Digital Commons Network^™

Resilience Of S309 And Azd7442 Monoclonal Antibody Treatments Against Infection By Sars-Cov-2 Omicron Lineage Strains, James Brett Case, Samantha Mackin, John M Errico, Zhenlu Chong, Emily A Madden, Bradley Whitener, Ana Jung, Lindsay Droit, Scott A Handley, Daved H Fremont, Herbert W Virgin, Michael S Diamond, Et Al

2020-Current year OA Pubs

Omicron variant strains encode large numbers of changes in the spike protein compared to historical SARS-CoV-2 isolates. Although in vitro studies have suggested that several monoclonal antibody therapies lose neutralizing activity against Omicron variants, the effects in vivo remain largely unknown. Here, we report on the protective efficacy against three SARS-CoV-2 Omicron lineage strains (BA.1, BA.1.1, and BA.2) of two monoclonal antibody therapeutics (S309 [Vir Biotechnology] monotherapy and AZD7442 [AstraZeneca] combination), which correspond to ones used to treat or prevent SARS-CoV-2 infections in humans. Despite losses in neutralization potency in cell culture, S309 or AZD7442 treatments reduced BA.1, BA.1.1, and …

Interim Outcomes Of Mechanical Thrombectomy For Deep Vein Thrombosis From The All-Comer Clout Registry, David J Dexter, Luis Sanchez, Et Al.

2020-Current year OA Pubs

OBJECTIVES: The multicenter, prospective, single arm CLOUT registry assesses the safety and effectiveness of the ClotTriever System (Inari Medical, Irvine, CA) for the treatment of acute and nonacute lower extremity deep vein thrombosis (DVT) in all-comer patients. Reported here are the outcomes of the first 250 patients.

METHODS: All-comer patients with lower extremity DVT were enrolled, including those with bilateral DVT, those with previously failed DVT treatment, and regardless of symptom duration. The primary effectiveness end point is complete or near-complete (≥75%) thrombus removal determined by independent core laboratory-adjudicated Marder scores. Safety outcomes include serious adverse events through 30 days …

Longitudinal Morphological And Functional Characterization Of Human Heart Organoids Using Optical Coherence Tomography, Yixuan Ming, Senyue Hao, Fei Wang, Yonatan R. Lewis-Israeli, Brett D. Volmert, Zhiyao Xu, Anna Goestenkors, Aitor Aguirre, Chao Zhou

2020-Current year OA Pubs

Organoids play an increasingly important role as in vitro models for studying organ development, disease mechanisms, and drug discovery. Organoids are self-organizing, organ-like three-dimensional (3D) cell cultures developing organ-specific cell types and functions. Recently, three groups independently developed self-assembling human heart organoids (hHOs) from human pluripotent stem cells (hPSCs). In this study, we utilized a customized spectral-domain optical coherence tomography (SD-OCT) system to characterize the growth of hHOs. Development of chamber structures and beating patterns of the hHOs were observed via OCT and calcium imaging. We demonstrated the capability of OCT to produce 3D images in a fast, label-free, and …

Recurrent Transcriptional Responses In Aml And Mds Patients Treated With Decitabine, Pawan Upadhyay, Jeremy Beales, Nakul M Shah, Agata Gruszczynska, Christopher A Miller, Allegra A Petti, Sai Mukund Ramakrishnan, Daniel C Link, Timothy J Ley, John S Welch

2020-Current year OA Pubs

The molecular events responsible for decitabine responses in myelodysplastic syndrome and acute myeloid leukemia patients are poorly understood. Decitabine has a short serum half-life and limited stability in tissue culture. Therefore, theoretical pharmacologic differences may exist between patient molecular changes in vitro and the consequences of in vivo treatment. To systematically identify the global genomic and transcriptomic alterations induced by decitabine in vivo, we evaluated primary bone marrow samples that were collected during patient treatment and applied whole-genome bisulfite sequencing, RNA-sequencing, and single-cell RNA sequencing. Decitabine induced global, reversible hypomethylation after 10 days of therapy in all patients, which was …

Safety Of Onasemnogene Abeparvovec For Patients With Spinal Muscular Atrophy 8.5 Kg Or Heavier In A Global Managed Access Program, Deepa H Chand, Susan Mitchell, Rui Sun, Nicole Lamarca, Sandra P Reyna, Thao Sutter

2020-Current year OA Pubs

BACKGROUND: Spinal muscular atrophy is a rare, neurodegenerative disorder caused by biallelic deletions in the survival motor neuron (SMN1) gene. Onasemnogene abeparvovec is a one-time, intravenous gene replacement therapy designed to deliver the SMN1 transgene. Although available in many geographies, it is not approved globally. The Global Managed Access Program (GMAP) expanded treatment access to patients in countries where treatment was not approved. Previous onasemnogene abeparvovec clinical trials included patients with body weight <8.5 kg. Through GMAP, children weighing ≥8.5 kg received onasemnogene abeparvovec. We describe safety data for heavier patients in GMAP.

METHODS: GMAP records were reviewed to identify patients weighing ≥8.5 kg at onasemnogene abeparvovec dosing. To obtain corresponding adverse event (AE) data, the Novartis ARGUS safety database …

Cd1d Expression Demarcates Cdx4+ Hemogenic Mesoderm With Definitive Hematopoietic Potential, J Philip Creamer, Stephanie A Luff, Hao Yu, Christopher M Sturgeon

2020-Current year OA Pubs

To achieve efficient, reproducible differentiation of human pluripotent stem cells (hPSCs) towards specific hematopoietic cell-types, a comprehensive understanding of the necessary cell signaling and developmental trajectories involved is required. Previous studies have identified the mesodermal progenitors of extra-embryonic-like and intra-embryonic-like hemogenic endothelium (HE), via stage-specific WNT and ACTIVIN/NODAL, with GYPA/GYPB (CD235a/b) expression serving as a positive selection marker for mesoderm harboring exclusively extra-embryonic-like hemogenic potential. However, a positive mesodermal cell-surface marker with exclusively intra-embryonic-like hemogenic potential has not been identified. Recently, we reported that early mesodermal expression of CDX4 critically regulates definitive HE specification, suggesting that CDX4 may act in …

Accuracy And Reliability Of Diffusion Imaging Models, Nicole A. Seider, Babatunde Adeyemo, Ryland Miller, Dillan J. Newbold, Jacqueline M. Hampton, Kristen M. Scheidter, Jerrel Rutlin, Timothy O. Laumann, Jarod L. Roland, David F. Montez, Andrew N. Van, Annie Zheng, Scott Marek, Benjamin P. Kay, G. Larry Bretthorst, Yong Wang, Steven E. Petersen, Deanna M. Barch, Evan M. Gordon, Abraham Z. Snyder, Joshua S. Shimony, Nico U. F. Dosenbach

2020-Current year OA Pubs

Diffusion imaging aims to non-invasively characterize the anatomy and integrity of the brain's white matter fibers. We evaluated the accuracy and reliability of commonly used diffusion imaging methods as a function of data quantity and analysis method, using both simulations and highly sampled individual-specific data (927-1442 diffusion weighted images [DWIs] per individual). Diffusion imaging methods that allow for crossing fibers (FSL's BedpostX [BPX], DSI Studio's Constant Solid Angle Q-Ball Imaging [CSA-QBI], MRtrix3's Constrained Spherical Deconvolution [CSD]) estimated excess fibers when insufficient data were present and/or when the data did not match the model priors. To reduce such overfitting, we developed …

Impact Of The Covid-19 Pandemic On Daily Life, Mood, And Behavior Of Adults With Down Syndrome, Sigan L Hartley, Beau M Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Down syndrome population has been disproportionately affected by Coronavirus 2019 (COVID-19) in terms of experiencing severe illness and death. Societal efforts to curb the spread of COVID-19 may also have taken a heavy toll on the daily lives of individuals with Down syndrome.

OBJECTIVE/HYPOTHESIS: The goal of the study was to understand how the COVID-19 pandemic has altered daily life (including residence, employment, and participation in adult disability day programs) and influenced the mood and behavior of adults with Down syndrome.

METHODS: Between September 2020 and February 2021, caregivers of 171 adults with Down syndrome (aged 22-66 years) …

Comparison Of Perioperative Outcomes Among Non-Small Cell Lung Cancer Patients With Neoadjuvant Immune Checkpoint Inhibitor Plus Chemotherapy, Egfr-Tki, And Chemotherapy Alone: A Real-World Evidence Study, Deping Zhao, Long Xu, Junqi Wu, Yunlang She, Hang Su, Likun Hou, Haoran E., Lei Zhang, Francesco Grossi, Melanie P. Subramanian, Anthony W. Kim, Yuming Zhu, Chang Chen

2020-Current year OA Pubs

Background: The utilization of neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy has increased significantly for resectable non-small cell lung cancer (NSCLC). It is still unclear whether such a treatment paradigm affects perioperative outcomes compared with other neoadjuvant treatment. We aimed to evaluate the perioperative outcomes of pulmonary resection after neoadjuvant ICI plus chemotherapy and to compare them with neoadjuvant epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) and neoadjuvant chemotherapy alone for resectable NSCLC.

Methods: A retrospective cohort including 194 stage IB-IIIB NSCLC underwent surgical resection after neoadjuvant treatment between 2018 and 2020 were reviewed. Perioperative complications were evaluated using the …

Performance Of A Multianalyte 'Rule-Out' Assay In Pregnant Individuals With Suspected Preeclampsia, Maged M Costantine, Georges Macones, Et Al

2020-Current year OA Pubs

BACKGROUND: The ability to diagnose preeclampsia clinically is suboptimal. Our objective was to validate a novel multianalyte assay and characterize its performance, when intended for use as an aid to rule-out preeclampsia.

METHODS: Prospective, multicenter cohort study of pregnant individuals presenting between 28

RESULTS: One thousand thirty-six pregnant individuals were enrolled in the study cohort with an incidence of preeclampsia of 30.3% (27.6%-33.2%). The time to develop preeclampsia was shorter for those with an at-risk compared with negative assay result (log-rank

CONCLUSIONS: We confirmed that a novel multianalyte assay was associated with the time to develop preeclampsia and has a …

Risk Of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage, Andrew J Durnford, Ridhima Guniganti, Akash P Kansagra, Gregory J Zipfel, Et Al

2020-Current year OA Pubs

BACKGROUND: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage.

METHODS: Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time …

Gan Training Acceleration Using Frechet Descriptor-Based Coreset, Yanzhe Xu, Teresa Wu, Jennifer R. Charlton, Kevin M. Bennett

2020-Current year OA Pubs

No abstract provided.

Design Of A Randomized, Placebo-Controlled, Phase 3 Trial Of Tofersen Initiated In Clinically Presymptomatic Sod1 Variant Carriers: The Atlas Study, Michael Benatar, Robert C Bucelli, Et Al.

2020-Current year OA Pubs

Despite extensive research, amyotrophic lateral sclerosis (ALS) remains a progressive and invariably fatal neurodegenerative disease. Limited knowledge of the underlying causes of ALS has made it difficult to target upstream biological mechanisms of disease, and therapeutic interventions are usually administered relatively late in the course of disease. Genetic forms of ALS offer a unique opportunity for therapeutic development, as genetic associations may reveal potential insights into disease etiology. Genetic ALS may also be amenable to investigating earlier intervention given the possibility of identifying clinically presymptomatic, at-risk individuals with causative genetic variants. There is increasing evidence for a presymptomatic phase of …

Assessment Of Ethno-Racial And Insurance-Based Disparities In Pediatric Forearm And Tibial Fracture Care In The United States, Andrew J Landau, Afolayan K Oladeji, Pooya Hosseinzadeh

2020-Current year OA Pubs

INTRODUCTION: Despite growing attention to healthcare disparities and interventions to improve inequalities, additional identification of disparities is needed, particularly in the pediatric population. We used state and nationwide databases to identify factors associated with the surgical treatment of pediatric forearm and tibial fractures.

METHODS: The Healthcare Cost and Utilization Project State Inpatient, Emergency Department, and Ambulatory Surgery and Services Databases from four US states and the Nationwide Emergency Department Sample database were quarried using International Classification of Diseases codes to identify patients from 2006 to 2015. Multivariable regression models were used to determine factors associated with surgical treatment.

RESULTS: State …

Technical Note: Institutional Solution Of Clinical Cine Mri For Tumor Motion Evaluation In Radiotherapy, Taeho Kim, Yu Wu, Zhen Ji, H Michael Gach, Nels Knutson, Stacie Mackey, Matthew Schmidt

2020-Current year OA Pubs

PURPOSE: Since 4D-MRI is inadequate to capture dynamic respiratory variations, real-time cinematographic (cine) MRI is actively used in MR-guided radiotherapy (MRgRT) for tumor motion evaluation, delineation, and tracking. However, most radiotherapy imaging platforms do not support the format of cine MRI from clinical MRI systems. This study developed an institutional solution of clinical cine MRI for tumor motion evaluation in radiotherapy applications.

METHODS: Cine MRI manipulation software (called Cine Viewer) was developed within a commercial Treatment Planning System (TPS). It consists of (1) single/orthogonal viewers, (2) display controllers, (3) measurement grids/markers, and (4) manual contouring tools.

RESULTS: The institutional solution …

Neurological Complications And Recovery Rates Of Patients With Adult Cervical Deformity Surgeries, Han Jo Kim, Yu-Cheng Yao, Christopher I. Shaffrey, Justin S. Smith, Michael P. Kelly, Munish Gupta, Todd J. Albert, Themistocles S. Protopsaltis, Gregory M. Mundis, Peter Passias, Eric Klineberg, Shay Bess, Virginie Lafage, Christopher P. Ames, International Spine Study Group

2020-Current year OA Pubs

STUDY DESIGN: Retrospective cohort study.

OBJECTIVE: This study aims to report the incidence, risk factors, and recovery rate of neurological complications (NC) in patients with adult cervical deformity (ACD) who underwent corrective surgery.

METHODS: ACD patients undergoing surgery from 2013 to 2015 were enrolled in a prospective, multicenter database. Patients were separated into 2 groups according to the presence of neurological complications (NC vs no-NC groups). The types, timing, recovery patterns, and interventions for NC were recorded. Patients' demographics, surgical details, radiographic parameters, and health-related quality of life (HRQOL) scores were compared.

RESULTS: 106 patients were prospectively included. Average age …

Outcomes After Intracranial Rescue Stenting For Acute Ischemic Stroke, Christine Tschoe, Joshua Osbun, Et Al.

2020-Current year OA Pubs

BACKGROUND: In cases of failed recanalization despite modern mechanical thrombectomy (MT) techniques, intracranial rescue stenting (RS) may be beneficial. However, outcomes and complications of RS relative to the natural history of ongoing emergent large vessel occlusion are unknown. To evaluate whether RS for ongoing emergent large vessel occlusion after failed MT achieves superior outcomes to the natural history of persistent emergent large vessel occlusion.

METHODS: Patients from the Stroke Thrombectomy and Aneurysm Registry who underwent RS after failed MT from 2014 to 2019 were analyzed. For outcome comparisons, patients were screened for inclusion/exclusion criteria of 3 major randomized, controlled MT …

Addressing Futility: A Practical Approach, Piroska K. Kopar, Adrienne Visani, Kyler Squirrell, Douglas E. Brown

2020-Current year OA Pubs

UNLABELLED: Limiting or withdrawing nonbeneficial medical care is considered ethically responsible throughout most of critical care and medical ethics literature. Practically, however, setting limits to treatment is often challenging. We review the literature to identify best practices for using the definition of futility as an anchoring concept to aid the ethical practice of ICU clinicians.

DATA SOURCES: Source data were obtained from a PubMed literature review.

STUDY SELECTION: English language articles were chosen based on relevance to medical futility ethics, end-of-life care in the ICU, or communication and conflict mitigation strategies.

DATA EXTRACTION: Independent evaluation of selected articles for recurrent …

Infection And Inflammation: New Perspectives On Alzheimer's Disease, Heather E Whitson, Robyn S Klein, Et Al.

2020-Current year OA Pubs

Neuroinflammation has been recognized as a component of Alzheimer's Disease (AD) pathology since the original descriptions by Alois Alzheimer and a role for infections in AD pathogenesis has long been hypothesized. More recently, this hypothesis has gained strength as human genetics and experimental data suggest key roles for inflammatory cells in AD pathogenesis. To review this topic, Duke/University of North Carolina (Duke/UNC) Alzheimer's Disease Research Center hosted a virtual symposium: "Infection and Inflammation: New Perspectives on Alzheimer's Disease (AD)." Participants considered current evidence for and against the hypothesis that AD could be caused or exacerbated by infection or commensal microbes. …

Is Combined Surgical Dislocation And Proximal Femoral Osteotomy A Safe Procedure For Correction Of Complex Hip Deformities?, Frank W Parilla, Jeffrey J Nepple, Gail E Pashos, Perry L Schoenecker, John C Clohisy

2020-Current year OA Pubs

Complex deformities of the hip requiring intra-articular and proximal femoral correction are challenging with regard to surgical access and complication risk. Combined surgical dislocation and proximal femoral osteotomy (SD/PFO) is a surgical strategy that provides unrestricted access to the joint with the capability for adjunctive PFO. Although providing excellent surgical access, concerns over a potentially high risk of postoperative complications remain, and published information on the safety of this technique remain scarce. In this study, we defined the early complication profile of combined surgery across 48 hips with a variety of complex deformities using a standardized, validated complication grading scheme …

Environmental Conditions To Promote Healthy Childhood Brain/Behavioral Development: Informing Early Preventive Interventions For Delivery In Routine Care, Joan L Luby, Cynthia Rogers, Katie A Mclaughlin

2020-Current year OA Pubs

Environmental experiences early in life have strong and enduring consequences for cognitive, emotional, and neurobiological development and related physical and mental health trajectories. The powerful influence of early caregiver nurturance and stimulation on promoting positive neurodevelopmental outcomes has been demonstrated across species. These findings elucidate the environmental conditions known to facilitate healthy neurodevelopment and underscore the potential for modifiable psychosocial factors in the environment to be harnessed to inform early preventive interventions to promote health and adaptive development. A framework for early preventive interventions to enhance nurturing and responsive caregiving for implementation during early sensitive periods of brain development delivered …

A Staged Reconstruction Technique Utilizing Bioprosthetic Mesh Reinforcement In The Repair Of Giant Omphalocele, Annahita R. Fotouhi, Justin M. Sacks, Martin S. Keller, Kamlesh B. Patel

2020-Current year OA Pubs

No abstract provided.

Online Learning For Infectious Disease Fellows-A Needs Assessment, Miguel A Chavez, Nathanial S Nolan, Emily Gleason, Saman Nematollahi, Emily Abdoler, Gerome Escota

2020-Current year OA Pubs

BACKGROUND: Online resources and social media have become increasingly ubiquitous in medical education. Little is known about the need for educational resources aimed at infectious disease (ID) fellows.

METHODS: We conducted an educational needs assessment through a survey that aimed to describe ID fellows' current use of online and social media tools, assess the value of online learning, and identify the educational content preferred by ID fellows. We subsequently convened focus groups with ID fellows to explore how digital tools contribute to fellow learning.

RESULTS: A total of 110 ID fellows responded to the survey. Over half were second-year fellows …

Changes In Adiposity Over The Life Course And Gene Expression In Postmenopausal Women, Yunan Han, Graham A Colditz, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Early life adiposity and changes in adiposity over the life course are associated with mammographic breast density among postmenopausal women. However, the underlying mechanisms are unknown; therefore, we comprehensively examined the associations of early life body mass index (BMI) and changes in BMI from ages 10, 18 to age at mammogram with growth factor, RANK pathway, and sex hormone gene expression in 372 postmenopausal women.

METHODS: We estimated early life BMI at age 10 using the validated 9-level Stunkard pictogram. We calculated BMI at other ages (18, 30, and current age at mammogram) by dividing weight in kilograms at …

Comparative Effectiveness Of Diversion Of Cerebrospinal Fluid For Children With Severe Traumatic Brain Injury, Michael J Bell, Jose Pineda, Et Al.

2020-Current year OA Pubs

Importance: Diversion of cerebrospinal fluid (CSF) has been used for decades as a treatment for children with severe traumatic brain injury (TBI) and is recommended by evidenced-based guidelines. However, these recommendations are based on limited studies.

Objective: To determine whether CSF diversion is associated with improved Glasgow Outcome Score-Extended for Pediatrics (GOS-EP) and decreased intracranial pressure (ICP) in children with severe TBI.

Design, Setting, and Participants: This observational comparative effectiveness study was performed at 51 clinical centers that routinely care for children with severe TBI in 8 countries (US, United Kingdom, Spain, the Netherlands, Australia, New Zealand, South Africa, and …

Treatment Patterns And Standardized Outcome Assessments Among Patients With Inflammatory Conditions Of The Pouch In A Prospective Multicenter Registry, Edward L Barnes, Parakkal Deepak, Poonam Beniwal-Patel, Laura Raffals, Maia Kayal, Marla Dubinsky, Shannon Chang, Peter D R Higgins, Jennifer I Barr, Joseph Galanko, Yue Jiang, Raymond K Cross, Millie D Long, Hans H Herfarth

2020-Current year OA Pubs

BACKGROUND: Much of our understanding about the natural history of pouch-related disorders has been generated from selected populations. We designed a geographically diverse, prospective registry to study the disease course among patients with 1 of 4 inflammatory conditions of the pouch. The primary objectives in this study were to demonstrate the feasibility of a prospective pouch registry and to evaluate the predominant treatment patterns for pouch-related disorders.

METHODS: We used standardized diagnostic criteria to prospectively enroll patients with acute pouchitis, chronic antibiotic-dependent pouchitis (CADP), chronic antibiotic refractory pouchitis (CARP), or Crohn's disease (CD) of the pouch. We obtained detailed clinical …

Prophetic Eu: Prospective Identification Of Pneumonia In Hospitalized Patients In The Intensive Care Unit In European And United States Cohorts, Stephen P Bergin, Marin H Kollef, Et Al.

2020-Current year OA Pubs

BACKGROUND: The prospective identification of patients at high risk for hospital-acquired/ventilator-associated bacterial pneumonia may improve clinical trial feasibility and foster antibacterial development. In a prior study conducted in the United States, clinical criteria were used to prospectively identify these patients; however, these criteria have not been applied in a European population.

METHODS: Adults considered high risk for pneumonia (treatment with ventilation or high levels of supplemental oxygen) in the intensive care units of 7 European hospitals were prospectively enrolled from June 12 to December 27, 2017. We estimated the proportion of high-risk patients developing pneumonia according to US Food and …

Association Between The Covid-19 Pandemic And Insurance-Based Disparities In Mortality After Major Surgery Among Us Adults, Laurent G Glance, Andrew W Dick, Ernie Shippey, Patrick J Mccormick, Richard Dutton, Patricia W Stone, Jingjing Shang, Stewart J Lustik, Heather L Lander, Igor Gosev, Karen E Joynt Maddox

2020-Current year OA Pubs

Importance: The COVID-19 pandemic caused significant disruptions in surgical care. Whether these disruptions disproportionately impacted economically disadvantaged individuals is unknown.

Objective: To evaluate the association between the COVID-19 pandemic and mortality after major surgery among patients with Medicaid insurance or without insurance compared with patients with commercial insurance.

Design, Setting, and Participants: This cross-sectional study used data from the Vizient Clinical Database for patients who underwent major surgery at hospitals in the US between January 1, 2018, and May 31, 2020.

Exposures: The hospital proportion of patients with COVID-19 during the first wave of COVID-19 cases between March 1 and …

Motor Network Reorganization Induced In Chronic Stroke Patients With The Use Of A Contralesionally-Controlled Brain Computer Interface, Joseph B. Humphries, Daniela J S Mattos, Jerrel Rutlin, Andy G S Daniel, Kathleen Rybczynski, Theresa Notestine, Joshua S. Shimony, Harold Burton, Alexandre Carter, Eric C. Leuthardt

2020-Current year OA Pubs

No abstract provided.

Epigenomic Analysis Reveals Prevalent Contribution Of Transposable Elements To Cis-Regulatory Elements, Tissue-Specific Expression, And Alternative Promoters In Zebrafish, Hyung Joo Lee, Yiran Hou, Ju Heon Maeng, Nakul M Shah, Yujie Chen, Heather A Lawson, Hongbo Yang, Feng Yue, Ting Wang

2020-Current year OA Pubs

Transposable elements (TEs) encode regulatory elements that impact gene expression in multiple species, yet a comprehensive analysis of zebrafish TEs in the context of gene regulation is lacking. Here, we systematically investigate the epigenomic and transcriptomic landscape of TEs across 11 adult zebrafish tissues using multidimensional sequencing data. We find that TEs contribute substantially to a diverse array of regulatory elements in the zebrafish genome and that 37% of TEs are positioned in active regulatory states in adult zebrafish tissues. We identify TE subfamilies enriched in highly specific regulatory elements among different tissues. We use transcript assembly to discover TE-derived …