Data Science Commons^™

Developing Electronic Clinical Quality Measures To Assess The Cancer Diagnostic Process, Daniel R Murphy, Andrew J Zimolzak, Divvy K Upadhyay, Li Wei, Preeti Jolly, Alexis Offner, Dean F Sittig, Saritha Korukonda, Riyaa Murugaesh Rekha, Hardeep Singh

Faculty, Staff and Student Publications

OBJECTIVE: Measures of diagnostic performance in cancer are underdeveloped. Electronic clinical quality measures (eCQMs) to assess quality of cancer diagnosis could help quantify and improve diagnostic performance.

MATERIALS AND METHODS: We developed 2 eCQMs to assess diagnostic evaluation of red-flag clinical findings for colorectal (CRC; based on abnormal stool-based cancer screening tests or labs suggestive of iron deficiency anemia) and lung (abnormal chest imaging) cancer. The 2 eCQMs quantified rates of red-flag follow-up in CRC and lung cancer using electronic health record data repositories at 2 large healthcare systems. Each measure used clinical data to identify abnormal results, evidence of …

Federated Generalized Linear Mixed Models For Collaborative Genome-Wide Association Studies, Wentao Li, Han Chen, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

Federated association testing is a powerful approach to conduct large-scale association studies where sites share intermediate statistics through a central server. There are, however, several standing challenges. Confounding factors like population stratification should be carefully modeled across sites. In addition, it is crucial to consider disease etiology using flexible models to prevent biases. Privacy protections for participants pose another significant challenge. Here, we propose distributed Mixed Effects Genome-wide Association study (

Systematic Design And Data-Driven Evaluation Of Social Determinants Of Health Ontology (Sdoho), Yifang Dang, Fang Li, Xinyue Hu, Vipina K Keloth, Meng Zhang, Sunyang Fu, Muhammad F Amith, J Wilfred Fan, Jingcheng Du, Evan Yu, Hongfang Liu, Xiaoqian Jiang, Hua Xu, Cui Tao

Faculty, Staff and Student Publications

Objective: Social determinants of health (SDoH) play critical roles in health outcomes and well-being. Understanding the interplay of SDoH and health outcomes is critical to reducing healthcare inequalities and transforming a "sick care" system into a "health-promoting" system. To address the SDOH terminology gap and better embed relevant elements in advanced biomedical informatics, we propose an SDoH ontology (SDoHO), which represents fundamental SDoH factors and their relationships in a standardized and measurable way.

Material and methods: Drawing on the content of existing ontologies relevant to certain aspects of SDoH, we used a top-down approach to formally model classes, relationships, and …

A Lifecycle Framework Illustrates Eight Stages Necessary For Realizing The Benefits Of Patient-Centered Clinical Decision Support, Dean F Sittig, Aziz Boxwala, Adam Wright, Courtney Zott, Priyanka Desai, Rina Dhopeshwarkar, James Swiger, Edwin A Lomotan, Angela Dobes, Prashila Dullabh

Faculty, Staff and Student Publications

The design, development, implementation, use, and evaluation of high-quality, patient-centered clinical decision support (PC CDS) is necessary if we are to achieve the quintuple aim in healthcare. We developed a PC CDS lifecycle framework to promote a common understanding and language for communication among researchers, patients, clinicians, and policymakers. The framework puts the patient, and/or their caregiver at the center and illustrates how they are involved in all the following stages: Computable Clinical Knowledge, Patient-specific Inference, Information Delivery, Clinical Decision, Patient Behaviors, Health Outcomes, Aggregate Data, and patient-centered outcomes research (PCOR) Evidence. Using this idealized framework reminds key stakeholders that …

Identifying Contributing Factors Associated With Dental Adverse Events Through A Pragmatic Electronic Health Record-Based Root Cause Analysis, Elsbeth Kalenderian, Suhasini Bangar, Alfa Yansane, Duong Tran, Emily Sedlock, Yan Xiao, Janelle Urata, Greg Olson, Amy Franklin, Krishna Kookal, Ana Ibarra-Noriega, Sayali Tungare, Oluwabunmi Tokede, Heiko Spallek, Joel M White, Muhammad F Walji

Faculty, Staff and Student Publications

OBJECTIVE: This study assessed contributing factors associated with dental adverse events (AEs).

METHODS: Seven electronic health record-based triggers were deployed identifying potential AEs at 2 dental institutions. From 4106 flagged charts, 2 reviewers examined 439 charts selected randomly to identify and classify AEs using our dental AE type and severity classification systems. Based on information captured in the electronic health record, we analyzed harmful AEs to assess potential contributing factors; harmful AEs were defined as those that resulted in temporary moderate to severe harm, required hospitalization, or resulted in permanent moderate to severe harm. We classified potential contributing factors according …

Knowledge Representation And Management 2022: Findings In Ontology Development And Applications, Jean Charlet, Licong Cui, Section Editors For The Imia Yearbook Section On Knowledge Representation And Management

Faculty, Staff and Student Publications

OBJECTIVES: To select, present, and summarize the best papers in 2022 for the Knowledge Representation and Management (KRM) section of the International Medical Informatics Association (IMIA) Yearbook.

METHODS: We conducted PubMed queries and followed the IMIA Yearbook guidelines for performing biomedical informatics literature review to select the best papers in KRM published in 2022.

RESULTS: We retrieved 1,847 publications from PubMed. We nominated 15 candidate best papers, and two of them were finally selected as the best papers in the KRM section. The topics covered by the candidate papers include ontology and knowledge graph creation, ontology applications, ontology quality assurance, …

Federated Generalized Linear Mixed Models For Collaborative Genome-Wide Association Studies, Wentao Li, Han Chen, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

Federated association testing is a powerful approach to conduct large-scale association studies where sites share intermediate statistics through a central server. There are, however, several standing challenges. Confounding factors like population stratification should be carefully modeled across sites. In addition, it is crucial to consider disease etiology using flexible models to prevent biases. Privacy protections for participants pose another significant challenge. Here, we propose distributed Mixed Effects Genome-wide Association study (dMEGA), a method that enables federated generalized linear mixed model-based association testing across multiple sites without explicitly sharing genotype and phenotype data. dMEGA employs a reference projection to …

Surface-Doped Zinc Gallate Colloidal Nanoparticles Exhibit Ph-Dependent Radioluminescence With Enhancement In Acidic Media, Navadeep Shrivastava, Jessa Guffie, Tamela L Moore, Burak Guzelturk, Amar S Kumbhar, Jianguo Wen, Zhiping Luo

Faculty, Staff and Student Publications

As abnormal acidic pH symbolizes dysfunctions of cells, it is highly desirable to develop pH-sensitive luminescent materials for diagnosing disease and imaging-guided therapy using high-energy radiation. Herein, we explored near-infrared-emitting Cr-doped zinc gallate ZnGa2O4 nanoparticles (NPs) in colloidal solutions with different pH levels under X-ray excitation. Ultrasmall NPs were synthesized via a facile hydrothermal method by controlling the addition of ammonium hydroxide precursor and reaction time, and structural characterization revealed Cr dopants on the surface of NPs. The synthesized NPs exhibited different photoluminescence and radioluminescence mechanisms, confirming the surface distribution of activators. It was observed that the colloidal NPs emit …

The Impact Framework And Implementation For Accessible In Silico Clinical Phenotyping In The Digital Era, Andrew Wen, Huan He, Sunyang Fu, Sijia Liu, Kurt Miller, Liwei Wang, Kirk E Roberts, Steven D Bedrick, William R Hersh, Hongfang Liu

Faculty, Staff and Student Publications

Clinical phenotyping is often a foundational requirement for obtaining datasets necessary for the development of digital health applications. Traditionally done via manual abstraction, this task is often a bottleneck in development due to time and cost requirements, therefore raising significant interest in accomplishing this task via in-silico means. Nevertheless, current in-silico phenotyping development tends to be focused on a single phenotyping task resulting in a dearth of reusable tools supporting cross-task generalizable in-silico phenotyping. In addition, in-silico phenotyping remains largely inaccessible for a substantial portion of potentially interested users. Here, we highlight the barriers to the usage of in-silico phenotyping …

Non-Invasive Arterial Blood Pressure Measurement And Spo2 Estimation Using Ppg Signal: A Deep Learning Framework, Yan Chu, Kaichen Tang, Yu-Chun Hsu, Tongtong Huang, Dulin Wang, Wentao Li, Sean I Savitz, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

BACKGROUND: Monitoring blood pressure and peripheral capillary oxygen saturation plays a crucial role in healthcare management for patients with chronic diseases, especially hypertension and vascular disease. However, current blood pressure measurement methods have intrinsic limitations; for instance, arterial blood pressure is measured by inserting a catheter in the artery causing discomfort and infection.

METHOD: Photoplethysmogram (PPG) signals can be collected via non-invasive devices, and therefore have stimulated researchers' interest in exploring blood pressure estimation using machine learning and PPG signals as a non-invasive alternative. In this paper, we propose a Transformer-based deep learning architecture that utilizes PPG signals to conduct …

The Screening Of The Protective Antigens Of Aeromonas Hydrophila Using The Reverse Vaccinology Approach: Potential Candidates For Subunit Vaccine Development, Ting Zhang, Minying Zhang, Zehua Xu, Yang He, Xiaoheng Zhao, Hanliang Cheng, Xiangning Chen, Jianhe Xu, Zhujin Ding

Faculty, Staff and Student Publications

The threat of bacterial septicemia caused by Aeromonas hydrophila infection to aquaculture growth can be prevented through vaccination, but differences among A. hydrophila strains may affect the effectiveness of non-conserved subunit vaccines or non-inactivated A. hydrophila vaccines, making the identification and development of conserved antigens crucial. In this study, a bioinformatics analysis of 4268 protein sequences encoded by the A. hydrophila J-1 strain whole genome was performed based on reverse vaccinology. The specific analysis included signal peptide prediction, transmembrane helical structure prediction, subcellular localization prediction, and antigenicity and adhesion evaluation, as well as interspecific and intraspecific homology comparison, thereby screening …

The Impact Of Covid-19 On The Financial Performance Of Largest Teaching Hospitals, Karima Lalani, Jeffrey Helton, Francine R Vega, Marylou Cardenas-Turanzas, Tiffany Champagne-Langabeer, James R Langabeer

Faculty, Staff and Student Publications

The COVID-19 pandemic disrupted hospital operations. Anecdotal evidence suggests financial performance likewise suffered, yet little empirical research supports this claim. This study aimed to explore the impact of the pandemic on the financial performance of the most prominent academic hospitals in the United States. Data from the 115 largest major teaching hospitals in the United States were extracted from the American Hospital Directory for three years (2019-2021). We hypothesized that the year and region would moderate the relationship between a hospital's return on assets (financial performance) and specific operational variables. We found evidence through descriptive statistics and multivariate moderated regressions …

Fast Inference Of Genetic Recombination Rates In Biobank Scale Data, Ardalan Naseri, William Yue, Shaojie Zhang, Degui Zhi

Faculty, Staff and Student Publications

Although rates of recombination events across the genome (genetic maps) are fundamental to genetic research, the majority of current studies only use one standard map. There is evidence suggesting population differences in genetic maps, and thus estimating population-specific maps, are of interest. Although the recent availability of biobank-scale data offers such opportunities, current methods are not efficient at leveraging very large sample sizes. The most accurate methods are still linkage disequilibrium (LD)-based methods that are only tractable for a few hundred samples. In this work, we propose a fast and memory-efficient method for estimating genetic maps from population genotyping data. …

Multi-Task Learning With Dynamic Re-Weighting To Achieve Fairness In Healthcare Predictive Modeling, Can Li, Sirui Ding, Na Zou, Xia Hu, Xiaoqian Jiang, Kai Zhang

Faculty, Staff and Student Publications

The emphasis on fairness in predictive healthcare modeling has increased in popularity as an approach for overcoming biases in automated decision-making systems. The aim is to guarantee that sensitive characteristics like gender, race, and ethnicity do not influence prediction outputs. Numerous algorithmic strategies have been proposed to reduce bias in prediction results, mitigate prejudice toward minority groups and promote prediction fairness. The goal of these strategies is to ensure that model prediction performance does not exhibit significant disparity among sensitive groups. In this study, we propose a novel fairness-achieving scheme based on multitask learning, which fundamentally differs from conventional fairness-achieving …

Weakly Supervised Spatial Relation Extraction From Radiology Reports, Surabhi Datta, Kirk Roberts

Faculty, Staff and Student Publications

OBJECTIVE: Weak supervision holds significant promise to improve clinical natural language processing by leveraging domain resources and expertise instead of large manually annotated datasets alone. Here, our objective is to evaluate a weak supervision approach to extract spatial information from radiology reports.

MATERIALS AND METHODS: Our weak supervision approach is based on data programming that uses rules (or labeling functions) relying on domain-specific dictionaries and radiology language characteristics to generate weak labels. The labels correspond to different spatial relations that are critical to understanding radiology reports. These weak labels are then used to fine-tune a pretrained Bidirectional Encoder Representations from …

Minimal Positional Substring Cover Is A Haplotype Threading Alternative To Li And Stephens Model, Ahsan Sanaullah, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

The Li and Stephens (LS) hidden Markov model (HMM) models the process of reconstructing a haplotype as a mosaic copy of haplotypes in a reference panel. For small panels, the probabilistic parameterization of LS enables modeling the uncertainties of such mosaics. However, LS becomes inefficient when sample size is large, because of its linear time complexity. Recently the PBWT, an efficient data structure capturing the local haplotype matching among haplotypes, was proposed to offer a fast method for giving some optimal solution (Viterbi) to the LS HMM. Previously, we introduced the minimal positional substring cover (MPSC) problem as an alternative …

Privacy Preserving Identification Of Population Stratification For Collaborative Genomic Research, Leonard Dervishi, Wenbiao Li, Anisa Halimi, Xiaoqian Jiang, Jaideep Vaidya, Erman Ayday

Faculty, Staff and Student Publications

The rapid improvements in genomic sequencing technology have led to the proliferation of locally collected genomic datasets. Given the sensitivity of genomic data, it is crucial to conduct collaborative studies while preserving the privacy of the individuals. However, before starting any collaborative research effort, the quality of the data needs to be assessed. One of the essential steps of the quality control process is population stratification: identifying the presence of genetic difference in individuals due to subpopulations. One of the common methods used to group genomes of individuals based on ancestry is principal component analysis (PCA). In this article, we …

Acquisition Of A Lexicon For Family History Information: Bidirectional Encoder Representations From Transformers-Assisted Sublanguage Analysis, Liwei Wang, Huan He, Andrew Wen, Sungrim Moon, Sunyang Fu, Kevin J Peterson, Xuguang Ai, Sijia Liu, Ramakanth Kavuluru, Hongfang Liu

Faculty, Staff and Student Publications

BACKGROUND: A patient's family history (FH) information significantly influences downstream clinical care. Despite this importance, there is no standardized method to capture FH information in electronic health records and a substantial portion of FH information is frequently embedded in clinical notes. This renders FH information difficult to use in downstream data analytics or clinical decision support applications. To address this issue, a natural language processing system capable of extracting and normalizing FH information can be used.

OBJECTIVE: In this study, we aimed to construct an FH lexical resource for information extraction and normalization.

METHODS: We exploited a transformer-based method to …

Using Ai-Generated Suggestions From Chatgpt To Optimize Clinical Decision Support, Siru Liu, Aileen P Wright, Barron L Patterson, Jonathan P Wanderer, Robert W Turer, Scott D Nelson, Allison B Mccoy, Dean F Sittig, Adam Wright

Faculty, Staff and Student Publications

OBJECTIVE: To determine if ChatGPT can generate useful suggestions for improving clinical decision support (CDS) logic and to assess noninferiority compared to human-generated suggestions.

METHODS: We supplied summaries of CDS logic to ChatGPT, an artificial intelligence (AI) tool for question answering that uses a large language model, and asked it to generate suggestions. We asked human clinician reviewers to review the AI-generated suggestions as well as human-generated suggestions for improving the same CDS alerts, and rate the suggestions for their usefulness, acceptance, relevance, understanding, workflow, bias, inversion, and redundancy.

RESULTS: Five clinicians analyzed 36 AI-generated suggestions and 29 human-generated suggestions …

A Nurse-Led Telehealth Program For Diabetes Foot Care: Feasibility And Usability Study, Hsiao-Hui Ju, Rashmi Momin, Stanley Cron, Jed Jularbal, Jeffery Alford, Constance Johnson

Faculty, Staff and Student Publications

BACKGROUND: Diabetes mellitus can lead to severe and debilitating foot complications, such as infections, ulcerations, and amputations. Despite substantial progress in diabetes care, foot disease remains a major challenge in managing this chronic condition that causes serious health complications worldwide.

OBJECTIVE: The primary aim of this study was to examine the feasibility and usability of a telehealth program focused on preventive diabetes foot care. A secondary aim was to descriptively measure self-reported changes in diabetes knowledge, self-care, and foot care behaviors before and after participating in the program.

METHODS: The study used a single-arm, pre-post design in 2 large family …

Variant Spectrum Of Von Hippel-Lindau Disease And Its Genomic Heterogeneity In Japan, Kenji Tamura, Yuki Kanazashi, Chiaki Kawada, Yuya Sekine, Kazuhiro Maejima, Shingo Ashida, Takashi Karashima, Shohei Kojima, Nickolas F Parrish, Shunichi Kosugi, Chikashi Terao, Shota Sasagawa, Masashi Fujita, Todd A Johnson, Yukihide Momozawa, Keiji Inoue, Taro Shuin, Hidewaki Nakagawa

Faculty, Staff and Student Publications

Von Hippel-Lindau (VHL) disease is an autosomal dominant, inherited syndrome with variants in the VHL gene, causing predisposition to multi-organ neoplasms with vessel abnormality. Germline variants in VHL can be detected in 80-90% of patients clinically diagnosed with VHL disease. Here, we summarize the results of genetic tests for 206 Japanese VHL families, and elucidate the molecular mechanisms of VHL disease, especially in variant-negative unsolved cases. Of the 206 families, genetic diagnosis was positive in 175 families (85%), including 134 families (65%) diagnosed by exon sequencing (15 novel variants) and 41 (20%) diagnosed by multiplex ligation-dependent probe amplification (MLPA) (one …

Mitotrace: A Computational Framework For Analyzing Mitochondrial Variation In Single-Cell Rna Sequencing Data, Mingqiang Wang, Wankun Deng, David C Samuels, Zhongming Zhao, Lukas M Simon

Faculty, Staff and Student Publications

Genetic variation in the mitochondrial genome is linked to important biological functions and various human diseases. Recent progress in single-cell genomics has established single-cell RNA sequencing (scRNAseq) as a popular and powerful technique to profile transcriptomics at the cellular level. While most studies focus on deciphering gene expression, polymorphisms including mitochondrial variants can also be readily inferred from scRNAseq. However, limited attention has been paid to investigate the single-cell landscape of mitochondrial variants, despite the rapid accumulation of scRNAseq data in the community. In addition, a diploid context is assumed for most variant calling tools, which is not appropriate for …

Digital Health Technologies For Peripartum Depression Management Among Low-Socioeconomic Populations: Perspectives From Patients, Providers, And Social Media Channels, Alexandra Zingg, Tavleen Singh, Amy Franklin, Angela Ross, Sudhakar Selvaraj, Jerrie Refuerzo, Sahiti Myneni

Faculty, Staff and Student Publications

BACKGROUND: Peripartum Depression (PPD) affects approximately 10-15% of perinatal women in the U.S., with those of low socioeconomic status (low-SES) more likely to develop symptoms. Multilevel treatment barriers including social stigma and not having appropriate access to mental health resources have played a major role in PPD-related disparities. Emerging advances in digital technologies and analytics provide opportunities to identify and address access barriers, knowledge gaps, and engagement issues. However, most market solutions for PPD prevention and management are produced generically without considering the specialized needs of low-SES populations. In this study, we examine and portray the information and technology needs …

Rapid-Query For Fast Identity By Descent Search And Genealogical Analysis, Yuan Wei, Ardalan Naseri, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

MOTIVATION: Due to the rapid growth of the genetic database size, genealogical search, a process of inferring familial relatedness by identifying DNA matches, has become a viable approach to help individuals finding missing family members or law enforcement agencies locating suspects. A fast and accurate method is needed to search an out-of-database individual against millions of individuals. Most existing approaches only offer all-versus-all within panel match. Some prototype algorithms offer one-versus-all query from out-of-panel individual, but they do not tolerate errors.

RESULTS: A new method, random projection-based identity-by-descent (IBD) detection (RaPID) query, is introduced to make fast genealogical search possible. …

A Guide To The Brain Initiative Cell Census Network Data Ecosystem, Michael Hawrylycz, Maryann E Martone, Giorgio A Ascoli, Jan G Bjaalie, Hong-Wei Dong, Satrajit S Ghosh, Jesse Gillis, Ronna Hertzano, David R Haynor, Patrick R Hof, Yongsoo Kim, Ed Lein, Yufeng Liu, Jeremy A Miller, Partha P Mitra, Eran Mukamel, Lydia Ng, David Osumi-Sutherland, Hanchuan Peng, Patrick L Ray, Raymond Sanchez, Aviv Regev, Alex Ropelewski, Richard H Scheuermann, Shawn Zheng Kai Tan, Carol L Thompson, Timothy Tickle, Hagen Tilgner, Merina Varghese, Brock Wester, Owen White, Hongkui Zeng, Brian Aevermann, David Allemang, Seth Ament, Thomas L Athey, Cody Baker, Katherine S Baker, Pamela M Baker, Anita Bandrowski, Samik Banerjee, Prajal Bishwakarma, Ambrose Carr, Min Chen, Roni Choudhury, Jonah Cool, Heather Creasy, Florence D'Orazi, Kylee Degatano, Benjamin Dichter, Song-Lin Ding, Tim Dolbeare, Joseph R Ecker, Rongxin Fang, Jean-Christophe Fillion-Robin, Timothy P Fliss, James Gee, Tom Gillespie, Nathan Gouwens, Guo-Qiang Zhang, Yaroslav O Halchenko, Nomi L Harris, Brian R Herb, Houri Hintiryan, Gregory Hood, Sam Horvath, Bingxing Huo, Dorota Jarecka, Shengdian Jiang, Farzaneh Khajouei, Elizabeth A Kiernan, Huseyin Kir, Lauren Kruse, Changkyu Lee, Boudewijn Lelieveldt, Yang Li, Hanqing Liu, Lijuan Liu, Anup Markuhar, James Mathews, Kaylee L Mathews, Chris Mezias, Michael I Miller, Tyler Mollenkopf, Shoaib Mufti, Christopher J Mungall, Joshua Orvis, Maja A Puchades, Lei Qu, Joseph P Receveur, Bing Ren, Nathan Sjoquist, Brian Staats, Daniel Tward, Cindy T J Van Velthoven, Quanxin Wang, Fangming Xie, Hua Xu, Zizhen Yao, Zhixi Yun, Yun Renee Zhang, W Jim Zheng, Brian Zingg

Faculty, Staff and Student Publications

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman …

Community Perspectives On Ai/Ml And Health Equity: Aim-Ahead Nationwide Stakeholder Listening Sessions, Jamboor K Vishwanatha, Allison Christian, Usha Sambamoorthi, Erika L Thompson, Katie Stinson, Toufeeq Ahmed Syed

Faculty, Staff and Student Publications

Artificial intelligence and machine learning (AI/ML) tools have the potential to improve health equity. However, many historically underrepresented communities have not been engaged in AI/ML training, research, and infrastructure development. Therefore, AIM-AHEAD (Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity) seeks to increase participation and engagement of researchers and communities through mutually beneficial partnerships. The purpose of this paper is to summarize feedback from listening sessions conducted by the AIM-AHEAD Coordinating Center in February 2022, titled the "AIM-AHEAD Community Building Convention (ACBC)." A total of six listening sessions were held over three days. A total of 977 …

A Novel Integrated Approach To Predicting Cancer Immunotherapy Efficacy, Ruihan Luo, Jacqueline Chyr, Jianguo Wen, Yanfei Wang, Weiling Zhao, Xiaobo Zhou

Faculty, Staff and Student Publications

Immunotherapies have revolutionized cancer treatment modalities; however, predicting clinical response accurately and reliably remains challenging. Neoantigen load is considered as a fundamental genetic determinant of therapeutic response. However, only a few predicted neoantigens are highly immunogenic, with little focus on intratumor heterogeneity (ITH) in the neoantigen landscape and its link with different features in the tumor microenvironment. To address this issue, we comprehensively characterized neoantigens arising from nonsynonymous mutations and gene fusions in lung cancer and melanoma. We developed a composite NEO2IS to characterize interplays between cancer and CD8+ T-cell populations. NEO2IS improved prediction accuracy of patient responses to immune-checkpoint …

Inferring Personalized Treatment Effect Of Antihypertensives On Alzheimer's Disease Using Deep Learning, Pulakesh Upadhyaya, Yaobin Ling, Luyao Chen, Yejin Kim, Xiaoqian Jiang

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is one of the leading causes of death in the United States, especially among the elderly. Recent studies have shown how hypertension is related to cognitive decline in elderly patients, which in turn leads to increased mortality as well as morbidity. There have been various studies that have looked at the effect of antihypertensive drugs in reducing cognitive decline, and their results have proved inconclusive. However, most of these studies assume the treatment effect is similar for all patients, thus considering only the average treatment effects of antihypertensive drugs. In this paper, we assume that the effect …

Predicting The Risk Of Alzheimer's Disease And Related Dementia In Patients With Mild Cognitive Impairment Using A Semi-Competing Risk Approach, Zhaoyi Chen, Yuchen Yang, Dazheng Zhang, Jingchuan Guo, Yi Guo, Xia Hu, Yong Chen, Jiang Bian

Faculty, Staff and Student Publications

Alzheimer's disease (AD) and AD-related dementias (AD/ADRD) are a group of progressive neurodegenerative diseases. The progression of AD can be conceptualized as a continuum in which patients progress from normal cognition to preclinical AD (i.e., no symptoms but biological changes in the brain) to mild cognitive impairment (MCI) due to AD (i.e., mild symptoms but not interfere with daily activities), followed by increasing severity of dementia due to AD. Early detection and prediction models for the transition of MCI to AD/ADRD are needed, and efforts have been made to build predictions of MCI conversion to AD/ADRD. However, most existing studies …

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 …