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Identifying Genetic Regulators Of Cancer Stem Cell Differentiation For Glioblastoma Therapy, Ann Chen, Yang Xiao, Rong Fan, Jiangbing Zhou 2019 Yale University

Identifying Genetic Regulators Of Cancer Stem Cell Differentiation For Glioblastoma Therapy, Ann Chen, Yang Xiao, Rong Fan, Jiangbing Zhou

Yale Day of Data

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain cancer. Even with treatment, GBM patients have a median survival rate of less than 15 months and a five-year survival rate of 2%. Poor therapeutic outcomes may be attributed to the presence of a subpopulation of cells within tumors, known as cancer stem cells (CSCs), which are resistant to conventional radiotherapy and chemotherapy. CSCs are capable of tumor initiation, sustained self-renewal, and differentiation into terminal cell types. These terminally differentiated cells make up the bulk of the tumor and are sensitive to GBM therapies. Therefore, CSC-directed therapies ...


A Novel Pathway-Based Distance Score Enhances Assessment Of Disease Heterogeneity In Gene Expression, Yunqing Liu, Xiting Yan 2019 Yale University School of Public Health

A Novel Pathway-Based Distance Score Enhances Assessment Of Disease Heterogeneity In Gene Expression, Yunqing Liu, Xiting Yan

Yale Day of Data

Distance-based unsupervised clustering of gene expression data is commonly used to identify heterogeneity in biologic samples. However, high noise levels in gene expression data and the relatively high correlation between genes are often encountered, so traditional distances such as Euclidean distance may not be effective at discriminating the biological differences between samples. In this study, we developed a novel computational method to assess the biological differences based on pathways by assuming that ontologically defined biological pathways in biologically similar samples have similar behavior. Application of this distance score results in more accurate, robust, and biologically meaningful clustering results in both ...


Exploring The Ipf Lung Through The Lens Of Single Cell Rna Sequencing, Taylor Adams, Jonas Schupp 2019 Yale School of Medicine

Exploring The Ipf Lung Through The Lens Of Single Cell Rna Sequencing, Taylor Adams, Jonas Schupp

Yale Day of Data

This poster illustrates the differences between the IPF disease-specific variety of lung macrophages and the two varieties of macrophages known to reside in the normal human lung.


Debrowser: Interactive Differential Expression Analysis And Visualization Tool For Count Data, Alper Kucukural, Onur Yukselen, Deniz M. Ozata, Melissa J. Moore, Manuel Garber 2019 University of Massachusetts Medical School

Debrowser: Interactive Differential Expression Analysis And Visualization Tool For Count Data, Alper Kucukural, Onur Yukselen, Deniz M. Ozata, Melissa J. Moore, Manuel Garber

Program in Bioinformatics and Integrative Biology Publications and Presentations

BACKGROUND: Sequencing data has become a standard measure of diverse cellular activities. For example, gene expression is accurately measured by RNA sequencing (RNA-Seq) libraries, protein-DNA interactions are captured by chromatin immunoprecipitation sequencing (ChIP-Seq), protein-RNA interactions by crosslinking immunoprecipitation sequencing (CLIP-Seq) or RNA immunoprecipitation (RIP-Seq) sequencing, DNA accessibility by assay for transposase-accessible chromatin (ATAC-Seq), DNase or MNase sequencing libraries. The processing of these sequencing techniques involves library-specific approaches. However, in all cases, once the sequencing libraries are processed, the result is a count table specifying the estimated number of reads originating from each genomic locus. Differential analysis to determine which loci ...


Undergraduates Contain Multitudes: Course-Based Metagenomics Analysis Using Dna Subway Purple Line, Ray A. Enke 2018 Selected Works

Undergraduates Contain Multitudes: Course-Based Metagenomics Analysis Using Dna Subway Purple Line, Ray A. Enke

Ray Enke Ph.D.

No abstract provided.


The Trim-Nhl Protein Nhl-2 Is A Co-Factor In The Nuclear And Somatic Rnai Pathways In C. Elegans, Gregory M. Davis, Shikui Tu, Jacqueline A. Wilce, Julie M. Claycomb, Zhiping Weng, Peter R. Boag 2018 Federation University

The Trim-Nhl Protein Nhl-2 Is A Co-Factor In The Nuclear And Somatic Rnai Pathways In C. Elegans, Gregory M. Davis, Shikui Tu, Jacqueline A. Wilce, Julie M. Claycomb, Zhiping Weng, Peter R. Boag

Program in Bioinformatics and Integrative Biology Publications and Presentations

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 ...


Hla-Do Modulates The Diversity Of The Mhc-Ii Self-Peptidome, Padma P. Nanaware, Mollie M. Jurewicz, John D. Leszyk, Scott A. Shaffer, Lawrence J. Stern 2018 University of Massachusetts Medical School

Hla-Do Modulates The Diversity Of The Mhc-Ii Self-Peptidome, Padma P. Nanaware, Mollie M. Jurewicz, John D. Leszyk, Scott A. Shaffer, Lawrence J. Stern

Open Access Articles

Presentation of antigenic peptides on MHC-II molecules is essential for tolerance to self and for initiation of immune responses against foreign antigens. DO (HLA-DO in humans, H2-O in mice) is a non-classical MHC-II protein that has been implicated in control of autoimmunity and regulation of neutralizing antibody responses to viruses. These effects likely are related to a role of DO in selecting MHC-II epitopes, but previous studies examining the effect of DO on presentation of selected CD4 T cell epitopes have been contradictory. To understand how DO modulates MHC-II antigen presentation, we characterized the full spectrum of peptides presented by ...


Dmk_Dissertation_11.19.18.Pdf, Dana King 2018 Washington University in St. Louis

Dmk_Dissertation_11.19.18.Pdf, Dana King

Dana King

No abstract provided.


Dmk_Dissertation_11.19.18.Pdf, Dana King 2018 Washington University in St. Louis

Dmk_Dissertation_11.19.18.Pdf, Dana King

Dana King

No abstract provided.


Genome-Wide Crispr Screens For Shiga Toxins And Ricin Reveal Golgi Proteins Critical For Glycosylation, Songhai Tian, Khaja Muneeruddin, Mei Yuk Choi, Liang Tao, Robiul H. Bhuiyan, Yuhsuke Ohmi, Keiko Furukawa, Koichi Furukawa, Sebastian Boland, Scott A. Shaffer, Rosalyn M. Adam, Min Dong 2018 Harvard Medical School

Genome-Wide Crispr Screens For Shiga Toxins And Ricin Reveal Golgi Proteins Critical For Glycosylation, Songhai Tian, Khaja Muneeruddin, Mei Yuk Choi, Liang Tao, Robiul H. Bhuiyan, Yuhsuke Ohmi, Keiko Furukawa, Koichi Furukawa, Sebastian Boland, Scott A. Shaffer, Rosalyn M. Adam, Min Dong

Open Access Articles

Glycosylation is a fundamental modification of proteins and membrane lipids. Toxins that utilize glycans as their receptors have served as powerful tools to identify key players in glycosylation processes. Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans. The Stxs screens identified major glycosyltransferases (GTs) and transporters involved in Gb3 biosynthesis, while the ricin screen identified GTs and transporters involved in N-linked ...


Orthogonal Cas9-Cas9 Chimeras Provide A Versatile Platform For Genome Editing, Mehmet F. Bolukbasi, Pengpeng Liu, Kevin Luk, Samantha F. Kwok, Ankit Gupta, Nadia Amrani, Erik J. Sontheimer, Lihua Julie Zhu, Scot A. Wolfe 2018 University of Massachusetts Medical School

Orthogonal Cas9-Cas9 Chimeras Provide A Versatile Platform For Genome Editing, Mehmet F. Bolukbasi, Pengpeng Liu, Kevin Luk, Samantha F. Kwok, Ankit Gupta, Nadia Amrani, Erik J. Sontheimer, Lihua Julie Zhu, Scot A. Wolfe

Open Access Articles

The development of robust, versatile and accurate toolsets is critical to facilitate therapeutic genome editing applications. Here we establish RNA-programmable Cas9-Cas9 chimeras, in single- and dual-nuclease formats, as versatile genome engineering systems. In both of these formats, Cas9-Cas9 fusions display an expanded targeting repertoire and achieve highly specific genome editing. Dual-nuclease Cas9-Cas9 chimeras have distinct advantages over monomeric Cas9s including higher target site activity and the generation of predictable precise deletion products between their target sites. At a therapeutically relevant site within the BCL11A erythroid enhancer, Cas9-Cas9 nucleases produced precise deletions that comprised up to 97% of all sequence alterations ...


Stochastic Difference Model For Evolutional Dynamics Of Large Antigen Repertoires In African Trypanosomes, Fan Yu 2018 Illinois State University

Stochastic Difference Model For Evolutional Dynamics Of Large Antigen Repertoires In African Trypanosomes, Fan Yu

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


The Future Of Biodiversity Assessment: Using Environmental Dna And Next-Generation Sequencing To Characterize Biological Communities In The Central Highlands Of Arizona, Courtney Turner-Rathbone 2018 Embry-Riddle Aeronautical University

The Future Of Biodiversity Assessment: Using Environmental Dna And Next-Generation Sequencing To Characterize Biological Communities In The Central Highlands Of Arizona, Courtney Turner-Rathbone

Undergraduate Research Symposium - Prescott

Historically ecological surveys require significant man hours in the field, utilizing methods which can stress species being observed. In using environmental DNA (eDNA) gathered from air, soil, and water, traditional methods may be supplemented or reduced in order to more efficiently utilize funding and reduce or eliminate stress on surveyed species. Water was collected in replicates using aseptic technique from two different sites, 60 miles apart, along the Verde River. Samples were vacuum filtered within 24 hours through 0.45 μm cellulose nitrate (CN) filters to collect eDNA. DNA extraction from the filters was performed. The polymerase chain reaction (PCR ...


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

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

Open Access Articles

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 that 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. A subset of recursive ...


The Temporal Landscape Of Recursive Splicing During Pol Ii Transcription Elongation In Human Cells, Xiao-Ou Zhang, Yu Fu, Haiwei Mou, Wen Xue, Zhiping Weng 2018 University of Massachusetts Medical School

The Temporal Landscape Of Recursive Splicing During Pol Ii Transcription Elongation In Human Cells, Xiao-Ou Zhang, Yu Fu, Haiwei Mou, Wen Xue, Zhiping Weng

Program in Bioinformatics and Integrative Biology Publications and Presentations

Recursive splicing (RS) is an evolutionarily conserved process of removing long introns via multiple steps of splicing. It was first discovered in Drosophila and recently proven to occur also in humans. The detailed mechanism of recursive splicing is not well understood, in particular, whether it is kinetically coupled with transcription. To investigate the dynamic process that underlies recursive splicing, we systematically characterized 342 RS sites in three human cell types using published time-series data that monitored synchronized Pol II elongation and nascent RNA production with 4-thiouridine labeling. We found that half of the RS events occurred post-transcriptionally with long delays ...


Differential Analysis Of Chromatin Accessibility And Histone Modifications For Predicting Mouse Developmental Enhancers, Shaliu Fu, Qin Wang, Jill E. Moore, Michael J. Purcaro, Henry E. Pratt, Kaili Fan, Cuihua Gu, Cizhong Jiang, Ruixin Zhu, Anshul Kundaje, Aiping Lu, Zhiping Weng 2018 Tongji University,China

Differential Analysis Of Chromatin Accessibility And Histone Modifications For Predicting Mouse Developmental Enhancers, Shaliu Fu, Qin Wang, Jill E. Moore, Michael J. Purcaro, Henry E. Pratt, Kaili Fan, Cuihua Gu, Cizhong Jiang, Ruixin Zhu, Anshul Kundaje, Aiping Lu, Zhiping Weng

Program in Bioinformatics and Integrative Biology Publications and Presentations

Enhancers are distal cis-regulatory elements that modulate gene expression. They are depleted of nucleosomes and enriched in specific histone modifications; thus, calling DNase-seq and histone mark ChIP-seq peaks can predict enhancers. We evaluated nine peak-calling algorithms for predicting enhancers validated by transgenic mouse assays. DNase and H3K27ac peaks were consistently more predictive than H3K4me1/2/3 and H3K9ac peaks. DFilter and Hotspot2 were the best DNase peak callers, while HOMER, MUSIC, MACS2, DFilter and F-seq were the best H3K27ac peak callers. We observed that the differential DNase or H3K27ac signals between two distant tissues increased the area under the precision-recall ...


Open-Source Tools For Dense Facial Tissue Depth Mapping (Ftdm) Of Computed Tomography Models, Terrie Simmons-Ehrhardt, Catyana Falsetti, Anthony B. Falsetti, Christopher J. Ehrhardt 2018 School of World Studies, Virginia Commonwealth University

Open-Source Tools For Dense Facial Tissue Depth Mapping (Ftdm) Of Computed Tomography Models, Terrie Simmons-Ehrhardt, Catyana Falsetti, Anthony B. Falsetti, Christopher J. Ehrhardt

Human Biology Open Access Pre-Prints

Computed tomography (CT) scans provide anthropologists with a resource to generate three- dimensional (3D) digital skeletal material to expand quantification methods and build more standardized reference collections. The ability to visualize and manipulate the bone and skin of the face simultaneously in a 3D digital environment introduces a new way for forensic facial approximation practitioners to access and study the face. Craniofacial relationships can be quantified with landmarks or with surface processing software that can quantify the geometric properties of the entire 3D facial surface. This paper describes tools for the generation of dense facial tissue depth maps (FTDMs) using ...


Drug-Resistance And Population Structure Of Plasmodium Falciparum Across The Democratic Republic Of Congo Using High-Throughput Molecular Inversion Probes, Ozkan Aydemir, Nicholas J. Hathaway, Patrick W. Marsh, Alice Tran, Thomas Reimonn, Jeffrey A. Bailey 2018 University of Massachusetts Medical School

Drug-Resistance And Population Structure Of Plasmodium Falciparum Across The Democratic Republic Of Congo Using High-Throughput Molecular Inversion Probes, Ozkan Aydemir, Nicholas J. Hathaway, Patrick W. Marsh, Alice Tran, Thomas Reimonn, Jeffrey A. Bailey

Open Access Articles

A better understanding of the drivers of the spread of malaria parasites and drug resistance across space and time is needed. These drivers can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations and a set of microsatellites was used to genotype Plasmodium falciparum infections of 552 children from the 2013-2014 Demographic and Health Survey conducted in the Democratic Republic of the Congo (DRC). Microsatellite-based analysis of population structure suggests that parasites within the DRC form a homogeneous population. In contrast, sulfadoxine-resistance markers in dihydropteroate synthase show marked spatial structure with ...


Genetic Architecture Of Gene Expression Traits Across Diverse Populations, Lauren S. Mogil, Angela Andaleon, Alexa Badalamenti, Scott P. Dickinson, Xiuqing Guo, Jerome I. Rotter, W. C. Johnson, Hae Kyung Im, Yongmei Liu, Heather E. Wheeler 2018 Loyola University Chicago

Genetic Architecture Of Gene Expression Traits Across Diverse Populations, Lauren S. Mogil, Angela Andaleon, Alexa Badalamenti, Scott P. Dickinson, Xiuqing Guo, Jerome I. Rotter, W. C. Johnson, Hae Kyung Im, Yongmei Liu, Heather E. Wheeler

Bioinformatics Faculty Publications

For many complex traits, gene regulation is likely to play a crucial mechanistic role. How the genetic architectures of complex traits vary between populations and subsequent effects on genetic prediction are not well understood, in part due to the historical paucity of GWAS in populations of non-European ancestry. We used data from the MESA (Multi-Ethnic Study of Atherosclerosis) cohort to characterize the genetic architecture of gene expression within and between diverse populations. Genotype and monocyte gene expression were available in individuals with African American (AFA, n = 233), Hispanic (HIS, n = 352), and European (CAU, n = 578) ancestry. We performed expression ...


The Transcriptome Of The Bermuda Fireworm Odontosyllis Enopla (Annelida: Syllidae): A Unique Luciferase Gene Family And Putative Epitoky-Related Genes, Mercer R. Brugler, M. Teresa Aguado, Michael Tessler, Mark Siddall 2018 NYC College of Technology (CUNY)

The Transcriptome Of The Bermuda Fireworm Odontosyllis Enopla (Annelida: Syllidae): A Unique Luciferase Gene Family And Putative Epitoky-Related Genes, Mercer R. Brugler, M. Teresa Aguado, Michael Tessler, Mark Siddall

Publications and Research

The Bermuda fireworm Odontosyllis enopla exhibits an extremely tight circalunar circadian behavior that results in an impressive bioluminescent mating swarm, thought to be due to a conventional luciferase-mediated oxidation of a light-emitting luciferin. In addition, the four eyes become hypertrophied and heavily pigmented, and the nephridial system is modified to store and release gametes and associated secretions. In an effort to elucidate transcripts related to bioluminescence, circadian or circalunar periodicity, as well as epitoky-related changes of the eyes and nephridial system, we examined the transcriptomic profile of three female O. enopladuring a bioluminescent swarm in Ferry Reach, Bermuda. Using ...


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