Biomedical Informatics Commons^™

3d Reconstruction Of Spatial Transcriptomics With Spatial Pattern Enhanced Graph Convolutional Neural Network, Chen Tang, Yuansheng Zhou, Xue Xiao, Lei Dong, Lei Yu, Qiwei Li, Guanghua Xiao, Lin Xu

Faculty, Staff and Student Publications

Spatially resolved transcriptomics (SRT) is a promising new technology that enables simultaneous analysis of gene expression and spatial information for biomedical research. However, the existing statistical and deep learning algorithms used for analyzing SRT data rely solely on two-dimensional (2D) spatial coordinates, which limits their ability to accurately identify spatial domains, spatially variable genes (SVGs), cell-to-cell communications, and developmental trajectories in a three-dimensional (3D) spatial manner. To address these limitations, we introduced Spa3D, which utilized the anti-leakage Fourier transform and graph convolutional neural network model to reconstruct 3D-based spatial structures from multiple 2D SRT slices. We demonstrate that Spa3D is …

Defective Dna Damage Response Is A Targetable Therapeutic Vulnerability In Esr1 Mutant Breast Cancer, Sarah K Herzog, Jessica H Stevens, Guowei Gu, Sandra L Grimm, Kloma Cardoza, Autumn G M Hawkins, Hangqing Lin, Daniela Ramos, Amanda R Beyer, David G Edwards, Derek Dustin, Harry J Yang, Nicole Liang, Ashfia F Khan, Tasneem Bawa-Khalfe, Daniel J Mcgrail, Shiaw-Yih Lin, Cristian Coarfa, Suzanne A W Fuqua

Faculty, Staff and Student Publications

ESR1 mutations are the leading cause of endocrine therapy resistance and progression in ER-positive metastatic breast cancer. ESR1 mutations are detected in ~50% of metastatic breast cancer patients, and identification of effective targeted therapeutics are critically needed. Here, we identified enrichment of dysregulated replication stress and DNA damage responses in multiple ESR1 mutant models. Targeting the replication stress response utilizing checkpoint inhibition in combination with PARP inhibition synergistically suppressed growth, induced cell cycle arrest, and attenuated DNA replication. PARP inhibition blocked metastatic dissemination in vivo and reduced both PARP1 and ER-regulated protein expression. PARP trapping by olaparib treatment with or …

Knockrbp: An Integrated Multi-Omics Database Of Functional Perturbation Profiles For Rna-Binding Proteins, Mengyuan Yang, Jiawei Li, Jiajia Liu, Xingzheng Lu, Xiaobo Zhou, Yungang Xu

Faculty, Staff and Student Publications

RNA-binding proteins (RBPs) regulate diverse post-transcriptional processes, yet their functional impacts across multiple molecular layers remain incompletely characterized. KnockRBP (https://knockrbp.xu-bioinfo.com) is presented as a comprehensive, multi-omics database systematically cataloging regulatory changes resulting from genetic perturbation of RBPs. The resource integrates 1453 datasets from GEO, ENA, and ENCORE, encompassing RNA-seq, Ribo-seq, microRNA (miRNA)-seq, and 3'RACE-seq across 639 RBPs, 182 cell lines, and 61 diseases. Regulatory outcomes covered include alternative splicing, alternative polyadenylation, RNA editing, transcript abundance, translation efficiency, and miRNA expression, with all events processed through standardized analytical pipelines and annotated with open reading frame consequences, predicted loss-of-function impacts, and established …

Inhibition Of Gpx4 Induces The Death Of P53-Mutant Triple-Negative Breast Cancer Cells, William M Tahaney, Amanda Lanier, Jing Qian, Cassandra L Moyer, Nghi Nguyen, Yanxia Ma, Jamal Hill, Reid T Powell, Clifford C Stephan, Peter J A Davies, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high rates of tumor protein 53 (TP53) mutation and with limited targeted therapies. Despite being clinically advantageous, direct targeting of mutant TP53 has been challenging. Therefore, we hypothesized that p53-mutant TNBC cells rely upon other potentially targetable survival pathways.

Methods: In vitro and in silico screens were used to identify drugs that induced preferential death in TP53-mutant cells. The effect of the ferroptosis inducer ML-162 was tested both in vitro and in vivo and the mechanism of cell death following ML-162 treatment or GPX4 knockout was …

Peripheral Nerve Injury Reduces Macrophage Efferocytosis To Facilitate Neuropathic Pain, Vipul K Pandey, Tusar K Acharya, Kendal F Willcox, Sandeep Dembla, Ajeena Ramanujan, Anamaria R Grieco, Younus A Zuberi, Rajasekaran Mahalingam, Andrew J Shepherd, Cobi J Heijnen, Peter M Grace

Faculty, Staff and Student Publications

For reasons not fully understood, proresolving immune processes sometimes fail to engage after peripheral nerve injury (PNI), leading to enhanced neuropathic pain and inflammation. Here, we implicate reduced efferocytosis due to proteolytic cleavage of surface MER tyrosine kinase (MERTK) from macrophages at the site of PNI. After PNI, the proportion of macrophages expressing MERTK progressively decreased, while soluble (cleaved) MER increased. Using male and female knock-in mice encoding cleavage-resistant Mertk, we demonstrated that cleavage of MERTK from macrophages at the PNI site led to exaggerated pain-related behaviors. PNI-induced hyperactivity of TRPV1+ sensory neurons and damage to myelin and myelinated …

Spatial2gwas: A Database For Linking Spatial Transcriptomic Regions With Gwas Traits, Xi Hu, Aoqi Wang, Huan Yu, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Spatial heterogeneity of gene expression within tissue regions has a critical influence on biological functions, thereby affecting disease pathogenesis. However, systematic associations between spatially resolved transcriptomes and phenotypes, especially in complex diseases, remain underexplored. Here, we developed spatial2GWAS (http://www.spatial2gwas.cn), a comprehensive resource linking spatial transcriptomic (ST) regions with GWAS traits. In the database, we collected 1196 ST slices (human and mouse) from five technologies and 812 GWAS traits spanning 18 phenotype categories and identified 29 701 ST slice-GWAS trait pairs containing 47 492 significant regions. Functional analyses reveal distinct patterns of cell type composition, gene expression, GO/KEGG pathway activation, and …

Correction: Sadagopan Et Al Reduced Computed Tomography Scan Speed Improves Alignment Errors For Patients Undergoing Thoracic Stereotactic Body Radiation Therapy, Ramaswamy Sadagopan, Rachael M Martin-Paulpeter, Christopher R Peeler, Xiaochun Wang, Paige Nitsch, Julianne M Pollard-Larkin

Faculty, Staff and Student Publications

In the original publication [...].

Modality-Agnostic, Patient-Specific Digital Twins Modeling Temporally Varying Digestive Motion, Jorge Tapias Gomez, Nishant Nadkarni, Lando S Bosma, Jue Jiang, Ergys D Subashi, William P Segars, James M Balter, Mert R Sabuncu, Neelam Tyagi, Harini Veeraraghavan

Faculty, Staff and Student Publications

No abstract provided.

A Prognostic Matrix Gene Expression Signature Defines Functional Glioblastoma Phenotypes And Niches, Monika Vishnoi, Zeynep Dereli, Zheng Yin, Elisabeth K Kong, Meric Kinali, Kisan Thapa, Ozgun Babur, Kyuson Yun, Nourhan Abdelfattah, Xubin Li, Behnaz Bozorgui, Mary C Farach-Carson, Robert C Rostomily, Anil Korkut

Faculty, Staff and Student Publications

Interactions among tumor, immune, and vascular niches play major roles in glioblastoma (GBM) malignancy and treatment responses. The composition and heterogeneity of extracellular core matrix proteins (CMPs) that mediate such interactions are not well understood. Here, we present an analysis of the clinical relevance of CMP expression in GBM at bulk, single-cell, and spatial anatomical resolution. We show that CMP enrichment is associated with worse patient survival, specific driver oncogenic alterations, mesenchymal state, pro-tumor immune infiltration, and immune checkpoint expression. Matrisome expression is enriched in vascular and leading edge/infiltrative niches that are known to harbor glioma stem cells. Finally, we …

Precision Targeting Of Sting: Challenges, Innovations, And Clinical Outlook For Cancer Therapy, Jiaqi Shi, Yingying Zhang, Na Zhao, Ekihiro Seki, Li Ma, Gordana Kocic, Xiaobo Li, Janoš Terzić, Tongsen Zheng

Faculty, Staff and Student Publications

The stimulator of interferon genes (STING) pathway plays a crucial role in immune responses and has emerged as a compelling target in cancer therapy. Despite promising preclinical studies, clinical trials of STING agonists have largely failed to deliver durable efficacy, with no agents progressing to phase III trials. This review examines the biological, pharmacological, and clinical barriers limiting STING pathway activation in cancer treatment. We discuss the inherent limitations of STING agonists as well as host-related resistance driven by tumor heterogeneity, immune suppression, and chronic STING activation. Mechanisms of acquired resistance, such as immune checkpoint upregulation and suppression of effector …

International Guidelines On The Diagnosis And Treatment Of Nut Carcinoma, Yu Zhang, Qi Zhang, Yue Hao, Jia Luo, Yingshi Piao, Wenxian Wang, Zhengbo Song, Ziming Li, Luka Brcic, Aijun Liu, Jinpu Yu, Yasuhiro Tsutani, Wenzhao Zhong, Wenfeng Fang, Zhijie Wang, Shengxiang Ren, Athanasios G Papavassiliou, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Ayten Kayi Cangir, Anwen Liu, Wen Li, Filippo Lococo, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfeng Min, Helmut Popper, Yu Chen, Jingping Yuan, Feng Wang, Zhansheng Jiang, Gen Lin, Long Huang, Xingxiang Pu, Rongbo Lin, Kalevi Kairemo, Weifeng Liu, Chuangzhou Rao, Dongqing Lv, Zongyang Yu, Ashrafian Leanne, Xiaoyan Li, Chuanhao Tang, Hifzur R Siddique, Chengzhi Zhou, Junping Zhang, Junli Xue, Vishal Shelat, Hui Guo, Qian Chu, Rui Meng, Fatemeh Ardeshir, Jingxun Wu, Rui Zhang, Jin Zhou, Robert A Kratzke, Zhengfei Zhu, Yongheng Li, Hong Qiu, Fan Xia, Fiorella Calabrese, Yang Xia, Alessandro Wasum Mariani, Yuanyuan Lu, Xiaofeng Chen, Mark A Klein, Rui Ge, Enyong Dai, Axel H Schönthal, Yu Han, Zhenying Guo, Jian Zhang, Yinghua Ji, Xianbin Liang, Hongmei Zhang, Xuelei Ma, Marco Chiappetta, Xuewen Liu, Francoise Galateau Salle, Yu Yao, Malgorzata Szolkowska, Weiwei Pan, Fei Pang, Fan Wu, Stefan B Watzka, Liping Wang, Youcai Zhu, Li Lin, Aparna Sharma, Jianfei Tu, Xinqing Lin, Jing Cai, Ling Xu, Jisheng Li, Xiaodong Jiao, Kainan Li, Marjorie G Zauderer, Jia Wei, Huijing Feng, Lin Wang, Yingying Du, Wang Yao, Elizabeth Dudnik, Xuefei Shi, Xiaomin Niu, Dongmei Yuan, Yanwen Yao, Jianhui Huang, Yue Feng, Yinbin Zhang, Binbin Song, Wenfeng Li, Jianfei Fu, Marina K Baine, Pingli Sun, Hong Wang, Mingxiang Ye, Dong Wang, Zhaofeng Wang, Jing Wu, Yunyun Yang, Yuan Fang, Zhen Wang, Bin Wan, Donglai Lv, Huafei Chen, Shengjie Yang, Jing Kang, Jiatao Zhang, Chao Zhang, Lin Shi, Yina Wang, Mohamed Emam Sobeih, Bihui Li, Bin Lian, Lili Mao, Zhang Zhang, Ke Wang, Zhongwu Li, Zhefeng Liu, Nong Yang, Lin Wu, Xiaobing Chen, Gu Jin, Miao Li, Guansong Wang, Thomas U Marron, Jiandong Wang, Sanjay Popat, Meiyu Fang, Yong Fang, Daniel Mansilla, Yuan Li, Xiaojia Wang, Jing Chen, Yiping Zhang, Xixu Zhu, Yi Shen, Shenglin Ma, Aaron S Mansfield, Biyun Wang, Lu Si, Anja C Roden, Bjørn H Grønberg, Yong Song, Geoffrey I Shapiro, Christopher A French, Yuanzhi Lu, Qian Wang, Chunwei Xu

Faculty, Staff and Student Publications

Nuclear protein in testis (NUT) carcinoma (NC) represents a rare, clinically aggressive cancer defined by pathognomonic NUT Midline Carcinoma Family Member 1 (NUTM1) gene fusions, with bromodomain and extraterminal domain (BET) protein 4 (BRD4)-NUTM1 being the predominant oncogenic driver. Since its description in 1991, gradual advances have clarified the pathologic mechanisms of NC and its diagnostic methods; however, NC treatment remains a significant challenge. Moreover, diagnostic and treatment approaches for this cancer require further validation and standardization. These guidelines were developed by the Chinese Alliance of Research for NC (ChARN) based on current evidence in …

Celltra: Aligning Cell Names With Gene Expression Via A Pathway-Informed Transformer, Zhao Li, Zaiyi Zheng, Rongbin Li, Wenbo Chen, Yuntao Yang, Meer A Ali, Jundong Li, W Jim Zheng

Faculty, Staff and Student Publications

Motivation: Single-cell RNA sequencing (scRNA-Seq) technology enables detailed exploration of gene expression at the individual cell level, crucial for annotating cell types and understanding cellular diversity. Traditional methods for cell type annotation often rely on marker genes and manual labeling, posing challenges due to low data quality and incomplete reference datasets.

Results: We developed CeLLTra, a novel contrastive learning framework that leverages a Transformer-based model integrating biological pathway information to group genes into super tokens, effectively capturing comprehensive gene expression from scRNA-Seq data. By combining this pathway-informed Transformer with a pretrained domain-specific language model, CeLLTra accurately aligns cell-type annotations with …

Circadian-Shaped Immune Variability Predicts Infection Outcome, Jonathan Lalsiamthara, Mariko Locke, Alejandro Aballay

Faculty, Staff and Student Publications

Disease risk and severity are influenced by genetics, epigenetics, and environmental factors. However, immune responses vary even among genetically similar or related individuals, shaped by inherited and noninherited factors. Using Caenorhabditis elegans, we found that pathogen susceptibility can be predicted by preinfection biomarkers. Individuals with high-basal expression of irg-5, an infection response gene regulated by the p38 mitogen-activated protein kinase-1 (PMK-1) pathway, were more susceptible to Pseudomonas aeruginosa infection. A genome-wide screen identified the myeloid ecotropic viral integration site-1 (MEIS) homeobox protein UNC-62 as a regulator of irg-5 expression, acting through PMK-1 and GATA binding erythroid-like transcription factor …

Cholesterol Efflux Protein, Abca1, Supports Anticancer Functions Of Myeloid Immune Cells, Shruti V Bendre, Yu Wang, Basel Hajyousif, Rajendra K C, Shounak G Bhogale, Dhanya Pradeep, Natalia Krawczynska, Claire P Schane, Erin Weisser, Avni Singh, Simon Han, Hannah Kim, Lara Kockaya, Anasuya Das Gupta, Adam T Nelczyk, Hashni Epa Vidana Gamage, Yifan Fei, Desirée Rodríguez-Casiano, Xingyu Guo, Haoyun Li, Ryan J Deaton, Fei Mo, Maria Sverdlov, Peter H Gann, Saurabh Sinha, Sahil Sahni, Kun Wang, Kevin Van Bortle, Emad Tajkorshid, Wendy A Woodward, Wonhwa Cho, Erik R Nelson

Faculty, Staff and Student Publications

Breast and other solid tumors respond poorly to immune therapy. Myeloid cells (MCs) such as macrophages contribute to resistance. Established clinical evidence links cholesterol to cancer outcomes, with MC function being regulated by cholesterol metabolism. We screened MC-expressed regulators of cholesterol homeostasis linked to survival and identified the cholesterol efflux protein ABCA1. ABCA1 activity increases anticancer functions of macrophages: enhancing tumor infiltration, decreasing angiogenic potential, reducing efferocytosis, and improving support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K-dependent and PI3K-independent mechanisms. Highlighting the clinical relevance of our findings are correlations between ABCA1 in macrophages …

Nf2 Loss Malignantly Transforms Human Pancreatic Acinar Cells And Enhances Cell Fitness Under Environmental Stress, Yi Xu, Michael H Nipper, Angel A Dominguez, Chenhui He, Francis E Sharkey, Sajid Khan, Han Xu, Daohong Zhou, Lei Zheng, Yu Luan, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) occurs as a complex, multifaceted event driven by the interplay of tumor-permissive genetic mutations, the nature of the cellular origin, and microenvironmental stress. In this study, using primary human pancreatic acinar 3D organoids, we performed a CRISPR-KO screen targeting 199 potential tumor suppressors curated from clinical PDAC samples. Our data revealed significant enrichment of a list of candidate genes, with neurofibromatosis type 2 associated gene (NF2) emerging as the top target. Functional validation confirmed that loss of NF2 promoted the transition of PDAC to an invasive state, potentially through extracellular matrix modulation. NF2 inactivation …

Racial, Ethnic, And Socioeconomic Survival Disparities In Early-Onset Metastatic Colorectal Cancer, Jennifer S Wang, Benny Johnson, Caitlin C Murphy

Faculty, Staff and Student Publications

Importance: Rates of metastatic colorectal cancer (mCRC) are rising among young adults. Disparities by race and ethnicity and neighborhood-level socioeconomic status (SES) among this population are understudied.

Objective: To examine the association of race and ethnicity and neighborhood-level SES with mortality among a community-based sample of young adults with mCRC.

Design, setting, and participants: This cohort study used a large electronic health record-derived database of young adults with cancer treated at 280 community-based US clinics between 2013 and 2021. Eligible patients were young adults aged 18 to 49 years diagnosed with de novo or recurrent mCRC. Patients were followed up …

Public Support For Alcohol-Control Policies And Political Ideology In The Us, Joël Fokom Domgue, Robert Yu, Ernest Hawk, Sanjay Shete

Faculty, Staff and Student Publications

This cross-sectional study examines the role of US adults’ political affiliation, perception about alcohol use and cancer, and sociodemographic and behavioral factors in banning outdoor alcohol advertising and adding cancer warnings on alcohol containers.

Peroxisomal Integrity In Demyelination-Associated Microglia Enables Cellular Debris Clearance And Myelin Renewal In Mice, Joseph A Barnes-Vélez, Xiaohong Zhang, Yaren L Peña Señeriz, Kiersten A Scott, Yinglu Guan, Jian Hu

Faculty, Staff and Student Publications

Demyelination associated microglia (DMAM) orchestrate the regenerative response to demyelination by clearing myelin debris and promoting oligodendrocyte maturation. Peroxisomal metabolism has emerged as a candidate regulator of DMAMs, though the cell-intrinsic contribution in microglia remains undefined. Here we elucidate the role of peroxisome integrity in DMAMs, using cuprizone-mediated demyelination coupled with conditional KO of peroxisome biogenesis factor 5 (PEX5) in microglia. Absent demyelination, PEX5 conditional KO (PEX5cKO) had minimal impact on homeostatic microglia. However, during cuprizone-induced demyelination, the emergence of DMAMs unmasked a critical requirement for peroxisome integrity. At peak demyelination, PEX5cKO DMAMs exhibited increased lipid droplet burden and reduced …

Metabolic Syndrome Beyond Diagnostic Criteria: Population-Scale Integrative Metabolomics Characterization, Marwa Talal

Theses and Dissertations

Background: Metabolic syndrome (MetS) is a complex cluster of interrelated metabolic abnormalities associated with elevated cardiometabolic risk. While diagnosis is based on well-established five clinical criteria, these may overlook early or atypical metabolic alterations. Large-scale metabolomic profiling offers an opportunity to identify biochemical signatures of MetS beyond diagnostic bias and to evaluate their relative importance across different presentations of the syndrome.

Methods: Data from 117,147 UK Biobank participants were analyzed in a cross-sectional design. High-throughput NMR quantified 75 circulating metabolites, for. Univariate analyses, MetS subtype stratification, and elastic net models with SHAP interpretation were applied to assess feature …

Frame: Fast Reference-Based Ancestry Makeup Estimation Tool, Pramesh Shakya, Ardalan Naseri, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

Motivation: The availability of large-scale genetic data presents a unique opportunity to study the genetic ancestries of individuals, which requires an efficient and scalable method. The existing global ancestry methods are accurate, but they cannot scale to large genetic datasets. Identity-by-descent (IBD) segments are DNA segments shared by individuals such that they are inherited from a common recent ancestor without recombination. These IBD segments, which reflect co-ancestry, provide an efficient alternative for inferring genetic ancestry.

Results: We introduced a reference-based global ancestry inference method called FRAME (Fast Reference-based Ancestry Makeup Estimation). FRAME utilizes partial local ancestry information estimated through IBD …

Adversarial Robustness In Biomedical Time-Series Models, Rohan Tiwari

Bioengineering Theses

This study investigates adversarial vulnerabilities in deep learning models for biomedical time-series classification across two clinically important modalities: electrocardiography (ECG) and electroencephalography (EEG). Using the MIT-BIH Arrhythmia and CHB-MIT seizure datasets, I evaluate time-domain attacks (FGSM, PGD), Fourier-domain constrained attacks, and learned spectral perturbations designed to reveal modality-specific sensitivity patterns. Across both tasks, a consistent trend emerges low-frequency components (0–5 Hz) constitute a dominant axis of adversarial vulnerability, with perturbations in this range producing the steepest degradation in classification performance. In ECG models, protecting the physiologically relevant QRS band (5–20 Hz) significantly improves robustness, whereas EEG models remain highly sensitive …

Clinical Outcomes With Perioperative Nivolumab By Nodal Status In Patients With Stage Iii Resectable Nsclc: Phase 3 Checkmate 77t Exploratory Analysis, Mariano Provencio, Mark M Awad, Jonathan D Spicer, Annelies Janssens, Fedor Moiseyenko, Yang Gao, Yasutaka Watanabe, Aurelia Alexandru, Florian Guisier, Nikolaj Frost, Fabio Franke, T Jeroen Nicolaas Hiltermann, Jie He, Fumihiro Tanaka, Shun Lu, Cinthya Coronado Erdmann, Padma Sathyanarayana, Phuong Tran, Vipul Devas, Tina Cascone

Faculty, Staff and Student Publications

Individuals with non-small-cell lung cancer (NSCLC) with metastases to the ipsilateral mediastinum or subcarinal lymph nodes (N2 disease) have poor long-term survival. This exploratory analysis from the randomized phase 3 CheckMate 77T study assessed clinical outcomes by nodal status in individuals with stage III NSCLC who received neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab (nivolumab) versus neoadjuvant chemotherapy followed by surgery and adjuvant placebo (placebo). Here we show that among patients with N2 disease, nivolumab versus placebo improved event-free survival (1-year rate, 70% versus 45%; hazard ratio, 0.46 (95% confidence interval, 0.30–0.70)) and pathological complete response rate …

Blood Flow Regulates Metabolism In Hematopoietic Development, Pamela L Wenzel

Faculty, Staff and Student Publications

Blood flow modifies oxygen availability and biomechanical forces within the vasculature of the embryo as the hematopoietic system develops. The aorta-gonad-mesonephros (AGM) envelops the largest artery in the body and is a critical site for the emergence of hematopoietic stem cells (HSCs). Herein, I discuss the role of hypoxia-inducible factors (HIFs) and force as determinants of metabolism and fate determination. To address the effects of blood flow on hematopoietic development, I employ mouse embryo models and biomimetic culture. Real-time cell metabolic analyses show that oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) are altered by flow in cultures of …

Recurrence And Co-Occurrence Of Enhancer-Promoter Interactions Across Human Samples, Satvik Gunjala

Honors Undergraduate Theses

Experimental mapping of enhancer-promoter interactions (EPIs) is resource-intensive, and current computational prediction methods struggle with intrinsic genomic complexity and reliance on limited training data. To address this bottleneck and provide insights for improved computational methods, this study systematically analyzed chromatin contact datasets to investigate the recurrence and co-occurrence of enhancer-promoter interactions across human samples. Putative interactions were evaluated across two HiChIP datasets comprising 218 total samples and one Hi-C dataset comprising 266 samples to assess recurrence across samples and assess sequencing depth related to unique EPIs. Additionally, a preliminary item-based collaborative filtering recommender model was developed to assess co-occurrence patterns …

Dietetic Guidance For Nutritional Management Of People With Phenylketonuria Receiving Sepiapterin, Anita Macdonald, Kirsten Ahring, Alexa Bledsoe, Hiroki Fujimoto, Sara Giorda, Christian Kogelmann, Jessica Kopesky, Laura Nagy, Sara O'Neill, Alex Pinto, Soraia Poloni, Paige Roberts, Annemiek M J Van Wegberg, Suzanne Hollander

Faculty, Staff and Student Publications

Background/objectives: Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism. If untreated, elevated blood phenylalanine (Phe) levels lead to neurological and behavioral impairments. Phe levels can be managed through a lifelong Phe-restricted diet; however, this can be challenging to maintain. Sepiapterin is an adjunct therapy for PKU that has shown efficacy in reducing blood Phe levels in both tetrahydrobiopterin (BH4)-responsive and BH4-non-responsive people with PKU in clinical trials. Practical guidance is needed for dietitians and other healthcare professionals supporting the dietary management of people with PKU who are initiating or receiving sepiapterin.

Methods: A group of international dietitians participated …

The Effects Of Measurement Errors On Minimum Ablative Margins After Thermal Ablation Of Liver Tumors: A Simulation Study, Iwan Paolucci, Jessica Albuquerque, Noreen S Siddiqi, A Kyle Jones, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Purpose: To develop a mathematical framework to estimate the in silico A0 threshold based on the technical specifications of a specific ablation confirmation software package for thermal ablation of liver tumors that can then be used to identify the impact of different sources of error.

Methods: To estimate in silico A0 thresholds, we developed a simulation framework incorporating technical parameters and biological effects. Technical parameters were segmentation error, registration error, and slice thickness, and biological effects were tissue shrinkage and microscopic satellite lesions; these parameters and effects were all modeled using statistical distributions. For each permutation of parameters, a logistic …

Dosimetric Effect Of Abdominal Compression In Online Adaptive Planning For Abdominal Cancers Treated With A 15 Tesla Magnetic Resonance-Guided Linear Accelerator, Moghadaseh Khaleghibizaki, Angela Sobremonte, Luis Perles, Surendra Prajapati, Ergys Subashi, Yao Ding, Kristy Brock, Roya Barati, Eugene Koay, Chad Tang, Jinzhong Yang

Faculty, Staff and Student Publications

Compression belts (CBs) are sometimes used to reduce respiratory motion during stereotactic body radiotherapy of abdominal cancers with magnetic resonance (MR)-guided online adaptive planning. This study evaluated the dosimetric effects of overriding the relative electron density (ED) value of CBs in creating synthetic computed tomography (CT) scans for MR-guided adaptive planning. We evaluated plans for 12 patients with abdominal cancer and identified that ED values between 0.2 and 0.3 achieved the best approximation of CB ED in dose calculation. Our study presented an approach to estimate appropriate ED overrides for CBs in MR-guided online adaptive planning.

Association Between Three-Dimensional Margin Assessment And Local Tumor Control In Percutaneous Lung Cryoablation Of Colorectal Metastases, Frank Mohn, Koustav Pal, Caleb O'Connor, Iwan Paolucci, Austin Castelo, Kamran Ahrar, Steven Yevich, Joshua D Kuban, Bruno C Odisio, Alda Lui Tam, Rahul A Sheth, Kristy K Brock

Faculty, Staff and Student Publications

Purpose

To evaluate the association of two minimum ablation margin (MAM) estimation methods: manual three-dimensional segmentation and biomechanical deformable image registration (DIR) with local tumor progression-free survival (LTPFS) after percutaneous lung cryoablation of colorectal pulmonary metastases.

Materials and Methods

This retrospective single-institution study included patients who underwent percutaneous lung cryoablation between May 2012 and March 2023 (median follow-up, 3.6 years; range, 0.8–9.6 years). Manual three-dimensional MAM was calculated for all tumors, and DIR-based MAM was estimated in a subset with intraprocedural full-thorax imaging. Cox proportional hazards regression assessed associations between MAM and LTPFS. The primary outcome was 2-year LTPFS, with …

Ai-Powered Immune Cell Knowledge Graph (Ickg) With Granular Immune Contexts Enables Immune Program Interpretation, Shan He, Yukun Tan, Qing Ye, Matthew M Gubin, Merve Dede, Hind Rafei, Weiyi Peng, Katayoun Rezvani, Vakul Mohanty, Ken Chen

Faculty, Staff and Student Publications

The widespread application of single-cell and spatial omics to models and patient samples has transformed immune cell profiling across physiological conditions. However, knowledge of immune cell states, functions, and gene regulation remains fragmented across publications, limiting our ability to synthesize insights and derive mechanistic understanding from the literature. To address this gap and facilitate literature integration, we constructed Immune Cell Knowledge Graphs (ICKGs)-four cell type-specific graphs derived from over 24,000 cancer immunotherapy-focused PubMed abstracts using large language models (LLMs) with "human verifiable" validation. Unlike conventional databases, which provide context-agnostic pathways, ICKGs capture directed, literature-supported relationships among genes, pathways and immune …

Outcomes Of Patients With Melanoma Brain Metastases Treated With Ipilimumab And Nivolumab With Or Without Upfront Comprehensive Stereotactic Radiosurgery, Troy J Kleber, Denái R Milton, Subhiksha Srinivasan, Bikash Panthi, Warren Floyd, Eric A Goethe, Michael A Davies, Hussein A Tawbi, Isabella C Glitza Oliva, Diana Kaya, Jing Li, Todd A Swanson, Subha Perni, Martin C Tom, Chenyang Wang, Sujit Prabhu, Jeffrey S Weinberg, Ian E Mccutcheon, Caroline Chung, Sherise D Ferguson, Thomas H Beckham

Faculty, Staff and Student Publications

Background: The efficacy of ipilimumab and nivolumab (ipi/nivo) for melanoma brain metastases (MBMs) has been previously reported, leading to uncertainty regarding the optimal role of comprehensive stereotactic radiosurgery (cSRS). We therefore conducted a single-institution retrospective study to compare outcomes of upfront versus deferred cSRS for MBM treated with ipi/nivo.

Methods: We identified patients who started ipi/nivo for newly diagnosed MBMs between 2018 and 2023, with or without upfront cSRS. Patients with >15 MBMs, leptomeningeal disease, or whole-brain radiotherapy at baseline were excluded. Outcomes were compared using multivariable regression and reported as adjusted hazard ratios (aHRs) with 95% CIs.

Results: Of …