Article
Oncology
Duo Liu, Jingjing Zhu, Dan Zhou, Emily G. Nikas, Nikos T. Mitanis, Yanfa Sun, Chong Wu, Nicholas Mancuso, Nancy J. Cox, Liang Wang, Stephen J. Freedland, Christopher A. Haiman, Eric R. Gamazon, Jason B. Nikas, Lang Wu
Summary: The study combines transcriptome-wide association study and validation to identify candidate genes potentially involved in prostate cancer development. Analysis revealed 573 genes associated with prostate cancer risk, including 451 novel genes and 122 previously reported genes.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Cardiac & Cardiovascular Systems
Ling Li, Zhifen Chen, Moritz von Scheidt, Shuangyue Li, Andrea Steiner, Ulrich Gueldener, Simon Koplev, Angela Ma, Ke Hao, Calvin Pan, Aldons J. Lusis, Shichao Pang, Thorsten Kessler, Raili Ermel, Katyayani Sukhavasi, Arno Ruusalepp, Julien Gagneur, Jeanette Erdmann, Jason C. Kovacic, Johan L. M. Bjorkegren, Heribert Schunkert
Summary: This study systematically identified susceptibility genes for coronary artery disease (CAD) using transcriptome-wide association studies (TWAS). The study prioritized candidate causal genes at known GWAS loci, identified 18 novel genes associated with CAD, and suggested potential tissues and pathways of action for these TWAS CAD genes.
BASIC RESEARCH IN CARDIOLOGY
(2022)
Article
Immunology
Kathryn A. A. Recto, Tianxiao Huan, Dong Heon Lee, Gha Young Lee, Jessica Gereige, Chen Yao, Shih-Jen Hwang, Roby Joehanes, Rachel S. S. Kelly, Jessica Lasky-Su, George O'Connor, Daniel Levy
Summary: Measurement of circulating immunoglobulin E (IgE) concentration is helpful for diagnosing and treating asthma and allergic diseases. Identifying gene expression signatures associated with IgE might elucidate novel pathways for IgE regulation. Our findings build upon prior knowledge of IgE regulation and provide a deeper understanding of underlying molecular mechanisms, offering promising therapeutic targets for asthma and IgE-related diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Psychiatry
Shi Yao, Hao Wu, Tong-Tong Liu, Jia-Hao Wang, Jing-Miao Ding, Jing Guo, Yu Rong, Xin Ke, Ruo-Han Hao, Shan-Shan Dong, Tie-Lin Yang, Yan Guo
Summary: The research focuses on identifying genes associated with bipolar disorder through a new transcriptome-wide association study method. This method, called ETWAS, takes into account genetic variants and epigenetic features to uncover novel candidate genes overlooked by previous studies. Several genes were identified as potentially linked to BD, shedding light on the complex genetic factors contributing to the disorder.
SCHIZOPHRENIA BULLETIN
(2021)
Article
Endocrinology & Metabolism
M. Zhu, P. Yin, F. Hu, J. Jiang, L. Yin, Y. Li, S. Wang
Summary: This study integrated large-scale GWAS summary data and utilized the predicted transcriptome-wide association study method to identify 204 candidate genes associated with osteoporosis, providing novel insights into the genetic mechanism and potential therapeutic targets. Further analysis confirmed 20 candidate genes directly linked to osteoporosis, with causative relationships found in pathways such as mineral absorption, MAPK signaling, Wnt signaling, and PI3K-Akt signaling, suggesting promising avenues for targeted therapeutics.
OSTEOPOROSIS INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Meng Zhu, Jingyi Fan, Chang Zhang, Jing Xu, Rong Yin, Erbao Zhang, Yuzhuo Wang, Mengmeng Ji, Qi Sun, Juncheng Dai, Guangfu Jin, Liang Chen, Lin Xu, Zhibin Hu, Hongxia Ma, Hongbing Shen
Summary: This study conducted a cross-tissue transcriptome-wide association study using UTMOST, identifying 6 known susceptibility genes and 12 novel ones for lung cancer susceptibility. Among these, 5 novel genes were significantly associated with lung cancer risk in both cross-tissue and lung tissue models. Further analysis indicated that specific genetic variants drove the GWAS association signals and influenced the expression of certain genes in lung tissue, supporting their role in lung carcinogenesis.
HUMAN MOLECULAR GENETICS
(2021)
Article
Immunology
Jiawen Xu, Jun Ma, Yi Zeng, Haibo Si, Yuangang Wu, Shaoyun Zhang, Bin Shen
Summary: In this study, a cross-tissue transcriptome-wide association study was conducted to identify a group of genes and pathways associated with JIA, providing novel clues to uncover the pathogenesis of JIA.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Psychiatry
Xiaoyan Li, Xi Su, Jiewei Liu, Huijuan Li, Ming Li, Wenqiang Li, Xiong-Jian Luo
Summary: The study identified 53 significant risk genes for depression through a transcriptome-wide association study, with 7 of them showing associations in two independent brain expression datasets. Pathway enrichment analysis revealed biologically pathways relevant to depression. Further mechanistic study and functional characterization of the risk genes may facilitate the diagnostics and therapeutics for depression.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Yanfa Sun, Dan Zhou, Md Rezanur Rahman, Jingjing Zhu, Dalia Ghoneim, Nancy J. Cox, Thomas G. Beach, Chong Wu, Eric R. Gamazon, Lang Wu
Summary: This study identifies 15 genes as potential biomarkers in blood for Alzheimer's disease risk through transcriptome-wide association study.
HUMAN MOLECULAR GENETICS
(2022)
Article
Multidisciplinary Sciences
Rodrigo R. R. Duarte, Oliver Pain, Robert L. Furler, Douglas F. Nixon, Timothy R. Powell
Summary: This study revealed the host genetic factors associated with protection against HIV-1, identifying 25 genetic loci and 15 susceptibility genes related to HIV-1 acquisition. Further functional studies and larger genetic research have the potential to enhance understanding of the host mechanisms related to protection against HIV-1.
Article
Biochemistry & Molecular Biology
Dongli Zhu, Shi Yao, Hao Wu, Xin Ke, Xiaorong Zhou, Songmei Geng, Shanshan Dong, Hao Chen, Tielin Yang, Ying Cheng, Yan Guo
Summary: A transcriptome-wide association study identified multiple novel candidate genes associated with psoriasis, which were further validated through public databases and knockout mice models. These genes were found to be enriched in known GO terms related to skin development, providing valuable insights into the genetic mechanism of psoriasis.
HUMAN MOLECULAR GENETICS
(2022)
Article
Multidisciplinary Sciences
Jingni He, Wanqing Wen, Alicia Beeghly, Zhishan Chen, Chen Cao, Xiao-Ou Shu, Wei Zheng, Quan Long, Xingyi Guo
Summary: This study develops an improved TWAS method, sTF-TWAS, which incorporates prior knowledge of susceptible transcription factor occupancy elements to predict disease susceptibility genes. The sTF-TWAS outperforms existing TWAS approaches and has been applied to identify putative susceptibility genes for various cancers and non-cancer diseases.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Tomohito Doke, Shizheng Huang, Chengxiang Qiu, Hongbo Liu, Yuting Guan, Hailong Hu, Ziyuan Ma, Junnan Wu, Zhen Miao, Xin Sheng, Jianfu Zhou, Aili Cao, Jianhua Li, Lewis Kaufman, Adriana Hung, Christopher D. Brown, Richard Pestell, Katalin Susztak
Summary: The study integrated various methods to identify Dachshund homolog 1 (DACH1) as a kidney disease risk gene, revealing its crucial role in regulating the development of renal fibrosis.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Neurosciences
Yanfa Sun, Ye Eun Bae, Jingjing Zhu, Zichen Zhang, Hua Zhong, Jie Yu, Chong Wu, Lang Wu
Summary: This study conducted a comprehensive splicing transcriptome-wide association study to identify susceptibility splicing introns associated with Alzheimer's disease (AD) risk. Using genetic prediction models, the study found significant associations between 233 splicing introns (143 genes) and AD risk. Fine-mapping analysis further supported causal associations of 83 splicing introns in 55 genes.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Genetics & Heredity
Kunling Huang, Yuchang Wu, Junha Shin, Ye Zheng, Alireza Fotuhi Siahpirani, Yupei Lin, Zheng Ni, Jiawen Chen, Jing You, Sunduz Keles, Daifeng Wang, Sushmita Roy, Qiongshi Lu
Summary: Author's summary emphasizes that autism spectrum disorder (ASD) is associated with complex genetic etiology involving both rare and common variants. The TITANS statistical framework integrates transmission disequilibrium information and tissue-specific regulatory annotations to infer risk genes, highlighting a novel autism gene, POU3F2. This study reveals a connection between rare and common variants in ASD by showing that ASD genes affected by rare mutations are regulated by an unlinked transcription factor affected by common genetic variations.
Meeting Abstract
Biochemistry & Molecular Biology
Lashodya V. Dissanayake, Adrian Zietara, Vladislav Levchenko, Oleg Palygin, Alexander Staruschenko
Meeting Abstract
Biochemistry & Molecular Biology
Ruslan Bohovyk, Oleg Palygin, Mykhailo Fedoriuk, Alexander Staruschenko
Review
Physiology
Alexander Staruschenko, Rong Ma, Oleg Palygin, Stuart E. Dryer
Summary: Glomerular filtration, an essential step in renal function, is regulated by intrinsic and extrinsic signals. The dynamics of glomerular filtration play a crucial role in determining blood flow in the kidney and can lead to end-stage kidney failure. This review discusses glomerular structure, disease processes, and the role of ion channels in glomerular cells in both physiological and pathological contexts.
PHYSIOLOGICAL REVIEWS
(2023)
Article
Cell Biology
Nawal A. Yahya, Janelle K. Lanham, Daniel J. Sprague, Oleg Palygin, John D. McCorvy, Jonathan S. Marchant
Summary: The anthelmintic drug praziquantel (PZQ) causes contraction of parasitic schistosomes and blood vessels. PZQ's action on the vasculature is mediated by the activation of host serotonergic 5-HT2B receptors. The molecular basis for PZQ interaction with these receptors and their location in the vessel wall have not been experimentally defined.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Parasitology
Evgeny G. Chulkov, Oleg Palygin, Nawal A. Yahya, Sang-Kyu Park, Jonathan S. Marchant
Summary: Ion channels have been identified as effective targets for anthelmintic chemotherapy, including a recently discovered flatworm ion channel targeted by praziquantel (PZQ) for the treatment of schistosomiasis. This study provides a detailed biophysical characterization of the properties of the PZQ-activated ion channel in various parasitic flatworms, identifying its distinctive features and calcium permeability. The findings contribute to a better understanding of the mechanism of action of PZQ and pave the way for future investigations into the regulation of this novel antiparasitic target.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Toray S. Akcan, Sergey Vilov, Matthias Heinig
Summary: DNA and RNA-binding trans-acting factors play a crucial role in regulating promoter-proximal RNA polymerase II (Pol II) pausing, which is a rate-limiting step in gene expression. In this study, we developed a machine learning model that accurately predicts the extent of Pol II pausing based on genomic and transcriptomic data, and identified previously unknown regulators of pausing.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Medicine, Research & Experimental
Ina Rohwedder, Lou Martha Wackerbarth, Kristina Heinig, Annamaria Ballweg, Johannes Altstaetter, Myriam Ripphahn, Claudia Nussbaum, Melanie Salvermoser, Susanne Bierschenk, Tobias Straub, Matthias Gunzer, Marc Schmidt-Supprian, Thomas Kolben, Christian Schulz, Averil Ma, Barbara Walzog, Matthias Heinig, Markus Sperandio
Summary: Newborns, especially premature infants, are prone to developing neonatal sepsis due to differences in immune system requirements during intrauterine and extrauterine life. Through transcriptomic analysis, we have identified the molecular mechanisms of neutrophil maturation and functional adaptation in fetal ontogeny. Our findings reveal constitutive activation of the noncanonical NF-KB pathway and upregulation of A20 in fetal neutrophils, leading to appropriate adaptation of neutrophil function during intrauterine fetal life but potentially hampering immune responses in prematurely born infants.
Article
Cell Biology
Pablo Montanes-Agudo, Ingeborg van der Made, Simona Aufiero, Anke J. Tijsen, Yigal M. Pinto, Esther E. Creemers
Summary: In this study, the role of QKI in the formation of circRNAs in the heart was investigated using RNA-sequencing on Qki-knockout mice. The results showed that QKI regulates the expression of a significant portion of circRNAs in adult mouse hearts, and a relationship was found between back-splicing and linear splicing. Additionally, comparison with another cardiac splicing factor, RBM20, revealed that QKI and RBM20 regulate the formation of a distinct but partially overlapping set of circRNAs in the heart.
JOURNAL OF CELL SCIENCE
(2023)
Article
Physiology
Adrian Zietara, Oleg Palygin, Vladislav Levchenko, Lashodya V. Dissanayake, Christine A. Klemens, Aron Geurts, Jerod S. Denton, Alexander Staruschenko
Summary: High K+ supplementation is associated with a lower risk of death, cardiovascular events, and improved blood pressure, but the mechanisms are not well understood. In this study, researchers examined the role of the K(ir)7.1 channel in salt-sensitive hypertension using genetic and pharmacological approaches. They found that reducing K(ir)7.1 expression had some impact on electrolyte balance but did not significantly affect the development or magnitude of salt-induced hypertension. These findings suggest that K(ir)7.1 works in conjunction with other K+ channels to regulate membrane potential in the kidneys.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Biochemical Research Methods
Sergey Vilov, Matthias Heinig
Summary: In this study, a convolutional neural network-based approach called DeepSom is presented for detecting somatic single nucleotide polymorphism and short insertion and deletion variants in tumor whole-genome sequencing samples without a matched normal. The performance of DeepSom is validated on five different cancer datasets and it is demonstrated to outperform previously proposed methods for tumor-only somatic variant calling on whole-genome sequencing samples.
Article
Biotechnology & Applied Microbiology
Shuang Li, Katharina T. Schmid, Dylan H. de Vries, Maryna Korshevniuk, Corinna Losert, Roy Oelen, Irene van Blokland, Hilde E. Groot, Morris A. Swertz, Pim van der Harst, Harm-Jan Westra, Monique G. P. van der Wijst, Matthias Heinig, Lude Franke
Summary: This study uses single-cell data to reconstruct personalized co-expression networks and identifies SNPs altering co-expression patterns. These co-eQTLs are replicated in a large bulk cohort and provide novel insights into disease-associated variants and regulatory networks.
Article
Multidisciplinary Sciences
Florin Ratajczak, Mitchell Joblin, Marcel Hildebrandt, Martin Ringsquandl, Pascal Falter-Braun, Matthias Heinig
Summary: Understanding phenotype-genotype relationships is a challenge in biology, and the authors use graph representation learning to identify human genes with core gene characteristics for complex diseases. The core-like genes exhibit similar properties to core genes and are attractive targets for drug development.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Bethany Wolf, Calvin R. K. Blaschke, Sandy Mungaray, Bryan T. Weselman, Mariia Stefanenko, Mykhailo Fedoriuk, Hongxia Bai, Jessalyn Rodgers, Oleg Palygin, Richard R. Drake, Tamara K. Nowling
Summary: Lupus nephritis (LN) is a serious complication primarily affecting women with systemic lupus erythematosus. Our study found significant differences in lactosylceramide (LacCer) and N-linked glycosylated proteins (N-glycans) in the urine of LN patients, with more pronounced differences in males. Female-derived primary human renal mesangial cells (hRMCs) showed higher levels of calcium ion (Ca2+) flux, cytokine secretion, and glycosphingolipids compared to male-derived hRMCs when stimulated with LN sera. These findings suggest that urine LacCers and N-glycan profiles could serve as definitive biomarkers for LN, and the differences in males may indicate worse disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Physiology
C. Alex Colvert, Kennedy P. Hawkins, Marharyta Semenikhina, Mariia Stefanenko, Olesia Pavlykivska, Jim C. Oates, Kristine Y. DeLeon-Pennell, Oleg Palygin, Justin P. Van Beusecum
Summary: Increased mechanical endothelial stretch regulates endothelial activation and immunological synapse interface formation in renal endothelial cells in a sex-dependent manner.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Meeting Abstract
Peripheral Vascular Disease
Michael Grzybowski, Mark Vanden Avond, Kristie Usa, Jason Klotz, Oleg Palygin, Melinda R. Dwinell, Allen W. Cowley, Alexander Staruschenko, Mingyu Liang, Aron M. Geurts