Medicine and Health Sciences Commons^™

Phantasus, A Web Application For Visual And Interactive Gene Expression Analysis, Maksim Kleverov, Daria Zenkova, Vladislav Kamenev, Margarita Sablina, Maxim N Artyomov, Alexey A Sergushichev

2020-Current year OA Pubs

Transcriptomic profiling became a standard approach to quantify a cell state, which led to the accumulation of huge amount of public gene expression datasets. However, both reuse of these datasets or analysis of newly generated ones requires significant technical expertise. Here, we present Phantasus: a user-friendly web application for interactive gene expression analysis which provides a streamlined access to more than 96,000 public gene expression datasets, as well as allows analysis of user-uploaded datasets. Phantasus integrates an intuitive and highly interactive JavaScript-based heatmap interface with an ability to run sophisticated R-based analysis methods. Overall Phantasus allows users to go all …

Measuring Accuracy Of Dolphin Imaging Software In Predicting Upper Jaw Soft Tissue Profile Changes In Class Ii Adult Patients Treated With Extraction Versus Non-Extraction., Amr Amin Arif, Esam Nasef, Amira Aboalnaga

Future Dental Journal

Abstract

Objective: To assess the accuracy of Dolphin Imaging software in predicting upper jaw profile changes in class II patients treated by extraction and non-extraction.

Methods: The records of 60 Class II div 1 patients were selected; 30 patients treated by extraction of upper first premolar and 30 patients treated by non-extraction. The Pre- and post-treatment lateral cephalometric x-rays of each patient were traced using Dolphin software. The actual hard tissue changes due to treatment were calculated and installed into the prediction module to generate the predicted profile. The soft tissue measurements of the actual post-treatment and predicted profiles were …

Single-Nucleotide Variant Calling In Single-Cell Sequencing Data With Monopogen, Jinzhuang Dou, Li Ding, Et Al.

2020-Current year OA Pubs

Single-cell omics technologies enable molecular characterization of diverse cell types and states, but how the resulting transcriptional and epigenetic profiles depend on the cell's genetic background remains understudied. We describe Monopogen, a computational tool to detect single-nucleotide variants (SNVs) from single-cell sequencing data. Monopogen leverages linkage disequilibrium from external reference panels to identify germline SNVs and detects putative somatic SNVs using allele cosegregating patterns at the cell population level. It can identify 100 K to 3 M germline SNVs achieving a genotyping accuracy of 95%, together with hundreds of putative somatic SNVs. Monopogen-derived genotypes enable global and local ancestry inference …

Arch: Improving The Performance Of Clonal Hematopoiesis Variant Calling And Interpretation, Irenaeus C C Chan, Alex Panchot, Evelyn Schmidt, Brian J Wiley, Jie Liu, Kimberly Turner, Duc Tran, J Scott Beeler, Armel Landry Batchi-Bouyou, Daniel C Link, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

MOTIVATION: The acquisition of somatic mutations in hematopoietic stem and progenitor stem cells with resultant clonal expansion, termed clonal hematopoiesis (CH), is associated with increased risk of hematologic malignancies and other adverse outcomes. CH is generally present at low allelic fractions, but clonal expansion and acquisition of additional mutations leads to hematologic cancers in a small proportion of individuals. With high depth and high sensitivity sequencing, CH can be detected in most adults and its clonal trajectory mapped over time. However, accurate CH variant calling is challenging due to the difficulty in distinguishing low frequency CH mutations from sequencing artifacts. …

Hecatomb: An Integrated Software Platform For Viral Metagenomics, Michael J Roach, Sarah J Beecroft, Kathie A Mihindukulasuriya, Leran Wang, Anne Paredes, Luis Alberto Chica Cárdenas, Kara Henry-Cocks, Lais Farias Oliveira Lima, Elizabeth A Dinsdale, Robert A Edwards, Scott A Handley

2020-Current year OA Pubs

BACKGROUND: Modern sequencing technologies offer extraordinary opportunities for virus discovery and virome analysis. Annotation of viral sequences from metagenomic data requires a complex series of steps to ensure accurate annotation of individual reads and assembled contigs. In addition, varying study designs will require project-specific statistical analyses.

FINDINGS: Here we introduce Hecatomb, a bioinformatic platform coordinating commonly used tasks required for virome analysis. Hecatomb means "a great sacrifice." In this setting, Hecatomb is "sacrificing" false-positive viral annotations using extensive quality control and tiered-database searches. Hecatomb processes metagenomic data obtained from both short- and long-read sequencing technologies, providing annotations to individual sequences …

Sc2menetdrug: A Computational Tool To Uncover Inter-Cell Signaling Targets And Identify Relevant Drugs Based On Single Cell Rna-Seq Data, Jiarui Feng, S. Peter Goedegebuure, Amanda Zeng, Ye Bi, Ting Wang, Philip Payne, Li Ding, David Denardo, William Hawkins, Ryan C. Fields, Fuhai Li

2020-Current year OA Pubs

Single-cell RNA sequencing (scRNA-seq) is a powerful technology to investigate the transcriptional programs in stromal, immune, and disease cells, like tumor cells or neurons within the Alzheimer's Disease (AD) brain or tumor microenvironment (ME) or niche. Cell-cell communications within ME play important roles in disease progression and immunotherapy response and are novel and critical therapeutic targets. Though many tools of scRNA-seq analysis have been developed to investigate the heterogeneity and sub-populations of cells, few were designed for uncovering cell-cell communications of ME and predicting the potentially effective drugs to inhibit the communications. Moreover, the data analysis processes of discovering signaling …

Automated Large Vessel Occlusion Detection Software And Thrombectomy Treatment Times: A Cluster Randomized Clinical Trial, Juan Carlos Martinez-Gutierrez, Youngran Kim, Sergio Salazar-Marioni, Muhammad Bilal Tariq, Rania Abdelkhaleq, Arash Niktabe, Anjan N Ballekere, Ananya S Iyyangar, Mai Le, Hussain Azeem, Charles C Miller, Jon E Tyson, Sandi Shaw, Peri Smith, Mallory Cowan, Isabel Gonzales, Louise D Mccullough, Andrew D Barreto, Luca Giancardo, Sunil A Sheth

Journal Articles

IMPORTANCE: The benefit of endovascular stroke therapy (EVT) in large vessel occlusion (LVO) ischemic stroke is highly time dependent. Process improvements to accelerate in-hospital workflows are critical.

OBJECTIVE: to determine whether automated computed tomography (CT) angiogram interpretation coupled with secure group messaging can improve in-hospital EVT workflows.

DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized stepped-wedge clinical trial took place from January 1, 2021, through February 27, 2022, at 4 comprehensive stroke centers (CSCs) in the greater Houston, Texas, area. All 443 participants with LVO stroke who presented through the emergency department were treated with EVT at the 4 CSCs. Exclusion …

Automated Large Vessel Occlusion Detection Software And Thrombectomy Treatment Times: A Cluster Randomized Clinical Trial, Juan Carlos Martinez-Gutierrez, Youngran Kim, Sergio Salazar-Marioni, Muhammad Bilal Tariq, Rania Abdelkhaleq, Arash Niktabe, Anjan N Ballekere, Ananya S Iyyangar, Mai Le, Hussain Azeem, Charles C Miller, Jon E Tyson, Sandi Shaw, Peri Smith, Mallory Cowan, Isabel Gonzales, Louise D Mccullough, Andrew D Barreto, Luca Giancardo, Sunil A Sheth

Journal Articles

Importance

The benefit of endovascular stroke therapy (EVT) in large vessel occlusion (LVO) ischemic stroke is highly time dependent. Process improvements to accelerate in-hospital workflows are critical.

Objective

To determine whether automated computed tomography (CT) angiogram interpretation coupled with secure group messaging can improve in-hospital EVT workflows.

Design, Setting, and Participants

This cluster randomized stepped-wedge clinical trial took place from January 1, 2021, through February 27, 2022, at 4 comprehensive stroke centers (CSCs) in the greater Houston, Texas, area. All 443 participants with LVO stroke who presented through the emergency department were treated with EVT at the 4 CSCs. Exclusion …

Accuracy And Reliability Of Chatbot Responses To Physician Questions, Rachel S Goodman, Isik Turker, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Natural language processing tools, such as ChatGPT (generative pretrained transformer, hereafter referred to as chatbot), have the potential to radically enhance the accessibility of medical information for health professionals and patients. Assessing the safety and efficacy of these tools in answering physician-generated questions is critical to determining their suitability in clinical settings, facilitating complex decision-making, and optimizing health care efficiency.

OBJECTIVE: To assess the accuracy and comprehensiveness of chatbot-generated responses to physician-developed medical queries, highlighting the reliability and limitations of artificial intelligence-generated medical information.

DESIGN, SETTING, AND PARTICIPANTS: Thirty-three physicians across 17 specialties generated 284 medical questions that they …

Comprehensive Mr Imaging Qa Of 0.35 T Mr-Linac Using A Multi-Purpose Large Fov Phantom: A Single-Institution Experience, Shanti Marasini, Hailei Zhang, Lara Dyke, Mike Cole, Benjamin Quinn, Austen Curcuru, Bruce Gu, Rocco Flores, Taeho Kim

2020-Current year OA Pubs

PURPOSE: Magnetic resonance-guided radiotherapy (MRgRT) is desired for the treatment of diseases in the abdominothoracic region, which has a broad imaging area and continuous motion. To ensure accurate treatment delivery, an effective image quality assurance (QA) program, with a phantom that covers the field of view (FOV) similar to a human torso, is required. However, routine image QA for a large FOV is not readily available at many MRgRT centers. In this work, we present the clinical experience of the large FOV MRgRT Insight phantom for periodic daily and monthly comprehensive magnetic resonance imaging (MRI)-QA and its feasibility compared to …

Virtual Blebbistatin: A Robust And Rapid Software Approach To Motion Artifact Removal In Optical Mapping Of Cardiomyocytes, Louis G Woodhams, Jingxuan Guo, David Schuftan, John J Boyle, Kenneth M Pryse, Elliot L Elson, Nathaniel Huebsch, Guy M Genin

2020-Current year OA Pubs

Fluorescent reporters of cardiac electrophysiology provide valuable information on heart cell and tissue function. However, motion artifacts caused by cardiac muscle contraction interfere with accurate measurement of fluorescence signals. Although drugs such as blebbistatin can be applied to stop cardiac tissue from contracting by uncoupling calcium-contraction, their usage prevents the study of excitation-contraction coupling and, as we show, impacts cellular structure. We therefore developed a robust method to remove motion computationally from images of contracting cardiac muscle and to map fluorescent reporters of cardiac electrophysiological activity onto images of undeformed tissue. When validated on cardiomyocytes derived from human induced pluripotent …

Acorn: An R Package For De Novo Variant Analysis, Tychele N Turner

2020-Current year OA Pubs

BACKGROUND: The study of de novo variation is important for assessing biological characteristics of new variation and for studies related to human phenotypes. Software programs exist to call de novo variants and programs also exist to test the burden of these variants in genomic regions; however, I am unaware of a program that fits in between these two aspects of de novo variant assessment. This intermediate space is important for assessing the quality of de novo variants and to understand the characteristics of the callsets. For this reason, I developed an R package called acorn.

RESULTS: Acorn is an R …

Shephard: A Modular And Extensible Software Architecture For Analyzing And Annotating Large Protein Datasets, Garrett M Ginell, Aidan J Flynn, Alex S Holehouse

2020-Current year OA Pubs

MOTIVATION: The emergence of high-throughput experiments and high-resolution computational predictions has led to an explosion in the quality and volume of protein sequence annotations at proteomic scales. Unfortunately, sanity checking, integrating, and analyzing complex sequence annotations remains logistically challenging and introduces a major barrier to entry for even superficial integrative bioinformatics.

RESULTS: To address this technical burden, we have developed SHEPHARD, a Python framework that trivializes large-scale integrative protein bioinformatics. SHEPHARD combines an object-oriented hierarchical data structure with database-like features, enabling programmatic annotation, integration, and analysis of complex datatypes. Importantly SHEPHARD is easy to use and enables a Pythonic interrogation …

Mird Pamphlet No. 28, Part 2: Comparative Evaluation Of Mirdcalc Dosimetry Software Across A Compendium Of Diagnostic Radiopharmaceuticals, Lukas M Carter, Juan C Ocampo Ramos, Edmond A Olguin, Justin L Brown, Daniel Lafontaine, Derek W Jokisch, Wesley E Bolch, Adam L Kesner

Journal Articles

Radiopharmaceutical dosimetry is usually estimated via organ-level MIRD schema-style formalisms, which form the computational basis for commonly used clinical and research dosimetry software. Recently, MIRDcalc internal dosimetry software was developed to provide a freely available organ-level dosimetry solution that incorporates up-to-date models of human anatomy, addresses uncertainty in radiopharmaceutical biokinetics and patient organ masses, and offers a 1-screen user interface as well as quality assurance tools. The present work describes the validation of MIRDcalc and, secondarily, provides a compendium of radiopharmaceutical dose coefficients obtained with MIRDcalc. Biokinetic data for about 70 currently and historically used radiopharmaceuticals were obtained from the …

Mird Pamphlet No. 28, Part 1: Mirdcalc-A Software Tool For Medical Internal Radiation Dosimetry, Adam L Kesner, Lukas M Carter, Juan C Ocampo Ramos, Daniel Lafontaine, Edmond A Olguin, Justin L Brown, Bonnie President, Derek W Jokisch, Darrell R Fisher, Wesley E Bolch

Journal Articles

Medical internal radiation dosimetry constitutes a fundamental aspect of diagnosis, treatment, optimization, and safety in nuclear medicine. The MIRD committee of the Society of Nuclear Medicine and Medical Imaging developed a new computational tool to support organ-level and suborgan tissue dosimetry (MIRDcalc, version 1). Based on a standard Excel spreadsheet platform, MIRDcalc provides enhanced capabilities to facilitate radiopharmaceutical internal dosimetry. This new computational tool implements the well-established MIRD schema for internal dosimetry. The spreadsheet incorporates a significantly enhanced database comprising details for 333 radionuclides, 12 phantom reference models (International Commission on Radiological Protection), 81 source regions, and 48 target regions, …

Finding Motifs Using Dna Images Derived From Sparse Representations, Shane K Chu, Gary D Stormo

2020-Current year OA Pubs

MOTIVATION: Motifs play a crucial role in computational biology, as they provide valuable information about the binding specificity of proteins. However, conventional motif discovery methods typically rely on simple combinatoric or probabilistic approaches, which can be biased by heuristics such as substring-masking for multiple motif discovery. In recent years, deep neural networks have become increasingly popular for motif discovery, as they are capable of capturing complex patterns in data. Nonetheless, inferring motifs from neural networks remains a challenging problem, both from a modeling and computational standpoint, despite the success of these networks in supervised learning tasks.

RESULTS: We present a …

Simple Combination Of Multiple Somatic Variant Callers To Increase Accuracy., Alexander J Trevarton, Jeffrey T Chang, W Fraser Symmans

Journal Articles

Publications comparing variant caller algorithms present discordant results with contradictory rankings. Caller performances are inconsistent and wide ranging, and dependent upon input data, application, parameter settings, and evaluation metric. With no single variant caller emerging as a superior standard, combinations or ensembles of variant callers have appeared in the literature. In this study, a whole genome somatic reference standard was used to derive principles to guide strategies for combining variant calls. Then, manually annotated variants called from the whole exome sequencing of a tumor were used to corroborate these general principles. Finally, we examined the ability of these principles to …

Comparing Genomic And Epigenomic Features Across Species Using The Washu Comparative Epigenome Browser, Xiaoyu Zhuo, Silas Hsu, Deepak Purushotham, Prashant Kumar Kuntala, Jessica K Harrison, Alan Y Du, Samuel Chen, Daofeng Li, Ting Wang

2020-Current year OA Pubs

Genome browsers have become an intuitive and critical tool to visualize and analyze genomic features and data. Conventional genome browsers display data/annotations on a single reference genome/assembly; there are also genomic alignment viewer/browsers that help users visualize alignment, mismatch, and rearrangement between syntenic regions. However, there is a growing need for a comparative epigenome browser that can display genomic and epigenomic data sets across different species and enable users to compare them between syntenic regions. Here, we present the WashU Comparative Epigenome Browser. It allows users to load functional genomic data sets/annotations mapped to different genomes and display them over …

Clinical Features And Shared Mechanisms Of Chronic Gastritis And Osteoporosis, Tao Han, Yili Zhang, Baoyu Qi, Ming Chen, Kai Sun, Xiaokuan Qin, Bowen Yang, He Yin, Aili Xu, Xu Wei, Liguo Zhu

Journal Articles

Chronic gastritis (CG) and osteoporosis (OP) are common and occult diseases in the elderly and the relationship of these two diseases have been increasingly exposed. We aimed to explore the clinical characteristics and shared mechanisms of CG patients combined with OP. In the cross-sectional study, all participants were selected from BEYOND study. The CG patients were included and classified into two groups, namely OP group and non-OP group. Univariable and multivariable logistic regression methods were used to evaluate the influencing factors. Furthermore, CG and OP-related genes were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified …

Clinical Application Of A Template-Guided Automated Planning Routine, Matthew C Schmidt, Christopher D Abraham, Jiayi Huang, Clifford G Robinson, Geoffrey Hugo, Nels C Knutson, Baozhou Sun, Chipo Raranje, Erno Sajo, Piotr Zygmanski, Marian Jandel, Peter Szentivanyi, Jessica Hilliard, Jessica Hamilton, Francisco J Reynoso

2020-Current year OA Pubs

PURPOSE: Determine the dosimetric quality and the planning time reduction when utilizing a template-based automated planning application.

METHODS: A software application integrated through the treatment planning system application programing interface, QuickPlan, was developed to facilitate automated planning using configurable templates for contouring, knowledge-based planning structure matching, field design, and algorithm settings. Validations are performed at various levels of the planning procedure and assist in the evaluation of readiness of the CT image, structure set, and plan layout for automated planning. QuickPlan is evaluated dosimetrically against 22 hippocampal-avoidance whole brain radiotherapy patients. The required times to treatment plan generation are compared …

Multi-Ancestry Transcriptome-Wide Association Analyses Yield Insights Into Tobacco Use Biology And Drug Repurposing, Fang Cheng, Xingyan Wang, Seon-Kyeong Jang, Bryan C. Quach, J. Dylan Weissenkampen, Chachrit Khunsriraksakul, Lina Yang, John Blangero, Joanne E. Curran, Ravindranath Duggirala, Juan M. Peralta

School of Medicine Publications and Presentations

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with …

Semantic Wikis As Flexible Database Interfaces For Biomedical Applications, Marco Falda, Manfredo Atzori, Maurizio Corbetta

2020-Current year OA Pubs

Several challenges prevent extracting knowledge from biomedical resources, including data heterogeneity and the difficulty to obtain and collaborate on data and annotations by medical doctors. Therefore, flexibility in their representation and interconnection is required; it is also essential to be able to interact easily with such data. In recent years, semantic tools have been developed: semantic wikis are collections of wiki pages that can be annotated with properties and so combine flexibility and expressiveness, two desirable aspects when modeling databases, especially in the dynamic biomedical domain. However, semantics and collaborative analysis of biomedical data is still an unsolved challenge. The …

Architectural Design Of A Blockchain-Enabled, Federated Learning Platform For Algorithmic Fairness In Predictive Health Care: Design Science Study, Xueping Liang, Juan Zhao, Yan Chen, Eranga Bandara, Sachin Shetty

VMASC Publications

Background: Developing effective and generalizable predictive models is critical for disease prediction and clinical decision-making, often requiring diverse samples to mitigate population bias and address algorithmic fairness. However, a major challenge is to retrieve learning models across multiple institutions without bringing in local biases and inequity, while preserving individual patients' privacy at each site.

Objective: This study aims to understand the issues of bias and fairness in the machine learning process used in the predictive health care domain. We proposed a software architecture that integrates federated learning and blockchain to improve fairness, while maintaining acceptable prediction accuracy and minimizing overhead …

Unttangling Irregular Actin Cytoskeleton Architectures In Tomograms Of The Cell With Struwwel Tracer, Salim Sazzed, Peter Scheible, Jing He, Willy Wriggers

Computer Science Faculty Publications

In this work, we established, validated, and optimized a novel computational framework for tracing arbitrarily oriented actin filaments in cryo-electron tomography maps. Our approach was designed for highly complex intracellular architectures in which a long-range cytoskeleton network extends throughout the cell bodies and protrusions. The irregular organization of the actin network, as well as cryo-electron-tomography-specific noise, missing wedge artifacts, and map dimensions call for a specialized implementation that is both robust and efficient. Our proposed solution, Struwwel Tracer, accumulates densities along paths of a specific length in various directions, starting from locally determined seed points. The highest-density paths originating …

Developing A Computer-Based Program For Language Rehabilitation Of Arabic-Speaking Aphasic Patients, Sara Elsherbeny, Ayman Amer, Hemmat Baz, Tamer Abou-Elsaad

Mansoura Medical Journal

Background: Aphasia is acquired selective impairment of language. Computerized aphasia therapy is useful in language therapy and offers chances for independent practice at home to maximize intensity and improve outcomes. The aim of this study was to develop a computer-based language rehabilitation program for Arabic-speaking Egyptian aphasic patients to be culturally, linguistically and socially suitable for them and to determine its effectiveness. Methods: We conducted a prospective interventional study on 20 aphasic patients in the age range 40-65 years who received rehabilitation for 3 months using a newly designed Arabic software program named “Takalam”. The program was pilot-studied on 10 …

Detecting Deceptive Dark-Pattern Web Advertisements For Blind Screen-Reader Users, Satwick Ram Kodandaram, Mohan Sunkara, Sampath Jayarathna, Vikas Ashok

Computer Science Faculty Publications

Advertisements have become commonplace on modern websites. While ads are typically designed for visual consumption, it is unclear how they affect blind users who interact with the ads using a screen reader. Existing research studies on non-visual web interaction predominantly focus on general web browsing; the specific impact of extraneous ad content on blind users' experience remains largely unexplored. To fill this gap, we conducted an interview study with 18 blind participants; we found that blind users are often deceived by ads that contextually blend in with the surrounding web page content. While ad blockers can address this problem via …

Dental Hygiene And Dental Assistant Students' Simulated Dvi Radiographic Match Accuracy: A Pilot Study, Samantha C. Vest, Brenda T. Bradshaw, Marsha A. Voelker, Ann M. Bruhn, Tara L. Newcomb, Sinjini Sikdar

Dental Hygiene Faculty Publications

Purpose Allied dental health care professionals have served on disaster victim identification (DVI) teams; however, the literature is void of statistical measures regarding transferable skills and disaster preparedness. The purpose of this study was to assess second year dental hygiene and dental assistant students’ match accuracy for simulated DVI radiographs and compare the match accuracy between the student groups.

Methods Five patient cases were chosen at random to retrospectively collect sets of digital bitewing radiographs from two time periods. The five retrospectively selected sets of images served as simulated antemortem (AM) and postmortem (PM) radiographs. A convenience sample of second …

Tissue Registration And Exploration User Interfaces In Support Of A Human Reference Atlas, Katy Börner, Andreas Bueckle, Bruce W Herr 2nd, Leonard E Cross, Ellen M Quardokus, Elizabeth G Record, Yingnan Ju, Jonathan C Silverstein, Kristen M Browne, Sanjay Jain, Clive H Wasserfall, Marda L Jorgensen, Jeffrey M Spraggins, N Heath Patterson, Griffin M Weber

2020-Current year OA Pubs

Seventeen international consortia are collaborating on a human reference atlas (HRA), a comprehensive, high-resolution, three-dimensional atlas of all the cells in the healthy human body. Laboratories around the world are collecting tissue specimens from donors varying in sex, age, ethnicity, and body mass index. However, harmonizing tissue data across 25 organs and more than 15 bulk and spatial single-cell assay types poses challenges. Here, we present software tools and user interfaces developed to spatially and semantically annotate ("register") and explore the tissue data and the evolving HRA. A key part of these tools is a common coordinate framework, providing standard …

Transgenic Force Sensors And Software To Measure Force Transmission Across The Mammalian Nuclear Envelope In Vivo, Kelli D Fenelon, Evan Thomas, Mohammad Samani, Min Zhu, Hirotaka Tao, Yu Sun, Helen Mcneill, Sevan Hopyan

2020-Current year OA Pubs

Nuclear mechanotransduction is a growing field with exciting implications for the regulation of gene expression and cellular function. Mechanical signals may be transduced to the nuclear interior biochemically or physically through connections between the cell surface and chromatin. To define mechanical stresses upon the nucleus in physiological settings, we generated transgenic mouse strains that harbour FRET-based tension sensors or control constructs in the outer and inner aspects of the nuclear envelope. We knocked-in a published esprin-2G sensor to measure tensions across the LINC complex and generated a new sensor that links the inner nuclear membrane to chromatin. To mitigate challenges …

A Framework For Detecting Noncoding Rare-Variant Associations Of Large-Scale Whole-Genome Sequencing Studies, Zilin Li, Xihao Li, Hufeng Zhou, Sheila M. Gaynor, Margaret Sunitha Selvaraj, Theodore Arapoglou, Corbin Quick, John Blangero, Joanne E. Curran, Ravindranath Duggirala, Harald H. H. Goring

School of Medicine Publications and Presentations

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate …