A5001292249- Gene Regulatory Network Analysis
- Single-cell and spatial transcriptomics
- Bioinformatics and Genomic Networks
- Pancreatic and Hepatic Oncology Research
- Cancer-related molecular mechanisms research
- Neuroinflammation and Neurodegeneration Mechanisms
- Vehicle Dynamics and Control Systems
- Genetic Associations and Epidemiology
- Cancer Genomics and Diagnostics
- Marine and coastal ecosystems
- Fractional Differential Equations Solutions
- T-cell and B-cell Immunology
- Aquatic Ecosystems and Phytoplankton Dynamics
- Systemic Lupus Erythematosus Research
- Differential Equations and Numerical Methods
- Epigenetics and DNA Methylation
- Malaria Research and Control
- Cancer, Lipids, and Metabolism
- MicroRNA in disease regulation
- Traffic control and management
- Pharmacogenetics and Drug Metabolism
- Statistical and numerical algorithms
- Drug-Induced Hepatotoxicity and Protection
- Iterative Methods for Nonlinear Equations
- Genetics, Bioinformatics, and Biomedical Research
Karolinska Institutet
2023-2025
Xuzhou Medical College
2020-2024
Southeast University
2012-2024
Personalis (United States)
2023
Linköping University
2019-2023
University of Chinese Academy of Sciences
2019-2021
Xiamen University
2016-2020
Bridge University
2020
Blood Center of Zhejiang Province
2019
Nanjing University
2013-2018
Personalized medicine requires the integration and processing of vast amounts data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models individual patients computationally treated with thousands drugs find drug optimal for patient.
Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune in microglia the brain. A soluble form of TREM2 (sTREM2) derived from proteolytic cleavage cell surface increased preclinical stages AD and positively correlates with amounts total phosphorylated tau cerebrospinal fluid. However, physiological pathological functions sTREM2 remain unknown. Here, we show that promotes microglial survival a PI3K/Akt-dependent manner stimulates production inflammatory cytokines...
Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets complex diseases, but is complicated by involvement of thousands variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows characterization such changes in whole organs. The based on applying network tools to organize analyze scRNA-seq data from a mouse model arthritis human rheumatoid arthritis, order find diagnostic therapeutic targets....
Apolipoprotein E (ApoE) is a major cholesterol carrier and plays an important role in maintaining lipid homeostasis both the periphery brain. Human APOE gene polymorphic at two single nucleotides (rs429358 rs7412) resulting three different alleles (ε2, ε3 ε4). ApoE isoforms modulate risk for variety of vascular neurodegenerative diseases; thus, genotyping crucial predicting disease designing individualized therapy based on genotype. We have developed method that allele-specific PCR...
DNAX-activating protein of 12 kDa (DAP12) is a signaling adapter expressed in cells that participate innate immune responses. By pairing with different triggering receptors on myeloid cell (TREM) proteins, DAP12 can mediate both positive and negative cellular In particular, TREM1 acts as an amplifier the response, while TREM2 functions regulator. has also been shown to stimulate phagocytosis apoptotic neurons define barrier function microglia. Notably, loss-of-function mutations either or...
Hepatocellular carcinoma (HCC) is among the most common malignancies and has an unfavorable prognosis. The hepatitis B virus-encoded X (HBx) protein closely associated with hepatocarcinogenesis. Sorafenib a unique targeted oral kinase inhibitor for advanced HCC. Long noncoding RNAs (lncRNAs) mediate HCC progression therapeutic resistance by acting as competing endogenous (ceRNAs). However, ceRNA regulatory mechanisms underlying sorafenib in HBx-associated remain largely unknown. In this...
Abstract Background Medical digital twins are computational disease models for drug discovery and treatment. Unresolved problems include how to organize prioritize between disease-associated changes in twins, on cellulome- genome-wide scales. We present a dynamic framework that can be used model such thereby upstream regulators (URs) biomarker- discovery. Methods started with seasonal allergic rhinitis (SAR) as model, by analyses of vitro allergen-stimulated peripheral blood mononuclear...
Abstract Background Ineffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions prioritisation and repurposing based on characterisation complex heterogeneous cellular molecular changes in IMIDs. Methods Here, we propose computational framework, scDrugPrio, which constructs network models disease single-cell RNA sequencing (scRNA-seq) data. scDrugPrio detailed that integrate...
Microcystins (MCs) are produced by cyanobacterial blooms, and microcystin-LR (MC-LR) is the most toxic among 80 MC variants. Data have shown that liver one of specific target organs for MC-LR, which can cause mitochondrial DNA (mtDNA) damage, resulting in dysfunction. However, underlying mechanism still unclear. In present study, we evaluated genetic toxicity MC-LR mice drinking water at different concentrations (1, 5, 10, 20, 40 μg/L) 12 months. Our results showed long-term persistent...
One of the limiting side effects cisplatin use in cancer chemotherapy is nephrotoxicity. Inflammation now believed to play a major role pathogenesis cisplatin-induced acute kidney injury (AKI), and mediators inflammation contribute it. CXCL1 was recently reported be involved renal physiology pathology ischemia mouse model; however, its roles mechanisms AKI are completely unknown. We observed that CXCR2 expression markedly increased on day 7 after treatment. Subsequently, we demonstrate...
Prioritization of disease mechanisms, biomarkers, and drug targets in immune-mediated inflammatory diseases (IMIDs) is complicated by altered interactions between thousands genes. Our multi-organ single-cell RNA sequencing a mouse IMID model, namely collagen-induced arthritis, shows highly complex heterogeneous expression changes all analyzed organs, even though only joints showed signs inflammation. We organized those into multicellular which predicted molecular within organs. That model...
Soybean seed coat exists in a range of colors from yellow, green, brown, black, to bicolor. Classical genetic analysis suggested that soybean color was moderately complex trait controlled by multi-loci. However, only couple loci could be detected using single biparental segregating population. In this study, combination association mapping and bulk segregation employed identify genes/loci governing soybean. A total 14 loci, including nine novel five previously reported ones, were identified...
Parkinson’s disease is a neurodegenerative disorder in which activated microglia may appear prior to motor symptoms, but the specific therapeutic mechanisms remain unclear. This study investigated potential effects of Edaravone (EDA) on M1/M2 polarization rats with dopaminergic neurons damage induced by lipopolysaccharide (LPS) and its mechanism. Rats were randomly grouped as following ( n = 10): Control, EDA alone (10 mg/kg), LPS-model (LPS 5 μg), LPS + (5 mg/kg) mg/kg). After intragastric...
Abstract Multiomics analyses have identified multiple potential biomarkers of the incidence and prevalence complex diseases. However, it is not known which type biomarker optimal for clinical purposes. Here, we make a systematic comparison 90 million genetic variants, 1453 proteins, 325 metabolites from 500,000 individuals with diseases UK Biobank. A machine learning pipeline consisting data cleaning, imputation, feature selection, model training using cross-validation results on holdout...
Pancreatic cysts, particularly intraductal papillary mucinous neoplasms (IPMNs), pose a potential risk for progressing to pancreatic cancer (PC). This study investigates the genetic architecture of benign cysts and its connection PC using genome-wide association studies (GWAS). The discovery GWAS identified significant variants associated with specifically rs142409042 variant near OPCML gene. A pairwise comparing revealed rs7190458 BCAR1 CTRB1 genes. Further analysis genes highlighted Actin...
Abstract Early cancer diagnosis is crucial but challenging owing to the lack of reliable biomarkers that can be measured using routine clinical methods. The identification for early detection complicated by each tumor involving changes in interactions between thousands genes. In addition this staggering complexity, these vary among patients with same as well within tumor. We hypothesized methods could identified exploiting three facts: (1) have multiple grades malignant transformation; (2)...
ABSTRACT Triptolide (TP) shows promising anti‐inflammatory and antitumor activity but with severe toxicity. TP is a natural reactive electrophile containing three epoxide groups, which are usually linked to hepatotoxicity via their ability covalently bind cellular macromolecules. In this study, metabolic pathways leading detoxification of were evaluated in glutathione (GSH)‐depleted (treated L‐buthionine‐S,R‐sulfoxinine, BSO) aminobenzotriazole (ABT; non‐specific inhibitor for P450s)‐treated...
Abstract Apolipoprotein E (apoE) mediates lipid metabolism both in peripheral and the brain. The human APOE gene has three polymorphic alleles that influence risk for various types of cancer neurodegenerative diseases. A potential association between allele gastric been implicated, but specific involved associations with subtype grade malignancy need further clarification. We screened genotype 550 patients non-cancer control individuals found presence ε2 lower serum total cholesterol are...
FSH plays a critical role in granulosa cell (GC) proliferation and steroidogenesis through modulation by factors including bone morphogenetic proteins family, which belongs to transforming growth factor β (TGFB) superfamily. TGFBs are the key maintaining differentiation ovaries. However, interaction of TGFB on GCs' remains be elucidated. In this study, we have investigated SMAD4, core molecule mediating intracellular TGFB/SMAD signal transduction pathway, FSH-mediated porcine GCs. SMAD4 was...