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2. MuSe-GNN: Learning Unified Gene Representation From Multimodal Biological Graph Data

Author

Liu, Tianyu, Wang, Yuge, Ying, Rex, and Zhao, Hongyu

Subjects
Computer Science - Machine Learning, Quantitative Biology - Genomics
Abstract

Discovering genes with similar functions across diverse biomedical contexts poses a significant challenge in gene representation learning due to data heterogeneity. In this study, we resolve this problem by introducing a novel model called Multimodal Similarity Learning Graph Neural Network, which combines Multimodal Machine Learning and Deep Graph Neural Networks to learn gene representations from single-cell sequencing and spatial transcriptomic data. Leveraging 82 training datasets from 10 tissues, three sequencing techniques, and three species, we create informative graph structures for model training and gene representations generation, while incorporating regularization with weighted similarity learning and contrastive learning to learn cross-data gene-gene relationships. This novel design ensures that we can offer gene representations containing functional similarity across different contexts in a joint space. Comprehensive benchmarking analysis shows our model's capacity to effectively capture gene function similarity across multiple modalities, outperforming state-of-the-art methods in gene representation learning by up to 97.5%. Moreover, we employ bioinformatics tools in conjunction with gene representations to uncover pathway enrichment, regulation causal networks, and functions of disease-associated or dosage-sensitive genes. Therefore, our model efficiently produces unified gene representations for the analysis of gene functions, tissue functions, diseases, and species evolution., Comment: Accepted by NeurIPS 2023

Published
2023

10. In vivo killing of primary HIV-infected cells by peripheral-injected early memory–enriched anti-HIV duoCAR T cells

Author

Anthony-Gonda, Kim, Ray, Alex, Su, Hang, Wang, Yuge, Xiong, Ying, Lee, Danica, Block, Ariele, Chilunda, Vanessa, Weiselberg, Jessica, Zemelko, Lily, Wang, Yen Y, Kleinsorge-Block, Sarah, Reese, Jane S, de Lima, Marcos, Ochsenbauer, Christina, Kappes, John C, Dimitrov, Dimiter S, Orentas, Rimas, Deeks, Steven G, Rutishauser, Rachel L, Berman, Joan W, Goldstein, Harris, and Dropulić, Boro

Subjects
Clinical Research, HIV/AIDS, Stem Cell Research - Nonembryonic - Human, Infectious Diseases, Genetics, Human Fetal Tissue, Immunization, Stem Cell Research, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Infection, Animals, Mice, CD4-Positive T-Lymphocytes, HIV Infections, HIV-1, Leukocytes, Mononuclear, Receptors, Chimeric Antigen, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, AIDS/HIV, Immunotherapy, Therapeutics
Abstract

HIV-specific chimeric antigen receptor-T cell (CAR T cell) therapies are candidates to functionally cure HIV infection in people with HIV (PWH) by eliminating reactivated HIV-infected cells derived from latently infected cells within the HIV reservoir. Paramount to translating such therapeutic candidates successfully into the clinic will require anti-HIV CAR T cells to localize to lymphoid tissues in the body and eliminate reactivated HIV-infected cells such as CD4+ T cells and monocytes/macrophages. Here we show that i.v. injected anti-HIV duoCAR T cells, generated using a clinical-grade anti-HIV duoCAR lentiviral vector, localized to the site of active HIV infection in the spleen of humanized mice and eliminated HIV-infected PBMCs. CyTOF analysis of preinfusion duoCAR T cells revealed an early memory phenotype composed predominantly of CCR7+ stem cell-like/central memory T cells (TSCM/TCM) with expression of some effector-like molecules. In addition, we show that anti-HIV duoCAR T cells effectively sense and kill HIV-infected CD4+ T cells and monocytes/macrophages. Furthermore, we demonstrate efficient genetic modification of T cells from PWH on suppressive ART into anti-HIV duoCAR T cells that subsequently kill autologous PBMCs superinfected with HIV. These studies support the safety and efficacy of anti-HIV duoCAR T cell therapy in our presently open phase I/IIa clinical trial (NCT04648046).

Published
2022

20. METTL14-mediated m6A epitranscriptomic modification contributes to chemotherapy-induced neuropathic pain by stabilizing GluN2A expression via IGF2BP2

Author

Lu, Weicheng, Yang, Xiaohua, Zhong, Weiqiang, Chen, Guojun, Guo, Xinqi, Ye, Qingqing, Xu, Yixin, Qi, Zhenhua, Ye, Yaqi, Zhang, Jingyun, Wang, Yuge, Wang, Xintong, Wang, Shu, Zhao, Qiyue, Zeng, Weian, Huang, Junting, Ma, Huijie, and Xie, Jingdun

Subjects
Thermo Fisher Scientific Inc., Methyl aspartate, Genes, Aspartate, Chemotherapy, Pain -- Care and treatment, Cancer -- Chemotherapy, Neurons, Scientific equipment and supplies industry, Gene expression, Methylation, Methyltransferases, Epigenetic inheritance, Neurophysiology, Health care industry
Abstract

Epigenetics is a biological process that modifies and regulates gene expression, affects neuronal function, and contributes to pain. However, the mechanism by which epigenetics facilitates and maintains chronic pain is poorly understood. We aimed to determine whether [N.sup.6]-methyladenosine (m6A) specifically modified by methyltransferase-like 14 (METTL14) alters neuronal activity and governs pain by sensitizing the GluN2A subunit of the N-methyl-D-aspartate receptor (NMDAR) in the dorsal root ganglion (DRG) neurons in a model of chemotherapy-induced neuropathic pain (CINP). Using dot blotting, immunofluorescence, gain/loss-of-function, and behavioral assays, we found that m6A levels were upregulated in L4-L6 DRG neurons in CINP in a DBP/METTL14-dependent manner, which was also confirmed in human DRGs. Blocking METTL14 reduced m6A methylation and attenuated pain hypersensitivity. Mechanistically, METTL14-mediated m6A modification facilitated the synaptic plasticity of DRG neurons by enhancing the GluN2A subunit of NMDAR, and inhibiting METTL14 blocked this effect. In contrast, overexpression of METTL14 upregulated m6A modifications, enhanced presynaptic NMDAR activity in DRG neurons, and facilitated pain sensation. Our findings reveal a previously unrecognized mechanism of METTL14-mediated m6A modification in DRG neurons to maintain neuropathic pain. Targeting these molecules may provide a new strategy for pain treatment., Introduction Chemotherapy-induced neuropathic pain (CINP) is a debilitating complication caused by damage to the peripheral nervous system by chemotherapeutic agents, including paclitaxel (1). CINP occurs in approximately 50% to 90% [...]

Published
2024
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25. Harmonic analysis in power distribution networks

Author

Wang, Yuge, Wang, Zhongdong, and Ding, Zhengtao

Subjects
621.319, Harmonic, Distribution Network
Abstract

Power system harmonics have received a great deal of attention in the past few decades due to the fact that harmonics can cause communication errors, overheating and hardware damage. Harmonic analysis is significant to effectively identify and help eliminate the harmonic sources in the system and thereby guarantees high levels of power quality. The research in this thesis focuses on the improvement of the accuracy and reliability of harmonic analysis in the power distribution network. First, an iterative observer-based algorithm is applied to harmonic estimation in the real-time environment. Comparing with the traditional harmonic estimation methods, the proposed algorithm goes beyond the framework of fixed frequencies, which can estimate harmonics with iteratively frequencies. Further, the analysis shows that the proposed method solves the time-delay problem during observer design for harmonic estimation. Second, the problem of harmonic sources identification is investigated. All the possible combinations of harmonic sources are carried out simultaneously in the power distribution network and consideration of time delays for the observer gain design. Finally, a passive filter method is presented for harmonic mitigation in power distribution networks with consideration of harmonic compensation. The parameters are mostly obtained by the first two algorithms, which make the three proposed methods to be a complete progress of harmonic analysis based on the iterative observer.

Published
2020

33. Agomelatine promotes differentiation of oligodendrocyte precursor cells and preserves white matter integrity after cerebral ischemic stroke

Author

Wang, Shisi, primary, Li, Chunyi, additional, Kang, Xinmei, additional, Su, Xiaotao, additional, Liu, Yuxin, additional, Wang, Yuge, additional, Liu, Sanxin, additional, Deng, Xiaohui, additional, Huang, Huipeng, additional, Li, Tiemei, additional, Lu, Danli, additional, Cai, Wei, additional, Lu, Zhengqi, additional, Wei, Lei, additional, and Lu, Tingting, additional

Published
2024
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37. Clinical Features of Multicenter Autoimmune Glial Fibrillary Acidic Protein Astrocytosis

Author

ZHENG Xiujun, LIN Qi, SHU Yaqing, SUN Xiaobo, ZHONG Xiaonan, LI Rui, CHANG Yanyu, QIU Wei, and WANG Yuge

Subjects
autoimmune glial fibrillary acidic protein astrocytopathy, anti-glial fibrillary acidic protein, progressive loss of consciousness, tubercular meningitis, Medicine
Abstract

Objective To investigate the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Methods We collected and analyzed the clinical and laboratory data and obtained the clinical characteristics of diagnosis and treatment from fifteen patients with positive GFAP antibody tested by cerebrospinal fluid and diagnosed autoimmune GFAP astrocytopathy by the multi-centers. Results The mean age of the first onset of autoimmune GFAP astrocytopathy was 39.73 years old (range 4-65 years), with no significant gender difference. In terms of clinical manifestations, we found the whole brain symptoms including abnormal mental behavior, disturbance of consciousness, epileptic attack accounting for more than 50, , meningitis accounting for 66.7%, myelitis (53.3%), limb tremor (53.3%), vision loss (33.3%); systemic symptoms including fever(100%) and fatigue(86.7%). 46.7% of patients were initially diagnosed with tuberculous meningoencephalitis and were treated with diagnostic antituberculous therapy. The MRI showed 46.7% of patients showed brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle. Conclusions Autoimmune GFAP astrocytopathy are acute or subacute dieases and the main clinical features include encephalitis, meningitis, myelitis and optic neuritis. They are likely to be misdiagnosed as tuberculous meningoencephalitis and can manifest progressive loss of consciousness in early phase, which is even life threatening.

Published
2022
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