Life Sciences Commons^™

Sars-Cov-2 Specific Antibody And Neutralization Assays Reveal The Wide Range Of The Humoral Immune Response To Virus., Mikail Dogan, Lina Kozhaya, Lindsey Placek, Courtney Gunter, Mesut Yigit, Rachel Hardy, Matthew Plassmeyer, Paige Coatney, Kimberleigh Lillard, Zaheer Bukhari, Michael Kleinberg, Chelsea Hayes, Moshe Arditi, Ellen Klapper, Noah Merin, Bruce Tsan-Tang Liang, Raavi Gupta, Oral Alpan, Derya Unutmaz

Faculty Research 2021

Development of antibody protection during SARS-CoV-2 infection is a pressing question for public health and for vaccine development. We developed highly sensitive SARS-CoV-2-specific antibody and neutralization assays. SARS-CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n = 115) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. SARS-CoV-2 neutralization was determined in COVID-19 and convalescent plasma at up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which were also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody …

Whole-Genome Screen Identifies Diverse Pathways That Negatively Regulate Ciliogenesis., Marion Failler, Ariadna Giro-Perafita, Mikito Owa, Shalini Srivastava, Chi Yun, David J Kahler, Derya Unutmaz, Francisco J Esteva, Irma Sánchez, Brian D Dynlacht

Faculty Research 2021

We performed a high-throughput whole-genome RNAi screen to identify novel inhibitors of ciliogenesis in normal and basal breast cancer cells. Our screen uncovered a previously undisclosed, extensive network of genes linking integrin signaling and cellular adhesion to the extracellular matrix (ECM) with inhibition of ciliation in both normal and cancer cells. Surprisingly, a cohort of genes encoding ECM proteins was also identified. We characterized several ciliation inhibitory genes and showed that their silencing was accompanied by altered cytoskeletal organization and induction of ciliation, which restricts cell growth and migration in normal and breast cancer cells. Conversely, supplying an integrin ligand, …

Multiwalled Carbon Nanotubes Co-Delivering Sorafenib And Epidermal Growth Factor Receptor Sirna Enhanced Tumor-Suppressing Effect On Liver Cancer., Zhili Wen, Yuliang Feng, Youwen Hu, Lingyan Lian, Hongyan Huang, Li Guo, Shanwen Chen, Qian Yang, Moran Zhang, Lijun Wan, Kedong Xu, Degejirifu, Xiaohua Yan

Faculty Research 2021

OBJECTIVE: This study aimed to investigate the effects of multiwalled carbon nanotubes (MWNTs) co-delivering sorafenib (Sor) and epidermal growth factor receptor (EGFR) siRNA (MWNT/Sor/siRNA) on tumor growth in liver cancer (LC).

RESULTS: MWNT/Sor/siRNA was proved to possess increased Sor release, high siRNA stability, and enhanced cellular uptake. In addition, MWNT treatment has few effects on cell proliferation and apoptosis in HepG2 cells; however, MWNT/Sor/siRNA treatment significantly inhibited clone number and induced cell apoptosis, which shows a more favorable antitumor effect than MWNT/Sor and free Sor and free siRNA in HepG2 cells. Moreover MWNT/Sor/siRNA treatment has the most significant antitumor effect …

Epihet For Intra-Tumoral Epigenetic Heterogeneity Analysis And Visualization., Xiaowen Chen, Haitham Ashoor, Ryan Musich, Jiahui Wang, Mingsheng Zhang, Chao Zhang, Mingyang Lu, Sheng Li

Faculty Research 2021

Intra-tumoral epigenetic heterogeneity is an indicator of tumor population fitness and is linked to the deregulation of transcription. However, there is no published computational tool to automate the measurement of intra-tumoral epigenetic allelic heterogeneity. We developed an R/Bioconductor package, epihet, to calculate the intra-tumoral epigenetic heterogeneity and to perform differential epigenetic heterogeneity analysis. Furthermore, epihet can implement a biological network analysis workflow for transforming cancer-specific differential epigenetic heterogeneity loci into cancer-related biological function and clinical biomarkers. Finally, we demonstrated epihet utility on acute myeloid leukemia. We found statistically significant differential epigenetic heterogeneity (DEH) loci compared to normal controls and constructed …

Kg-Covid-19: A Framework To Produce Customized Knowledge Graphs For Covid-19 Response., Justin T Reese, Deepak Unni, Tiffany J Callahan, Luca Cappelletti, Vida Ravanmehr, Seth Carbon, Kent A Shefchek, Benjamin M Good, James P Balhoff, Tommaso Fontana, Hannah Blau, Nicolas Matentzoglu, Nomi L Harris, Monica C Munoz-Torres, Melissa A Haendel, Peter N Robinson, Marcin P Joachimiak, Christopher J Mungall

Faculty Research 2021

Integrated, up-to-date data about SARS-CoV-2 and COVID-19 is crucial for the ongoing response to the COVID-19 pandemic by the biomedical research community. While rich biological knowledge exists for SARS-CoV-2 and related viruses (SARS-CoV, MERS-CoV), integrating this knowledge is difficult and time-consuming, since much of it is in siloed databases or in textual format. Furthermore, the data required by the research community vary drastically for different tasks; the optimal data for a machine learning task, for example, is much different from the data used to populate a browsable user interface for clinicians. To address these challenges, we created KG-COVID-19, a flexible …

The Human Phenotype Ontology In 2021., Sebastian Köhler, Michael Gargano, Nicolas Matentzoglu, Leigh Carmody, David Lewis-Smith, Nicole A Vasilevsky, Daniel Danis, Ganna Balagura, Gareth Baynam, Amy M Brower, Tiffany J Callahan, Christopher G Chute, Johanna L Est, Peter D Galer, Shiva Ganesan, Matthias Griese, Matthias Haimel, Julia Pazmandi, Marc Hanauer, Nomi L Harris, Michael J Hartnett, Maximilian Hastreiter, Fabian Hauck, Yongqun He, Tim Jeske, Hugh Kearney, Gerhard Kindle, Christoph Klein, Katrin Knoflach, Roland Krause, David Lagorce, Julie A Mcmurry, Jillian A Miller, Monica C Munoz-Torres, Rebecca L Peters, Christina K Rapp, Ana M Rath, Shahmir A Rind, Avi Z Rosenberg, Michael M Segal, Markus G Seidel, Damian Smedley, Tomer Talmy, Yarlalu Thomas, Samuel A Wiafe, Julie Xian, Zafer Yüksel, Ingo Helbig, Christopher J Mungall, Melissa A Haendel, Peter N Robinson

Faculty Research 2021

The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical …

Icsdb: An Integrated Database Of Crispr Screens., Ahyoung Choi, Insu Jang, Heewon Han, Min-Seo Kim, Jinhyuk Choi, Jieun Lee, Sung-Yup Cho, Yukyung Jun, Charles Lee, Jaesang Kim, Byungwook Lee, Sanghyuk Lee

Faculty Research 2021

High-throughput screening based on CRISPR-Cas9 libraries has become an attractive and powerful technique to identify target genes for functional studies. However, accessibility of public data is limited due to the lack of user-friendly utilities and up-to-date resources covering experiments from third parties. Here, we describe iCSDB, an integrated database of CRISPR screening experiments using human cell lines. We compiled two major sources of CRISPR-Cas9 screening: the DepMap portal and BioGRID ORCS. DepMap portal itself is an integrated database that includes three large-scale projects of CRISPR screening. We additionally aggregated CRISPR screens from BioGRID ORCS that is a collection of screening …

Genomic Profile Of Metastatic Breast Cancer Patient-Derived Xenografts Established Using Percutaneous Biopsy., Seongyeong Kim, Dongjin Shin, Ahrum Min, Minjung Kim, Deukchae Na, Han-Byeol Lee, Han Suk Ryu, Yaewon Yang, Go-Un Woo, Kyung-Hun Lee, Dae-Won Lee, Tae-Yong Kim, Charles Lee, Seock-Ah Im, Jong-Il Kim

Faculty Research 2021

BACKGROUND: Metastatic breast cancer (mBC) is a complex and life-threatening disease and although it is difficult to cure, patients can benefit from sequential anticancer treatment, including endocrine therapy, targeted therapy and cytotoxic chemotherapy. The patient-derived xenograft (PDX) model is suggested as a practical tool to predict the clinical outcome of this disease as well as to screen novel drugs. This study aimed to establish PDX models in Korean patients and analyze their genomic profiles and utility for translational research.

METHODS: Percutaneous core needle biopsy or punch biopsy samples were used for xenotransplantation. Whole exome sequencing and transcriptome analysis were performed …

Development Of A Novel Orthotopic Gastric Cancer Mouse Model., Wonyoung Kang, Leigh Maher, Michael Michaud, Seong-Woo Bae, Seongyeong Kim, Hye Seung Lee, Seock-Ah Im, Han-Kwang Yang, Charles Lee

Faculty Research 2021

BACKGROUND: Gastric cancer metastasis is a highly fatal disease with a five-year survival rate of less than 5%. One major obstacle in studying gastric cancer metastasis is the lack of faithful models available. The cancer xenograft mouse models are widely used to elucidate the mechanisms of cancer development and progression. Current procedures for creating cancer xenografts include both heterotopic (i.e., subcutaneous) and orthotopic transplantation methods. Compared to the heterotopic model, the orthotopic model has been shown to be the more clinically relevant design as it enables the development of cancer metastasis. Although there are several methods in use to develop …

A Validated Integrated Clinical And Molecular Glioblastoma Long-Term Survival-Predictive Nomogram., Sherise D Ferguson, Tiffany R Hodges, Nazanin K Majd, Kristin Alfaro-Munoz, Wajd N Al-Holou, Dima Suki, John F De Groot, Gregory N Fuller, Lee Xue, Miao Li, Carmen Jacobs, Ganesh Rao, Rivka R Colen, Joanne Xiu, Roel G W Verhaak, David Spetzler, Mustafa Khasraw, Raymond Sawaya, James P Long, Amy B Heimberger

Faculty Research 2021

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adulthood. Despite multimodality treatments, including maximal safe resection followed by irradiation and chemotherapy, the median overall survival times range from 14 to 16 months. However, a small subset of GBM patients live beyond 5 years and are thus considered long-term survivors.

Methods: A retrospective analysis of the clinical, radiographic, and molecular features of patients with newly diagnosed primary GBM who underwent treatment at The University of Texas MD Anderson Cancer Center was conducted. Eighty patients had sufficient quantity and quality of tissue available for next-generation sequencing and immunohistochemical …

A Functional Variant On 20q13.33 Related To Glioma Risk Alters Enhancer Activity And Modulates Expression Of Multiple Genes., Mourad Wagdy Ali, C Pawan K Patro, Jacqueline Jufen Zhu, Christopher H Dampier, Sarah J Plummer, Cem Kuscu, Mazhar Adli, Ching C Lau, Rose K Lai, Graham Casey

Faculty Research 2021

Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with glioma risk on 20q13.33, but the biological mechanisms underlying this association are unknown. We tested the hypothesis that a functional SNP on 20q13.33 impacted the activity of an enhancer, leading to an altered expression of nearby genes. To identify candidate functional SNPs, we identified all SNPs in linkage disequilibrium with the risk-associated SNP rs2297440 that mapped to putative enhancers. Putative enhancers containing candidate functional SNPs were tested for allele-specific effects in luciferase enhancer activity assays against glioblastoma multiforme (GBM) cell lines. An enhancer containing SNP rs3761124 exhibited allele-specific effects …

Gender-Based Deep Learning Firefly Optimization Method For Test Data Generation., Wenning Zhang, Chongyang Jiao, Qinglei Zhou, Yang Liu, Ting Xu

Faculty Research 2021

Software testing is a widespread validation means of software quality assurance in industry. Intelligent optimization algorithms have been proved to be an effective way of automatic test data generation. Firefly algorithm has received extensive attention and been widely used to solve optimization problems because of less parameters and simple implement. To overcome slow convergence rate and low accuracy of the firefly algorithm, a novel firefly algorithm with deep learning is proposed to generate structural test data. Initially, the population is divided into male subgroup and female subgroup. Following the randomly attracted model, each male firefly will be attracted by another …

The Gut Microbiome And Substance Use Disorder., Jordan T Russell, Yanjiao Zhou, George M. Weinstock, Jason A. Bubier

Faculty Research 2021

Substance use disorders (SUDs) remain a significant public health challenge, affecting tens of millions of individuals worldwide each year. Often comorbid with other psychiatric disorders, SUD can be poly-drug and involve several different substances including cocaine, opiates, nicotine, and alcohol. SUD has a strong genetic component. Much of SUD research has focused on the neurologic and genetic facets of consumption behavior. There is now interest in the role of the gut microbiome in the pathogenesis of SUD. In this review, we summarize current animal and clinical evidence that the gut microbiome is involved in SUD, then address the underlying mechanisms …

A Computational Systems Analyses To Identify Biomarkers And Mechanistic Link In Psoriasis And Cutaneous Squamous Cell Carcinoma., Sidra Adil, Rehan Zafar Paracha, Salma Tariq, Maryum Nisar, Sadaf Ijaz, Amnah Siddiqa, Zamir Hussain, Afreenish Amir

Faculty Research 2021

Psoriasis is the most common and chronic skin disease that affects individuals from every age group. The rate of psoriasis is increasing over the time in both developed and developing countries. Studies have revealed the possibility of association of psoriasis with skin cancers, particularly non-melanoma skin cancers (NMSC), which, include basal cell carcinoma and cutaneous squamous cell carcinoma (cSCC). There is a need to analyze the disease at molecular level to propose potential biomarkers and therapeutic targets in comparison to cSCC. Therefore, the second analyzed disease of this study is cSCC. It is the second most common prevalent skin cancer …

A New Graph-Based Clustering Method With Application To Single-Cell Rna-Seq Data From Human Pancreatic Islets., Hao Wu, Disheng Mao, Yuping Zhang, Zhiyi Chi, Michael L. Stitzel, Zhengqing Ouyang

Faculty Research 2021

Traditional bulk RNA-sequencing of human pancreatic islets mainly reflects transcriptional response of major cell types. Single-cell RNA sequencing technology enables transcriptional characterization of individual cells, and thus makes it possible to detect cell types and subtypes. To tackle the heterogeneity of single-cell RNA-seq data, powerful and appropriate clustering is required to facilitate the discovery of cell types. In this paper, we propose a new clustering framework based on a graph-based model with various types of dissimilarity measures. We take the compositional nature of single-cell RNA-seq data into account and employ log-ratio transformations. The practical merit of the proposed method is …

Lumos - Low And Intermediate Grade Glioma Umbrella Study Of Molecular Guided Therapies At Relapse: Protocol For A Pilot Study, Benjamin Y Kong, Hao-Wen Sim, Anna K Nowak, Sonia Yip, Elizabeth H Barnes, Bryan W Day, Michael E Buckland, Roel G W Verhaak, Terrance Johns, Cleo Robinson, Et Al

Faculty Research 2021

Grades 2 and 3 gliomas (G2/3 gliomas), when combined, are the second largest group of malignant brain tumours in adults. The outcomes for G2/3 gliomas at progression approach the dismal outcomes for glioblastoma (GBM), yet there is a paucity of trials for Australian patients with relapsed G2/3 gliomas compared with patients with GBM. LUMOS will be a pilot umbrella study for patients with relapsed G2/3 gliomas that aims to match patients to targeted therapies based on molecular screening with contemporaneous tumour tissue. Participants in whom no actionable or no druggable mutation is found, or in whom the matching drug is …