Article
Biochemistry & Molecular Biology
Kofi Amoah, Yun-Hua Esther Hsiao, Jae Hoon Bahn, Yiwei Sun, Christina Burghard, Boon Xin Tan, Ei-Wen Yang, Xinshu Xiao
Summary: Alternative splicing is a RNA processing mechanism that affects most genes in human, and can be modulated by genetic variants. Utilizing GTEx data, the study of genetically modulated alternative splicing (GMAS) reveals that GMAS events are shared more frequently across tissues and individuals than expected by chance, indicating a genetically driven nature.
Article
Biochemistry & Molecular Biology
Shuo Cao, Haoran Zhu, Jinru Cui, Sun Liu, Yuhe Li, Junfang Shi, Junyuan Mo, Zihan Wang, Hailan Wang, Jiaxin Hu, Lizhi Chen, Yuan Li, Laixin Xia, Shan Xiao
Summary: This study developed a method to accurately detect allele-specific m(6)A and identified genetic variants associated with common diseases. It reveals the important role of m(6)A and genetics in human health and disease.
Article
Multidisciplinary Sciences
Michelle P. Harwood, Isabel Alves, Hilary Edgington, Mawusse Agbessi, Vanessa Bruat, David Soave, Fabien C. Lamaze, Marie-Julie Fave, Philip Awadalla
Summary: Understanding how the genetic composition of a population changes through processes like genetic drift and selection is crucial for understanding phenotypic variation in time and space. This study shows how evolutionary forces, including recombination and effective population size, affect genomic patterns of allele-specific expression (ASE). The research integrates tissue-specific genetic and transcriptomic data from two cohorts and demonstrates that ASE is influenced by recombination rates and can be used to underexpress harmful mutations. Genetic ancestry and local environment also have an impact on ASE variability.
Article
Biochemistry & Molecular Biology
Christine K. Rummel, Miriam Gagliardi, Ruhel Ahmad, Alexander Herholt, Laura Jimenez-Barron, Vanessa Murek, Liesa Weigert, Anna Hausruckinger, Susanne Maidl, Barbara Hauger, Florian J. Raabe, Christina Fuerle, Lucia Trastulla, Gustavo Turecki, Matthias Eder, Moritz J. Rossner, Michael J. Ziller
Summary: This study conducted variant-to-function mapping in disease-relevant neural cell types to investigate the role of genetic variants in schizophrenia. By integrating multiple datasets, the functional variants were linked to target genes, biological processes, and alterations in neuronal physiology, providing insights into the context-dependent molecular processes modulated by schizophrenia-associated genetic variation.
Article
Genetics & Heredity
Margaret G. Guo, David L. Reynolds, Cheen E. Ang, Yingfei Liu, Yang Zhao, Laura K. H. Donohue, Zurab Siprashvili, Xue Yang, Yongjin Yoo, Smarajit Mondal, Audrey Hong, Jessica Kain, Lindsey Meservey, Tania Fabo, Ibtihal Elfaki, Laura N. Kellman, Nathan S. Abell, Yash Pershad, Vafa Bayat, Payam Etminani, Mark Holodniy, Daniel H. Geschwind, Stephen B. Montgomery, Laramie E. Duncan, Alexander E. Urban, Russ B. Altman, Marius Wernig, Paul A. Khavari
Summary: Noncoding variants play a role in the heritability of neuropsychiatric diseases. A study in developing human neural cells investigated 2,221 noncoding variants associated with ten neuropsychiatric disorders and identified differentially-active single-nucleotide variants (daSNVs) in specific neural cell types. Integrating epigenomic and transcriptomic data helped identify candidate disease-relevant target genes modulated by these daSNVs.
Article
Medicine, General & Internal
Rui Chen, Jiewei Liu, Shiwu Li, Xiaoyan Li, Yongxia Huo, Yong-Gang Yao, Xiao Xiao, Ming Li, Xiong-Jian Luo
Summary: Through functional genomics study, we have systematically revealed the gene regulatory mechanisms of PD risk variants, generated the landscape of potential PD causal variants, and identified promising candidate genes for further functional characterization and drug development.
Article
Oncology
Daniel Haag, Norman Mack, Patricia Benites Goncalves da Silva, Britta Statz, Jessica Clark, Koji Tanabe, Tanvi Sharma, Natalie Jaeger, David T. W. Jones, Daisuke Kawauchi, Marius Wernig, Stefan M. Pfister
Summary: The study found that the H3.3-K27M mutation has different effects on different neural cell types, with only neural stem cells capable of giving rise to tumors in an in vivo model by inducing H3.3-K27M and TP53 inactivation.
Article
Biochemistry & Molecular Biology
Shengcheng Dong, Alan P. Boyle
Summary: A computational tool called TURF is introduced to prioritize regulatory variants with tissue-specific function, showing overall top performance in prediction. TURF can generate prediction scores for non-coding variants based on functional genomics datasets and pick out regulatory variants with tissue-specific function from candidate lists. Additionally, GWAS traits exhibit enrichment of regulatory variants predicted by TURF scores in trait-relevant organs, suggesting their value for future studies.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Engineering, Biomedical
Minoru Hirano, Yike Huang, Daniel Vela Jarquin, Rosakaren Ludivina De la Garza Hernandez, Yasamin A. Jodat, Eder Luna Ceron, Luis Enrique Garcia-Rivera, Su Ryon Shin
Summary: This study introduces a biofabrication approach using 3D bioprinting and human pluripotent stem cell (hPSC) technologies to engineer sensible tissue constructs with complex microarchitecture wiring, demonstrating responsiveness to external stimuli with the potential for regenerating and enhancing sensory functions.
Article
Biochemistry & Molecular Biology
Xi Rao, Kriti S. Thapa, Andy B. Chen, Hai Lin, Hongyu Gao, Jill L. Reiter, Katherine A. Hargreaves, Joseph Ipe, Dongbing Lai, Xiaoling Xuei, Yue Wang, Hongmei Gu, Manav Kapoor, Sean P. Farris, Jay Tischfield, Tatiana Foroud, Alison M. Goate, Todd C. Skaar, R. Dayne Mayfield, Howard J. Edenberg, Yunlong Liu
Summary: This study integrated data from RNA-seq and GWAS to identify 88 genes with differential allele-specific expression in subjects with alcohol use disorders compared to controls. Further analysis of SNPs in the 3' untranslated regions of these genes revealed potential causal variants contributing to the differential ASE. Experimental assays confirmed 25 SNPs affecting RNA levels consistently in two neuroblastoma cell lines, suggesting these SNPs are likely to be causal variants associated with alcohol use disorders.
MOLECULAR PSYCHIATRY
(2021)
Article
Cell & Tissue Engineering
Yuling Han, Lei Tan, Ting Zhou, Liuliu Yang, Lucia Carrau, Lauretta A. Lacko, Mohsan Saeed, Jiajun Zhu, Zeping Zhao, Benjamin E. Nilsson-Payant, Filipe Tenorio Lira Neto, Clare Cahir, Alice Maria Giani, Jin Chou Chai, Yang Li, Xue Dong, Dorota Moroziewicz, Daniel Paull, Tuo Zhang, Soyeon Koo, Christina Tan, Ron Danziger, Qian Ba, Lingling Feng, Zhengming Chen, Aaron Zhong, Gilbert J. Wise, Jenny Z. Xiang, Hui Wang, Robert E. Schwartz, Benjamin R. tenOever, Scott A. Noggle, Charles M. Rice, Qibin Qi, Todd Evans, Shuibing Chen
Summary: This study demonstrates the use of human-induced pluripotent stem cells (hiPSCs) to link human genetics with viral infectivity. It identifies a cis-regulatory region of the NDUFA4 gene associated with susceptibility to Zika virus infection. Loss of NDUFA4 reduces sensitivity to multiple viral infections, and mechanistic studies reveal that loss/reduction of NDUFA4 induces mitochondrial stress and upregulation of interferon signaling.
Article
Multidisciplinary Sciences
Christopher M. Uyehara, Mary Leatham-Jensen, Daniel J. McKay
Summary: This study investigates the role of EcR in controlling tissue-specific responses to the ecdysone steroid hormone in Drosophila. The researchers find that EcR functions bimodally, with both gene repressive and activating functions, and plays a direct role in controlling enhancer activity. They also conclude that while EcR contributes extensively to tissue-specific ecdysone responses, other transcription factors ultimately control access to its binding sites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Maria G. Otero, Shaughn Bell, Alexander H. Laperle, George Lawless, Zachary Myers, Marian A. Castro, Jaquelyn M. Villalba, Clive N. Svendsen
Summary: Conventional tissue culture platforms limit the study of cell biology due to lack of maturity, while organ-chip microfluidic systems provide a more physiological environment for cell growth. In this study, organ-chip cultures showed a higher proportion and homogeneity of mature dopamine neurons compared to multi-well cultures. These organ-chips are ideal for studying the biology of mature dopamine neurons in health and neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Benjamin J. Stauch, Alina Peter, Heike Schuler, Pascal Fries
Summary: Stimulus repetition can modulate neuronal-gamma band synchronization and induce plastic changes in activated neuronal circuits. These changes are stimulus-specific and persist even after intervening stimuli. The strongest effects are observed in the early visual cortex, where there is an increase in interareal feedforward influences.
Article
Immunology
Josephine R. Giles, Sasikanth Manne, Elizabeth Freilich, Derek A. Oldridge, Amy E. Baxter, Sangeeth George, Zeyu Chen, Hua Huang, Lakshmi Chilukuri, Mary Carberry, Lydia Giles, Nan-Ping P. Weng, Regina M. Young, Carl H. June, Lynn M. Schuchter, Ravi K. Amaravadi, Xiaowei Xu, Giorgos C. Karakousis, Tara C. Mitchell, Alexander C. Huang, Junwei Shi, E. John Wherry
Summary: This study generated an epigenetic and transcriptional atlas of T cell differentiation from healthy humans and applied it to explore disease-specific biology. The study identified molecular regulations of gene expression and chromatin accessibility during T cell differentiation and provided insights into disease biology through three research settings. The study also successfully predicted genome-wide cis-regulatory elements and validated the approach for functional annotation of key effector genes, demonstrating the potential of identifying targets for non-coding cellular engineering.
Article
Neurosciences
Alena Kozlova, Robert R. Butler, Siwei Zhang, Thomas Ujas, Hanwen Zhang, Stephan Steidl, Alan R. Sanders, Zhiping P. Pang, Paul Vezina, Jubao Duan
Summary: Repeated nicotine exposure leads to sensitization and enhances self-administration in rodents with sex-specific differences and parental effects. Genes associated with these behaviors are enriched for synaptic processes, myelin sheath, and tobacco use disorder or chemdependency, providing mechanistic links to human addictive behaviors.
NEUROPSYCHOPHARMACOLOGY
(2021)
Correction
Psychology, Biological
Brendan P. Zietsch, Morgan J. Sidari, Abdel Abdellaoui, Robert Maier, Niklas Langstrom, Shengru Guo, Gary W. Beecham, Eden R. Martin, Alan R. Sanders, Karin J. H. Verweij
NATURE HUMAN BEHAVIOUR
(2021)
Article
Psychology, Biological
Brendan P. Zietsch, Morgan J. Sidari, Abdel Abdellaoui, Robert Maier, Niklas Langstrom, Shengru Guo, Gary W. Beecham, Eden R. Martin, Alan R. Sanders, Karin J. H. Verweij
Summary: This research finds that genetic effects associated with same-sex sexual behavior are associated with more sexual partners in individuals who only engage in opposite-sex sexual behavior. This could help explain the evolutionary maintenance of same-sex sexual behavior.
NATURE HUMAN BEHAVIOUR
(2021)
Article
Multidisciplinary Sciences
Yin Yao, Wei Guo, Siwei Zhang, Hao Yu, Hao Yan, Hanwen Zhang, Alan R. Sanders, Weihua Yue, Jubao Duan
Summary: The study analyzed the PRS of neuronal MIR137-target genes in SZ samples, finding that it better explains SZ risk compared to other gene sets. The research demonstrated a cell type-specific polygenic contribution of MIR137-target genes to SZ risk.
Article
Psychology, Clinical
Alan R. Sanders, Gary W. Beecham, Shengru Guo, Judith A. Badner, Sven Bocklandt, Brian S. Mustanski, Dean H. Hamer, Eden R. Martin
Summary: The study analyzed two main datasets on male sexual orientation, finding the strongest genetic linkage at chromosome 8 and Xq28. While genetic contributions to male sexual orientation are increasingly evident, understanding of contributory loci remains limited, emphasizing the complexity of the trait. Further genetic research, particularly through large GWAS, is needed to advance understanding of this important trait.
ARCHIVES OF SEXUAL BEHAVIOR
(2021)
Article
Psychology, Clinical
Alan R. Sanders, Gary W. Beecham, Shengru Guo, Khytam Dawood, Gerulf Rieger, Ritesha S. Krishnappa, Alana B. Kolundzija, J. Michael Bailey, Eden R. Martin
Summary: Male sexual orientation is influenced by environmental and complex genetic factors, with childhood gender nonconformity being strongly correlated with homosexuality. Through a genome-wide linkage scan and family-based association analyses, specific loci associated with childhood gender nonconformity were identified, shedding light on the genetic basis of these traits.
ARCHIVES OF SEXUAL BEHAVIOR
(2021)
Article
Biochemical Research Methods
Boqiao Lai, Sheng Qian, Hanwei Zhang, Siwei Zhang, Alena Kozlova, Jubao Duan, Jinbo Xu, Xin He
Summary: This study developed a tool called MetaChrom by collecting a large amount of data from neurodevelopment-related cell/tissue types and training deep learning models. Compared with current methods, MetaChrom can better predict experimentally determined regulatory variants and identify potential risk genes for schizophrenia. The approach of MetaChrom can also be extended to other disease-related cell or tissue types.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Editorial Material
Neurosciences
Siwei Zhang, Alan R. Sanders, Jubao Duan
Summary: This study aims to investigate how genetic and environmental risk factors interact and trigger the development of PTSD by examining transcriptomic responses to glucocorticoids in neurons, modeling stress hypersensitivity as a potential mechanism.
NATURE NEUROSCIENCE
(2022)
Article
Biochemical Research Methods
Yifan Zhou, Kaixuan Luo, Lifan Liang, Mengjie Chen, Xin He
Summary: Guided sparse factor analysis (GSFA) is a statistical method specifically designed for analyzing single-cell CRISPR screening data to detect changes in gene expression caused by genetic perturbations. This method infers latent factors representing coregulated genes or gene modules and determines the effects of genetic perturbations on individual genes by leveraging information from these factors. Through simulation studies and applications on human T cells and neural progenitor cells, GSFA outperforms existing methods in detecting perturbation effects and provides new insights into the functions of genes involved in T cell activation and neurodevelopment.
Article
Cell Biology
Siwei Zhang, Hanwen Zhang, Marc P. Forrest, Yifan Zhou, Xiaotong Sun, Vikram A. Bagchi, Alena Kozlova, Marc Dos Santos, Nicolas H. Piguel, Leonardo E. Dionisio, Alan R. Sanders, Zhiping P. Pang, Xin He, Peter Penzes, Jubao Duan
Summary: Using human induced pluripotent stem cell (hiPSC)-derived neurons as a neurodevelopmental model, this study reveals the mechanistic link between schizophrenia (SZ) risk variants and disease-related cellular phenotypes. Multiple SZ risk variants were found to display allele-specific open chromatin (ASoC) and affect the expression of relevant genes. Neurons carrying the risk allele exhibit increased dendritic complexity and hyperactivity. Interestingly, individual/combinatorial gene knockdown shows that these genes alter cellular phenotypes in a non-additive synergistic manner.
Article
Biochemical Research Methods
Siwei Zhang
Summary: This article presents a quick-start protocol for performing generalized gene-set analysis of GWAS data on a metaset of gene lists. It utilizes the MAGMA software package and Hi-C coupled H-MAGMA annotation data for the analysis. The protocol is tailored to take advantage of the multithreading capability in modern computers, which is common in both personal computers and high-performance clusters.
Article
Biology
Hanwen Zhang, Siwei Zhang
Summary: A new workflow is introduced to engineer isogenic iPSC lines by SNP editing, allowing for the conversion from disease risk alleles to non-risk alleles.
