Data Science Commons^™

Comparative Analyses Define Differences Between Bhd-Associated Renal Tumour And Sporadic Chromophobe Renal Cell Carcinoma, Ryosuke Jikuya, Todd A Johnson, Kazuhiro Maejima, Jisong An, Young-Seok Ju, Hwajin Lee, Kyungsik Ha, Woojeung Song, Youngwook Kim, Yuki Okawa, Shota Sasagawa, Yuki Kanazashi, Masashi Fujita, Seiya Imoto, Taku Mitome, Shinji Ohtake, Go Noguchi, Sachi Kawaura, Yasuhiro Iribe, Kota Aomori, Tomoyuki Tatenuma, Mitsuru Komeya, Hiroki Ito, Yusuke Ito, Kentaro Muraoka, Mitsuko Furuya, Ikuma Kato, Satoshi Fujii, Haruka Hamanoue, Tomohiko Tamura, Masaya Baba, Toshio Suda, Tatsuhiko Kodama, Kazuhide Makiyama, Masahiro Yao, Brian M Shuch, Christopher J Ricketts, Laura S Schmidt, W Marston Linehan, Hidewaki Nakagawa, Hisashi Hasumi

Faculty, Staff and Student Publications

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated.

METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated …

The Integrative Studies On The Functional A-To-I Rna Editing Events In Human Cancers, Sijia Wu, Zhiwei Fan, Pora Kim, Liyu Huang, Xiaobo Zhou

Faculty, Staff and Student Publications

Adenosine-to-inosine (A-to-I) RNA editing, constituting nearly 90% of all RNA editing events in humans, has been reported to contribute to the tumorigenesis in diverse cancers. However, the comprehensive map for functional A-to-I RNA editing events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ∼ 1,500,000 quantified RNA editing events, we performed diverse types of downstream functional annotations. Finally, we identified 24,236 potentially functional A-to-I RNA editing events, including the cases …

Target Cell-Specific Synaptic Dynamics Of Excitatory To Inhibitory Neuron Connections In Supragranular Layers Of Human Neocortex, Mean-Hwan Kim, Cristina Radaelli, Elliot R Thomsen, Deja Monet, Thomas Chartrand, Nikolas L Jorstad, Joseph T Mahoney, Michael J Taormina, Brian Long, Katherine Baker, Trygve E Bakken, Luke Campagnola, Tamara Casper, Michael Clark, Nick Dee, Florence D'Orazi, Clare Gamlin, Brian E Kalmbach, Sara Kebede, Brian R Lee, Lindsay Ng, Jessica Trinh, Charles Cobbs, Ryder P Gwinn, C Dirk Keene, Andrew L Ko, Jeffrey G Ojemann, Daniel L Silbergeld, Staci A Sorensen, Jim Berg, Kimberly A Smith, Philip R Nicovich, Tim Jarsky, Hongkui Zeng, Jonathan T Ting, Boaz P Levi, Ed Lein

Faculty, Staff and Student Publications

Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings, post-hoc fluorescent in situ hybridization (FISH), machine learning-based cell type classification and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- …

Nanoscratch-Induced Formation Of Metallic Micro/Nanostructures With Resin Masks, Mingyong Xin, Qihui Feng, Changbao Xu, Licong Cui, Jie Zhu, Yinkai Gan, Bingjun Yu

Faculty, Staff and Student Publications

Metallic micro/nanostructures present a wide range of applications due to the small size and superior performances. In order to obtain high-performance devices, it is of great importance to develop new methods for preparing metallic micro/nanostructures with high quality, low cost, and precise position. It is found that metallic micro/nanostructures can be obtained by scratch-induced directional deposition of metals on silicon surface, where the mask plays a key role in the process. This study is focused on the preparation of keto-aldehyde resin masks and their effects on the formation of scratch-induced gold (Au) micro/nanostructures. It is also found that the keto-aldehyde …

Genome-Wide Association Study Of Lung Adenocarcinoma In East Asia And Comparison With A European Population, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Juncheng Dai, Rayjean J Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Bao Song, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Karen M Funderburk, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Batel Blechter, Bryan A Bassig, Jin Hee Kim, Demetrius Albanes, Jason Y Y Wong, Min-Ho Shin, Lap Ping Chung, Yang Yang, She-Juan An, Hong Zheng, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E Caporaso, Jiang Chang, James Chung Man Ho, Michiaki Kubo, Yataro Daigo, Minsun Song, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, Dean H Hosgood, Hideo Kunitoh, Harsh Patel, Shun-Ichi Watanabe, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Yuichiro Ohe, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Hongji Dai, Mitchell J Machiela, Jian Su, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Ying-Huang Tsai, Kuan-Yu Chen, Ming-Shyan Huang, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Kun-Chieh Chen, Yu-Tang Gao, Biyun Qian, Chen Wu, Daru Lu, Jianjun Liu, Ann G Schwartz, Richard Houlston, Margaret R Spitz, Ivan P Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu-Tian Ji, H-Erich Wichmann, David C Christiani, Gadi Rennert, Susanne Arnold, Paul Brennan, James Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Mikael Johansson, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Jae Sook Sung, Chung-Hsing Chen, Chin-Fu Hsiao, Yoo Jin Jung, Huan Guo, Zhibin Hu, Laurie Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Bin Zhu, Sonja I Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jun Suk Kim, Ho-Il Yoon, In Kyu Park, Ping Xu, Qincheng He, Chih-Liang Wang, Hsiao-Han Hung, Roel C H Vermeulen, Iona Cheng, Junjie Wu, Wei-Yen Lim, Fang-Yu Tsai, John K C Chan, Jihua Li, Hongyan Chen, Hsien-Chih Lin, Li Jin, Jie Liu, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Shengchao A Li, Hongxia Ma, Meng Zhu, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen, Pan-Chyr Yang, Jinming Yu, Victoria L Stevens, Joseph F Fraumeni, Nilanjan Chatterjee, Olga Y Gorlova, Chao Agnes Hsiung, Christopher I Amos, Hongbing Shen, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan

Faculty, Staff and Student Publications

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European …

Quehry: A Question Answering System To Query Electronic Health Records, Sarvesh Soni, Surabhi Datta, Kirk Roberts

Faculty, Staff and Student Publications

OBJECTIVE: We propose a system, quEHRy, to retrieve precise, interpretable answers to natural language questions from structured data in electronic health records (EHRs).

MATERIALS AND METHODS: We develop/synthesize the main components of quEHRy: concept normalization (MetaMap), time frame classification (new), semantic parsing (existing), visualization with question understanding (new), and query module for FHIR mapping/processing (new). We evaluate quEHRy on 2 clinical question answering (QA) datasets. We evaluate each component separately as well as holistically to gain deeper insights. We also conduct a thorough error analysis for a crucial subcomponent, medical concept normalization.

RESULTS: Using gold concepts, the precision of quEHRy …

Shared Decision Making In Acute Pain Management In Patients With Opioid Use Disorder: A Scoping Review, Peter D Vu, Aila Malik, A Sarah Cohen, Vishal Bansal, Morgan R Cowan, Gregory M Blazek, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

The treatment of acute pain over the years has changed with increasing alternative therapies and increased scrutiny of opioid prescriptions. Shared Decision Making (SDM) has become a vital tool in increasing patient engagement and satisfaction in treatment decisions. SDM has been successfully implemented in the management of pain in a variety of settings; however, information regarding the use of SDM for treating acute pain in patients with a history of opioid use disorder (OUD) remains scarce. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews (PRISMA-ScR), we conducted a review to understand how SDM is …

Mesoporous Silica Nanoparticles As A Gene Delivery Platform For Cancer Therapy, Nisar Ul Khaliq, Juyeon Lee, Joohyeon Kim, Yejin Kim, Sohyeon Yu, Jisu Kim, Sangwoo Kim, Daekyung Sung, Hyungjun Kim

Faculty, Staff and Student Publications

Cancer remains a major global health challenge. Traditional chemotherapy often results in side effects and drug resistance, necessitating the development of alternative treatment strategies such as gene therapy. Mesoporous silica nanoparticles (MSNs) offer many advantages as a gene delivery carrier, including high loading capacity, controlled drug release, and easy surface functionalization. MSNs are biodegradable and biocompatible, making them promising candidates for drug delivery applications. Recent studies demonstrating the use of MSNs for the delivery of therapeutic nucleic acids to cancer cells have been reviewed, along with their potential as a tool for cancer therapy. The major challenges and future interventions …

A Vlp-Based Vaccine Displaying Hbha And Mtp Antigens Of Mycobacterium Tuberculosis Induces Potentially Protective Immune Responses In M Tuberculosis H37ra Infected Mice, Juan Wang, Tao Xie, Inayat Ullah, Youjun Mi, Xiaoping Li, Yang Gong, Pu He, Yuqi Liu, Fei Li, Jixi Li, Zengjun Lu, Bingdong Zhu

Faculty, Staff and Student Publications

Heparin-binding hemagglutinin (HBHA) and M. tuberculosis pili (MTP) are important antigens on the surface of Mycobacterium tuberculosis. To display these antigens effectively, the fusion protein HBHA-MTP with a molecular weight of 20 kD (L20) was inserted into the receptor-binding hemagglutinin (HA) fragment of influenza virus and was expressed along with matrix protein M1 in Sf9 insect cells to generate influenza virus-like particles (LV20 in short). The results showed that the insertion of L20 into the envelope of the influenza virus did not affect the self-assembly and morphology of LV20 VLPs. The expression of L20 was successfully verified by transmission …

Deephtlv: A Deep Learning Framework For Detecting Human T-Lymphotrophic Virus 1 Integration Sites, Johnathan Jia, Johnathan Jia

Dissertations and Theses (Open Access)

In the 1980s, researchers found the first human oncogenic retrovirus called human T-lymphotrophic virus type 1 (HTLV-1). Since then, HTLV-1 has been identified as the causative agent behind several diseases such as adult T-cell leukemia/lymphoma (ATL) and a HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). As part of its normal replication cycle, the genome is converted into DNA and integrated into the genome. With several hundreds to thousands of unique viral integration sites (VISs) distributed with indeterminate preference throughout the genome, detection of HTLV-1 VISs is a challenging task. Experimental studies typically use molecular biology …

Toward A Neural Semantic Parsing System For Ehr Question Answering, Sarvesh Soni, Kirk Roberts

Faculty, Staff and Student Publications

Clinical semantic parsing (SP) is an important step toward identifying the exact information need (as a machine-understandable logical form) from a natural language query aimed at retrieving information from electronic health records (EHRs). Current approaches to clinical SP are largely based on traditional machine learning and require hand-building a lexicon. The recent advancements in neural SP show a promise for building a robust and flexible semantic parser without much human effort. Thus, in this paper, we aim to systematically assess the performance of two such neural SP models for EHR question answering (QA). We found that the performance of these …

Learning In A Virtual Environment To Improve Type 2 Diabetes Outcomes: Randomized Controlled Trial, Constance M Johnson, Gail D'Eramo Melkus, Louise Reagan, Wei Pan, Sathya Amarasekara, Katherine Pereira, Nancy Hassell, Sarah Nowlin, Allison Vorderstrasse

Faculty, Staff and Student Publications

Background: Given the importance of self-management in type 2 diabetes mellitus (T2DM), a major aspect of health is providing diabetes self-management education and support. Known barriers include access, availability, and the lack of follow through on referral to education programs. Virtual education and support have increased in use over the last few years.

Objective: The purpose of the Diabetes Learning in a Virtual Environment (LIVE) study was to compare the effects of the LIVE intervention (educational 3D world) to a diabetes self-management education and support control website on diet and physical activity behaviors and behavioral and metabolic outcomes in adults …

A Multi-Site Randomized Trial Of A Clinical Decision Support Intervention To Improve Problem List Completeness, Adam Wright, Richard Schreiber, David W Bates, Skye Aaron, Angela Ai, Raja Arul Cholan, Akshay Desai, Miguel Divo, David A Dorr, Thu-Trang Hickman, Salman Hussain, Shari Just, Brian Koh, Stuart Lipsitz, Dustin Mcevoy, Trent Rosenbloom, Elise Russo, David Yut-Chee Ting, Asli Weitkamp, Dean F Sittig

Faculty, Staff and Student Publications

OBJECTIVE: To improve problem list documentation and care quality.

MATERIALS AND METHODS: We developed algorithms to infer clinical problems a patient has that are not recorded on the coded problem list using structured data in the electronic health record (EHR) for 12 clinically significant heart, lung, and blood diseases. We also developed a clinical decision support (CDS) intervention which suggests adding missing problems to the problem list. We evaluated the intervention at 4 diverse healthcare systems using 3 different EHRs in a randomized trial using 3 predetermined outcome measures: alert acceptance, problem addition, and National Committee for Quality Assurance Healthcare …

The Potential Regulation Of A-To-I Rna Editing On Genes In Parkinson's Disease, Sijia Wu, Qiuping Xue, Xinyu Qin, Xiaoming Wu, Pora Kim, Jacqueline Chyr, Xiaobo Zhou, Liyu Huang

Faculty, Staff and Student Publications

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration and an abnormal accumulation of α-synuclein aggregates. A number of genetic factors have been shown to increase the risk of PD. Exploring the underlying molecular mechanisms that mediate PD's transcriptomic diversity can help us understand neurodegenerative pathogenesis. In this study, we identified 9897 A-to-I RNA editing events associated with 6286 genes across 372 PD patients. Of them, 72 RNA editing events altered miRNA binding sites and this may directly affect miRNA regulations of their host genes. However, RNA editing effects on the miRNA regulation of genes are more complex. They can (1) …

Physio-Psycho-Social Interaction Mechanism In Dyadic Health Of Young And Middle-Aged Stroke Survivors And Their Spousal Caregivers: A Longitudinal Observational Study Protocol, Dandan Xiang, Zhen-Xiang Zhang, Song Ge, Wen Na Wang, Bei-Lei Lin, Su-Yan Chen, Er-Feng Guo, Peng-Bo Zhang, Zhi-Wei Liu, Hui Li, Yong-Xia Mei

Faculty, Staff and Student Publications

Introduction: In recent years, stroke has become more common among young people. Stroke not only has a profound impact on patients' health but also incurs stress and health threats to their caregivers, especially spousal caregivers. Moreover, the health of stroke survivors and their caregivers is interdependent. To our knowledge, no study has explored dyadic health of young and middle-aged stroke survivors and their spousal caregivers from physiological, psychological and social perspectives. Therefore, this proposed study aims to explore the mechanism of how physiological, psychological and social factors affect dyadic health of young and middle-aged stroke survivors and their spousal caregivers. …

Quantitative Proteomic Screening Uncovers Candidate Diagnostic And Monitoring Serum Biomarkers Of Ankylosing Spondylitis, Mark Hwang, Shervin Assassi, Jim Zheng, Jessica Castillo, Reyna Chavez, Kamala Vanarsa, Chandra Mohan, John Reveille

Faculty, Staff and Student Publications

BACKGROUND: We sought to discover serum biomarkers of ankylosing spondylitis (AS) for diagnosis and monitoring disease activity.

METHODS: We studied biologic-treatment-naïve AS and healthy control (HC) patients' sera. Eighty samples matched by age, gender, and race (1:1:1 ratio) for AS patients with active disease, inactive disease, and HC were analyzed with SOMAscan™, an aptamer-based discovery platform. T-tests tests were performed for high/low-disease activity AS patients versus HCs (diagnosis) and high versus low disease activity (Monitoring) in a 2:1 and 1:1 ratio, respectively, to identify differentially expressed proteins (DEPs). We used the Cytoscape Molecular Complex Detection (MCODE) plugin to find clusters …

Distribution Of Serum Uric Acid Concentration And Its Association With Lipid Profiles: A Single-Center Retrospective Study In Children Aged 3 To 12 Years With Adenoid And Tonsillar Hypertrophy, Jiating Yu, Xin Liu, Honglei Ji, Yawei Zhang, Hanqiang Zhan, Ziyin Zhang, Jianguo Wen, Zhimin Wang

Faculty, Staff and Student Publications

BACKGROUND: Presently, there is no consensus regarding the optimal serum uric acid (SUA) concentration for pediatric patients. Adenoid and tonsillar hypertrophy is considered to be closely associated with pediatric metabolic syndrome and cardiovascular risk and is a common condition in children admitted to the hospital. Therefore, we aimed to evaluate the relationship between SUA and dyslipidemia and propose a reference range for SUA concentration that is associated with a healthy lipid profile in hospitalized children with adenoid and tonsillar hypertrophy.

METHODS: Preoperative data from 4922 children admitted for elective adenoidectomy and/or tonsillectomy surgery due to adenoid and tonsillar hypertrophy were …

Discerning Conversational Context In Online Health Communities For Personalized Digital Behavior Change Solutions Using Pragmatics To Reveal Intent In Social Media (Prism) Framework, Tavleen Singh, Kirk Roberts, Trevor Cohen, Nathan Cobb, Amy Franklin, Sahiti Myneni

Faculty, Staff and Student Publications

BACKGROUND: Online health communities (OHCs) have emerged as prominent platforms for behavior modification, and the digitization of online peer interactions has afforded researchers with unique opportunities to model multilevel mechanisms that drive behavior change. Existing studies, however, have been limited by a lack of methods that allow the capture of conversational context and socio-behavioral dynamics at scale, as manifested in these digital platforms.

OBJECTIVE: We develop, evaluate, and apply a novel methodological framework, Pragmatics to Reveal Intent in Social Media (PRISM), to facilitate granular characterization of peer interactions by combining multidimensional facets of human communication.

METHODS: We developed and applied …

Prediction Of Brain Metastases Development In Patients With Lung Cancer By Explainable Artificial Intelligence From Electronic Health Records, Zhao Li, Rongbin Li, Yujia Zhou, Laila Rasmy, Degui Zhi, Ping Zhu, Antonio Dono, Xiaoqian Jiang, Hua Xu, Yoshua Esquenazi, W Jim Zheng

Faculty, Staff and Student Publications

PURPOSE: Early detection of brain metastases (BMs) is critical for prompt treatment and optimal control of the disease. In this study, we seek to predict the risk of developing BM among patients diagnosed with lung cancer on the basis of electronic health record (EHR) data and to understand what factors are important for the model to predict BM development through explainable artificial intelligence approaches accurately.

MATERIALS AND METHODS: We trained a recurrent neural network model, REverse Time AttentIoN (RETAIN), to predict the risk of developing BM using structured EHR data. To interpret the model's decision process, we analyzed the attention …

Why Is Biomedical Informatics Hard? A Fundamental Framework, Todd R Johnson, Elmer V Bernstam

Faculty, Staff and Student Publications

Building on previous work to define the scientific discipline of biomedical informatics, we present a framework that categorizes fundamental challenges into groups based on data, information, and knowledge, along with the transitions between these levels. We define each level and argue that the framework provides a basis for separating informatics problems from non-informatics problems, identifying fundamental challenges in biomedical informatics, and provides guidance regarding the search for general, reusable solutions to informatics problems. We distinguish between processing data (symbols) and processing meaning. Computational systems, that are the basis for modern information technology (IT), process data. In contrast, many important challenges …

Convolutional Neural Network For Biomarker Discovery For Triple Negative Breast Cancer With Rna Sequencing Data, Xiangning Chen, Justin M Balko, Fei Ling, Yabin Jin, Anneliese Gonzalez, Zhongming Zhao, Jingchun Chen

Faculty, Staff and Student Publications

Triple negative breast cancers (TNBCs) are tumors with a poor treatment response and prognosis. In this study, we propose a new approach, candidate extraction from convolutional neural network (CNN) elements (CECE), for discovery of biomarkers for TNBCs. We used the GSE96058 and GSE81538 datasets to build a CNN model to classify TNBCs and non-TNBCs and used the model to make TNBC predictions for two additional datasets, the cancer genome atlas (TCGA) breast cancer RNA sequencing data and the data from Fudan University Shanghai Cancer Center (FUSCC). Using correctly predicted TNBCs from the GSE96058 and TCGA datasets, we calculated saliency maps …

Application Of An Ontology For Model Cards To Generate Computable Artifacts For Linking Machine Learning Information From Biomedical Research, Muhammad Tuan Amith, Licong Cui, Kirk Roberts, Cui Tao

Faculty, Staff and Student Publications

Model card reports provide a transparent description of machine learning models which includes information about their evaluation, limitations, intended use, etc. Federal health agencies have expressed an interest in model cards report for research studies using machine-learning based AI. Previously, we have developed an ontology model for model card reports to structure and formalize these reports. In this paper, we demonstrate a Java-based library (OWL API, FaCT++) that leverages our ontology to publish computable model card reports. We discuss future directions and other use cases that highlight applicability and feasibility of ontology-driven systems to support FAIR challenges.

De Novo Mutations Disturb Early Brain Development More Frequently Than Common Variants In Schizophrenia, Toshiyuki Itai, Peilin Jia, Yulin Dai, Jingchun Chen, Xiangning Chen, Zhongming Zhao

Faculty, Staff and Student Publications

Investigating functional, temporal, and cell-type expression features of mutations is important for understanding a complex disease. Here, we collected and analyzed common variants and de novo mutations (DNMs) in schizophrenia (SCZ). We collected 2,636 missense and loss-of-function (LoF) DNMs in 2,263 genes across 3,477 SCZ patients (SCZ-DNMs). We curated three gene lists: (a) SCZ-neuroGenes (159 genes), which are intolerant to LoF and missense DNMs and are neurologically important, (b) SCZ-moduleGenes (52 genes), which were derived from network analyses of SCZ-DNMs, and (c) SCZ-commonGenes (120 genes) from a recent GWAS as reference. To compare temporal gene expression, we used the BrainSpan …

Genetic Correlations Between Alzheimer’S Disease And Gut Microbiome Genera, Davis Cammann, Yimei Lu, Melika J Cummings, Mark L Zhang, Joan Manuel Cue, Jenifer Do, Jeffrey Ebersole, Xiangning Chen, Edwin C Oh, Jeffrey L Cummings, Jingchun Chen

Faculty, Staff and Student Publications

A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer's disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual's risk for the disease. Using the largest genome-wide …

Hsc-Independent Definitive Hematopoiesis Persists Into Adult Life, Michihiro Kobayashi, Haichao Wei, Takashi Yamanashi, Nathalia Azevedo Portilho, Samuel Cornelius, Noemi Valiente, Chika Nishida, Haizi Cheng, Augusto Latorre, W Jim Zheng, Joonsoo Kang, Jun Seita, David J Shih, Jia Qian Wu, Momoko Yoshimoto

Faculty, Staff and Student Publications

It is widely believed that hematopoiesis after birth is established by hematopoietic stem cells (HSCs) in the bone marrow and that HSC-independent hematopoiesis is limited only to primitive erythro-myeloid cells and tissue-resident innate immune cells arising in the embryo. Here, surprisingly, we find that significant percentages of lymphocytes are not derived from HSCs, even in 1-year-old mice. Instead, multiple waves of hematopoiesis occur from embryonic day 7.5 (E7.5) to E11.5 endothelial cells, which simultaneously produce HSCs and lymphoid progenitors that constitute many layers of adaptive T and B lymphocytes in adult mice. Additionally, HSC lineage tracing reveals that the contribution …

Genetic Control Of Rna Editing In Neurodegenerative Disease, Sijia Wu, Qiuping Xue, Mengyuan Yang, Yanfei Wang, Pora Kim, Xiaobo Zhou, Liyu Huang

Faculty, Staff and Student Publications

A-to-I RNA editing diversifies human transcriptome to confer its functional effects on the downstream genes or regulations, potentially involving in neurodegenerative pathogenesis. Its variabilities are attributed to multiple regulators, including the key factor of genetic variants. To comprehensively investigate the potentials of neurodegenerative disease-susceptibility variants from the view of A-to-I RNA editing, we analyzed matched genetic and transcriptomic data of 1596 samples across nine brain tissues and whole blood from two large consortiums, Accelerating Medicines Partnership-Alzheimer's Disease and Parkinson's Progression Markers Initiative. The large-scale and genome-wide identification of 95 198 RNA editing quantitative trait loci revealed the preferred genetic effects …

Global Scientific Trends On Healthy Eating From 2002 To 2021: A Bibliometric And Visualized Analysis, Te Fang, Hongyi Cao, Yue Wang, Yang Gong, Zhongqing Wang

Faculty, Staff and Student Publications

Diet has been recognized as a vital risk factor for non-communicable diseases (NCDs), climate changes, and increasing population, which has been reflected by a rapidly growing body of the literature related to healthy eating. To reveal a panorama of the topics related to healthy eating, this study aimed to characterize and visualize the knowledge structure, hotspots, and trends in this field over the past two decades through bibliometric analyses. Publications related to healthy eating between 1 January 2002 and 31 December 2021 were retrieved and extracted from the Web of Science database. The characteristics of articles including publication years, journals, …

A Scoping Review Of Digital Health Interventions For Combating Covid-19 Misinformation And Disinformation, Katarzyna Czerniak, Raji Pillai, Abhi Parmar, Kavita Ramnath, Joseph Krocker, Sahiti Myneni

Faculty, Staff and Student Publications

OBJECTIVE: We provide a scoping review of Digital Health Interventions (DHIs) that mitigate COVID-19 misinformation and disinformation seeding and spread.

MATERIALS AND METHODS: We applied our search protocol to PubMed, PsychINFO, and Web of Science to screen 1666 articles. The 17 articles included in this paper are experimental and interventional studies that developed and tested public consumer-facing DHIs. We examined these DHIs to understand digital features, incorporation of theory, the role of healthcare professionals, end-user experience, and implementation issues.

RESULTS: The majority of studies (n = 11) used social media in DHIs, but there was a lack of platform-agnostic generalizability. …

A Gene Regulatory Network Approach Harmonizes Genetic And Epigenetic Signals And Reveals Repurposable Drug Candidates For Multiple Sclerosis, Astrid M Manuel, Yulin Dai, Peilin Jia, Leorah A Freeman, Zhongming Zhao

Faculty, Staff and Student Publications

Multiple sclerosis (MS) is a complex dysimmune disorder of the central nervous system. Genome-wide association studies (GWAS) have identified 233 genetic variations associated with MS at the genome-wide significant level. Epigenetic studies have pinpointed differentially methylated CpG sites in MS patients. However, the interplay between genetic risk factors and epigenetic regulation remains elusive. Here, we employed a network model to integrate GWAS summary statistics of 14 802 MS cases and 26 703 controls with DNA methylation profiles from 140 MS cases and 139 controls and the human interactome. We identified differentially methylated genes by aggregating additive effects of differentially methylated …

Identifying A Clinical Informatics Or Electronic Health Record Expert Witness For Medical Professional Liability Cases, Dean F Sittig, Adam Wright

Faculty, Staff and Student Publications

BACKGROUND: The health care field is experiencing widespread electronic health record (EHR) adoption. New medical professional liability (i.e., malpractice) cases will likely involve the review of data extracted from EHRs as well as EHR workflows, audit logs, and even the potential role of the EHR in causing harm.

OBJECTIVES: Reviewing printed versions of a patient's EHRs can be difficult due to differences in printed versus on-screen presentations, redundancies, and the way printouts are often grouped by document or information type rather than chronologically. Simply recreating an accurate timeline often requires experts with training and experience in designing, developing, using, and …