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Rare And Low Frequency Genomic Variants Impacting Neuronal Functions Modify The Dup7q11.23 Phenotype, Farah Qaiser, Yue Yin, Carolyn B. Mervis, Colleen A. Morris, Bonita P. Klein-Tasman, Elaine Tam, Lucy R. Osborne, Ryan K.C. Yuen Dec 2021

Rare And Low Frequency Genomic Variants Impacting Neuronal Functions Modify The Dup7q11.23 Phenotype, Farah Qaiser, Yue Yin, Carolyn B. Mervis, Colleen A. Morris, Bonita P. Klein-Tasman, Elaine Tam, Lucy R. Osborne, Ryan K.C. Yuen

School of Medicine Faculty Publications

© 2021, The Author(s). Background: 7q11.23 duplication (Dup7) is one of the most frequent recurrent copy number variants (CNVs) in individuals with autism spectrum disorder (ASD), but based on gold-standard assessments, only 19% of Dup7 carriers have ASD, suggesting that additional genetic factors are necessary to manifest the ASD phenotype. To assess the contribution of additional genetic variants to the Dup7 phenotype, we conducted whole-genome sequencing analysis of 20 Dup7 carriers: nine with ASD (Dup7-ASD) and 11 without ASD (Dup7-non-ASD). Results: We identified three rare variants of potential clinical relevance for ASD: a 1q21.1 microdeletion (Dup7-non-ASD) and two deletions which …


Dual Activities Of Acc Synthase: Novel Clues Regarding The Molecular Evolution Of Acs Genes, Chang Xu, Bowei Hao, Gongling Sun, Yuanyuan Mei, Lifang Sun, Yunmei Sun, Yibo Wang, Yongyan Zhang, Wei Zhang, Mengyuan Zhang, Yue Zhang, Dan Wang, Zihe Rao, Xin Li, Jeffery Shen, Ning Ning Wang Nov 2021

Dual Activities Of Acc Synthase: Novel Clues Regarding The Molecular Evolution Of Acs Genes, Chang Xu, Bowei Hao, Gongling Sun, Yuanyuan Mei, Lifang Sun, Yunmei Sun, Yibo Wang, Yongyan Zhang, Wei Zhang, Mengyuan Zhang, Yue Zhang, Dan Wang, Zihe Rao, Xin Li, Jeffery Shen, Ning Ning Wang

Life Sciences Faculty Research

Ethylene plays profound roles in plant development. The rate-limiting enzyme of ethylene biosynthesis is 1-aminocyclopropane-1-carboxylate (ACC) synthase (ACS), which is generally believed to be a single-activity enzyme evolving from aspartate aminotransferases. Here, we demonstrate that, in addition to catalyzing the conversion of S-adenosyl-methionine to the ethylene precursor ACC, genuine ACSs widely have Cβ-S lyase activity. Two N-terminal motifs, including a glutamine residue, are essential for conferring ACS activity to ACS-like proteins. Motif and activity analyses of ACS-like proteins from plants at different evolutionary stages suggest that the ACC-dependent pathway is uniquely developed in seed plants. A putative catalytic mechanism for …


Complete Genome Sequences Of Cluster A6 And Cluster G1 Mycobacterium Smegmatis Phages Hoot And Jolene, Jon Thompson, Asli Özdemir, Arsen M. Topchyan, Maxwell Torosian, Victoria Z. Thymianos, Angelica Eagle, Juliana Mccormick, Leon Kyle G. Boyles, Azucena A. Benito, Kurt Regner, Christy Strong, Philippos K. Tsourkas Oct 2021

Complete Genome Sequences Of Cluster A6 And Cluster G1 Mycobacterium Smegmatis Phages Hoot And Jolene, Jon Thompson, Asli Özdemir, Arsen M. Topchyan, Maxwell Torosian, Victoria Z. Thymianos, Angelica Eagle, Juliana Mccormick, Leon Kyle G. Boyles, Azucena A. Benito, Kurt Regner, Christy Strong, Philippos K. Tsourkas

Life Sciences Faculty Research

We present the complete genome sequences of Mycobacterium smegmatis phages Hoot and Jolene, isolated in Las Vegas, NV. The phages were isolated and annotated by students enrolled in an undergraduate research course at the University of Nevada, Las Vegas. Hoot is a cluster A6 mycobacteriophage, while Jolene is in cluster G1.


Artificial Image Objects For Classification Of Schizophrenia With Gwas-Selected Snvs And Convolutional Neural Network, Xiangning Chen, Daniel G. Chen, Zhongming Zhao, Justin Zhan, Changrong Ji, Jingchun Chen Aug 2021

Artificial Image Objects For Classification Of Schizophrenia With Gwas-Selected Snvs And Convolutional Neural Network, Xiangning Chen, Daniel G. Chen, Zhongming Zhao, Justin Zhan, Changrong Ji, Jingchun Chen

School of Medicine Faculty Publications

In this article, we propose a new approach to analyze large genomics data. We considered individual genetic variants as pixels in an image and transformed a collection of variants into an artificial image object (AIO), which could be classified as a regular image by CNN algorithms. Using schizophrenia as a case study, we demonstrate the principles and their applications with 3 datasets. With 4,096 SNVs, the CNN models achieved an accuracy of 0.678 ± 0.007 and an AUC of 0.738 ± 0.008 for the diagnosis phenotype. With 44,100 SNVs, the models achieved class-specific accuracies of 0.806 ± 0.032 and 0.820 …


Deciphering Symbiotic Interactions Of “Candidatus Aenigmarchaeota” With Inferred Horizontal Gene Transfers And Co-Occurrence Networks, Yu-Xian Li, Yang-Zhi Rao, Yan-Ling Qi, Yan-Ni Qu, Ya-Ting Chen, Jian-Yu Jiao, Wen-Sheng Shu, Hongchen Jiang, Brian P. Hedlund, Zheng-Shuang Hua, Wen-Jun Li Jul 2021

Deciphering Symbiotic Interactions Of “Candidatus Aenigmarchaeota” With Inferred Horizontal Gene Transfers And Co-Occurrence Networks, Yu-Xian Li, Yang-Zhi Rao, Yan-Ling Qi, Yan-Ni Qu, Ya-Ting Chen, Jian-Yu Jiao, Wen-Sheng Shu, Hongchen Jiang, Brian P. Hedlund, Zheng-Shuang Hua, Wen-Jun Li

Life Sciences Faculty Research

"Candidatus Aenigmarchaeota"("Ca. Aenigmarchaeota") represents one of the earliest proposed evolutionary branches within the Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, and Nanohaloarchaeota (DPANN) superphylum. However, their ecological roles and potential host-symbiont interactions are still poorly understood. Here, eight metagenome-assembled genomes (MAGs) were reconstructed from hot spring ecosystems, and further in-depth comparative and evolutionary genomic analyses were conducted on these MAGs and other genomes downloaded from public databases. Although with limited metabolic capacities, we reported that "Ca. Aenigmarchaeota"in thermal environments harbor more genes related to carbohydrate metabolism than "Ca. Aenigmarchaeota"in nonthermal environments. Evolutionary analyses suggested that members from the Thaumarchaeota, Aigarchaeota, Crenarchaeota, and Korarchaeota …


Comparative Genomics Reveals Thermal Adaptation And A High Metabolic Diversity In “Candidatus Bathyarchaeia”, Yan-Ling Qi, Paul N. Evans, Yu-Xian Li, Yang-Zhi Rao, Yan-Ni Qu, Sha Tan, Jian-Yu Jiao, Ya-Ting Chen, Brian P. Hedlund, Wen-Sheng Shu, Zheng-Shuang Hua, Wen Jun Li Jul 2021

Comparative Genomics Reveals Thermal Adaptation And A High Metabolic Diversity In “Candidatus Bathyarchaeia”, Yan-Ling Qi, Paul N. Evans, Yu-Xian Li, Yang-Zhi Rao, Yan-Ni Qu, Sha Tan, Jian-Yu Jiao, Ya-Ting Chen, Brian P. Hedlund, Wen-Sheng Shu, Zheng-Shuang Hua, Wen Jun Li

Life Sciences Faculty Research

"Candidatus Bathyarchaeia"is a phylogenetically diverse and widely distributed lineage often in high abundance in anoxic submarine sediments; however, their evolution and ecological roles in terrestrial geothermal habitats are poorly understood. In the present study, 35 Ca. Bathyarchaeia metagenome-assembled genomes (MAGs) were recovered from hot spring sediments in Tibet and Yunnan, China. Phylogenetic analysis revealed all MAGs of Ca. Bathyarchaeia can be classified into 7 orders and 15 families. Among them, 4 families have been first discovered in the present study, significantly expanding the known diversity of Ca. Bathyarchaeia. Comparative genomics demonstrated Ca. Bathyarchaeia MAGs from thermal habitats to encode a …


Highly Contiguous Assemblies Of 101 Drosophilid Genomes, Bernard Y. Kim, Jeremy R. Wang, Danny E. Miller, Olga Barmina, Emily Delaney, Ammon Thompson, Aaron A. Comeault, David Peede, Emmanuel R.R. D’Agostino, Julianne Pelaez, Jessica M. Aguilar, Diler Haji, Teruyuki Matsunaga, Ellie E. Armstrong, Molly Zych, Yoshitaka Ogawa, Marina Stamenković-Radak, Mihailo Jelić, Marija Savić Veselinović, Marija Tanasković, Pavle Erić, Jian Jun Gao, Takehiro K. Katoh, Masanori J. Toda, Hideaki Watabe, Masayoshi Watada, Jeremy S. Davis, Leonie C. Moyle, Giulia Manoli, Enrico Bertolini, Vladimír Košťál, R. Scott Hawley, Aya Takahashi, Corbin D. Jones, Donald K. Price, Noah Whiteman, Artyom Kopp, Daniel R. Matute, Dmitri A. Petrov Jul 2021

Highly Contiguous Assemblies Of 101 Drosophilid Genomes, Bernard Y. Kim, Jeremy R. Wang, Danny E. Miller, Olga Barmina, Emily Delaney, Ammon Thompson, Aaron A. Comeault, David Peede, Emmanuel R.R. D’Agostino, Julianne Pelaez, Jessica M. Aguilar, Diler Haji, Teruyuki Matsunaga, Ellie E. Armstrong, Molly Zych, Yoshitaka Ogawa, Marina Stamenković-Radak, Mihailo Jelić, Marija Savić Veselinović, Marija Tanasković, Pavle Erić, Jian Jun Gao, Takehiro K. Katoh, Masanori J. Toda, Hideaki Watabe, Masayoshi Watada, Jeremy S. Davis, Leonie C. Moyle, Giulia Manoli, Enrico Bertolini, Vladimír Košťál, R. Scott Hawley, Aya Takahashi, Corbin D. Jones, Donald K. Price, Noah Whiteman, Artyom Kopp, Daniel R. Matute, Dmitri A. Petrov

Life Sciences Faculty Research

Over 100 years of studies in Drosophila melanogaster and related species in the genus Drosophila have facilitated key discoveries in genetics, genomics, and evolution. While high-quality genome assemblies exist for several species in this group, they only encompass a small fraction of the genus. Recent advances in long-read sequencing allow high-quality genome assemblies for tens or even hundreds of species to be efficiently generated. Here, we utilize Oxford Nanopore sequencing to build an open community resource of genome assemblies for 101 lines of 93 drosophilid species encompassing 14 species groups and 35 sub-groups. The genomes are highly contiguous and complete, …


A Screen For Sleep And Starvation Resistance Identifies A Wake-Promoting Role For The Auxiliary Channel Unc79, Kazuma Murakami, Justin Palermo, Bethany A. Stanhope, Allen G. Gibbs, Alex C. Keene Jun 2021

A Screen For Sleep And Starvation Resistance Identifies A Wake-Promoting Role For The Auxiliary Channel Unc79, Kazuma Murakami, Justin Palermo, Bethany A. Stanhope, Allen G. Gibbs, Alex C. Keene

Life Sciences Faculty Research

The regulation of sleep and metabolism are highly interconnected, and dysregulation of sleep is linked to metabolic diseases that include obesity, diabetes, and heart disease. Furthermore, both acute and long-term changes in diet potently impact sleep duration and quality. To identify novel factors that modulate interactions between sleep and metabolic state, we performed a genetic screen for their roles in regulating sleep duration, starvation resistance, and starvation-dependent modulation of sleep. This screen identified a number of genes with potential roles in regulating sleep, metabolism, or both processes. One such gene encodes the auxiliary ion channel UNC79, which was implicated in …


Genomics, Exometabolomics, And Metabolic Probing Reveal Conserved Proteolytic Metabolism Of Thermoflexus Hugenholtzii And Three Candidate Species From China And Japan, Scott C. Thomas, Devon Payne, Kevin O. Tamadonfar, Cale O. Seymour, Jian Yu Jiao, Senthil K. Murugapiran, Dengxun Lai, Rebecca Lau, Benjamin P. Bowen, Leslie P. Silva, Katherine B. Louie, Marcel Huntemann, Alicia Clum, Alex Spunde, Manoj Pillay, Krishnaveni Palaniappan, Neha Varghese, Natalia Mikhailova, I. Min Chen, Dimitrios Stamatis, T. B.K. Reddy, Ronan O’Malley, Chris Daum, Nicole Shapiro, Natalia Ivanova, Nikos C. Kyrpides, Tanja Woyke, Emiley Eloe-Fadrosh, Trinity L. Hamilton, Paul Dijkstra, Brian P. Hedlund May 2021

Genomics, Exometabolomics, And Metabolic Probing Reveal Conserved Proteolytic Metabolism Of Thermoflexus Hugenholtzii And Three Candidate Species From China And Japan, Scott C. Thomas, Devon Payne, Kevin O. Tamadonfar, Cale O. Seymour, Jian Yu Jiao, Senthil K. Murugapiran, Dengxun Lai, Rebecca Lau, Benjamin P. Bowen, Leslie P. Silva, Katherine B. Louie, Marcel Huntemann, Alicia Clum, Alex Spunde, Manoj Pillay, Krishnaveni Palaniappan, Neha Varghese, Natalia Mikhailova, I. Min Chen, Dimitrios Stamatis, T. B.K. Reddy, Ronan O’Malley, Chris Daum, Nicole Shapiro, Natalia Ivanova, Nikos C. Kyrpides, Tanja Woyke, Emiley Eloe-Fadrosh, Trinity L. Hamilton, Paul Dijkstra, Brian P. Hedlund

Life Sciences Faculty Research

Thermoflexus hugenholtzii JAD2 , the only cultured representative of the Chloroflexota order Thermoflexales, is abundant in Great Boiling Spring (GBS), NV, United States, and close relatives inhabit geothermal systems globally. However, no defined medium exists for T. hugenholtzii JAD2 and no single carbon source is known to support its growth, leaving key knowledge gaps in its metabolism and nutritional needs. Here, we report comparative genomic analysis of the draft genome of T. hugenholtzii JAD2 and eight closely related metagenome-assembled genomes (MAGs) from geothermal sites in China, Japan, and the United States, representing “Candidatus Thermoflexus japonica,” “Candidatus Thermoflexus tengchongensis,” and “Candidatus …


Genomic Analysis Of Paenibacillus Larvae Bacteriophages, Casey Stamereilers May 2021

Genomic Analysis Of Paenibacillus Larvae Bacteriophages, Casey Stamereilers

UNLV Theses, Dissertations, Professional Papers, and Capstones

American Foulbrood is the most destructive bacterial infection of the honeybee (Apis mellifera) and is caused by the Gram-positive, spore forming bacterium Paenibacillus larvae. Current treatment methods rely on antibiotics, but antibiotics treatments are experiencing a reduction in efficacy due to the recent rise in antibiotic resistant strains of P. larvae. This has been a major catalyst for exploration of alternative treatment methods. Phage therapy is an alternative treatment method that uses viruses that exclusively infect bacteria, known as bacteriophages (phages), to combat bacterial infections. Several experimental studies have shown that phages P. larvae phages are effective at lysing P. …


Rewired Pathways And Disrupted Pathway Crosstalk In Schizophrenia Transcriptomes By Multiple Differential Coexpression Methods, Hui Yu, Yan Guo, Jingchun Chen, Xiangning Chen, Peilin Jia, Zhongming Zhao Apr 2021

Rewired Pathways And Disrupted Pathway Crosstalk In Schizophrenia Transcriptomes By Multiple Differential Coexpression Methods, Hui Yu, Yan Guo, Jingchun Chen, Xiangning Chen, Peilin Jia, Zhongming Zhao

School of Medicine Faculty Publications

Transcriptomic studies of mental disorders using the human brain tissues have been limited, and gene expression signatures in schizophrenia (SCZ) remain elusive. In this study, we applied three differential co-expression methods to analyze five transcriptomic datasets (three RNA-Seq and two microarray datasets) derived from SCZ and matched normal postmortem brain samples. We aimed to uncover biological pathways where internal correlation structure was rewired or intercoordination was disrupted in SCZ. In total, we identified 60 rewired pathways, many of which were related to neurotransmitter, synapse, immune, and cell adhesion. We found the hub genes, which were on the center of rewired …


A Novel Jumbo Phage Phima05 Inhibits Harmful Microcystis Sp., Ampapan Naknaen, Oramas Suttinun, Komwit Surachat, Eakalak Khan, Rattanaruji Pomwised Apr 2021

A Novel Jumbo Phage Phima05 Inhibits Harmful Microcystis Sp., Ampapan Naknaen, Oramas Suttinun, Komwit Surachat, Eakalak Khan, Rattanaruji Pomwised

Civil and Environmental Engineering and Construction Faculty Research

Microcystis poses a concern because of its potential contribution to eutrophication and production of microcystins (MCs). Phage treatment has been proposed as a novel biocontrol method for Microcystis. Here, we isolated a lytic cyanophage named PhiMa05 with high efficiency against MCs-producing Microcystis strains. Its burst size was large, with approximately 127 phage particles/infected cell, a short latent period (1 day), and high stability to broad salinity, pH and temperature ranges. The PhiMa05 structure was composed of an icosahedral capsid (100 nm) and tail (120 nm), suggesting that the PhiMa05 belongs to the Myoviridae family. PhiMa05 inhibited both planktonic and aggregated …


A Whole-Genome Scan For Association With Invasion Success In The Fruit Fly Drosophila Suzukii Using Contrasts Of Allele Frequencies Corrected For Population Structure, Laure Olazcuaga, Anne Loiseau, Hugues Parrinello, Mathilde Paris, Antoine Fraimout, Christelle Guedot, Lauren M. Diepenbrock, Marc Kenis, Jinping Zhang, Xiao Chen, Nicolas Borowiec, Benoit Facon, Heidrun Vogt, Donald K. Price, Heiko Vogel, Benjamin Prud'homme, Arnaud Estoup, Mathieu Gautier Apr 2021

A Whole-Genome Scan For Association With Invasion Success In The Fruit Fly Drosophila Suzukii Using Contrasts Of Allele Frequencies Corrected For Population Structure, Laure Olazcuaga, Anne Loiseau, Hugues Parrinello, Mathilde Paris, Antoine Fraimout, Christelle Guedot, Lauren M. Diepenbrock, Marc Kenis, Jinping Zhang, Xiao Chen, Nicolas Borowiec, Benoit Facon, Heidrun Vogt, Donald K. Price, Heiko Vogel, Benjamin Prud'homme, Arnaud Estoup, Mathieu Gautier

Life Sciences Faculty Research

Evidence is accumulating that evolutionary changes are not only common during biological invasions but may also contribute directly to invasion success. The genomic basis of such changes is still largely unexplored. Yet, understanding the genomic response to invasion may help to predict the conditions under which invasiveness can be enhanced or suppressed. Here, we characterized the genome response of the spotted wing drosophila Drosophila suzukii during the worldwide invasion of this pest insect species, by conducting a genome-wide association study to identify genes involved in adaptive processes during invasion. Genomic data from 22 population samples were analyzed to detect genetic …


Study Of Sickle Cell Disease, Aaron Guevarra, Carlos Herrera, Faysal Ali Apr 2021

Study Of Sickle Cell Disease, Aaron Guevarra, Carlos Herrera, Faysal Ali

Undergraduate Research Symposium Posters

The purpose of this research timeline is to explore the history, prevalence, and effects of Sickle Cell Disease (SCD) so that treatments and possible future experiments or cures may be discussed. In SCD, abnormal red blood cells appear as sickle shaped as opposed to the round shape of normal red blood cells. It is inherited in an autosomal recessive pattern, so an individual must inherit two copies of the allele. The gene mutation is a single nucleotide mutation in the gene which codes for β-globin. In 1910, James B. Herrick first described the disease, and in 1949, its inheritance pattern …


The History And Future Of Cystic Fibrosis, Randall Combs, Che Fung Andy Chan, Daisy Sahagun Apr 2021

The History And Future Of Cystic Fibrosis, Randall Combs, Che Fung Andy Chan, Daisy Sahagun

Undergraduate Research Symposium Posters

The purpose of this research timeline is to highlight the tumultuous yet inspiring history of Cystic Fibrosis disease and treatment to give us a more pragmatic understanding of its current state. Cystic Fibrosis is an autosomal recessive disease, most often caused by a single amino-acid deletion of phenylalanine at position 508 in the nucleotide binding domain, which results in a loss of the cystic fibrosis transmembrane conductance regulator (CFTR). Symptomatology varies considerably but a buildup of mucus in the respiratory tract leading to lung failure, and exocrine pancreatic insufficiency which results in digestive and metabolic dysfunction are commonly, if not …


A Timeline Of Oculocutaneous Albinism, Mohammed Abushanab, Maria Ceroni, Kimberly Morán Apr 2021

A Timeline Of Oculocutaneous Albinism, Mohammed Abushanab, Maria Ceroni, Kimberly Morán

Undergraduate Research Symposium Posters

The purpose of this research timeline is to synthesize the natural history of Oculocutaneous Albinism (OCA), discover gaps in knowledge, as well as understand the genes and mutations that incite the disease. It is through methods of literature-based research that we found the earliest recognition of OCA and investigated it up to its most current state of research. The rate of research remains steady and continuous with the focus varying widely; either by examining more of the genes involved in the disease or by taking more in-depth looks at mutational analyses of genes that are already observed to be linked …


An Investigation On The History And Current Research Of Fragile X Syndrome, Makeda Asare, Isabelle Avenido, Maxene Vergonia-Fehlman Apr 2021

An Investigation On The History And Current Research Of Fragile X Syndrome, Makeda Asare, Isabelle Avenido, Maxene Vergonia-Fehlman

Undergraduate Research Symposium Posters

The purpose of this research is to synthesize the history of Fragile X Syndrome through literature-based research in order to assess the scope of research, population variation, social impact, and treatment. Fragile X was first documented in 1943 by Dr. Julia Bell and Dr. James Purdon Martin in a report of a family case study in which eleven males across two generations showed symptoms of intellectual disabilities. Fragile X Syndrome is an X-linked disorder caused by mutation in the Fragile X mental retardation 1(FMR1) gene on chromosome Xq27.3. The FMR1 mutations are triplet repeat expansion of the CGG repeat sequences …


Retinoblastoma: Past, Present, And Future, Izabela Daneva, Crysty-Ann Olaco, Albert Tran Apr 2021

Retinoblastoma: Past, Present, And Future, Izabela Daneva, Crysty-Ann Olaco, Albert Tran

Undergraduate Research Symposium Posters

The purpose of this research timeline is to synthesize the natural history of retinoblastoma to understand its societal effects and develop a public health message to raise awareness of the disease. We used literature-based research in order to gain an understanding about the discovery of this disease and investigate its most current state of knowledge. Retinoblastoma is an intraocular cancer that manifests early in childhood. It is typically linked to a somatic or germline insertion, deletion, or single-base substitution mutation on both alleles of RB1, a tumor-suppressor gene. Retinoblastoma was first identified in 1809 by James Wardrop, and since then, …


Machine Learning Approaches For The Prediction Of Bone Mineral Density By Using Genomic And Phenotypic Data Of 5130 Older Men, Qing Wu, Fatma Nasoz, Jongyun Jung, Bibek Bhattarai, Mira V. Han, Robert A. Greenes, Kenneth G. Saag Feb 2021

Machine Learning Approaches For The Prediction Of Bone Mineral Density By Using Genomic And Phenotypic Data Of 5130 Older Men, Qing Wu, Fatma Nasoz, Jongyun Jung, Bibek Bhattarai, Mira V. Han, Robert A. Greenes, Kenneth G. Saag

School of Medicine Faculty Publications

The study aimed to utilize machine learning (ML) approaches and genomic data to develop a prediction model for bone mineral density (BMD) and identify the best modeling approach for BMD prediction. The genomic and phenotypic data of Osteoporotic Fractures in Men Study (n = 5130) was analyzed. Genetic risk score (GRS) was calculated from 1103 associated SNPs for each participant after a comprehensive genotype imputation. Data were normalized and divided into a training set (80%) and a validation set (20%) for analysis. Random forest, gradient boosting, neural network, and linear regression were used to develop BMD prediction models separately. Ten-fold …


Multimodal Single-Cell/Nucleus Rna Sequencing Data Analysis Uncovers Molecular Networks Between Disease-Associated Microglia And Astrocytes With Implications For Drug Repurposing In Alzheimer’S Disease, Jielin Xu, Pengyue Zhang, Yin Huang, Yadi Zhou, Yuan Hou, Lynn M. Bekris, Justin Lathia, Chien-Wei Chiang, Lang Li, Andrew A. Pieper, James B. Leverenz, Jeffrey Cummings, Feixiong Cheng Feb 2021

Multimodal Single-Cell/Nucleus Rna Sequencing Data Analysis Uncovers Molecular Networks Between Disease-Associated Microglia And Astrocytes With Implications For Drug Repurposing In Alzheimer’S Disease, Jielin Xu, Pengyue Zhang, Yin Huang, Yadi Zhou, Yuan Hou, Lynn M. Bekris, Justin Lathia, Chien-Wei Chiang, Lang Li, Andrew A. Pieper, James B. Leverenz, Jeffrey Cummings, Feixiong Cheng

School of Medicine Faculty Publications

Because disease-associated microglia (DAM) and disease-associated astrocytes (DAA) are involved in the pathophysiology of Alzheimer's disease (AD), we systematically identified molecular networks between DAM and DAA to uncover novel therapeutic targets for AD. Specifically, we develop a network-based methodology that leverages single-cell/nucleus RNA sequencing data from both transgenic mouse models and AD patient brains, as well as drug-target network, metaboliteenzyme associations, the human protein-protein interactome, and large-scale longitudinal patient data. Through this approach, we find both common and unique gene network regulators between DAM (i.e., PAK1, MAPK14, and CSF1R) and DAA (i.e., NFKB1, FOS, and JUN) that are significantly enriched …