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Computational Analysis Of Papionini Evolution Using Alu Insertions, Vallmer Edward Jordan II 2018 Louisiana State University and Agricultural and Mechanical College

Computational Analysis Of Papionini Evolution Using Alu Insertions, Vallmer Edward Jordan Ii

LSU Doctoral Dissertations

Alu elements are primate specific retrotransposons that have remained active throughout the course of primate evolution. As a result of this sustained mobilization. Alu elements are present in greater copy number in primate genomes than any other transposable element. An average of over one million Alu elements has been identified in every sequenced haplorrhine genome to date. These characteristics qualify Alu elements as ideal characters for studying evolutionary relationship among primates.

The increasing availability of whole genome sequencing data presents novel challenges and opportunities for comparative genomic analyses. Genomic data is now publicly available for most primate species. Such an ...


Omega: A Software Tool For The Management, Analysis, And Dissemination Of Intracellular Trafficking Data That Incorporates Motion Type Classification And Quality Control, Alessandro Rigano, Vanni Galli, Jasmine M. Clark, Lara E. Pereira, Loris Grossi, Jeremy Luban, Raffaello Giulietti, Tiziano Leidi, Eric Hunter, Mario Valle, Ivo F. Sbalzarini, Caterina Strambio-De-Castilla 2018 University of Massachusetts Medical School

Omega: A Software Tool For The Management, Analysis, And Dissemination Of Intracellular Trafficking Data That Incorporates Motion Type Classification And Quality Control, Alessandro Rigano, Vanni Galli, Jasmine M. Clark, Lara E. Pereira, Loris Grossi, Jeremy Luban, Raffaello Giulietti, Tiziano Leidi, Eric Hunter, Mario Valle, Ivo F. Sbalzarini, Caterina Strambio-De-Castilla

University of Massachusetts Medical School Faculty Publications

MOTIVATION: Particle tracking coupled with time-lapse microscopy is critical for understanding the dynamics of intracellular processes of clinical importance. Spurred on by advances in the spatiotemporal resolution of microscopy and automated computational methods, this field is increasingly amenable to multi-dimensional high-throughput data collection schemes (Snijder et al, 2012). Typically, complex particle tracking datasets generated by individual laboratories are produced with incompatible methodologies that preclude comparison to each other. There is therefore an unmet need for data management systems that facilitate data standardization, meta-analysis, and structured data dissemination. The integration of analysis, visualization, and quality control capabilities into such systems would ...


Systematic Pan-Cancer Analysis Of Somatic Allele Frequency, Liam Spurr, Muzi Li, Nawaf Alomran, Qianqian Zhang, Paula Restrepo, Mercedeh Movassagh, Chris Trenkov, Nerissa Tunnessen, Tatiyana Apanasovich, Keith A. Crandall, Nathan Edwards, Anelia Horvath 2018 George Washington University

Systematic Pan-Cancer Analysis Of Somatic Allele Frequency, Liam Spurr, Muzi Li, Nawaf Alomran, Qianqian Zhang, Paula Restrepo, Mercedeh Movassagh, Chris Trenkov, Nerissa Tunnessen, Tatiyana Apanasovich, Keith A. Crandall, Nathan Edwards, Anelia Horvath

Open Access Articles

Imbalanced expression of somatic alleles in cancer can suggest functional and selective features, and can therefore indicate possible driving potential of the underlying genetic variants. To explore the correlation between allele frequency of somatic variants and total gene expression of their harboring gene, we used the unique data set of matched tumor and normal RNA and DNA sequencing data of 5523 distinct single nucleotide variants in 381 individuals across 10 cancer types obtained from The Cancer Genome Atlas (TCGA). We analyzed the allele frequency in the context of the variant and gene functional features and linked it with changes in ...


Characterization Of An N-Terminal Non-Core Domain Of Rag1 Gene Disrupted Syrian Hamster Model Generated By Crispr Cas9, Jinxin Miao, Baoling Ying, Rong Li, Ann E. Tollefson, Jacqueline F. Spencer, William S.M. Wold, Seok-Hwan Song, Il-Keun Kong, Karoly Toth, Yaohe Wang, Zhongde Wang 2018 Zhengzhou University

Characterization Of An N-Terminal Non-Core Domain Of Rag1 Gene Disrupted Syrian Hamster Model Generated By Crispr Cas9, Jinxin Miao, Baoling Ying, Rong Li, Ann E. Tollefson, Jacqueline F. Spencer, William S.M. Wold, Seok-Hwan Song, Il-Keun Kong, Karoly Toth, Yaohe Wang, Zhongde Wang

Animal, Dairy, and Veterinary Science Faculty Publications

The accumulating evidence demonstrates that Syrian hamsters have advantages as models for various diseases. To develop a Syrian hamster (Mesocricetus auratus) model of human immunodeficiency caused by RAG1 gene mutations, we employed the CRISPR/Cas9 system and introduced an 86-nucleotide frameshift deletion in the hamster RAG1 gene encoding part of the N-terminal non-core domain of RAG1. Histological and immunohistochemical analyses demonstrated that these hamsters (referred herein as RAG1-86nt hamsters) had atrophic spleen and thymus, and developed significantly less white pulp and were almost completely devoid of splenic lymphoid follicles. The RAG1-nt86 hamsters had barely detectable CD3+ and CD4+ T cells ...


Modeling And Analyzing An Optogenetic System For Photoactivatable Protein Dissociation, Anvin Thomas, James Schaff 2018 University of Connecticut

Modeling And Analyzing An Optogenetic System For Photoactivatable Protein Dissociation, Anvin Thomas, James Schaff

Honors Scholar Theses

Computational modeling of cell-cell interactions can grant clues and can answer questions about an experiment, especially for observations about binding interactions and kinetics. This approach was used to investigate an interaction between a light-oxygen-voltage (LOV) domain and an engineered protein called Zdark (Zdk). The LOV domain is membrane-bound while Zdk is cytosolic. The LOV domain and Zdk bind strongly in dark (Kd 26.2 nM), and weakly upon exposure to blue light (Kd > 4 μM). Total internal reflection fluorescence (TIRF) images are acquired of Zdk, the fluorescent species bound to a mCherry tag, and the loss of fluorescence ...


Region Based Gene Expression Via Reanalysis Of Publicly Available Microarray Data Sets., Ernur Saka 2018 University of Louisville

Region Based Gene Expression Via Reanalysis Of Publicly Available Microarray Data Sets., Ernur Saka

Electronic Theses and Dissertations

A DNA microarray is a high-throughput technology used to identify relative gene expression. One of the most widely used platforms is the Affymetrix® GeneChip® technology which detects gene expression levels based on probe sets composed of a set of twenty-five nucleotide probes designed to hybridize with specific gene targets. Given a particular Affymetrix® GeneChip® platform, the design of the probes is fixed. However, the method of analysis is dynamic in nature due to the ability to annotate and group probes into uniquely defined groupings. This is particularly important since publicly available repositories of microarray datasets, such as ArrayExpress and NCBI ...


Bayesian Nonparametric Discovery Of Isoforms And Individual Specific Quantification, Derek Aguiar, Li-Fang Cheng, Bianca Dumitrascu, Fantine Mordelet, Athma A. Pai, Barbara E. Engelhardt 2018 Princeton University

Bayesian Nonparametric Discovery Of Isoforms And Individual Specific Quantification, Derek Aguiar, Li-Fang Cheng, Bianca Dumitrascu, Fantine Mordelet, Athma A. Pai, Barbara E. Engelhardt

Open Access Articles

Most human protein-coding genes can be transcribed into multiple distinct mRNA isoforms. These alternative splicing patterns encourage molecular diversity, and dysregulation of isoform expression plays an important role in disease etiology. However, isoforms are difficult to characterize from short-read RNA-seq data because they share identical subsequences and occur in different frequencies across tissues and samples. Here, we develop BIISQ, a Bayesian nonparametric model for isoform discovery and individual specific quantification from short-read RNA-seq data. BIISQ does not require isoform reference sequences but instead estimates an isoform catalog shared across samples. We use stochastic variational inference for efficient posterior estimates and ...


Deconvolution Of Subcellular Protrusion Heterogeneity And The Underlying Actin Regulator Dynamics From Live Cell Imaging, Chuangqi Wang, Hee June Choi, Sung-Jin Kim, Aesha Desai, Namgyu Lee, Dohoon Kim, Yongho Bae, Kwonmoo Lee 2018 Worcester Polytechnic Institute

Deconvolution Of Subcellular Protrusion Heterogeneity And The Underlying Actin Regulator Dynamics From Live Cell Imaging, Chuangqi Wang, Hee June Choi, Sung-Jin Kim, Aesha Desai, Namgyu Lee, Dohoon Kim, Yongho Bae, Kwonmoo Lee

Open Access Articles

Cell protrusion is morphodynamically heterogeneous at the subcellular level. However, the mechanism of cell protrusion has been understood based on the ensemble average of actin regulator dynamics. Here, we establish a computational framework called HACKS (deconvolution of heterogeneous activity in coordination of cytoskeleton at the subcellular level) to deconvolve the subcellular heterogeneity of lamellipodial protrusion from live cell imaging. HACKS identifies distinct subcellular protrusion phenotypes based on machine-learning algorithms and reveals their underlying actin regulator dynamics at the leading edge. Using our method, we discover "accelerating protrusion", which is driven by the temporally ordered coordination of Arp2/3 and VASP ...


Diversity, Structure And Sources Of Bacterial Communities In Earthworm Cocoons., Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez 2018 George Washington University

Diversity, Structure And Sources Of Bacterial Communities In Earthworm Cocoons., Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez

Computational Biology Institute

Animals start interactions with the bacteria that will constitute their microbiomes at embryonic stage. After mating, earthworms produce cocoons externally which will be colonized with bacteria from their parents and the environment. Due to the key role bacterial symbionts play on earthworm fitness, it is important to study bacterial colonization during cocoon formation. Here we describe the cocoon microbiome of the earthworms Eisenia andrei and E. fetida, which included 275 and 176 bacterial species, respectively. They were dominated by three vertically-transmitted symbionts, Microbacteriaceae, Verminephrobacter and Ca. Nephrothrix, which accounted for 88% and 66% of the sequences respectively. Verminephrobacter and Ca ...


A Unified Encyclopedia Of Human Functional Dna Elements Through Fully Automated Annotation Of 164 Human Cell Types, Maxwell Wing Libbrecht, Oscar Rodriguez, Zhiping Weng, Michael Hoffman, Jeffrey A. Bilmes, William Stafford Noble 2018 University of Washington

A Unified Encyclopedia Of Human Functional Dna Elements Through Fully Automated Annotation Of 164 Human Cell Types, Maxwell Wing Libbrecht, Oscar Rodriguez, Zhiping Weng, Michael Hoffman, Jeffrey A. Bilmes, William Stafford Noble

University of Massachusetts Medical School Faculty Publications

Semi-automated genome annotation methods such as Segway enable understanding of chromatin activity. Here we present chromatin state annotations of 164 human cell types using 1,615 genomics data sets. To produce these annotations, we developed a fully-automated annotation strategy in which we train separate unsupervised annotation models on each cell type and use a machine learning classifier to automate the state interpretation step. Using these annotations, we developed a measure of the functional importance of each genomic position called the "functionality score," which allows us to aggregate information across cell types into a multi-cell type view. This score provides a ...


Exploiting Glycan Topography For Computational Design Of Env Glycoprotein Antigenicity, Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, Galit Alter 2018 Massachusetts Institute of Technology

Exploiting Glycan Topography For Computational Design Of Env Glycoprotein Antigenicity, Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, Galit Alter

Open Access Articles

Mounting evidence suggests that glycans, rather than merely serving as a "shield", contribute critically to antigenicity of the HIV envelope (Env) glycoprotein, representing critical antigenic determinants for many broadly neutralizing antibodies (bNAbs). While many studies have focused on defining the role of individual glycans or groups of proximal glycans in bNAb binding, little is known about the effects of changes in the overall glycan landscape in modulating antibody access and Env antigenicity. Here we developed a systems glycobiology approach to reverse engineer the complexity of HIV glycan heterogeneity to guide antigenicity-based de novo glycoprotein design. bNAb binding was assessed against ...


Viper: Visualization Pipeline For Rna-Seq, A Snakemake Workflow For Efficient And Complete Rna-Seq Analysis, MacIntosh Cornwell, Mahesh Vangala, Len Taing, Zachary Herbert, Johannes Koster, Bo Li, Hanfei Sun, Taiwen Li, Jian Zhang, Xintao Qiu, Matthew Pun, Rinath Jeselsohn, Myles Brown, X Shirley Liu, Henry W. Long 2018 Dana-Farber Cancer Institute

Viper: Visualization Pipeline For Rna-Seq, A Snakemake Workflow For Efficient And Complete Rna-Seq Analysis, Macintosh Cornwell, Mahesh Vangala, Len Taing, Zachary Herbert, Johannes Koster, Bo Li, Hanfei Sun, Taiwen Li, Jian Zhang, Xintao Qiu, Matthew Pun, Rinath Jeselsohn, Myles Brown, X Shirley Liu, Henry W. Long

Open Access Articles

BACKGROUND: RNA sequencing has become a ubiquitous technology used throughout life sciences as an effective method of measuring RNA abundance quantitatively in tissues and cells. The increase in use of RNA-seq technology has led to the continuous development of new tools for every step of analysis from alignment to downstream pathway analysis. However, effectively using these analysis tools in a scalable and reproducible way can be challenging, especially for non-experts.

RESULTS: Using the workflow management system Snakemake we have developed a user friendly, fast, efficient, and comprehensive pipeline for RNA-seq analysis. VIPER (Visualization Pipeline for RNA-seq analysis) is an analysis ...


Glucocorticoids Modulate Gastrointestinal Microbiome In A Wild Bird., José C Noguera, Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez, Alberto Velando 2018 George Washington University

Glucocorticoids Modulate Gastrointestinal Microbiome In A Wild Bird., José C Noguera, Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez, Alberto Velando

Computational Biology Institute

It has recently been hypothesized that stress exposure (e.g. via glucocorticoid secretion) may dysregulate the bacterial gut microbiome, a crucial 'organ' in animal health. However, whether stress exposure (e.g. via glucocorticoid secretion) affects the bacterial gut microbiome of natural populations is unknown. We have experimentally altered the basal glucocorticoid level (corticosterone implants) in a wild avian species, the yellow-legged gull


Numerous Recursive Sites Contribute To Accuracy Of Splicing Of Long Introns In Flies, Athma A. Pai, Joseph Paggi, Karen Adelman, Christopher B. Burge 2018 University of Massachusetts Medical School

Numerous Recursive Sites Contribute To Accuracy Of Splicing Of Long Introns In Flies, Athma A. Pai, Joseph Paggi, Karen Adelman, Christopher B. Burge

University of Massachusetts Medical School Faculty Publications

Recursive splicing, a process by which a single intron is removed from pre-mRNA transcripts in multiple distinct segments, has been observed in a small subset of Drosophila melanogaster introns. However, detection of recursive splicing requires observation of splicing intermediates which are inherently unstable, making it difficult to study. Here we developed new computational approaches to identify recursively spliced introns and applied them, in combination with existing methods, to nascent RNA sequencing data from Drosophila S2 cells. These approaches identified hundreds of novel sites of recursive splicing, expanding the catalog of recursively spliced fly introns by 4-fold. Recursive sites occur in ...


Copy Number Variation In The Porcine Genome Detected From Whole-Genome Sequence, Rebecca Anderson 2018 University of Nebraska-Lincoln

Copy Number Variation In The Porcine Genome Detected From Whole-Genome Sequence, Rebecca Anderson

Honors Theses, University of Nebraska-Lincoln

Copy number variations (CNVs) are large insertions, deletions, and duplications in the genome that vary between individuals in a species. These variations are known to impact a broad range of phenotypes from molecular-level traits to higher-order clinical phenotypes. CNVs have been linked to complex traits in humans such as autism, attention deficit hyperactivity disorder, nervous system disorders, and early-onset extreme obesity. In this study, whole-genome sequence was obtained from 72 founders of an intensely phenotyped experimental swine herd at the U.S. Meat Animal Research Center (USMARC) in Clay Center, Nebraska. This included 24 boars (12 Duroc and 12 Landrace ...


Atacseqqc: A Bioconductor Package For Post-Alignment Quality Assessment Of Atac-Seq Data, Jianhong Ou, Haibo Liu, Jun Yu, Michelle A. Kelliher, Lucio H. Castilla, Nathan D. Lawson, Lihua Julie Zhu 2018 Duke University

Atacseqqc: A Bioconductor Package For Post-Alignment Quality Assessment Of Atac-Seq Data, Jianhong Ou, Haibo Liu, Jun Yu, Michelle A. Kelliher, Lucio H. Castilla, Nathan D. Lawson, Lihua Julie Zhu

University of Massachusetts Medical School Faculty Publications

BACKGROUND: ATAC-seq (Assays for Transposase-Accessible Chromatin using sequencing) is a recently developed technique for genome-wide analysis of chromatin accessibility. Compared to earlier methods for assaying chromatin accessibility, ATAC-seq is faster and easier to perform, does not require cross-linking, has higher signal to noise ratio, and can be performed on small cell numbers. However, to ensure a successful ATAC-seq experiment, step-by-step quality assurance processes, including both wet lab quality control and in silico quality assessment, are essential. While several tools have been developed or adopted for assessing read quality, identifying nucleosome occupancy and accessible regions from ATAC-seq data, none of the ...


Seekdeep: Single-Base Resolution De Novo Clustering For Amplicon Deep Sequencing, Nicholas J. Hathaway, Christian M. Parobek, Jonathan J. Juliano, Jeffrey A. Bailey 2018 University of Massachusetts Medical School

Seekdeep: Single-Base Resolution De Novo Clustering For Amplicon Deep Sequencing, Nicholas J. Hathaway, Christian M. Parobek, Jonathan J. Juliano, Jeffrey A. Bailey

Open Access Articles

PCR amplicon deep sequencing continues to transform the investigation of genetic diversity in viral, bacterial, and eukaryotic populations. In eukaryotic populations such as Plasmodium falciparum infections, it is important to discriminate sequences differing by a single nucleotide polymorphism. In bacterial populations, single-base resolution can provide improved resolution towards species and strains. Here, we introduce the SeekDeep suite built around the qluster algorithm, which is capable of accurately building de novo clusters representing true, biological local haplotypes differing by just a single base. It outperforms current software, particularly at low frequencies and at low input read depths, whether resolving single-base differences ...


Identification Of Novel Genetic Variations For Amyotrophic Lateral Sclerosis (Als), Guang Xu 2018 University of Massachusetts Medical School

Identification Of Novel Genetic Variations For Amyotrophic Lateral Sclerosis (Als), Guang Xu

GSBS Dissertations and Theses

A list of genes have been identified to carry mutations causing familial ALS such as SOD1, TARDBP, C9orf72. But for sporadic ALS, which is 90% of all ALS cases, the underlying genetic variants are still largely unknown. There are multiple genome-wide association study (GWAS) for sporadic ALS, but usually a large number nominated SNP can hardly be replicated in larger cohort analysis. Also majority of GWAS SNP lie within noncoding region of genome, imposing a huge challenge to study their biological role in ALS pathology. With the rapid development of next-generation sequencing technology, we are able to sequence exome and ...


Evolution Of Extrema Features Reveals Optimal Stimuli For Biological State Transitions, Joshua TsuKang Chang, David Paydarfar 2018 University of Massachusetts Medical School Worcester

Evolution Of Extrema Features Reveals Optimal Stimuli For Biological State Transitions, Joshua Tsukang Chang, David Paydarfar

Open Access Articles

The ability to define the unique features of an input stimulus needed to control switch-like behavior in biological systems is an important problem in computational biology and medicine. We show in this study how highly complex and intractable optimization problems can be simplified by restricting the search to the signal's extrema as key feature points, and evolving the extrema features towards optimal solutions that closely match solutions derived from gradient-based methods. Our results suggest a model-independent approach for solving a class of optimization problems related to controlling switch-like state transitions.


Efficient Alignment Algorithms For Dna Sequencing Data, Nilesh Vinod Khiste 2018 The University of Western Ontario

Efficient Alignment Algorithms For Dna Sequencing Data, Nilesh Vinod Khiste

Electronic Thesis and Dissertation Repository

The DNA Next Generation Sequencing (NGS) technologies produce data at a low cost, enabling their application to many ambitious fields such as cancer research, disease control, personalized medicine etc. However, even after a decade of research, the modern aligners and assemblers are far from providing efficient and error free genome alignments and assemblies respectively. This is due to the inherent nature of the genome alignment and assembly problem, which involves many complexities. Many algorithms to address this problem have been proposed over the years, but there still is a huge scope for improvement in this research space.

Many new genome ...


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