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Characterizing Long Covid: Deep Phenotype Of A Complex Condition, Rachel R. Deer, Feifan Liu, Melissa A. Haendel, Peter N. Robinson 2021 University of Texas Medical Branch

Characterizing Long Covid: Deep Phenotype Of A Complex Condition, Rachel R. Deer, Feifan Liu, Melissa A. Haendel, Peter N. Robinson

COVID-19 Publications by UMass Chan Authors

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies.

METHODS: The Human Phenotype Ontology ...


Wormcat 2.0 Defines Characteristics And Conservation Of Poorly Annotated Genes In Caenorhabditis Elegans [Preprint], Daniel P. Higgins, Caroline M. Weisman, Dominique Lui, Frank A. D’Agostino, Amy K. Walker 2021 UMass Chan Medical School

Wormcat 2.0 Defines Characteristics And Conservation Of Poorly Annotated Genes In Caenorhabditis Elegans [Preprint], Daniel P. Higgins, Caroline M. Weisman, Dominique Lui, Frank A. D’Agostino, Amy K. Walker

University of Massachusetts Medical School Faculty Publications

Genome-wide measurement of mRNA or protein levels provides broad data sets for biological discovery. However, subsequent computational methods are essential for uncovering the functional implications of the data as well as intuitively visualizing the findings. Current computational tools are biased toward well-described pathways, limiting their utility for novel discovery. Recently, we developed an annotation and category enrichment tool for Caenorhabditis elegans genomic data, WormCat, that provides an intuitive visualization output. Unlike GO, which excludes genes with no annotation information, WormCat 2.0 retains these genes as a special UNASSIGNED category. Here, we show that the UNASSIGNED gene category enrichment exhibits ...


Improved Radiation Expression Profiling In Blood By Sequential Application Of Sensitive And Specific Gene Signatures, Eliseos J. Mucaki, Ben C. Shirley, Peter K. Rogan 2021 Western University

Improved Radiation Expression Profiling In Blood By Sequential Application Of Sensitive And Specific Gene Signatures, Eliseos J. Mucaki, Ben C. Shirley, Peter K. Rogan

Biochemistry Publications

Purpose. Combinations of expressed genes can discriminate radiation-exposed from normal control blood samples by machine learning based signatures (with 8 to 20% misclassification rates). These signatures can quantify therapeutically-relevant as well as accidental radiation exposures. The prodromal symptoms of Acute Radiation Syndrome (ARS) overlap those present in Influenza and Dengue Fever infections. Surprisingly, these human radiation signatures misclassified gene expression profiles of virally infected samples as false positive exposures. The present study investigates these and other confounders, and then mitigates their impact on signature accuracy.

Methods. This study investigated recall by previous and novel radiation signatures independently derived from multiple ...


Metabolic Modeling Of Cystic Fibrosis Airway Microbiota From Patient Samples, Arsh Vyas 2021 University of Massachusetts Amherst

Metabolic Modeling Of Cystic Fibrosis Airway Microbiota From Patient Samples, Arsh Vyas

Masters Theses

Cystic Fibrosis (CF) is a genetic disorder, found with higher prevalence in the Caucasian population, affecting > 30,000 individuals in the United States and > 70,000 worldwide. Due to the astoundingly high rate of mortality among CF patients being attributed to respiratory failure brought on by chronic bacterial infections and subsequent airway inflammation, there has been a lot of focus on systematically analyzing CF lung airway communities. While it is observed traditionally that Pseudomonas aeruginosa is the most threatening and persistent CF colonizer due to high antibiotic resistance, recent studies have elicited the roles of other pathogens and it has ...


Factorbook: An Updated Catalog Of Transcription Factor Motifs And Candidate Regulatory Motif Sites [Preprint], Henry E. Pratt, Gregory Andrews, Nishigandha Phalke, Michael J. Purcaro, Arjan van der Velde, Jill E. Moore, Zhiping Weng 2021 University of Massachusetts Medical School

Factorbook: An Updated Catalog Of Transcription Factor Motifs And Candidate Regulatory Motif Sites [Preprint], Henry E. Pratt, Gregory Andrews, Nishigandha Phalke, Michael J. Purcaro, Arjan Van Der Velde, Jill E. Moore, Zhiping Weng

University of Massachusetts Medical School Faculty Publications

The human genome contains roughly 1,600 transcription factors (TFs) (1), DNA-binding proteins recognizing characteristic sequence motifs to exert regulatory effects on gene expression. The binding specificities of these factors have been profiled both in vitro, using techniques such as HT-SELEX (2), and in vivo, using techniques including ChIP-seq (3, 4). We previously developed Factorbook, a TF-centric database of annotations, motifs, and integrative analyses based on ChIP-seq data from Phase II of the ENCODE Project. Here we present an update to Factorbook which significantly expands the breadth of cell type and TF coverage. The update includes an expanded motif catalog ...


Human 5’-Tailed Mirtrons Are Processed By Rnasep, Mohammad Farid Zia 2021 The University of Southern Mississippi

Human 5’-Tailed Mirtrons Are Processed By Rnasep, Mohammad Farid Zia

Dissertations

Approximately a thousand microRNAs (miRNAs) are documented from human cells. A third appear to transit non-canonical pathways that typically bypass processing by Drosha, the dedicated nuclear miRNA producing enzyme. The largest class of non-canonical miRNAs are mirtrons which eschew Drosha to mature through spliceosome activity. While mirtrons are found in several configurations, the vast majority of human mirtron species are 5’-tailed. For these mirtrons, a 3’ splice site defines the 3’ end of their hairpin precursor while a “tail” of variable length separates the 5’ base of the hairpin from the nearest splice site. How this tail is removed ...


In Silico Identification Of A Streptococcus Phage From An Unpasteurized Dairy Product, 2021 Kennesaw State University

In Silico Identification Of A Streptococcus Phage From An Unpasteurized Dairy Product

Symposium of Student Scholars

This study aimed to identify novel phages from a West African dairy product, nunu, to better understand the uncharacterized virosphere of a food microbiome. Nunu is a yogurt-like product from spontaneous fermentation of unpasteurized cow milk without a standardized starter culture. Phages and their bacterial hosts make up a microbiome, where their collective metagenome can be studied in silico, or computationally, after next generation sequencing (NGS). The targeted dataset for our study can be found in the Sequence Read Archives under the accession number of ERX2041567. This study utilized several bioinformatics software tools with customized settings: Kraken2, MetaVelvet, Edena, NCBI-BLAST ...


In Silico Isolation Of A Novel Phage For Food Safety Applications Against Pathogenic E. Coli, Daisy McGrath 2021 Kennesaw State University

In Silico Isolation Of A Novel Phage For Food Safety Applications Against Pathogenic E. Coli, Daisy Mcgrath

Symposium of Student Scholars

With the advent of next-generation sequencing (NGS) on metagenomes, the elucidation of all genetic material from microbiomes has prompted a renewed interest towards uncultivated members of the virosphere. We describe the discovery of a novel phage from a metagenomic dataset on the West African fermented dairy product, nunu, with a custom bioinformatics workflow to potentially serve as a biocontrol agent against pathogenic E. coli. Initial dataset of ERR2014814 from NCBI was first subjected to Kraken2 to extract novel sequencing reads for further de novo assembly into contigs by MetaVelvet. Resultant contigs served as potential partial phage genomes, then searched against ...


The Origins And Future Of Sentinel: An Early-Warning System For Pandemic Preemption And Response, Yolanda Botti-Lodovico, Andres Colubri, Pardis C. Sabeti, Christian Happi 2021 Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard

The Origins And Future Of Sentinel: An Early-Warning System For Pandemic Preemption And Response, Yolanda Botti-Lodovico, Andres Colubri, Pardis C. Sabeti, Christian Happi

COVID-19 Publications by UMass Chan Authors

While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an intriguing finding by Dr. Stefan Kunz that the gene plays a critical role in Lassa virus binding and entry. This led us to pursue field work to test our hypothesis that natural selection acting on LARGE-detected in the Yoruba population of Nigeria-conferred resistance to Lassa Fever in some West African populations. As we delved further, we conjectured that the "emerging" nature of recently discovered diseases like Lassa fever is related to a newfound capacity for detection, rather than a novel viral presence, and that ...


Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, Ashley Duche 2021 Chapman University

Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, Ashley Duche

Pharmaceutical Sciences (MS) Theses

Lung cancer remains the leading cause of cancer related deaths worldwide, reportedly contributing to 1.8 million of the 10.0 million mortalities documented in the year 2020. Although advancements have been made in therapeutics and diagnostic methods, formulation of effective treatments and development of drug resistance continues to be a challenge. These challenges arise from our lack of understanding of intricate signaling pathways, such as the Growth Factor Receptor Network (GFRN), which contributes to complex lung tumor heterogeneity allowing for drug resistance development. In this study, gene expression signatures of six GFRN oncogenes overexpressed in human mammary epithelial cells ...


Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula 2021 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

G-quadruplexes are non-B DNA structures formed by four or more runs of repeated guanines that confer unique features to living organism’s genomes. These sequences are enriched in regulatory regions, such as promoters and 5’ UTRs, and have distinct regulatory roles in both health and disease states. Even though previous studies showed the impact of G4 in gene expression, none of them summarized the location-specific effect of G4. Also, there is no broad understanding about the most common G4 repeat in the human genome, named here as G4-22, and how it links to the evolution of mammals and their biology ...


Drug Repurposing For Covid-19 Using Molecular Docking Tools, Deniz Yasar Oztas 2021 Chapman University

Drug Repurposing For Covid-19 Using Molecular Docking Tools, Deniz Yasar Oztas

Computational and Data Sciences (MS) Theses

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and mortal, finding a treatment is time critical. Drug repurposing is probably the quickest and safest approach in our arsenal. However, testing every drug in a brute force manner would require a lot of resources, and a more sophisticated method is required to filter possible candidates. Since several molecules have already been shown to be effective against SARS-CoV-2 in wet-lab experiments, choosing drugs with similar characteristics would increase our chances of success. In this study, we compare the molecular docking results of FDA-approved drugs from the ZINC database against ...


Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino 2021 Thomas Jefferson University

Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino

Computational Medicine Center Faculty Papers

In animal germlines, PIWI proteins and the associated PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposons. Here we report the extensive sequence and quantitative correlations between 2′,3′-cyclic phosphate-containing RNAs (cP-RNAs), identified using cP-RNA-seq, and piRNAs in the Bombyx germ cell line and mouse testes. The cP-RNAs containing 5′-phosphate (P-cP-RNAs) identified by P-cP-RNA-seq harbor highly consistent 5′-end positions as the piRNAs and are loaded onto PIWI protein, suggesting their direct utilization as piRNA precursors. We identified Bombyx RNase Kappa (BmRNase κ) as a mitochondria-associated endoribonuclease which produces cP-RNAs during piRNA biogenesis. BmRNase κ-depletion elevated transposon levels ...


Hi-C 3.0: Improved Protocol For Genome-Wide Chromosome Conformation Capture, Denis L. Lafontaine, Liyan Yang, Job Dekker, Johan H. Gibcus 2021 University of Massachusetts Medical School

Hi-C 3.0: Improved Protocol For Genome-Wide Chromosome Conformation Capture, Denis L. Lafontaine, Liyan Yang, Job Dekker, Johan H. Gibcus

Open Access Publications by UMass Chan Authors

The intricate folding of chromatin enables living organisms to store genomic material in an extremely small volume while facilitating proper cell function. Hi-C is a chromosome conformation capture (3C)-based technology to detect pair-wise chromatin interactions genome-wide, and has become a benchmark tool to study genome organization. In Hi-C, chromatin conformation is first captured by chemical cross-linking of cells. Cells are then lysed and subjected to restriction enzyme digestion, before the ends of the resulting fragments are marked with biotin. Fragments within close 3D proximity are ligated, and the biotin label is used to selectively enrich for ligated junctions. Finally ...


The Differences Of Prokaryotic Pan-Genome Analysis On Complete Genomes And Simulated Metagenome-Assembled Genomes, Tang Li 2021 University of Nebraska-Lincoln

The Differences Of Prokaryotic Pan-Genome Analysis On Complete Genomes And Simulated Metagenome-Assembled Genomes, Tang Li

Dissertations, Theses, & Student Research in Food Science and Technology

Metagenomic assembly is often used in microbiome research. In metagenomic assembly, contigs are binned based on the shared nucleotide composition. These contig bins are called metagenome-assembled genomes (MAGs), each representing a unique bacterial genome recovered from metagenome sequencing. Hundreds of thousands of high-quality MAGs of various ecological environments have been published since 2017, and increasingly more MAGs are being used in pan-genome analyses where unculturable species or species without reference genomes are studied in microbiome research. However, compared to the traditional pan-genome analysis that uses isolate genomes (from a pure strain isolated from a mixed bacterial population), it is not ...


Characterizing Long Covid: Deep Phenotype Of A Complex Condition [Preprint], Rachel R. Deer, Feifan Liu, Melissa Haendel, Peter N. Robinson 2021 University of Texas

Characterizing Long Covid: Deep Phenotype Of A Complex Condition [Preprint], Rachel R. Deer, Feifan Liu, Melissa Haendel, Peter N. Robinson

University of Massachusetts Medical School Faculty Publications

Importance Since late 2019, the novel coronavirus SARS-CoV-2 has given rise to a global pandemic and introduced many health challenges with economic, social, and political consequences. In addition to a complex acute presentation that can affect multiple organ systems, there is mounting evidence of various persistent long-term sequelae. The worldwide scientific community is characterizing a diverse range of seemingly common long-term outcomes associated with SARS-CoV-2 infection, but the underlying assumptions in these studies vary widely making comparisons difficult. Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC or “long COVID”), but they are difficult to integrate ...


Wormpaths: Caenorhabditis Elegans Metabolic Pathway Annotation And Visualization, Melissa D. Walker, Gabrielle E. Giese, Amy D. Holdorf, Sushila Bhattacharya, Cedric Diot, Aurian Garcia-Gonzalez, Brent Horowitz, Yong-Uk Lee, Thomas Leland, Xuhang Li, Zeynep Mirza, Huimin Na, Shivani Nanda, Olga Ponomarova, Hefei Zhang, Jingyan Zhang, L. Safak Yilmaz, Albertha J. M. Walhout 2021 University of Massachusetts Medical School

Wormpaths: Caenorhabditis Elegans Metabolic Pathway Annotation And Visualization, Melissa D. Walker, Gabrielle E. Giese, Amy D. Holdorf, Sushila Bhattacharya, Cedric Diot, Aurian Garcia-Gonzalez, Brent Horowitz, Yong-Uk Lee, Thomas Leland, Xuhang Li, Zeynep Mirza, Huimin Na, Shivani Nanda, Olga Ponomarova, Hefei Zhang, Jingyan Zhang, L. Safak Yilmaz, Albertha J. M. Walhout

Open Access Publications by UMass Chan Authors

In our group, we aim to understand metabolism in the nematode Caenorhabditis elegans and its relationships with gene expression, physiology and the response to therapeutic drugs. Visualization of the metabolic pathways that comprise the metabolic network is extremely useful for interpreting a wide variety of experiments. Detailed annotated metabolic pathway maps for C. elegans is mostly limited to pan-organismal maps, many with incomplete or inaccurate pathway and enzyme annotations. Here we present WormPaths, which is composed of two parts: 1) the careful manual annotation of metabolic genes into pathways, categories and levels, and 2) 62 pathway maps that include metabolites ...


Genetic And Epigenetic Features Of Promoters With Ubiquitous Chromatin Accessibility Support Ubiquitous Transcription Of Cell-Essential Genes, Kaili Fan, Jill E. Moore, Xiao-Ou Zhang, Zhiping Weng 2021 University of Massachusetts Medical School

Genetic And Epigenetic Features Of Promoters With Ubiquitous Chromatin Accessibility Support Ubiquitous Transcription Of Cell-Essential Genes, Kaili Fan, Jill E. Moore, Xiao-Ou Zhang, Zhiping Weng

University of Massachusetts Medical School Faculty Publications

Gene expression is controlled by regulatory elements within accessible chromatin. Although most regulatory elements are cell type-specific, a subset is accessible in nearly all the 517 human and 94 mouse cell and tissue types assayed by the ENCODE consortium. We systematically analyzed 9000 human and 8000 mouse ubiquitously-accessible candidate cis-regulatory elements (cCREs) with promoter-like signatures (PLSs) from ENCODE, which we denote ubi-PLSs. These are more CpG-rich than non-ubi-PLSs and correspond to genes with ubiquitously high transcription, including a majority of cell-essential genes. ubi-PLSs are enriched with motifs of ubiquitously-expressed transcription factors and preferentially bound by transcriptional cofactors regulating ubiquitously-expressed genes ...


Genomic And Ecological Dimensions Of Malagasy Reptile And Amphibian Biodiversity, Arianna L. Kuhn 2021 The Graduate Center, City University of New York

Genomic And Ecological Dimensions Of Malagasy Reptile And Amphibian Biodiversity, Arianna L. Kuhn

Dissertations, Theses, and Capstone Projects

A long history of isolation coupled with complex topographic and ecological landscapes makes Madagascar ideal for exploring the historical factors that have shaped patterns of population diversity and endemism. Many species-level studies have suggested Late Quaternary climate change may have influenced population dynamics in the tropics, but Madagascar’s ecologically unique biomes or individual species properties may have driven idiosyncratic responses to these shifts. Using community-scale population genetic data I implement a hierarchical approximate Bayesian computation (hABC) approach to evaluate the degree of synchronous population expansion during glacial cycles across herpetofaunal assemblages both within and across discrete biomes and taxonomic ...


Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He 2021 University of Connecticut

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to ...


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