Digital Commons Network^™

Large-Scale Annotated Dataset For Cochlear Hair Cell Detection And Classification., Christopher J Buswinka, David B Rosenberg, Rubina G Simikyan, Richard T Osgood, Katharine Fernandez, Hidetomi Nitta, Yushi Hayashi, Leslie W Liberman, Emily Nguyen, Erdem Yildiz, Jinkyung Kim, Amandine Jarysta, Justine Renauld, Ella Wesson, Haobing Wang, Punam Thapa, Pierrick Bordiga, Noah Mcmurtry, Juan Llamas, Siân R Kitcher, Ana I López-Porras, Runjia Cui, Ghazaleh Behnammanesh, Jonathan E Bird, Angela Ballesteros, A Catalina Vélez-Ortega, Albert S B Edge, Michael R Deans, Ksenia Gnedeva, Brikha R Shrestha, Uri Manor, Bo Zhao, Anthony J Ricci, Basile Tarchini, Martín L Basch, Ruben Stepanyan, Lukas D Landegger, Mark A Rutherford, M Charles Liberman, Bradley J Walters, Corné J Kros, Guy P Richardson, Lisa L Cunningham, Artur A Indzhykulian

Faculty Research 2024

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. …

Genetic Diversity Promotes Resilience In A Mouse Model Of Alzheimer's Disease., Neelakshi Soni, Lindsay A Hohsfield, Kristine M Tran, Shimako Kawauchi, Amber Walker, Dominic Javonillo, Jimmy Phan, Dina Matheos, Celia Da Cunha, Asli Uyar, Giedre Milinkeviciute, Angela Gomez-Arboledas, Katelynn Tran, Catherine C Kaczorowski, Marcelo A Wood, Andrea J Tenner, Frank M Laferla, Gregory W. Carter, Ali Mortazavi, Vivek Swarup, Grant R Macgregor, Kim N Green

Faculty Research 2024

INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder with multifactorial etiology, including genetic factors that play a significant role in disease risk and resilience. However, the role of genetic diversity in preclinical AD studies has received limited attention.

METHODS: We crossed five Collaborative Cross strains with 5xFAD C57BL/6J female mice to generate F1 mice with and without the 5xFAD transgene. Amyloid plaque pathology, microglial and astrocytic responses, neurofilament light chain levels, and gene expression were assessed at various ages.

RESULTS: Genetic diversity significantly impacts AD-related pathology. Hybrid strains showed resistance to amyloid plaque formation and neuronal damage. Transcriptome diversity was …

Genome-Wide Association Study Identifies Human Genetic Variants Associated With Fatal Outcome From Lassa Fever., Dylan Kotliar, Siddharth Raju, Shervin Tabrizi, Ikponmwosa Odia, Augustine Goba, Mambu Momoh, John Demby Sandi, Parvathy Nair, Eric Phelan, Ridhi Tariyal, Philomena E Eromon, Samar Mehta, Refugio Robles-Sikisaka, Katherine J Siddle, Matt Stremlau, Simbirie Jalloh, Stephen K Gire, Sarah Winnicki, Bridget Chak, Stephen F Schaffner, Matthias Pauthner, Elinor K Karlsson, Sarah R Chapin, Sharon G Kennedy, Luis M Branco, Lansana Kanneh, Joseph J Vitti, Nisha Broodie, Adrianne Gladden-Young, Omowunmi Omoniwa, Pan-Pan Jiang, Nathan Yozwiak, Shannon Heuklom, Lina M Moses, George O Akpede, Danny A Asogun, Kathleen Rubins, Susan Kales, Anise N Happi, Christopher O Iruolagbe, Mercy Dic-Ijiewere, Kelly Iraoyah, Omoregie O Osazuwa, Alexander K Okonkwo, Stefan Kunz, Joseph B Mccormick, S Humarr Khan, Anna N Honko, Eric S Lander, Michael B A Oldstone, Lisa Hensley, Onikepe A Folarin, Sylvanus A Okogbenin, Stephan Günther, Hanna M Ollila, Ryan Tewhey, Peter O Okokhere, John S Schieffelin, Kristian G Andersen, Steven K Reilly, Donald S Grant, Robert F Garry, Kayla G Barnes, Christian T Happi, Pardis C Sabeti

Faculty Research 2024

Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa …

Phenotypic Similarity-Based Approach For Variant Prioritization For Unsolved Rare Disease: A Preliminary Methodological Report., David Lagorce, Emeline Lebreton, Leslie Matalonga, Oscar Hongnat, Maroua Chahdil, Davide Piscia, Ida Paramonov, Kornelia Ellwanger, Sebastian Köhler, Peter N Robinson, Holm Graessner, Sergi Beltran, Caterina Lucano, Marc Hanauer, Ana Rath

Faculty Research 2024

Rare diseases (RD) have a prevalence of not more than 1/2000 persons in the European population, and are characterised by the difficulty experienced in obtaining a correct and timely diagnosis. According to Orphanet, 72.5% of RD have a genetic origin although 35% of them do not yet have an identified causative gene. A significant proportion of patients suspected to have a genetic RD receive an inconclusive exome/genome sequencing. Working towards the International Rare Diseases Research Consortium (IRDiRC)'s goal for 2027 to ensure that all people living with a RD receive a diagnosis within one year of coming to medical attention, …

The Human Phenotype Ontology In 2024: Phenotypes Around The World., Michael Gargano, Nicolas Matentzoglu, Ben D Coleman, Eunice B Addo-Lartey, Anna V Anagnostopoulos, Joel Anderton, Paul Avillach, Anita M Bagley, Eduard Bakštein, James P Balhoff, Gareth Baynam, Susan M Bello, Michael Berk, Holli Bertram, Somer Bishop, Hannah Blau, David F Bodenstein, Pablo Botas, Kaan Boztug, Jolana Čady, Tiffany J Callahan, Rhiannon Cameron, Seth J Carbon, Francisco Castellanos, J Harry Caufield, Lauren E Chan, Christopher G Chute, Jaime Cruz-Rojo, Noémi Dahan-Oliel, Jon R Davids, Maud De Dieuleveult, Vinicius De Souza, Bert B A De Vries, Esther De Vries, J Raymond Depaulo, Beata Derfalvi, Ferdinand Dhombres, Claudia Diaz-Byrd, Alexander J M Dingemans, Bruno Donadille, Michael Duyzend, Reem Elfeky, Shahim Essaid, Carolina Fabrizzi, Giovanna Fico, Helen V Firth, Yun Freudenberg-Hua, Janice M Fullerton, Davera L Gabriel, Kimberly Gilmour, Jessica Giordano, Fernando S Goes, Rachel Gore Moses, Ian Green, Matthias Griese, Tudor Groza, Weihong Gu, Julia Guthrie, Benjamin Gyori, Ada Hamosh, Marc Hanauer, Kateřina Hanušová, Yongqun Oliver He, Harshad Hegde, Ingo Helbig, Kateřina Holasová, Charles Tapley Hoyt, Shangzhi Huang, Eric Hurwitz, Julius O B Jacobsen, Xiaofeng Jiang, Lisa Joseph, Kamyar Keramatian, Bryan King, Katrin Knoflach, David A Koolen, Megan L Kraus, Carlo Kroll, Maaike Kusters, Markus S Ladewig, David Lagorce, Meng-Chuan Lai, Pablo Lapunzina, Bryan Laraway, David Lewis-Smith, Xiarong Li, Caterina Lucano, Marzieh Majd, Mary L Marazita, Victor Martinez-Glez, Toby H Mchenry, Melvin G Mcinnis, Julie A Mcmurry, Michaela Mihulová, Caitlin E Millett, Philip B Mitchell, Veronika Moslerová, Kenji Narutomi, Shahrzad Nematollahi, Julian Nevado, Andrew A Nierenberg, Nikola Novák Čajbiková, John I Nurnberger, Soichi Ogishima, Daniel Olson, Abigail Ortiz, Harry Pachajoa, Guiomar Perez De Nanclares, Amy Peters, Tim Putman, Christina K Rapp, Ana Rath, Justin Reese, Lauren Rekerle, Angharad M Roberts, Suzy Roy, Stephan J Sanders, Catharina Schuetz, Eva C Schulte, Thomas G Schulze, Martin Schwarz, Katie Scott, Dominik Seelow, Berthold Seitz, Yiping Shen, Morgan N Similuk, Eric S Simon, Balwinder Singh, Damian Smedley, Cynthia Smith, Jake T Smolinsky, Sarah Sperry, Elizabeth Stafford, Ray Stefancsik, Robin Steinhaus, Rebecca Strawbridge, Jagadish Chandrabose Sundaramurthi, Polina Talapova, Jair A Tenorio Castano, Pavel Tesner, Rhys H Thomas, Audrey Thurm, Marek Turnovec, Marielle E Van Gijn, Nicole A Vasilevsky, Markéta Vlčková, Anita Walden, Kai Wang, Ron Wapner, James S Ware, Addo A Wiafe, Samuel A Wiafe, Lisa D Wiggins, Andrew E Williams, Chen Wu, Margot J Wyrwoll, Hui Xiong, Nefize Yalin, Yasunori Yamamoto, Lakshmi N Yatham, Anastasia K Yocum, Allan H Young, Zafer Yüksel, Peter P Zandi, Andreas Zankl, Ignacio Zarante, Miroslav Zvolský, Sabrina Toro, Leigh Carmody, Nomi L Harris, Monica C Munoz-Torres, Daniel Danis, Christopher J Mungall, Sebastian Köhler, Melissa A Haendel, Peter N Robinson

Faculty Research 2024

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition …

Aging And Urinary Control: Alterations In The Brain-Bladder Axis., Cara C Hardy, Ron Korstanje

Faculty Research 2023

Age-associated alterations in bladder control affect millions of older adults, with a heavy burden added to families both economically and in quality of life. Therapeutic options are limited with poor efficacy in older adults, lending to a growing need to address the gaps in our current understanding of urinary tract aging. This review summarizes the current knowledge of age-associated alterations in the structure and function of the brain-bladder axis and identifies important gaps in the field that have yet to be addressed. Urinary aging is associated with decreased tissue responsiveness, decreased control over the voiding reflex, signaling dysfunction along the …

A Transcriptomic Appreciation Of Childhood Meningococcal And Polymicrobial Sepsis From A Pro-Inflammatory And Trajectorial Perspective, A Role For Vascular Endothelial Growth Factor A And B Modulation?, Asrar Rashid, Berit S Brusletto, Feras Al-Obeidat, Mohammed Toufiq, Govind Benakatti, Joe Brierley, Zainab A Malik, Zain Hussain, Hoda Alkhazaimi, Javed Sharief, Raziya Kadwa, Amrita Sarpal, Damien Chaussabel, Rayaz A Malik, Nasir Quraishi, Praveen Khilnani, Syed A Zaki, Rashid Nadeem, Guftar Shaikh, Ahmed Al-Dubai, Wael Hafez, Amir Hussain

Faculty Research 2023

This study investigated the temporal dynamics of childhood sepsis by analyzing gene expression changes associated with proinflammatory processes. Five datasets, including four meningococcal sepsis shock (MSS) datasets (two temporal and two longitudinal) and one polymicrobial sepsis dataset, were selected to track temporal changes in gene expression. Hierarchical clustering revealed three temporal phases: early, intermediate, and late, providing a framework for understanding sepsis progression. Principal component analysis supported the identification of gene expression trajectories. Differential gene analysis highlighted consistent upregulation of vascular endothelial growth factor A (VEGF-A) and nuclear factor κB1 (NFKB1), genes involved in inflammation, across the sepsis datasets. NFKB1 …

High-Throughput Bioprinting Of The Nasal Epithelium Using Patient-Derived Nasal Epithelial Cells., I Deniz Derman, Miji Yeo, Diana Cadena, Megan Callender, Mian Horvath, Zengshuo Mo, Ruoyun Xiong, Elizabeth Fleming, Phylip Chen, Mark E Peeples, Karolina Palucka, Julia Oh, Ibrahim T Ozbolat

Faculty Research 2023

Progenitor human nasal epithelial cells (hNECs) are an essential cell source for the reconstruction of the respiratory pseudostratified columnar epithelium composed of multiple cell types in the context of infection studies and disease modeling. Hitherto, manual seeding has been the dominant method for creating nasal epithelial tissue models through biofabrication. However, this approach has limitations in terms of achieving the intricate three-dimensional (3D) structure of the natural nasal epithelium. 3D bioprinting has been utilized to reconstruct various epithelial tissue models, such as cutaneous, intestinal, alveolar, and bronchial epithelium, but there has been no attempt to use of 3D bioprinting technologies …

Priorities To Promote Participant Engagement In The Participant Engagement And Cancer Genome Sequencing (Pe-Cgs) Network., Anne Lr Schuster, Norah L Crossnohere, Melinda Bachini, Cindy K Blair, John D Carpten, Elizabeth B Claus, Graham A Colditz, Li Ding, Bettina F Drake, Ryan C Fields, Katherine A Janeway, Bethany M Kwan, Heinz-Josef Lenz, Qin Ma, Shiraz I Mishra, Electra D Paskett, Timothy R Rebbeck, Charité Ricker, Mariana C Stern, Andrew L Sussman, Jessica C Tiner, Jeffrey M Trent, Roel G W Verhaak, Nikhil Wagle, Cheryl Willman, John Fp Bridges

Faculty Research 2023

BACKGROUND: Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers. PE-CGS sought to set priorities in participant engagement for conducting the network's research.

METHODS: PE-CGS deliberatively engaged its stakeholders in the following four-phase process to set the network's research priorities …

Tmem161b Modulates Radial Glial Scaffolding In Neocortical Development., Lu Wang, Caleb Heffner, Keng Ioi Vong, Chelsea Barrows, Yoo-Jin Ha, Sangmoon Lee, Pablo Lara-Gonzalez, Ishani Jhamb, Dennis Van Der Meer, Robert Loughnan, Nadine Parker, David Sievert, Swapnil Mittal, Mahmoud Y Issa, Ole A Andreassen, Anders Dale, William B Dobyns, Maha S Zaki, Stephen A Murray, Joseph G Gleeson

Faculty Research 2023

TMEM161B encodes an evolutionarily conserved widely expressed novel 8-pass trans- membrane protein of unknown function in human. Here we identify TMEM161B homozygous hypomorphic missense variants in our recessive polymicrogyria (PMG) cohort. Patients carrying TMEM161B mutations exhibit striking neocortical PMG and intellectual disability. Tmem161b knockout mice fail to develop midline hem- ispheric cleavage, whereas knock-in of patient mutations and patient-derived brain organoids show defects in apical cell polarity and radial glial scaffolding. We found that TMEM161B modulates actin filopodia, functioning upstream of the Rho-GTPase CDC42. Our data link TMEM161B with human PMG, likely regulating radial glia apical polarity during neocortical development.

Hiv Associated Cell Death: Peptide-Induced Apoptosis Restricts Viral Transmission., Qiongyu Chen, Yan Zhao, Yonghong Zhang, Jianbo Zhang, Wenshu Lu, Chih-Hao Chang, Shisong Jiang

Faculty Research 2023

The human immunodeficiency virus (HIV) is still a global pandemic and despite the successful use of anti-retroviral therapy, a well-established cure remains to be identified. Viral modulation of cell death has a significant role in HIV pathogenesis. Here we sought to understand the major mechanisms of HIV- induced death of lymphocytes and the effects on viral transmission. Flow cytometry analysis of lymphocytes from five latent HIV-infected patients, and HIV IIIB-infected MT2 cells demonstrated both necrosis and apoptosis to be the major mechanisms of cell death in CD4+ and CD4-/CD8- lymphocytes. Significantly, pro-apoptotic tumor necrosis factor (TNF) peptide (P13) was found …

Phenopacket-Tools: Building And Validating Ga4gh Phenopackets., Daniel Danis, Julius O B Jacobsen, Alex H Wagner, Tudor Groza, Martha A Beckwith, Lauren Rekerle, Leigh Carmody, Justin Reese, Harshad Hegde, Markus S Ladewig, Berthold Seitz, Monica Munoz-Torres, Nomi L Harris, Jordi Rambla, Michael Baudis, Christopher J Mungall, Melissa A Haendel, Peter N Robinson

Faculty Research 2023

The Global Alliance for Genomics and Health (GA4GH) is a standards-setting organization that is developing a suite of coordinated standards for genomics. The GA4GH Phenopacket Schema is a standard for sharing disease and phenotype information that characterizes an individual person or biosample. The Phenopacket Schema is flexible and can represent clinical data for any kind of human disease including rare disease, complex disease, and cancer. It also allows consortia or databases to apply additional constraints to ensure uniform data collection for specific goals. We present phenopacket-tools, an open-source Java library and command-line application for construction, conversion, and validation of phenopackets. …

A Comparison Of Dna Sequencing And Gene Expression Profiling To Assist Tissue Of Origin Diagnosis In Cancer Of Unknown Primary., Atara Posner, Owen Wj Prall, Tharani Sivakumaran, Dariush Etemadamoghadam, Niko Thio, Andrew Pattison, Shiva Balachander, Krista Fisher, Samantha Webb, Colin Wood, Anna Defazio, Nicholas Wilcken, Bo Gao, Christos S Karapetis, Madhu Singh, Ian M Collins, Gary Richardson, Christopher Steer, Mark Warren, Narayan Karanth, Gavin Wright, Scott Williams, Joshy George, Rodney J Hicks, Alex Boussioutas, Anthony J Gill, Benjamin J Solomon, Huiling Xu, Andrew Fellowes, Stephen B Fox, Penelope Schofield, David Bowtell, Linda Mileshkin, Richard W Tothill

Faculty Research 2023

Cancer of unknown primary (CUP) is a syndrome defined by clinical absence of a primary cancer after standardised investigations. Gene expression profiling (GEP) and DNA sequencing have been used to predict primary tissue of origin (TOO) in CUP and find molecularly guided treatments; however, a detailed comparison of the diagnostic yield from these two tests has not been described. Here, we compared the diagnostic utility of RNA and DNA tests in 215 CUP patients (82% received both tests) in a prospective Australian study. Based on retrospective assessment of clinicopathological data, 77% (166/215) of CUPs had insufficient evidence to support TOO …

Blackcurrants Reduce The Risk Of Postmenopausal Osteoporosis: A Pilot Double-Blind, Randomized, Placebo-Controlled Clinical Trial., Briana M Nosal, Junichi R Sakaki, Zachary Macdonald, Kyle Mahoney, Kijoon Kim, Matthew Madore, Staci Thornton, Thi Dong Binh Tran, George M. Weinstock, Elaine Choung-Hee Lee, Ock K Chun

Faculty Research 2022

Beneficial effects of blackcurrant supplementation on bone metabolism in mice has recently been demonstrated, but no studies are available in humans. The current study aimed to examine the dose-dependent effects of blackcurrant in preventing bone loss and the underlying mechanisms of action in adult women. Forty peri- and early postmenopausal women were randomly assigned into one of three treatment groups for 6 months: (1) a placebo (control group, n = 13); (2) 392 mg/day of blackcurrant powder (low blackcurrant, BC, group, n = 16); and (3) 784 mg/day of blackcurrant powder (high BC group, n = 11). The significance of …

A Genomically And Clinically Annotated Patient-Derived Xenograft Resource For Preclinical Research In Non-Small Cell Lung Cancer., Xing Yi Woo, Anuj Srivastava, Philip C Mack, Joel H. Graber, Brian J Sanderson, Michael W Lloyd, Mandy Chen, Sergii Domanskyi, Regina Gandour-Edwards, Rebekah A Tsai, James G. Keck, Mingshan Cheng, Margaret Bundy, Emily L Jocoy, Jonathan W Riess, William Holland, Stephen C. Grubb, James G Peterson, Grace Stafford, Carolyn Paisie, Steven Neuhauser, Radha Krishna Murthy Karuturi, Joshy George, Allen K. Simons, Margaret Chavaree, Clifford G Tepper, Neal Goodwin, Susan Airhart, Primo N Lara, Thomas H Openshaw, Edison Liu, David R Gandara, Carol J Bult

Faculty Research 2022

UNLABELLED: Patient-derived xenograft (PDX) models are an effective preclinical in vivo platform for testing the efficacy of novel drugs and drug combinations for cancer therapeutics. Here we describe a repository of 79 genomically and clinically annotated lung cancer PDXs available from The Jackson Laboratory that have been extensively characterized for histopathologic features, mutational profiles, gene expression, and copy-number aberrations. Most of the PDXs are models of non-small cell lung cancer (NSCLC), including 37 lung adenocarcinoma (LUAD) and 33 lung squamous cell carcinoma (LUSC) models. Other lung cancer models in the repository include four small cell carcinomas, two large cell neuroendocrine …

Gzmk(High) Cd8(+) T Effector Memory Cells Are Associated With Cd15(High) Neutrophil Abundance In Non-Metastatic Colorectal Tumors And Predict Poor Clinical Outcome, Silvia Tiberti, Carlotta Catozzi, Ottavio Croci, Mattia Ballerini, Danilo Cagnina, Chiara Soriani, Caterina Scirgolea, Zheng Gong, Jiatai He, Angeli D Macandog, Amir Nabinejad, Carina B Nava Lauson, Arianna Quinte', Giovanni Bertalot, Wanda L Petz, Simona P Ravenda, Valerio Licursi, Paola Paci, Marco Rasponi, Luca Rotta, Nicola Fazio, Guangwen Ren, Uberto Fumagalli-Romario, Martin H Schaefer, Stefano Campaner, Enrico Lugli, Luigi Nezi, Teresa Manzo

Faculty Research 2022

CD8+ T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils expressing high levels of CD15 with CD8+ T effector memory cells (TEM) correlates with tumor progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/ SDF-1) promotes the retention of neutrophils within tumors, increasing the crosstalk with CD8+ T cells. As a consequence of the contact-mediated inter- action with neutrophils, CD8+ T cells are skewed to produce high levels of GZMK, …

Advancing Clinical And Translational Research In Germ Cell Tumours (Gct): Recommendations From The Malignant Germ Cell International Consortium., Adriana Fonseca, João Lobo, Florette K Hazard, Joanna J Gell, Peter K Nicholls, Robert S Weiss, Lindsay Klosterkemper, Samuel L Volchenboum, James C Nicholson, A Lindsay Frazier, James F Amatruda, Aditya Bagrodia, Michelle Lockley, Matthew J Murray

Faculty Research 2022

Germ cell tumours (GCTs) are a heterogeneous group of rare neoplasms that present in different anatomical sites and across a wide spectrum of patient ages from birth through to adulthood. Once these strata are applied, cohort numbers become modest, hindering inferences regarding management and therapeutic advances. Moreover, patients with GCTs are treated by different medical professionals including paediatric oncologists, neuro-oncologists, medical oncologists, neurosurgeons, gynaecological oncologists, surgeons, and urologists. Silos of care have thus formed, further hampering knowledge dissemination between specialists. Dedicated biobank specimen collection is therefore critical to foster continuous growth in our understanding of similarities and differences by age, …

Integrated Dna Copy Number And Expression Profiling Identifies Igf1r As A Prognostic Biomarker In Pediatric Osteosarcoma., Aaron M Taylor, Jiayi M Sun, Alexander Yu, Horatiu Voicu, Jianhe Shen, Donald A Barkauskas, Timothy J Triche, Julie M Gastier-Foster, Tsz-Kwong Man, Ching C Lau

Faculty Research 2022

Osteosarcoma is a primary malignant bone tumor arising from bone-forming mesenchymal cells in children and adolescents. Despite efforts to understand the biology of the disease and identify novel therapeutics, the survival of osteosarcoma patients remains dismal. We have concurrently profiled the copy number and gene expression of 226 osteosarcoma samples as part of the Strategic Partnering to Evaluate Cancer Signatures (SPECS) initiative. Our results demonstrate the heterogeneous landscape of osteosarcoma in younger populations by showing the presence of genome-wide copy number abnormalities occurring both recurrently among samples and in a high frequency. Insulin growth factor receptor 1 (IGF1R) is a …

Mortality Prediction Analysis Among Covid-19 Inpatients Using Clinical Variables And Deep Learning Chest Radiography Imaging Features., Xuan V Nguyen, Engin Dikici, Sema Candemir, Robyn L Ball, Luciano M Prevedello

Faculty Research 2022

The emergence of the COVID-19 pandemic over a relatively brief interval illustrates the need for rapid data-driven approaches to facilitate clinical decision making. We examined a machine learning process to predict inpatient mortality among COVID-19 patients using clinical and chest radiographic data. Modeling was performed with a de-identified dataset of encounters prior to widespread vaccine availability. Non-imaging predictors included demographics, pre-admission clinical history, and past medical history variables. Imaging features were extracted from chest radiographs by applying a deep convolutional neural network with transfer learning. A multi-layer perceptron combining 64 deep learning features from chest radiographs with 98 patient clinical …

A Research Agenda To Support The Development And Implementation Of Genomics-Based Clinical Informatics Tools And Resources., Ken Wiley, Laura Findley, Madison Goldrich, Tejinder K Rakhra-Burris, Ana Stevens, Pamela Williams, Carol J Bult, Rex Chisholm, Patricia Deverka, Geoffrey S Ginsburg, Eric D Green, Gail Jarvik, George A Mensah, Erin Ramos, Mary V Relling, Dan M Roden, Robb Rowley, Gil Alterovitz, Samuel Aronson, Lisa Bastarache, James J Cimino, Erin L Crowgey, Guilherme Del Fiol, Robert R Freimuth, Mark A Hoffman, Janina Jeff, Kevin Johnson, Kensaku Kawamoto, Subha Madhavan, Eneida A Mendonca, Lucila Ohno-Machado, Siddharth Pratap, Casey Overby Taylor, Marylyn D Ritchie, Nephi Walton, Chunhua Weng, Teresa Zayas-Cabán, Teri A Manolio, Marc S Williams

Faculty Research 2022

OBJECTIVE: The Genomic Medicine Working Group of the National Advisory Council for Human Genome Research virtually hosted its 13th genomic medicine meeting titled "Developing a Clinical Genomic Informatics Research Agenda". The meeting's goal was to articulate a research strategy to develop Genomics-based Clinical Informatics Tools and Resources (GCIT) to improve the detection, treatment, and reporting of genetic disorders in clinical settings.

MATERIALS AND METHODS: Experts from government agencies, the private sector, and academia in genomic medicine and clinical informatics were invited to address the meeting's goals. Invitees were also asked to complete a survey to assess important considerations needed to …

The Th1/Tfh-Like Biased Responses Elicited By The Rasp-1 Innate Adjuvant Are Dependent On Trif And Type I Ifn Receptor Pathways., Parakkal Jovvian George, Radu Marches, Djamel Nehar-Belaid, Jacques Banchereau, Sara Lustigman

Faculty Research 2022

No abstract provided.

Identification Of Quantitative Trait Loci For Survival In The Mutant Dynactin P150glued Mouse Model Of Motor Neuron Disease., Guillermo M Alexander, Terry D Heiman-Patterson, Frank Bearoff, Roger B Sher, Laura Hennessy, Shannon Terek, Nicole Caccavo, Gregory A Cox, Vivek M. Philip, Elizabeth A Blankenhorn

Faculty Research 2022

Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron disorder. Although most cases of ALS are sporadic, 5-10% of cases are familial, with mutations associated with over 40 genes. There is variation of ALS symptoms within families carrying the same mutation; the disease may develop in one sibling and not in another despite the presence of the mutation in both. Although the cause of this phenotypic variation is unknown, it is likely related to genetic modifiers of disease expression. The identification of ALS causing genes has led to the development of transgenic mouse models of motor neuron disease. …

Comprehensive Characterization Of 536 Patient-Derived Xenograft Models Prioritizes Candidatesfor Targeted Treatment., Hua Sun, Song Cao, R Jay Mashl, Chia-Kuei Mo, Simone Zaccaria, Michael C Wendl, Sherri R Davies, Matthew H Bailey, Tina M Primeau, Jeremy Hoog, Jacqueline L Mudd, Dennis A Dean, Rajesh Patidar, Li Chen, Matthew A Wyczalkowski, Reyka G Jayasinghe, Fernanda Martins Rodrigues, Nadezhda V Terekhanova, Yize Li, Kian-Huat Lim, Andrea Wang-Gillam, Brian A Van Tine, Cynthia X Ma, Rebecca Aft, Katherine C Fuh, Julie K Schwarz, Jose P Zevallos, Sidharth V Puram, John F Dipersio, Nci Pdxnet Consortium, Brandi Davis-Dusenbery, Matthew J Ellis, Michael T Lewis, Michael A Davies, Meenhard Herlyn, Bingliang Fang, Jack A Roth, Alana L Welm, Bryan E Welm, Funda Meric-Bernstam, Feng Chen, Ryan C Fields, Shunqiang Li, Ramaswamy Govindan, James H Doroshow, Jeffrey A Moscow, Yvonne A Evrard, Jeffrey Chuang, Benjamin J Raphael, Li Ding, Carol J Bult, Peter N Robinson

Faculty Research 2021

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications …