Article
Engineering, Environmental
Jessica D. Ewald, Niladri Basu, Doug Crump, Emily Boulanger, Jessica Head
Summary: Transcriptomics dose-response analysis (TDRA) is a promising approach for integrating toxicogenomics data into risk assessment. This study evaluated the variability and uncertainty associated with experimental design in TDRA. The results showed that the selection of dose range and spacing is more important than the number of replicates, and tPOD values should be interpreted as order-of-magnitude estimates.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elvira Immacolata Parrotta, Anna Procopio, Stefania Scalise, Claudia Esposito, Giovanni Nicoletta, Gianluca Santamaria, Maria Teresa De Angelis, Tatjana Dorn, Alessandra Moretti, Karl-Ludwig Laugwitz, Francesco Montefusco, Carlo Cosentino, Giovanni Cuda
Summary: Arrhythmogenic Right Ventricular cardiomyopathy (ARVC) is a genetically inherited cardiac muscle disease characterized by fibro-fatty replacement of the right ventricle, leading to arrhythmias and sudden cardiac death. A mathematical model was proposed to investigate the molecular dynamics underlying heart remodeling and loss of cardiac myocytes identity during ARVC. Inactive Wnt/beta-catenin and RhoA-ROCK pathways are necessary for a significant increase in PPAR gamma expression, indicating a potential crosstalk mechanism in ARVC pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Ryan Christian Mailem, Lemmuel L. Tayo
Summary: This paper utilizes computational biology techniques to identify possible repurposed drugs for post-COVID-19 treatment. By analyzing the genetic similarities and differences in symptoms associated with COVID-19, the study identifies seven candidate drugs that have been shown to treat immune-system related ailments. The findings have the potential to drive drug design and discovery for more effective post-COVID-19 therapeutics, and demonstrate the importance of computational techniques in speeding up the drug development process.
Article
Biochemical Research Methods
Jayadev Joshi, Daniel Blankenberg
Summary: PDAUG is a collection of tools, workflows, and datasets for peptide design and analysis, based on the Galaxy platform and powered by Python. It offers an integrated GUI-based toolset, providing flexibility to build and distribute reproducible pipelines and workflows without programming expertise.
BMC BIOINFORMATICS
(2022)
Article
Cardiac & Cardiovascular Systems
Kimberly J. McCabe, Padmini Rangamani
Summary: The cAMP/PKA pathway plays a crucial role in regulating excitation-contraction coupling in cardiomyocytes, with downstream effects on cardiac function. Experimental advances have revealed compartmentation of cAMP and PKA, while computational modeling helps to understand the spatial and temporal complexities of this system. Various compartmental and spatial signaling models have been used to study adrenergic signaling pathways in different simulation conditions, with newer subcellular models of cardiovascular function being explored for future study.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Environmental Sciences
Deoclecio Jardim Amorim, Afranio Marcio Correa Vieira, Cleanderson Romualdo Fidelis, Jania Claudia Camilo dos Santos, Marcelo de Almeida Silva, Clarice Garcia Borges Dem
Summary: In this study, a multivariate nonlinear modeling approach that takes into account the interdependencies among components of a plant system is proposed and evaluated using simulation and experimental data.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Immunology
Roc Farriol-Duran, Ruben Lopez-Aladid, Eduard Porta-Pardo, Antoni Torres, Laia Fernandez-Barat
Summary: Brewpitopes is a powerful pipeline that optimizes experimental validation of therapeutic antibodies and candidate vaccines in a high-throughput capacity during public health emergencies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Dentistry, Oral Surgery & Medicine
W. Awotoye, C. Comnick, C. Pendleton, E. Zeng, A. Alade, P. A. Mossey, L. J. J. Gowans, M. A. Eshete, W. L. Adeyemo, T. Naicker, C. Adeleke, T. Busch, M. Li, A. Petrin, J. Olotu, M. Hassan, J. Pape, S. E. Miller, P. Donkor, D. Anand, S. A. Lachke, M. L. Marazita, A. A. Adeyemo, J. C. Murray, D. Albokhari, N. Sobreira, A. Butali
Summary: Through genome-wide gene x sex interaction study in a sub-Saharan African population with orofacial clefts, a novel risk locus on chromosome 8p22 with sex-specific effects was identified. The genetic variant at this locus showed different impacts on the risk of cleft lip with or without cleft palate between males and females. The locus contains genes related to craniofacial development and rare coding mutations, supporting its role in the genetic etiology of nonsyndromic orofacial clefts.
JOURNAL OF DENTAL RESEARCH
(2022)
Review
Physiology
Karim Azer, Chanchala D. Kaddi, Jeffrey S. Barrett, Jane P. F. Bai, Sean T. McQuade, Nathaniel J. Merrill, Benedetto Piccoli, Susana Neves-Zaph, Luca Marchetti, Rosario Lombardo, Silvia Parolo, Selva Rupa Christinal Immanuel, Nitin S. Baliga
Summary: This paper reviews the history of mathematical biology and pharmacology models, highlights some gaps and challenges in the development and application of systems pharmacology models, and proposes an integrated strategy to overcome these challenges by leveraging advances in adjacent fields.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemical Research Methods
Vineet K. Raghu, Xiaoyu Ge, Arun Balajiee, Daniel J. Shirer, Isha Das, Panayiotis Benos, Panos K. Chrysanthis
Summary: Genome sequencing technologies have the potential to transform clinical decision making and biomedical research by enabling high-throughput measurements of the genome at a granular level. It is important to integrate high-throughput genomic data with demographic, phenotypic, environmental, and behavioral information, and infer relationships between these data types for better understanding of disease mechanisms and prediction of medical interventions. A new methodology called piPref-Div has been proposed to select informative variables for probabilistic graphical models, improving breast cancer outcome prediction and providing biologically interpretable views of gene expression data.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2021)
Article
Genetics & Heredity
Kimia Sadat Hashemi, Mohadese Koohi Aliabadi, Arian Mehrara, Elham Talebi, Ali Akbar Hemmati, Radin Dabbagh Rezaeiye, Mohammad Javad Ghanbary, Maryam Motealleh, Behnaz Dayeri, Shayan Khalili Alashti
Summary: This study utilized microarray bioinformatic analysis to identify potential biomarkers of AD by analyzing six microarray datasets of AD patients and control groups. The results identified CXCR4, TGFB1, ITGB1, MYH11, and SELE genes as hub genes in this study. These genes were significantly enriched in actin cytoskeleton regulation, ECM-receptor interaction, and hypertrophic cardiomyopathy. Additionally, multiple miRNAs exhibited significant interactions with most of the hub genes.
FRONTIERS IN GENETICS
(2023)
Article
Biochemical Research Methods
Laxman Ramya, Divakar Swathi, Santhanahalli Siddalingappa Archana, Maharajan Lavanya, Sivashanmugam Parthipan, Sellappan Selvaraju
Summary: The study established a bioinformatics pipeline for analyzing fragmented sperm RNA, with TopHat2 identified as the most effective tool. EdgeR and limma were found to identify the largest number of significantly differentially expressed genes with biological relevance in the differential gene expression analysis.
ANALYTICAL BIOCHEMISTRY
(2021)
Article
Virology
Kristen L. Beck, Edward Seabolt, Akshay Agarwal, Gowri Nayar, Simone Bianco, Harsha Krishnareddy, Timothy A. Ngo, Mark Kunitomi, Vandana Mukherjee, James H. Kaufman
Summary: SARS-CoV-2 genomic sequencing efforts have expanded significantly to combat the global pandemic. A novel semi-supervised pipeline was developed for automated annotation of genes, proteins, and functional domains, achieving high accuracy in sequence identification and prediction. This work provides crucial molecular targets for refining biomedical interventions and analyzing newly sequenced infections.
Article
Public, Environmental & Occupational Health
Kara Dean, Sushil Tamrakar, Yin Huang, Joan B. Rose, Jade Mitchell
Summary: This study developed dose-response models for various strains of Acanthamoeba to determine the probability of eye or central nervous system infections. Results showed different infectivity patterns for different strains under different experimental conditions, highlighting the importance of assessing the risk associated with free-living amoeba in drinking water distribution systems.
Article
Multidisciplinary Sciences
Marijana Croon, Karolina Szczepanowska, Milica Popovic, Christina Lienkamp, Katharina Senft, Christoph Paul Brandscheid, Theresa Bock, Leoni Gnatzy-Feik, Artem Ashurov, Richard James Acton, Harshita Kaul, Claire Pujol, Stephan Rosenkranz, Marcus Krueger, Aleksandra Trifunovic
Summary: The mitochondrial integrated stress response (mitoISR) is an important pathway for adapting to respiratory chain deficiency, with tissue specificity and dose dependency. FGF21, a cytokine, regulates a portion of mitoISR.
Article
Health Care Sciences & Services
John S. House, Carrie R. Hyde, Howard L. Corwin, Sarah E. Harrington, Kevin W. Sexton, Saleema A. Karim, Kyle J. Kalkwarf, Hanna K. Jensen
Summary: Among postsurgical patients requiring prolonged mechanical ventilation, receiving palliative medicine consultation was associated with lower readmission rates and hospitalization costs. However, utilization of palliative care in surgical patients remains low.
JOINT COMMISSION JOURNAL ON QUALITY AND PATIENT SAFETY
(2022)
Meeting Abstract
Endocrinology & Metabolism
John S. House, Daniel M. Rotroff, Vivian Fonseca, James M. Hempe, Josyf Mychaleckyj, Alessandro Doria, John B. Buse, Alison Motsinger-Reif
Article
Public, Environmental & Occupational Health
Amy Wolkin, Sarah Collier, John House, David Reif, Alison Motsinger-Reif, Lindsey Duca, Danielle Sharpe
Summary: This article describes the three vulnerability indices used by the CDC for the COVID-19 response, including the CDC Social Vulnerability Index (CDC-SVI), the US COVID-19 Community Vulnerability Index (CCVI), and the Pandemic Vulnerability Index (PVI). These indices provide important information for public health officials to understand the vulnerability of communities to disease and help plan resources and interventions.
PUBLIC HEALTH REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Dereje D. Jima, David A. Skaar, Antonio Planchart, Alison Motsinger-Reif, Sebnem E. Cevik, Sarah S. Park, Michael Cowley, Fred Wright, John House, Andy Liu, Randy L. Jirtle, Cathrine Hoyo
Summary: This study identified potential imprint control regions (ICRs) in the human genome using whole-genome bisulphite sequencing. The researchers found that the methylation patterns of these regions are similar across different cell types and are located in known binding sites and hypersensitive regions. This research is of great importance for studying the mechanisms underlying human diseases and developmental and behavioral disorders.
Article
Endocrinology & Metabolism
Farida S. S. Akhtari, Dillon Lloyd, Adam Burkholder, Xiaoran Tong, John S. S. House, Eunice Y. Y. Lee, John Buse, Shepherd H. H. Schurman, David C. C. Fargo, Charles P. P. Schmitt, Janet Hall, Alison A. A. Motsinger-Reif
Summary: This study found that environmental exposures may have a stronger predictive power for type 2 diabetes than polygenic scores. They also discovered associations between type 2 diabetes and environmental factors such as exposure to asbestos and coal dust. Environmental factors have a greater impact on the disease compared to genetic factors. The study highlights the importance of conducting comprehensive genetic and exposome studies in diverse populations.
Article
Toxicology
Matthew W. Wheeler, Sooyeong Lim, John S. House, Keith R. Shockley, A. John Bailer, Jennifer Fostel, Longlong Yang, Dawan Talley, Ashwin Raghuraman, Jeffery S. Gift, J. Allen Davis, Scott S. Auerbach, Alison A. Motsinger-Reif
Summary: The need to analyze complex relationships in high-throughput toxicogenomic and other omic platforms has led to methodological advances in computational toxicology. However, the development of software often lags behind advancements in the literature, leading to a demand for stable and open-source platforms. To fill this gap, the Biostatistics and Computational Biology Branch of the National Institute of Environmental Health Sciences, in collaboration with the National Toxicology Program and US Environmental Protection Agency, developed ToxicR, an open-source R programming package. ToxicR implements standard analyses used by the NTP and EPA, providing increased flexibility compared to existing software.
COMPUTATIONAL TOXICOLOGY
(2023)
Article
Critical Care Medicine
Yi-Hui Zhou, Paul J. Gallins, Rhonda G. Pace, Hong Dang, Melis A. Aksit, Elizabeth E. Blue, Kati J. Buckingham, Joseph M. Collaco, Anna V. Faino, William W. Gordon, Kurt N. Hetrick, Hua Ling, Weifang Liu, Frankline M. Onchiri, Kymberleigh Pagel, Elizabeth W. Pugh, Karen S. Raraigh, Margaret Rosenfeld, Quan Sun, Jia Wen, Yun Li, Harriet Corvol, Lisa J. Strug, Michael J. Bamshad, Scott M. Blackman, Garry R. Cutting, Ronald L. Gibson, Wanda K. O'Neal, Fred A. Wright, Michael R. Knowles
Summary: This study aims to identify genetic modifier loci associated with pulmonary disease severity in patients with cystic fibrosis. The research used whole-genome sequencing data and genetic genotypes to discover two loci associated with lung disease. These findings support mechanistic studies and the development of novel therapeutics for CF lung disease.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Mathematical & Computational Biology
Bryan W. W. Ting, Fred A. Wright, Yi-Hui Zhou
Summary: In recent years, there has been increasing attention on multivariate heterogeneous responses and heteroskedasticity. Effective simultaneous modeling of multiple phenotypes can enhance statistical power and interpretability in genome-wide association studies. However, developing a flexible common modeling system for heterogeneous data types can be challenging. In this study, we propose a method that extends a previous approach for multivariate probit estimation to incorporate multivariate responses of different data types and possible heteroskedasticity. The method has wide applications, particularly in genomics, precision medicine, and individual biomedical prediction, and shows promising performance in hypothesis testing and coverage percentages under various settings.
BIOMETRICAL JOURNAL
(2023)
Article
Toxicology
Han-Hsuan Doris Tsai, John S. House, Fred A. Wright, Weihsueh A. Chiu, Ivan Rusyn
Summary: Hazard evaluation of UVCBs is challenging due to their difficult-to-determine chemical composition. A combination of phenotypic and transcriptomic data can aid in selecting representative worst-case petroleum UVCBs for toxicity evaluation. iPSC-derived hepatocytes and cardiomyocytes are the most informative cell types for this purpose.
TOXICOLOGICAL SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Kuncheng Song, Yi-Hui Zhou
Summary: The microbiota is an important factor for many diseases and researchers have been using microbiome data for disease prediction. However, models trained on one independent microbiome study may not be easily applicable to other studies due to high variability in microbiome data. This study developed a method to improve the generalizability and interpretability of machine learning models for predicting three different diseases using nine independent microbiome datasets. The results showed that combining a smaller dataset with a larger dataset and using at least 25% of the target samples in the source data improved model performance.
BIOENGINEERING-BASEL
(2023)
Article
Engineering, Environmental
Oladayo Oladeji, Mariana Saitas, Toriq Mustapha, Natalie M. M. Johnson, Weihsueh A. A. Chiu, Ivan Rusyn, Allen L. L. Robinson, Albert A. A. Presto
Summary: On February 3, 2023, a train carrying hazardous chemicals derailed in East Palestine, OH, leading to temporary evacuation and controlled burn of some of the hazardous cargo. Residents reported health symptoms, and initial data from air monitoring indicated potential concern for air toxics. Mobile air monitoring conducted later showed that the levels of some chemicals were below risk levels, but acrolein levels were high and additional unique compounds were found, suggesting the need for further monitoring to characterize long-term exposure and risk levels.
ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS
(2023)
Article
Environmental Sciences
Alexandra C. Cordova, William D. Klaren, Lucie C. Ford, Fabian A. Grimm, Erin S. Baker, Yi-Hui Zhou, Fred A. Wright, Ivan Rusyn
Summary: This study used representative high production volume categories of petroleum UVCBs to compare the chemical composition and bioactivity data, finding that existing categories are not accurate enough and identifying specific constituents that influence these associations. This suggests that combining chemical composition and bioactivity data is a promising approach to better characterize the variability within manufacturing categories of petroleum UVCBs.
Article
Biochemistry & Molecular Biology
John S. House, Sophia Gray, Jennifer R. Owen, Dereje D. Jima, Robert C. Smart, Jonathan R. Hall
Summary: The skin acts as the first line of defense against cutaneous microbes and viruses, with epidermal keratinocytes playing a critical role in preventing infection through activation of the type I interferon response. The deletion of the C/EBP beta transcription factor led to the upregulation of IFN beta and numerous ISGs in the mouse epidermis. This resulted in an increased expression of cPRRs, which recognize viral RNA and DNA, and a heightened type I IFN response, ultimately leading to cell death.
Article
Medicine, Research & Experimental
John S. House, Fabian A. Grimm, William D. Klaren, Abigail Dalzell, Srikeerthana Kuchi, Shu-Dong Zhang, Klaus Lenz, Peter J. Boogaard, Hans B. Ketelslegers, Timothy W. Gant, Ivan Rusyn, Fred A. Wright
Summary: Transcriptomic profiling can be used to group UVCB substances and gain deeper mechanistic understanding of in vitro biological responses.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2022)
Correction
Public, Environmental & Occupational Health
A. Wolkin, S. Collier, J. S. House, D. Reif, A. Motsinger-Reif, L. Duca, J. D. Sharpe
PUBLIC HEALTH REPORTS
(2022)