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Articles 61 - 90 of 273

Full-Text Articles in Genetics and Genomics

Strong, Recent Selective Sweeps Reshape Genetic Diversity In Freshwater Bivalve Megalonaias Nervosa, Rebekah L. Rogers, Stephanie L. Grizzard, Jeffrey T. Garner Jan 2023

Strong, Recent Selective Sweeps Reshape Genetic Diversity In Freshwater Bivalve Megalonaias Nervosa, Rebekah L. Rogers, Stephanie L. Grizzard, Jeffrey T. Garner

Biological Sciences Faculty Publications

Freshwater Unionid bivalves have recently faced ecological upheaval through pollution, barriers to dispersal, harvesting, and changes in fish–host prevalence. Currently, over 70% of species in North America are threatened, endangered or extinct. To characterize the genetic response to recent selective pressures, we collected population genetic data for one successful bivalve species, Megalonaias nervosa. We identify megabase-sized regions that are nearly monomorphic across the population, signals of strong, recent selection reshaping diversity across 73 Mb total. These signatures of selection are greater than is commonly seen in population genetic models. We observe 102 duplicate genes with high dN/d …


Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G. Izquierdo, Jing Chen, Richard Packer, Robert J. Hall, Anna L. Guyatt, Chiara Batini, Rebecca J. Thompson, Chandan Puvuluri, Vidhi Malik, Brian D. Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A. Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Sinjini Sikdar, Martin D. Tobin, Et Al. Jan 2023

Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G. Izquierdo, Jing Chen, Richard Packer, Robert J. Hall, Anna L. Guyatt, Chiara Batini, Rebecca J. Thompson, Chandan Puvuluri, Vidhi Malik, Brian D. Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A. Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Sinjini Sikdar, Martin D. Tobin, Et Al.

Mathematics & Statistics Faculty Publications

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of …


Disparate Population And Holobiont Structure Of Pocilloporid Corals Across The Red Sea Gradient Demonstrate Species-Specific Evolutionary Trajectories, Carol Buitrago-López, Anny Cárdenas, Benjamin C.C. Hume, Thierry Gosselin, Fabian Staubach, Manuel Aranda, Daniel J. Barshis, Yvonne Sawall, Christian R. Voolstra Jan 2023

Disparate Population And Holobiont Structure Of Pocilloporid Corals Across The Red Sea Gradient Demonstrate Species-Specific Evolutionary Trajectories, Carol Buitrago-López, Anny Cárdenas, Benjamin C.C. Hume, Thierry Gosselin, Fabian Staubach, Manuel Aranda, Daniel J. Barshis, Yvonne Sawall, Christian R. Voolstra

Biological Sciences Faculty Publications

Global habitat degradation heightens the need to better understand patterns of genetic connectivity and diversity of marine biota across geographical ranges to guide conservation efforts. Corals across the Red Sea are subject to pronounced environmental differences, but studies so far suggest that animal populations are largely connected, excepting evidence for a genetic break between the northern-central and southern regions. Here, we investigated population structure and holobiont assemblage of two common pocilloporid corals, Pocillopora verrucosa and Stylophora pistillata, across the Red Sea. We found little evidence for population differentiation in P. verrucosa, except for the southernmost site. Conversely, S. …


Biodiversity Of Philippine Marine Fishes: A Dna Barcode Reference Library Based On Voucher Specimens, Katherine E. Bemis, Matthew G. Girard, Mudjekeewis D. Santos, Kent E. Carpenter, Jonathan R. Deeds, Diane E. Pitassy, Nicko Amor L. Flores, Elizabeth S. Hunter, Amy C. Driskell, Kenneth S. Macdonald Iii, Lee A. Weigt, Jeffrey T. Williams Jan 2023

Biodiversity Of Philippine Marine Fishes: A Dna Barcode Reference Library Based On Voucher Specimens, Katherine E. Bemis, Matthew G. Girard, Mudjekeewis D. Santos, Kent E. Carpenter, Jonathan R. Deeds, Diane E. Pitassy, Nicko Amor L. Flores, Elizabeth S. Hunter, Amy C. Driskell, Kenneth S. Macdonald Iii, Lee A. Weigt, Jeffrey T. Williams

Biological Sciences Faculty Publications

Accurate identification of fishes is essential for understanding their biology and to ensure food safety for consumers. DNA barcoding is an important tool because it can verify identifications of both whole and processed fishes that have had key morphological characters removed (e.g., filets, fish meal); however, DNA reference libraries are incomplete, and public repositories for sequence data contain incorrectly identified sequences. During a nine-year sampling program in the Philippines, a global biodiversity hotspot for marine fishes, we developed a verified reference library of cytochrome c oxidase subunit I (COI) sequences for 2,525 specimens representing 984 species. Specimens were primarily purchased …


Fine-Scale Genetic Structure In Rhizosphere Microbial Communities Associated With Chamaecrista Fasciculata (Fabaceae), Mahboubeh Hosseinalizadeh Nobarinezhad, Lisa E. Wallace Jan 2023

Fine-Scale Genetic Structure In Rhizosphere Microbial Communities Associated With Chamaecrista Fasciculata (Fabaceae), Mahboubeh Hosseinalizadeh Nobarinezhad, Lisa E. Wallace

Biological Sciences Faculty Publications

Soil microbiota of the rhizosphere are an important extension of the plant phenotype because they impact the health and fitness of host plants. The composition of these communities is expected to differ among host plants due to influence by host genotype. Given that many plant populations exhibit fine-scale genetic structure (SGS), associated microbial communities may also exhibit SGS. In this study, we tested this hypothesis using Chamaecrista fasciculata, a legume species that has previously been determined to have significant SGS. We collected genetic data from prokaryotic and fungal rhizosphere communities in association with 70 plants in an area of …


Adjusting For Gene-Specific Covariates To Improve Rna-Seq Analysis, Hyeongseon Jeon, Kyu-Sang Lim, Yet Nguyen, Dan Nettleton Jan 2023

Adjusting For Gene-Specific Covariates To Improve Rna-Seq Analysis, Hyeongseon Jeon, Kyu-Sang Lim, Yet Nguyen, Dan Nettleton

Mathematics & Statistics Faculty Publications

Summary

This paper suggests a novel positive false discovery rate (pFDR) controlling method for testing gene-specific hypotheses using a gene-specific covariate variable, such as gene length. We suppose the null probability depends on the covariate variable. In this context, we propose a rejection rule that accounts for heterogeneity among tests by employing two distinct types of null probabilities. We establish a pFDR estimator for a given rejection rule by following Storey's q-value framework. A condition on a type 1 error posterior probability is provided that equivalently characterizes our rejection rule. We also present a suitable procedure for selecting a tuning …


Expanding Our Grasp Of Two-Component Signaling In Clostridioides Difficile, Orlando Berumen Alvarez, Erin B. Purcell Jan 2023

Expanding Our Grasp Of Two-Component Signaling In Clostridioides Difficile, Orlando Berumen Alvarez, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The intestinal pathogen Clostridioides difficile encodes roughly 50 TCS, but very few have been characterized in terms of their activating signals or their regulatory roles. A. G. Pannullo, B. R. Zbylicki, and C. D. Ellermeier (J Bacteriol 205:e00164-23, 2023, https://doi.org/10.1128/jb.00164-23) have identified both for the novel C. difficile TCD DraRS. DraRS responds to antibiotics that target lipid-II molecules in the bacterial cell envelope, and regulates the production of a novel glycolipid necessary for bacitracin and daptomycin resistance in C. difficile.


Dfhic: A Dilated Full Convolution Model To Enhance The Resolution Of Hi-C Data, Bin Wang, Kun Liu, Yaohang Li, Jianxin Wang Jan 2023

Dfhic: A Dilated Full Convolution Model To Enhance The Resolution Of Hi-C Data, Bin Wang, Kun Liu, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Hi-C technology has been the most widely used chromosome conformation capture(3C) experiment that measures the frequency of all paired interactions in the entire genome, which is a powerful tool for studying the 3D structure of the genome. The fineness of the constructed genome structure depends on the resolution of Hi-C data. However, due to the fact that high-resolution Hi-C data require deep sequencing and thus high experimental cost, most available Hi-C data are in low-resolution. Hence, it is essential to enhance the quality of Hi-C data by developing the effective computational methods.

Results: In this work, we propose …


A Single-Cell Atlas Of Bovine Skeletal Muscle Reveals Mechanisms Regulating Intramuscular Adipogenesis And Fibrogenesis, Leshan Wang, Peidong Gao, Chaoyang Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth Mcmillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu Jan 2023

A Single-Cell Atlas Of Bovine Skeletal Muscle Reveals Mechanisms Regulating Intramuscular Adipogenesis And Fibrogenesis, Leshan Wang, Peidong Gao, Chaoyang Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth Mcmillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu

Computer Science Faculty Publications

Background

Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.

Methods

Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate …


An Approach To Developing Benchmark Datasets For Protein Secondary Structure Segmentation From Cryo-Em Density Maps, Thu Nguyen, Yongcheng Mu, Jiangwen Sun, Jing He Jan 2023

An Approach To Developing Benchmark Datasets For Protein Secondary Structure Segmentation From Cryo-Em Density Maps, Thu Nguyen, Yongcheng Mu, Jiangwen Sun, Jing He

Computer Science Faculty Publications

More and more deep learning approaches have been proposed to segment secondary structures from cryo-electron density maps at medium resolution range (5--10Å). Although the deep learning approaches show great potential, only a few small experimental data sets have been used to test the approaches. There is limited understanding about potential factors, in data, that affect the performance of segmentation. We propose an approach to generate data sets with desired specifications in three potential factors - the protein sequence identity, structural contents, and data quality. The approach was implemented and has generated a test set and various training sets to study …


Intergenic Transcription In In Vivo Developed Bovine Oocytes And Pre-Implantation Embryos, Saurav Ranjitkar, Mohammad Shiri, Jiangwen Sun, Xiuchun Tian Jan 2023

Intergenic Transcription In In Vivo Developed Bovine Oocytes And Pre-Implantation Embryos, Saurav Ranjitkar, Mohammad Shiri, Jiangwen Sun, Xiuchun Tian

Computer Science Faculty Publications

Background

Intergenic transcription, either failure to terminate at the transcription end site (TES), or transcription initiation at other intergenic regions, is present in cultured cells and enhanced in the presence of stressors such as viral infection. Transcription termination failure has not been characterized in natural biological samples such as pre-implantation embryos which express more than 10,000 genes and undergo drastic changes in DNA methylation.

Results

Using Automatic Readthrough Transcription Detection (ARTDeco) and data of in vivo developed bovine oocytes and embryos, we found abundant intergenic transcripts that we termed as read-outs (transcribed from 5 to 15 kb after TES) and …


Cellbrf: A Feature Selection Method For Single-Cell Clustering Using Cell Balance And Random Forest, Yunpei Xu, Hong-Dong Li, Cui-Xiang Lin, Ruiqing Zheng, Yaohang Li, Jinhui Xu, Jianxin Wang Jan 2023

Cellbrf: A Feature Selection Method For Single-Cell Clustering Using Cell Balance And Random Forest, Yunpei Xu, Hong-Dong Li, Cui-Xiang Lin, Ruiqing Zheng, Yaohang Li, Jinhui Xu, Jianxin Wang

Computer Science Faculty Publications

Motivation

Single-cell RNA sequencing (scRNA-seq) offers a powerful tool to dissect the complexity of biological tissues through cell sub-population identification in combination with clustering approaches. Feature selection is a critical step for improving the accuracy and interpretability of single-cell clustering. Existing feature selection methods underutilize the discriminatory potential of genes across distinct cell types. We hypothesize that incorporating such information could further boost the performance of single cell clustering. Results

We develop CellBRF, a feature selection method that considers genes’ relevance to cell types for single-cell clustering. The key idea is to identify genes that are most important for discriminating …


Npgreat: Assembly Of The Human Subtelomere Regions With The Use Of Ultralong Nanopore Reads And Linked Reads, Eleni Adam, Desh Ranjan, Harold Riethman Dec 2022

Npgreat: Assembly Of The Human Subtelomere Regions With The Use Of Ultralong Nanopore Reads And Linked Reads, Eleni Adam, Desh Ranjan, Harold Riethman

Computer Science Faculty Publications

Background: Human subtelomeric DNA regulates the length and stability of adjacent telomeres that are critical for cellular function, and contains many gene/pseudogene families. Large evolutionarily recent segmental duplications and associated structural variation in human subtelomeres has made complete sequencing and assembly of these regions difficult to impossible for many loci, complicating or precluding a wide range of genetic analyses to investigate their function.

Results: We present a hybrid assembly method, NanoPore Guided REgional Assembly Tool (NPGREAT), which combines Linked-Read data with mapped ultralong nanopore reads spanning subtelomeric segmental duplications to potentially overcome these difficulties. Linked-Read sets of DNA sequences identified …


Investigating The Biorisk Of Genetically Engineered Thermosynechococcus Elongatus Bp1, Cherrelle Leah Barnes Aug 2022

Investigating The Biorisk Of Genetically Engineered Thermosynechococcus Elongatus Bp1, Cherrelle Leah Barnes

Chemistry & Biochemistry Theses & Dissertations

Cyanobacteria, also known as blue-green algae, are an ancient group of microorganisms that use simple materials, such as sunlight, carbon dioxide and water, to produce energy while providing oxygen to the atmosphere by performing photosynthesis. Synthetic biology approaches have been employed with cyanobacteria as a platform to produce a range of products, such as biofuels, by inserting a series of genes into the cyanobacterial genome that will allow the conversion of metabolic intermediates to such desired products. Although these methods are promising, it is important to understand any potential bio-risk they pose. This research evaluates the potential bio-risk of genetically …


Statistical Genetic Discoveries Using Restricted Maximum Likelihood Method, Erika Wu Jul 2022

Statistical Genetic Discoveries Using Restricted Maximum Likelihood Method, Erika Wu

2022 REYES Proceedings

In statistical genetics, genetic association and genomic prediction become more successful with a highly heritable trait. Identifying highly heritable components of a complex disease can thus advance scientific understanding of the disease and potentially lead to effective prevention and treatments. Using Matlab and existing large-scale genome datasets, we evaluate a restricted maximum likelihood approach to identify highly heritable components of a complex disease as a function of multiple clinical variables.


Pulmonary Function And Blood Dna Methylation: A Multiancestry Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Tianxiao Huan, Daniel L. Mccartney, Geetha Chittoor, Maaike De Vries, Lies Lahousse, Jennifer N. Nguyen, Jennifer A. Brody, Juan Castillo-Fernandez, Natalie Terzikhan, Cancan Qi, Roby Joehanes, Josine L. Min, Gordon J. Smilnak, Jessica R. Shaw, Chen Xi Yang, Elena Colicino, Thanh T. Hoang, Mairead L. Bermingham, Hanfei Xu, Anne E. Justice, Cheng-Jian Xu, Stephen S. Rich, Simon R. Cox, Judith M. Vonk, Ivana Prokić, Nona Sotoodehnia, Pei-Chien Tsai, Joel D. Schwartz, Janice M. Leung, Sinjini Sikdar, Rosie M. Walker, Sarah E. Harris, Diana A. Van Der Plaat, David J. Van Den Berg, Traci M. Bartz, Tim D. Spector, Pantel S. Vokonas, Riccardo E. Marioni, Adele M. Taylor, Yongmei Liu, R. Graham Barr, Leslie A. Lange, Andrea A. Baccarelli, Ma'en Obeidat, Myriam Fornage, Tianyuan Wang, James M. Ward, Alison A. Motsinger-Reif, Gibran Hemani, Gerard H. Koppelman, Jordana T. Bell, Sina A. Gharib, Guy Brusselle, H. Marike Boezen, Kari E. North, Daniel Levy, Kathryn L. Evans, Josée Dupris, Charles E. Breeze, Ani Manichaikul, Stephanie J. London Jan 2022

Pulmonary Function And Blood Dna Methylation: A Multiancestry Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Tianxiao Huan, Daniel L. Mccartney, Geetha Chittoor, Maaike De Vries, Lies Lahousse, Jennifer N. Nguyen, Jennifer A. Brody, Juan Castillo-Fernandez, Natalie Terzikhan, Cancan Qi, Roby Joehanes, Josine L. Min, Gordon J. Smilnak, Jessica R. Shaw, Chen Xi Yang, Elena Colicino, Thanh T. Hoang, Mairead L. Bermingham, Hanfei Xu, Anne E. Justice, Cheng-Jian Xu, Stephen S. Rich, Simon R. Cox, Judith M. Vonk, Ivana Prokić, Nona Sotoodehnia, Pei-Chien Tsai, Joel D. Schwartz, Janice M. Leung, Sinjini Sikdar, Rosie M. Walker, Sarah E. Harris, Diana A. Van Der Plaat, David J. Van Den Berg, Traci M. Bartz, Tim D. Spector, Pantel S. Vokonas, Riccardo E. Marioni, Adele M. Taylor, Yongmei Liu, R. Graham Barr, Leslie A. Lange, Andrea A. Baccarelli, Ma'en Obeidat, Myriam Fornage, Tianyuan Wang, James M. Ward, Alison A. Motsinger-Reif, Gibran Hemani, Gerard H. Koppelman, Jordana T. Bell, Sina A. Gharib, Guy Brusselle, H. Marike Boezen, Kari E. North, Daniel Levy, Kathryn L. Evans, Josée Dupris, Charles E. Breeze, Ani Manichaikul, Stephanie J. London

Mathematics & Statistics Faculty Publications

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication.

Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function.

Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics.

Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery …


Prevalence Of Mutations In The Pfdhfr, Pfdhps, And Pfmdr1 Genes Of Malarial Parasites Isolated From Symptomatic Patients In Dogondoutchi, Niger, Ibrahima Issa, Mahaman Moustapha Lamine, Veronique Hubert, Amadou Ilagouma, Eric Adehossi, Aboubacar Mahamadou, Neil F. Lobo, Demba Sarr, Lisa M. Shollenberger, Houze Sandrine, Ronan Jambou, Ibrahim Maman Laminou Jan 2022

Prevalence Of Mutations In The Pfdhfr, Pfdhps, And Pfmdr1 Genes Of Malarial Parasites Isolated From Symptomatic Patients In Dogondoutchi, Niger, Ibrahima Issa, Mahaman Moustapha Lamine, Veronique Hubert, Amadou Ilagouma, Eric Adehossi, Aboubacar Mahamadou, Neil F. Lobo, Demba Sarr, Lisa M. Shollenberger, Houze Sandrine, Ronan Jambou, Ibrahim Maman Laminou

Biological Sciences Faculty Publications

The effectiveness of artemisinin-based combination therapies (ACTs) depends not only on that of artemisinin but also on that of partner molecules. This study aims to evaluate the prevalence of mutations in the Pfdhfr, Pfdhps, and Pfmdr1 genes from isolates collected during a clinical study. Plasmodium genomic DNA samples extracted from symptomatic malaria patients from Dogondoutchi, Niger, were sequenced by the Sanger method to determine mutations in the Pfdhfr (codons 51, 59, 108, and 164), Pfdhps (codons 436, 437, 540, 581, and 613), and Pfmdr1 (codons 86, 184, 1034, and 1246) genes. One hundred fifty-five (155) pre-treatment samples were …


Reduction Of Plasmid Vector Backbone Length Enhances Reporter Gene Expression, Carly Boye, Sezgi Arpag, Michael Francis, Scott Declemente, Aislin West, Richard Heller, Anna Bulysheva Jan 2022

Reduction Of Plasmid Vector Backbone Length Enhances Reporter Gene Expression, Carly Boye, Sezgi Arpag, Michael Francis, Scott Declemente, Aislin West, Richard Heller, Anna Bulysheva

Electrical & Computer Engineering Faculty Publications

Gene therapy has a wide range of applications for various types of pathologies. Viral methods of gene delivery provide high levels of gene expression but have various safety concerns. Non-viral methods are largely known to provide lower levels of expression. We aim to address this issue by using plasmid DNA with smaller backbones to increase gene expression levels when delivered using non-viral methods. In this study we compare gene expression levels between two vectors with firefly luciferase encoding gene insert using liposome complexes and gene electrotransfer as delivery methods. A 2-fold reduction in plasmid vector backbone size, disproportionately enhanced gene …


Genomic Degeneration And Reduction In The Fish Pathogen Mycobacterium Shottsi, David T. Gauthier, Janis H. Doss, M. Lagatta, T. Gupta, R.K. Karls, F. D. Quinn Jan 2022

Genomic Degeneration And Reduction In The Fish Pathogen Mycobacterium Shottsi, David T. Gauthier, Janis H. Doss, M. Lagatta, T. Gupta, R.K. Karls, F. D. Quinn

Biological Sciences Faculty Publications

Mycobacterium shottsii is a dysgonic, nonpigmented mycobacterium originally isolated from diseased striped bass (Morone saxatilis) in the Chesapeake Bay, USA. Genomic analysis reveals that M. shottsii is a Mycobacterium ulcerans/Mycobacterium marinum clade (MuMC) member, but unlike the superficially similar M. pseudoshottsii, also isolated from striped bass, it is not an M. ulcerans ecovar, instead belonging to a transitional group of strains basal to proposed “Aronson” and “M” lineages. Although phylogenetically distinct from the human pathogen M. ulcerans, the M. shottsii genome shows parallel but nonhomologous genomic degeneration, including massive accumulation of pseudogenes accompanied by proliferation of …


Rickettsial Pathogen Perturbs Tick Circadian Gene To Infect The Vertebrate Host, Supreet Khanal, Vikas Taank, John F. Anderson, Hameeda Sultana, Girish Neelakanta Jan 2022

Rickettsial Pathogen Perturbs Tick Circadian Gene To Infect The Vertebrate Host, Supreet Khanal, Vikas Taank, John F. Anderson, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ixodes scapularis is a medically important tick that transmits several microbes to humans, including rickettsial pathogen Anaplasma phagocytophilum. In nature, these ticks encounter several abiotic factors including changes in temperature, humidity, and light. Many organisms use endogenously generated circadian pathways to encounter abiotic factors. In this study, we provide evidence for the first time to show that A. phagocytophilum modulates the arthropod circadian gene for its transmission to the vertebrate host. We noted a circadian oscillation in the expression of arthropod clock, bmal1, period and timeless genes when ticks or tick cells were exposed to alternate 12 h …


Robust Meta-Analysis For Large-Scale Genomic Experiments Based On An Empirical Approach, Sinjini Sikdar Jan 2022

Robust Meta-Analysis For Large-Scale Genomic Experiments Based On An Empirical Approach, Sinjini Sikdar

Mathematics & Statistics Faculty Publications

BACKGROUND: Recent high-throughput technologies have opened avenues for simultaneous analyses of thousands of genes. With the availability of a multitude of public databases, one can easily access multiple genomic study results where each study comprises of significance testing results of thousands of genes. Researchers currently tend to combine this genomic information from these multiple studies in the form of a meta-analysis. As the number of genes involved is very large, the classical meta-analysis approaches need to be updated to acknowledge this large-scale aspect of the data.

METHODS: In this article, we discuss how application of standard theoretical null distributional assumptions …


Opioid Medication Use And Blood Dna Methylation: Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Roby Joehanes, Daniel L. Mccartney, Minjung Kho, Anke Hüls, Annah B. Wyss, Chunyu Liu, Rosie M. Walker, Sharon L.R. Kardia, Thomas S. Wingo, Adam Burkholder, Jiantao Ma, Archie Campbell, Aliza P. Wingo, Tianxiao Huan, Sinjini Sikdar, Amena Keshawarz, David A. Bennett, Jennifer A. Smith, Kathryn L. Evans, Daniel Levy, Stephanie J. London Jan 2022

Opioid Medication Use And Blood Dna Methylation: Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Roby Joehanes, Daniel L. Mccartney, Minjung Kho, Anke Hüls, Annah B. Wyss, Chunyu Liu, Rosie M. Walker, Sharon L.R. Kardia, Thomas S. Wingo, Adam Burkholder, Jiantao Ma, Archie Campbell, Aliza P. Wingo, Tianxiao Huan, Sinjini Sikdar, Amena Keshawarz, David A. Bennett, Jennifer A. Smith, Kathryn L. Evans, Daniel Levy, Stephanie J. London

Mathematics & Statistics Faculty Publications

Aim: To identify differential methylation related to prescribed opioid use. Methods: This study examined whether blood DNA methylation, measured using Illumina arrays, differs by recent opioid medication use in four population-based cohorts. We meta-analyzed results (282 users; 10,560 nonusers) using inverse-variance weighting. Results: Differential methylation (false discovery rate <0.05) was observed at six CpGs annotated to the following genes: KIAA0226, CPLX2, TDRP, RNF38, TTC23 and GPR179. Integrative epigenomic analyses linked implicated loci to regulatory elements in blood and/or brain. Additionally, 74 CpGs were differentially methylated in males or females. Methylation at significant CpGs correlated with gene expression in blood and/or brain. Conclusion: This study identified DNA …


The Landscape Of Accessible Chromatin In Quiescent Cardiac Fibroblasts And Cardiac Fibroblasts Activated After Myocardial Infarction, Chaoyang Yi, Jiangwen Sun, Qianglin Liu, Sanjeeva Dodlapati, Hao Ming, Leshan Wang, Yuxia Li, Rui Li, Zongliang Jiang, Joseph Francis, Xing Fu Jan 2022

The Landscape Of Accessible Chromatin In Quiescent Cardiac Fibroblasts And Cardiac Fibroblasts Activated After Myocardial Infarction, Chaoyang Yi, Jiangwen Sun, Qianglin Liu, Sanjeeva Dodlapati, Hao Ming, Leshan Wang, Yuxia Li, Rui Li, Zongliang Jiang, Joseph Francis, Xing Fu

Computer Science Faculty Publications

After myocardial infarction, the massive death of cardiomyocytes leads to cardiac fibroblast proliferation and myofibroblast differentiation, which contributes to the extracellular matrix remodelling of the infarcted myocardium. We recently found that myofibroblasts further differentiate into matrifibrocytes, a newly identified cardiac fibroblast differentiation state. Cardiac fibroblasts of different states have distinct gene expression profiles closely related to their functions. However, the mechanism responsible for the gene expression changes during these activation and differentiation events is still not clear. In this study, the gene expression profiling and genome-wide accessible chromatin mapping of mouse cardiac fibroblasts isolated from the uninjured myocardium and the …


Completing Single-Cell Dna Methylome Profiles Via Transfer Learning Together With Kl-Divergence, Sanjeeva Dodlapati, Zongliang Jiang, Jiangwen Sun Jan 2022

Completing Single-Cell Dna Methylome Profiles Via Transfer Learning Together With Kl-Divergence, Sanjeeva Dodlapati, Zongliang Jiang, Jiangwen Sun

Computer Science Faculty Publications

The high level of sparsity in methylome profiles obtained using whole-genome bisulfite sequencing in the case of low biological material amount limits its value in the study of systems in which large samples are difficult to assemble, such as mammalian preimplantation embryonic development. The recently developed computational methods for addressing the sparsity by imputing missing have their limits when the required minimum data coverage or profiles of the same tissue in other modalities are not available. In this study, we explored the use of transfer learning together with Kullback-Leibler (KL) divergence to train predictive models for completing methylome profiles with …


For Whom The Bell Tolls: Psychopathological And Neurobiological Correlates Of The Dna Methylation Index Of Time-To-Death, Sage E. Hawn, Xiang Zhao, Danielle R. Sullivan, Mark Logue, Dana Fein-Schaffer, William Milberg, Regina Mcglinchey, Mark W. Miller, Erika J. Wolf Jan 2022

For Whom The Bell Tolls: Psychopathological And Neurobiological Correlates Of The Dna Methylation Index Of Time-To-Death, Sage E. Hawn, Xiang Zhao, Danielle R. Sullivan, Mark Logue, Dana Fein-Schaffer, William Milberg, Regina Mcglinchey, Mark W. Miller, Erika J. Wolf

Psychology Faculty Publications

Psychopathology is a risk factor for accelerated biological aging and early mortality. We examined associations between broad underlying dimensions of psychopathology (reflecting internalizing and externalizing psychiatric symptoms), PTSD, and age-adjusted GrimAge (“GrimAge residuals”), a DNA methylation biomarker of mortality risk relative to age. We also examined neurobiological correlates of GrimAge residuals, including neurocognitive functioning, blood-based biomarkers (of inflammation, neuropathology, metabolic disease), and cortical thickness. Data from two independent trauma-exposed military cohorts (n = 647 [62.9% male, Mage = 52], n = 434 [90% male, Mage = 32]) were evaluated using linear regression models to test associations between …


Evaluation Of Horizontal Gene Transfer Between Genetically Engineered Cyanobacteria And Gram-Negative Bacteria, Andriana Chrysovalanti Zourou Jul 2021

Evaluation Of Horizontal Gene Transfer Between Genetically Engineered Cyanobacteria And Gram-Negative Bacteria, Andriana Chrysovalanti Zourou

Chemistry & Biochemistry Theses & Dissertations

As the world population is increasing and societies become more technology driven, there is an imperative to develop ‘green energy’ sources to protect our planet. Cyanobacteria that have been genetically engineered to produce organic compounds that may be burnt as fuels show great potential, as they are an environmentally friendly and self-renewable, net carbon-neutral option. However, there are potential risks in the development and use of genetically modified organisms (GMOs). We need to understand in advance the risks that GMOs may pose to our environment and to animal and human health. This will enable experimental procedures, containment strategies and policies …


Nanopore Guided Regional Assembly, Eleni Adam, Desh Ranjan, Harold Riethman Apr 2021

Nanopore Guided Regional Assembly, Eleni Adam, Desh Ranjan, Harold Riethman

College of Sciences Posters

The telomeres are the “caps” of the chromosomes and their vital role is to protect them. Possible telomere dysfunction caused by telomere rearrangements can be fatal for the cell and result in age-related diseases, including cancer. The telomeres and subtelomeres are regions that are hard to investigate. The current technology cannot provide their complete sequence, instead the DNA is given in multiple pieces. Current methods of assembling the pieces of these regions are not accurate enough due to the region’s high variability and complex repeated patterns. We propose a hybrid assembly method, the NPGREAT, which utilizes two of the latest …


Determination Of The Presence Of Rickettsia Spp. And Borrelia Spp. Carried By Tortoise Ticks From Madagascar, Anna Phan Apr 2021

Determination Of The Presence Of Rickettsia Spp. And Borrelia Spp. Carried By Tortoise Ticks From Madagascar, Anna Phan

Biological Sciences Theses & Dissertations

Ticks were removed from three species of Malagasy tortoises, Astrochelys yniphora, A. radiata, and Pyxis arachnoides (comprising two subspecies P. a. arachnoides and P. a. oblonga), between 2012 and 2015. The ticks were presumed to be from the genus Amblyomma. Ticks were morphologically identified and then checked molecularly to confirm their classification or identify any ticks that could not be morphologically identified. Molecular identification was done via end-point PCR that amplified tick cytochrome oxidase (CO1) and tick 12S rRNA genes. Ticks were screened via a real-time polymerase chain reaction assay for the presence of Rickettsia spp. …


Haplotype Network Branch Diversity, A New Metric Combining Genetic And Topological Diversity To Compare The Complexity Of Haplotype Networks, Eric Garcia, Daniel Wright, Remy Gatkins, May B. Roberts, Hudson T. Pinheiro, Eva Salas, Jei-Ying Chen, Jacob R. Winnikoff, Giacomo Bernardi Jan 2021

Haplotype Network Branch Diversity, A New Metric Combining Genetic And Topological Diversity To Compare The Complexity Of Haplotype Networks, Eric Garcia, Daniel Wright, Remy Gatkins, May B. Roberts, Hudson T. Pinheiro, Eva Salas, Jei-Ying Chen, Jacob R. Winnikoff, Giacomo Bernardi

Biological Sciences Faculty Publications

A common way of illustrating phylogeographic results is through the use of haplotype networks. While these networks help to visualize relationships between individuals, populations, and species, evolutionary studies often only quantitatively analyze genetic diversity among haplotypes and ignore other network properties. Here, we present a new metric, haplotype network branch diversity (HBd), as an easy way to quantifiably compare haplotype network complexity. Our metric builds off the logic of combining genetic and topological diversity to estimate complexity previously used by the published metric haplotype network diversity (HNd). However, unlike HNd which uses a combination of network …


A Hybrid Gene Selection Strategy Based On Fisher And Ant Colony Optimization Algorithm For Breast Cancer Classification, Mohammed Hamim, Ismail El Moudden, Mohan D. Pant, Hicham Moutachaouik, Mustapha Hain Jan 2021

A Hybrid Gene Selection Strategy Based On Fisher And Ant Colony Optimization Algorithm For Breast Cancer Classification, Mohammed Hamim, Ismail El Moudden, Mohan D. Pant, Hicham Moutachaouik, Mustapha Hain

EVMS School of Health Professions Faculty Publications

Breast cancer poses the greatest threat to human life and especially to women's life. Despite the progress made in data mining technology in recent years, the ability to predict and diagnose such fatal diseases based on gene expression data still reveals a limited prediction performance, which may not be surprising since most of the genes in expression data are believed to be irrelevant or redundant. The dimensionality reduction process may be considered as a crucial step to analyze gene expression data, as it can reduce the high dimensionality of the breast cancer datasets, which may result into a better prediction …