been developed to estimate cell-type proportions and gene expressions in bulk-tissue samples. However, the performance of these methods and their biological applications has not been evaluated, particularly on human brain transcriptomic data. Here, nine deconvolution methods were evaluated with sample-matched...

Regulation of the immune response to Salmonella enterica serovar Typhimurium (S. Typhimurium) infection is a complex process, influenced by the interaction between genetic and environmental factors. Different inbred strains of mice exhibit distinct levels of resistance to S. Typhimurium infection, ranging from susceptible (e.g., C57BL/6J) to resist...

Recent proteome and transcriptome profiling of Alzheimer’s disease (AD) brains reveals RNA splicing dysfunction and U1 small nuclear ribonucleoprotein (snRNP) pathology containing U1-70K and its N-terminal 40-KDa fragment (N40K). Here we present a causative role of U1 snRNP dysfunction to neurodegeneration in primary neurons and transgenic mice (N4...

Protein kinases are a crucial component of signaling pathways involved in a wide range of cellular responses, including growth, proliferation, differentiation, and migration. Systematic investigation of protein kinases is critical to better understand phosphorylation‐mediated signaling pathways and may provide insights into the development of poten...

Psychiatric disorders are highly heritable yet polygenetic, potentially involving hundreds of risk genes. Genome-wide association studies (GWAS) have identified hundreds of genomic susceptibility loci for psychiatric disorders, but how these loci contribute to the underlying psychopathology and etiology remains elusive. Here we generated a deep hum...

The integration of genomics and proteomics data (proteogenomics) holds the promise of furthering the in-depth understanding of human disease. However, sample mix-up is a pervasive problem in proteogenomics because of the complexity of sample processing. Here, we present a pipeline for Sample Matching in Proteogenomics (SMAP) to verify sample identi...

Regulation of the immune response to Salmonella typhimurium ( S . Typhimurium) infection is a complex process, influenced by genetic and environmental factors. Different inbred mouse strains show distinct levels of resistance to S . Typhimurium infection, ranging from susceptible (e.g., C57BL/6J) to resistant (e.g., DBA/2J) strains. However, the un...

Background Natural variation in protein expression is common in all organisms and contributes to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein expression have lagged considerably behind. Here we investigat...

Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer’s disease (AD). Here we review the advances and limitations in historic and recent AD proteomic research. Complementary to genetic mapping, proteomic studies not only validate canonical amyloid and tau pathways, but...

Deep reinforcement learning (DRL) provides a new solution for rehabilitation robot trajectory planning in the unstructured working environment, which can bring great convenience to patients. Previous researches mainly focused on optimization strategies but ignored the construction of reward functions, which leads to low efficiency. Different from t...

To provide stroke patients with good rehabilitation training, the rehabilitation robot should ensure that each joint of the limb of the patient does not exceed its joint range of motion. Based on the machine vision combined with an RGB-Depth (RGB-D) camera, a convenient and quick human-machine interaction method to measure the lower limb joint rang...

Carrying out the immediate rehabilitation interventional therapy will better improve the curative effect of rehabilitation therapy, after the condition of bedridden stroke patients becomes stable. A new lower limb rehabilitation training module, as a component of a synchronous rehabilitation robot for bedridden stroke patients’ upper and lower limb...

Integration of genomics and proteomics (proteogenomics) offers unprecedented promise for an in-depth understanding of human diseases. However, sample mix-up is a pervasive, recurring problem, due to complex sample processing in proteogenomics. Here we present a pipeline for Sample Matching in Proteogenomics (SMAP) for verifying sample identity to e...

Cellular heterogeneity in the human brain obscures the identification of robust cellular regulatory networks, which is necessary to understand the function of non-coding elements and the impact of non-coding genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons and glia with transcriptomic and enhancer...

Background Natural variation in protein expression is common in all organisms and contributes to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein expression have lagged considerably behind. Here we investigat...

The portable and inexpensive hand rehabilitation robot has become a practical rehabilitation device for patients with hand dysfunction. A pneumatic rehabilitation glove with an active trigger control system is proposed, which is based on surface electromyography (sEMG) signals. It can trigger the hand movement based on the patient's hand movement t...

For stroke patients with upper limb motor dysfunction, rehabilitation training with the help of rehabilitation robots is a social development trend. Existing upper limb rehabilitation robots have difficulty fully fitting the complex motion of the human shoulder joint and have poor human–robot compatibility. In this paper, based on the anatomical st...

Person transfer is a major problem for nursing in home and clinical, and this problem is becoming more prominent with the development of aging society and the change of population structure. In this paper, a novel person transfer assist system named E-Pat (Easy-Patient Transfer), which can meet the transfer needs of the patient between beds, has be...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background: Based on amyloid cascade and tau hypotheses, protein biomarkers of different Aβ and tau species in cerebrospinal fluid (CSF) and blood/plasma/serum have been examined to correlate with brain pathology. Recently, unbiased proteomic profiling of these human samples has been initiated to identify a large number of novel AD biomarker candi...

Alzheimer’s disease (AD) displays a long asymptomatic stage prior to development of dementia. Identification of molecular alterations during AD progression would provide insight into temporal alterations associated with AD. AD stage‐associated molecular networks were characterized by mass spectrometry in 90 frontal cortical tissue samples in five g...

G-protein-coupled receptors (GPCRs) are membrane proteins that modulate physiology across human tissues in response to extracellular signals. GPCR-mediated signalling can differ because of changes in the sequence1,2 or expression³ of the receptors, leading to signalling bias when comparing diverse physiological systems⁴. An underexplored source of...

Metabolomics is increasingly important for biomedical research, but large-scale metabolite identification in untargeted metabolomics is still challenging. Here, we present Jumbo Mass spectrometry-based Program of Metabolomics (JUMPm) software, a streamlined software tool for identifying potential metabolite formulas and structures in mass spectrome...

Alzheimer's disease (AD) displays a long asymptomatic stage before dementia. We characterize AD stage-associated molecular networks by profiling 14,513 proteins and 34,173 phosphosites in the human brain with mass spectrometry, highlighting 173 protein changes in 17 pathways. The altered proteins are validated in two independent cohorts, showing pa...

Background Blood-based protein measurement is a routine practice for detecting biomarkers in human disease. Comprehensive profiling of blood/plasma/serum proteome is a challenge due to an extremely large dynamic range, as exemplified by a small subset of highly abundant proteins. Antibody-based depletion of these abundant proteins alleviates the pr...

High throughput omics approaches provide an unprecedented opportunity for dissecting molecular mechanisms in cancer biology. Here we present deep profiling of whole proteome, phosphoproteome and transcriptome in two high-grade glioma (HGG) mouse models driven by mutated RTK oncogenes, PDGFRA and NTRK1, analyzing 13,860 proteins and 30,431 phosphosi...

GABA type-A (GABA-A) receptors containing the α2 subunit (GABRA2) are expressed in most brain regions and are critical in modulating inhibitory synaptic function. Genetic variation at the GABRA2 locus has been implicated in epilepsy, affective and psychiatric disorders, alcoholism and drug abuse. Gabra2 expression varies as a function of genotype a...

Original blots from founder mouse analysis in Figure 3B. Blots were incubated overnight with anti-GABRA2 (PhosphoSolutions #822-GA2CL) and anti-GAPDH (Fitzgerald #10R-G109A) antibodies, followed by fluorescent-conjugated secondary antibodies, and developed on an Odyssey imaging system. (A,B) show unedited whole-blot GABRA2 and GAPDH staining of cor...

Summary of genes with significantly enriched functional terms. Summary of results are provided in the first worksheet (C = total number of genes in category; O = number of observed genes in category; E = number of genes in category expected by chance). Remaining worksheets contain all enriched categories and genes.

Strain distribution pattern of expression of Gabra2. A 2 to 3-fold reduction in expression of mRNA levels in hippocampus [GN110 Hippocampus Consortium M430v2 (Jun06) RMA] that is only segregating in the new BXD strains (BXD33 and higher) that have inherited the Gabra2 B6J private mutation. The Y-axis provides an estimate of the expression of Gabra2...

Mode of inheritance of Gabra2 alleles. In a large eQTL transcriptome analysis of 400 F2 intercross progeny between B6J and CAST/EiJ, the LOD peak is precisely aligned on the Gabra2 gene (purple triangle), the effect size is about 0.20 z per allele (right Y-axis). Note also that the dominance effect is complete (compare peak of the purple and green...

Relative protein expression of the hippocampus in C57BL/6J and DBA/2J mice profiled by 6-plex TMT-LC/LC-MS/MS. A total of 18 hippocampal samples from 3- and 12-month-old C57BL/6J and DBA/2J mice were used in this study. Three hippocampal samples were lysed and pooled into 6 groups (3 groups per strain). The samples were analyzed by 6-plex TMT-LC/LC...

Summary of Predicted Off-Targets. Predictions made using the CRISPOR program and prioritized based on CFD score.

Overrepresented functional terms for differentially expressed genes in the striatum of CRISPR engineered Gabra2 KI mice. Gene members are shown for categories with less than 20 members. All gene members for each category are shown in Supplementary Table S4.

Original blots from Figure 1H analysis. Blots were incubated overnight with anti-GABRA2 antibody (PhosphoSolutions #822-GA2CL), followed by a horseradish peroxidase-conjugated anti-rabbit secondary, and developed on a BioRad ChemiChem chemiluminescent detection system. (A) Unedited whole-blot GABRA2 staining. Following development, blots were strip...

GABA type-A (GABA-A) receptors containing the α2 subunit (Gabra2) are expressed in most brain regions and are critical in modulating inhibitory synaptic function. Genetic variation at the GABRA2 locus has been implicated in epilepsy, affective and psychiatric disorders, alcoholism and drug abuse. Gabra2 expression varies as a function of genotype a...

Genetic analyses have linked microRNA-137 (MIR137) to neuropsychiatric disorders, including schizophrenia and autism spectrum disorder. miR-137 plays important roles in neurogenesis and neuronal maturation, but the impact of miR-137 loss-of-function in vivo remains unclear. Here we show the complete loss of miR-137 in the mouse germline knockout or...

Tandem mass tag (TMT)-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a proven approach for large-scale multiplexed protein quantification. However, the identification of TMT-labeled peptides is compromised by the labeling during traditional sequence database search. In this study, we aim to use spectral library search to increas...

Personalized cancer therapy targeting somatic mutations in patient tumors is increasingly being incorporated into practice. Other therapeutic vulnerabilities resulting from changes in gene expression due to tumor specific epigenetic perturbations are progressively being recognized. These genomic and epigenomic changes are ultimately manifest in the...

High throughput untargeted metabolomics usually relies on complementary liquid chromatography-mass spectrometry (LC-MS) methods to expand the coverage of diverse metabolites, but the integration of those methods is not fully characterized. We systematically investigated the performance of hydrophilic interaction liquid chromatography (HILIC)-MS and...

Metabolite identification is a crucial step in mass spectrometry (MS)-based metabolomics. However, it is still challenging to assess the confidence of assigned metabolites. In this study, we report a novel method for estimating false discovery rate (FDR) of metabolite assignment with a target-decoy strategy, in which the decoys are generated throug...

Many exceptional advances have been made in mass spectrometry (MS)-based proteomics, with particular technical progress in liquid chromatography (LC) coupled to tandem mass spectrometry (LC-MS/MS) and isobaric labeling multiplexing capacity. Here, we introduce a deep-proteomics profiling protocol that combines 10-plex tandem mass tag (TMT) labeling...

N-terminal acetylation is an abundant modification influencing protein functions. Because ∼80% of mammalian cytosolic proteins are N-terminally acetylated, this modification is potentially an untapped target for chemical control of their functions. Structural studies have revealed that, like lysine acetylation, N-terminal acetylation converts a pos...

The molecular circuits by which antigens activate quiescent T cells remain poorly understood. We combined temporal profiling of the whole proteome and phosphoproteome via multiplexed isobaric labeling proteomics technology, computational pipelines for integrating multi-omics datasets, and functional perturbation to systemically reconstruct regulato...

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 by the interference from co-isolated ions, resulting in ratio compression. Here we report that the ratio compression can be essentially resolved by...

We introduce a formula-based strategy and algorithm (JUMPm) for global metabolite identification and false discovery analysis in untargeted mass spectrometry-based metabolomics. JUMPm determines the chemical formulas of metabolites from unlabeled and stable-isotope labeled metabolome data, and derives the most likely metabolite identity by searchin...