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24 results on '"Zhang, David"'

3. Whole genome sequence analysis of blood lipid levels in >66,000 individuals

Author

Selvaraj, Margaret Sunitha, Li, Xihao, Li, Zilin, Pampana, Akhil, Zhang, David Y, Park, Joseph, Aslibekyan, Stella, Bis, Joshua C, Brody, Jennifer A, Cade, Brian E, Chuang, Lee-Ming, Chung, Ren-Hua, Curran, Joanne E, de las Fuentes, Lisa, de Vries, Paul S, Duggirala, Ravindranath, Freedman, Barry I, Graff, Mariaelisa, Guo, Xiuqing, Heard-Costa, Nancy, Hidalgo, Bertha, Hwu, Chii-Min, Irvin, Marguerite R, Kelly, Tanika N, Kral, Brian G, Lange, Leslie, Li, Xiaohui, Lisa, Martin, Lubitz, Steven A, Manichaikul, Ani W, Michael, Preuss, Montasser, May E, Morrison, Alanna C, Naseri, Take, O’Connell, Jeffrey R, Palmer, Nicholette D, Peyser, Patricia A, Reupena, Muagututia S, Smith, Jennifer A, Sun, Xiao, Taylor, Kent D, Tracy, Russell P, Tsai, Michael Y, Wang, Zhe, Wang, Yuxuan, Bao, Wei, Wilkins, John T, Yanek, Lisa R, Zhao, Wei, Arnett, Donna K, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Chen, Yii-Der Ida, Correa, Adolfo, Cupples, L Adrienne, Dutcher, Susan K, Ellinor, Patrick T, Fornage, Myriam, Gabriel, Stacey, Germer, Soren, Gibbs, Richard, He, Jiang, Kaplan, Robert C, Kardia, Sharon LR, Kim, Ryan, Kooperberg, Charles, Loos, Ruth JF, Viaud-Martinez, Karine A, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, Nickerson, Deborah, North, Kari E, Psaty, Bruce M, Redline, Susan, Reiner, Alexander P, Vasan, Ramachandran S, Rich, Stephen S, Willer, Cristen, Rotter, Jerome I, Rader, Daniel J, Lin, Xihong, Peloso, Gina M, and Natarajan, Pradeep

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Biotechnology, Heart Disease - Coronary Heart Disease, Cardiovascular, Heart Disease, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Alleles, Cholesterol, LDL, Genome-Wide Association Study, Humans, Lipids, Whole Genome Sequencing, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Abstract

Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.

Published
2022

4. Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage

Author

Chen, Zhongbo, Zhang, David, Reynolds, Regina H, Gustavsson, Emil K, García-Ruiz, Sonia, D’Sa, Karishma, Fairbrother-Browne, Aine, Vandrovcova, Jana, Hardy, John, Houlden, Henry, Gagliano Taliun, Sarah A, Botía, Juan, and Ryten, Mina

Subjects
Human Genome, Brain Disorders, Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurosciences, Dementia, Biotechnology, Alzheimer's Disease, Neurodegenerative, Aging, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Underpinning research, Aetiology, Neurological, Alzheimer Disease, Apolipoproteins E, Brain, Chromosomes, Human, Pair 19, Conserved Sequence, DNA, Intergenic, Gene Ontology, Genome, Human, Humans, Introns, Linkage Disequilibrium, Molecular Sequence Annotation, Neurodegenerative Diseases, Phenotype, Phylogeny, Polymorphism, Single Nucleotide, RNA, Long Noncoding, RNA, Messenger, Regression Analysis, International Parkinson’s Disease Genomics Consortium
Abstract

Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer's disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease.

Published
2021

6. Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo

Author

Virga, Daniel M., Hamilton, Stevie, Osei, Bertha, Morgan, Abigail, Kneis, Parker, Zamponi, Emiliano, Park, Natalie J., Hewitt, Victoria L., Zhang, David, Gonzalez, Kevin C., Russell, Fiona M., Grahame Hardie, D., Prudent, Julien, Bloss, Erik, Losonczy, Attila, Polleux, Franck, and Lewis, Jr, Tommy L.

Published
2024
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8. Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information.

Author

Guelfi, Sebastian, D'Sa, Karishma, Botía, Juan A, Vandrovcova, Jana, Reynolds, Regina H, Zhang, David, Trabzuni, Daniah, Collado-Torres, Leonardo, Thomason, Andrew, Quijada Leyton, Pedro, Gagliano Taliun, Sarah A, Nalls, Mike A, International Parkinson’s Disease Genomics Consortium (IPDGC), UK Brain Expression Consortium (UKBEC), Small, Kerrin S, Smith, Colin, Ramasamy, Adaikalavan, Hardy, John, Weale, Michael E, and Ryten, Mina

Subjects
International Parkinson’s Disease Genomics Consortium, UK Brain Expression Consortium
Abstract

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/.

Published
2020

17. Wafer-scale functional circuits based on two dimensional semiconductors with fabrication optimized by machine learning

Author

Chen, Xinyu, Xie, Yufeng, Sheng, Yaochen, Tang, Hongwei, Wang, Zeming, Wang, Yu, Wang, Yin, Liao, Fuyou, Ma, Jingyi, Guo, Xiaojiao, Tong, Ling, Liu, Hanqi, Liu, Hao, Wu, Tianxiang, Cao, Jiaxin, Bu, Sitong, Shen, Hui, Bai, Fuyu, Huang, Daming, Deng, Jianan, Riaud, Antoine, Xu, Zihan, Wu, Chenjian, Xing, Shiwei, Lu, Ye, Ma, Shunli, Sun, Zhengzong, Xue, Zhongyin, Di, Zengfeng, Gong, Xiao, Zhang, David Wei, Zhou, Peng, Wan, Jing, and Bao, Wenzhong

Published
2021
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21. Adoptive T cell transfer and host antigen-presenting cell recruitment with cryogel scaffolds promotes long-term protection against solid tumors.

Author

Adu-Berchie, Kwasi, Brockman, Joshua M., Liu, Yutong, To, Tania W., Zhang, David K. Y., Najibi, Alexander J., Binenbaum, Yoav, Stafford, Alexander, Dimitrakakis, Nikolaos, Sobral, Miguel C., Dellacherie, Maxence O., and Mooney, David J.

Subjects
T cells, T cell receptors, T-cell exhaustion, INTRAVENOUS injections, TUMOR antigens, IMMUNE recognition, INTRAVENOUS therapy
Abstract

Although adoptive T cell therapy provides the T cell pool needed for immediate tumor debulking, the infused T cells generally have a narrow repertoire for antigen recognition and limited ability for long-term protection. Here, we present a hydrogel that locally delivers adoptively transferred T cells to the tumor site while recruiting and activating host antigen-presenting cells with GMCSF or FLT3L and CpG, respectively. T cells alone loaded into these localized cell depots provided significantly better control of subcutaneous B16-F10 tumors than T cells delivered through direct peritumoral injection or intravenous infusion. T cell delivery combined with biomaterial-driven accumulation and activation of host immune cells prolonged the activation of the delivered T cells, minimized host T cell exhaustion, and enabled long-term tumor control. These findings highlight how this integrated approach provide both immediate tumor debulking and long-term protection against solid tumors, including against tumor antigen escape. Adoptive T cell therapy has shown remarkable promise for the treatment of haematological malignancies. Here, the authors show that a cryogel platform for the simultaneous delivery of autologous T cells and recruitment of local antigen-presenting cells promotes long-lasting responses against solid tumours in mice. [ABSTRACT FROM AUTHOR]

Published
2023
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