Article
Multidisciplinary Sciences
Dafni A. Glinos, Garrett Garborcauskas, Paul Hoffman, Nava Ehsan, Lihua Jiang, Alper Gokden, Xiaoguang Dai, Francois Aguet, Kathleen L. Brown, Kiran Garimella, Tera Bowers, Maura Costello, Kristin Ardlie, Ruiqi Jian, Nathan R. Tucker, Patrick T. Ellinor, Eoghan D. Harrington, Hua Tang, Michael Snyder, Sissel Juul, Pejman Mohammadi, Daniel G. MacArthur, Tuuli Lappalainen, Beryl Cummings
Summary: Regulation of transcript structure has a significant impact on transcript diversity and human disease. This study presents a large human long-read RNA-seq dataset, which allows for the analysis of the effects of genetic variation on transcript structure. Through allele-specific analysis of long reads, the researchers identified novel transcripts, characterized allele-specific expression and transcript structure events, and gained new insights into the impact of common and rare genetic variants on transcript alterations. The study also highlighted the regulatory effects modified by the cellular environment and enhanced variant interpretation for aberrant splicing patterns caused by rare variants.
Article
Biotechnology & Applied Microbiology
Fei Zhang, Deborah Velez-Irizarry, Catherine W. Ernst, Wen Huang
Summary: In this study, genome-wide analysis of alternative splicing in skeletal muscle of a Duroc x Pietrain F2 pig population was performed. It was found that the heritability of alternative splicing scores was lower than that of overall gene expression. Additionally, there was little correlation between alternative splicing and overall gene expression. Integration of splice QTL mapping with phenotype QTL mapping identified potential mediators of phenotype QTL effects through alternative splicing.
Article
Multidisciplinary Sciences
Nelson Johansen, Saroja Somasundaram, Kyle J. Travaglini, Anna Marie Yanny, Maya Shumyatcher, Tamara Casper, Charles Cobbs, Nick Dee, Richard Ellenbogen, Manuel Ferreira, Jeff Goldy, Junitta Guzman, Ryder Gwinn, Daniel Hirschstein, Nikolas L. Jorstad, C. Dirk Keene, Andrew Ko, Boaz P. Levi, Jeffrey G. Ojemann, Thanh Pham, Nadiya Shapovalova, Daniel Silbergeld, Josef Sulc, Amy Torkelson, Herman Tung, Kimberly Smith, Ed S. Lein, Trygve E. Bakken, Rebecca D. Hodge, Jeremy A. Miller
Summary: This study explores interindividual variation in the human brain at the cell type-level resolution. Using single-nucleus RNA sequencing and whole-genome sequencing, the researchers profiled the transcriptome and genome of cortical tissues from a large cohort of donors. They found that while the cellular makeup of the brain is highly consistent across individuals, there is substantial variation in gene expression and cellular abundance driven by donor characteristics, disease conditions, and genetic regulation.
Review
Genetics & Heredity
Haley A. Vecchiarelli, Marie-Eve Tremblay
Summary: Microglia, the resident immune cells of the CNS, play important roles in physiology and immunity, with their gene expression patterns varying in different states. Understanding the functional roles of microglia and targeting them for therapy are important directions in the field.
ANNUAL REVIEW OF GENETICS
(2023)
Article
Multidisciplinary Sciences
Sergey Aganezov, Stephanie M. Yan, Daniela C. Soto, Melanie Kirsche, Samantha Zarate, Pavel Avdeyev, Dylan J. Taylor, Kishwar Shafin, Alaina Shumate, Chunlin Xiao, Justin Wagner, Jennifer McDaniel, Nathan D. Olson, Michael E. G. Sauria, Mitchell R. Vollger, Arang Rhie, Melissa Meredith, Skylar Martin, Joyce Lee, Sergey Koren, Jeffrey A. Rosenfeld, Benedict Paten, Ryan Layer, Chen-Shan Chin, Fritz J. Sedlazeck, Nancy F. Hansen, Danny E. Miller, Adam M. Phillippy, Karen H. Miga, Rajiv C. McCoy, Megan Y. Dennis, Justin M. Zook, Michael C. Schatz
Summary: Compared to its predecessors, the Telomere-to-Telomere CHM13 genome has significant improvements in sequence length and structural accuracy, enabling more comprehensive study of the human genome. The application of the T2T-CHM13 reference has demonstrated improved accuracy in read mapping and variant calling for globally diverse samples, leading to the discovery of previously unresolved variants and the removal of false positives. These advancements position T2T-CHM13 as a potential replacement for GRCh38 as the dominant reference for human genetics.
Article
Biochemical Research Methods
Yanyu Li, Xuecang Li, Yongsan Yang, Meng Li, Fengcui Qian, Zhidong Tang, Jianmei Zhao, Jian Zhang, Xuefeng Bai, Yong Jiang, Jianyuan Zhou, Yuexin Zhang, Liwei Zhou, Jianjun Xie, Enmin Li, Qiuyu Wang, Chunquan Li
Summary: TRlnc is a comprehensive database for human regulatory information of lncRNAs, providing detailed genetic and epigenetic annotation within transcriptional regulatory regions of lncRNAs, which aims at helping users gain in-depth insights into the transcriptional regulatory mechanisms of lncRNAs.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Immunology
Kousuke Yonemoto, Fumihiko Fujii, Ryoji Taira, Masahiro Ohgidani, Katsuhide Eguchi, Sayaka Okuzono, Yuko Ichimiya, Yuri Sonoda, Pin Fee Chong, Hironori Goto, Hikaru Kanemasa, Yoshitomo Motomura, Masataka Ishimura, Yuhki Koga, Keita Tsujimura, Takao Hashiguchi, Hiroyuki Torisu, Ryutaro Kira, Takahiro A. Kato, Yasunari Sakai, Shouichi Ohga
Summary: This study investigated the response of human induced microglia-like (iMG) cells to innate immune ligands and found that cell heterogeneity and mitochondrial stability underlie the immunoreactivity of iMG.
CLINICAL IMMUNOLOGY
(2023)
Article
Clinical Neurology
Amy M. Smith, Karen Davey, Stergios Tsartsalis, Combiz Khozoie, Nurun Fancy, See Swee Tang, Eirini Liaptsi, Maria Weinert, Aisling McGarry, Robert C. J. Muirhead, Steve Gentleman, David R. Owen, Paul M. Matthews
Summary: The study reveals significant differences in gene expression in astrocytes and microglia in the brains of AD patients, correlated with amyloid-beta or pTau expression. There are distinct gene expression patterns in the two cell types and pathologies, but common gene sets exist in each cell type. Additionally, different sub-clusters are found in astrocytes and microglia, characterized by transcriptional signatures related to either homeostatic functions or disease pathology.
ACTA NEUROPATHOLOGICA
(2022)
Article
Multidisciplinary Sciences
Zu-Qiang Liu, Hao Dai, Lu Yao, Wei-Feng Chen, Yun Wang, Li-Yun Ma, Xiao-Qing Li, Sheng-Li Lin, Meng-Jiang He, Ping-Ting Gao, Xin-Yang Liu, Jia-Xin Xu, Xiao-Yue Xu, Ke-Hao Wang, Li Wang, Luonan Chen, Ping-Hong Zhou, Quan-Lin Li
Summary: Using single-cell RNA sequencing, researchers identified C1QC(+) macrophages and tissue-resident memory T cells in the peripheral blood mononuclear cells (PBMC) and lower esophageal sphincter tissue of patients with achalasia, revealing alterations in their compositions and transcriptional profiles.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Tulsi Patel, Troy P. Carnwath, Xue Wang, Mariet Allen, Sarah J. Lincoln, Laura J. Lewis-Tuffin, Zachary S. Quicksall, Shu Lin, Frederick Q. Tutor-New, Charlotte C. G. Ho, Yuhao Min, Kimberly G. Malphrus, Thuy T. Nguyen, Elizabeth Martin, Cesar A. Garcia, Rawan M. Alkharboosh, Sanjeet Grewal, Kaisorn Chaichana, Robert Wharen, Hugo Guerrero-Cazares, Alfredo Quinones-Hinojosa, Nilufer Ertekin-Taner
Summary: This study comprehensively characterizes the transcriptomes of human microglia and explores the effects of age, sex, and APOE. The study identifies microglial co-expression network modules associated with age, sex, and APOE-epsilon 4 that are enriched for lipid and carbohydrate metabolism genes. These modules and disease-associated microglial clusters contain known neurodegenerative disease genes.
Article
Biology
Xu Zhang, Francesca Florini, Joseph E. Visone, Irina Lionardi, Mackensie R. Gross, Valay Patel, Kirk W. Deitsch
Summary: Malaria parasites use transcriptional control and a gene network anchored by var2csa to coordinate switching of antigen exposure and maintain chronic infections, despite possessing a small repertoire of variant antigen-encoding genes.
Article
Oncology
Zhenyuan Yu, Yufang Lv, Cheng Su, Wenhao Lu, RuiRui Zhang, Jiaping Li, Bingqian Guo, Haibiao Yan, Deyun Liu, Zhanbin Yang, Hua Mi, Linjian Mo, Yi Guo, Wenyu Feng, Haotian Xu, Wenyi Peng, Jiwen Cheng, Aruo Nan, Zengnan Mo
Summary: This study performed single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on 19 ccRCC samples to construct single-cell transcriptome and chromatin accessibility maps. It revealed the regulatory characteristics of different tumor cell subtypes in ccRCC and identified two long noncoding RNAs that promote ccRCC invasion and migration. This comprehensive analysis provides new insights into the biology and treatment of ccRCC.
Article
Biochemistry & Molecular Biology
Jaime A. Castro-Mondragon, Miriam Ragle Aure, Ole Christian Lingjaerde, Anita Langerod, John W. M. Martens, Anne-Lise Borresen-Dale, Vessela N. Kristensen, Anthony Mathelier
Summary: Most cancer alterations occur in the noncoding portion of the genome, where regulatory regions control gene expression. This study shows that transcription factor binding sites (TFBSs) have similar mutation loads to protein-coding exons. By analyzing cancer somatic mutations in TFBSs and gene expression data, the combined effects of transcriptional and post-transcriptional alterations on regulatory programs in cancer can be evaluated.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Immunology
Lucy C. Garner, Ali Amini, Michael E. B. FitzPatrick, Martin J. Lett, Gabriel F. Hess, Magdalena Filipowicz Sinnreich, Nicholas M. Provine, Paul Klenerman
Summary: Garner et al. analyzed the single-cell transcriptome and TCR repertoire of matched blood and liver, and resting and activated, human MAIT cells. They identify donor-specific TCR repertoires shared across tissues and a transcriptome that is largely homogeneous at rest, but highly adaptive to different tissue and stimulation environments.
Article
Genetics & Heredity
Yu Gao, Chenchen Feng, Yuexin Zhang, Chao Song, Jiaxin Chen, Yanyu Li, Ling Wei, Fengcui Qian, Bo Ai, Yuejuan Liu, Jiang Zhu, Xiaojie Su, Chunquan Li, Qiuyu Wang
Summary: This study developed a comprehensive database called TRmir for the human transcriptional regulation of miRNAs, which provides extensive information about miRNA transcriptional regulatory regions and annotates their potential roles in miRNA regulation.
FRONTIERS IN GENETICS
(2022)
Article
Clinical Neurology
Andrew Edwards-Bailey, Howra Ktayen, Georgios Solomou, Emily Bligh, Abbey Boyle, Aref-Ali Gharooni, Guan Hui Tricia Lim, Adithya Varma, Susan Standring, Thomas Santarius, Daniel Fountain
Summary: This study investigated the teaching and assessment of neuroanatomy in UK and Ireland medical schools in 2019/2020, revealing significant variations in teaching methods and knowledge evaluation. The findings suggest the need for developing and standardizing national undergraduate neuroanatomy curricula to enhance student confidence and achievement.
BRITISH JOURNAL OF NEUROSURGERY
(2022)
Article
Multidisciplinary Sciences
Masahiro Yoshida, Kaylee B. Worlock, Ni Huang, Rik G. H. Lindeboom, Colin R. Butler, Natsuhiko Kumasaka, Cecilia Dominguez Conde, Lira Mamanova, Liam Bolt, Laura Richardson, Krzysztof Polanski, Elo Madissoon, Josephine L. Barnes, Jessica Allen-Hyttinen, Eliz Kilich, Brendan C. Jones, Angus de Wilton, Anna Wilbrey-Clark, Waradon Sungnak, J. Patrick Pett, Elena Prigmore, Henry Yung, Puja Mehta, Aarash Saleh, Anita Saigal, Vivian Chu, Jonathan M. Cohen, Clare Cane, Aikaterini Iordanidou, Soichi Shibuya, Ann-Kathrin Reuschl, Ivan T. Herczeg, A. Christine Argento, Richard G. Wunderink, Sean B. Smith, Taylor A. Poor, Catherine A. Gao, Jane E. Dematte, Gary Reynolds, Muzlifah Haniffa, Georgina S. Bowyer, Matthew Coates, Menna R. Clatworthy, Fernando J. Calero-Nieto, Berthold Goettgens, Christopher O'Callaghan, Neil J. Sebire, Clare Jolly, Paolo de Coppi, Claire M. Smith, Alexander Misharin, Sam M. Janes, Sarah A. Teichmann, Marko Z. Nikolic, Kerstin B. Meyer
Summary: Higher innate interferon responses in children may restrict viral replication and disease progression, while the response to SARS-CoV-2 infection differs between children and adults.
Article
Genetics & Heredity
Johann S. Hawe, Rory Wilson, Katharina T. Schmid, Li Zhou, Lakshmi Narayanan Lakshmanan, Benjamin C. Lehne, Brigitte Kuehnel, William R. Scott, Matthias Wielscher, Yik Weng Yew, Clemens Baumbach, Dominic P. Lee, Eirini Marouli, Manon Bernard, Liliane Pfeiffer, Pamela R. Matias-Garcia, Matias Autio, Stephane Bourgeois, Christian Herder, Ville Karhunen, Thomas Meitinger, Holger Prokisch, Wolfgang Rathmann, Michael Roden, Sylvain Sebert, Jean Shin, Konstantin Strauch, Weihua Zhang, Wilson L. W. Tan, Stefanie M. Hauck, Juliane Merl-Pham, Harald Grallert, Eudes G. Barbosa, Thomas Illig, Annette Peters, Tomas Paus, Zdenka Pausova, Panos Deloukas, Roger S. Y. Foo, Marjo-Riitta Jarvelin, Jaspal S. Kooner, Marie Loh, Matthias Heinig, Christian Gieger, Melanie Waldenberger, John C. Chambers
Summary: This study focuses on the relationships between DNA sequence variation and DNA methylation, using blood samples from Europeans and South Asians. The findings reveal numerous SNP-CpG associations (meQTL) that are functionally relevant and associated with gene expression, metabolic variation, and clinical traits. Molecular interaction and colocalization analyses identified regulatory pathways linking meQTL loci to phenotypic variation.
Article
Oncology
Jack Bartram, Gary Wright, Stuart Adams, Paul Archer, Tony Brooks, Darren Edwards, Jerry Hancock, Henrik Knecht, Sarah Inglott, Edward Mountjoy, Marie Roynane, Stephanie Wakeman, John Moppett, Mike Hubank, Nick Goulden
Summary: This study demonstrates that high-throughput sequencing can be used to measure MRD in peripheral blood, which helps guide treatment for children with acute lymphoblastic leukemia. This method is cost-effective, rapid, accurate, and can improve relapse prediction and detection speed.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Cell Biology
Lucy J. Goudswaard, Laura J. Corbin, Kate L. Burley, Andrew Mumford, Parsa Akbari, Nicole Soranzo, Adam S. Butterworth, Nicholas A. Watkins, Dimitri J. Pournaras, Jessica Harris, Nicholas J. Timpson, Ingeborg Hers
Summary: Higher BMI is associated with changes in platelet characteristics and increased risk of thrombosis. The study found a positive association between higher BMI and platelet traits such as plateletcrit, platelet count, immature platelet count, and side fluorescence. Higher BMI leads to an increase in the number of immature platelets, which is associated with increased platelet aggregation.
Article
Genetics & Heredity
Kousik Kundu, Alice L. Mann, Manuel Tardaguila, Stephen Watt, Hannes Ponstingl, Louella Vasquez, Nicholas W. Morrell, Oliver Stegle, Tomi Pastinen, Stephen J. Sawcer, Carl A. Anderson, Klaudia Walter, Nicole Soranzo
Summary: The colocalization of regulatory quantitative trait loci from the BLUEPRINT project with genetic association data aids in the fine-mapping of putative causal variants for 12 immune-mediated diseases.
Article
Gastroenterology & Hepatology
Andreas W. Schmidt, Andreas Kuehnapfel, Holger Kirsten, Harald Grallert, Claus Hellerbrand, Falk Kiefer, Karl Mann, Sebastian Mueller, Markus M. No, Annette Peters, Monika Ridinger, Josef Frank, Marcella Rietschel, Nicole Soranzo, Michael Soyka, Norbert Wodarz, Giovanni Malerba, Giovanni Gambaro, Christian Gieger, Markus Scholz, Sebastian Krug, Patrick Michl, Maren Ewers, Heiko Witt, Helmut Laumen, Jonas Rosendahl
Summary: This study conducted a GWAS in non-alcoholic chronic pancreatitis (NACP) patients and identified risk loci associated with the disease. Through colocalization analysis, candidate causal genes and shared causal variants were prioritized. The results suggest that a shared causal CTRC risk variant may affect the pathogenesis of both alcoholic chronic pancreatitis (ACP) and NACP by reducing CTRC expression, while a shared causal variant rs12688220 may modify the risk of both diseases by increasing CLDN2 expression.
Article
Clinical Neurology
Christopher E. McMurran, Trisha Mukherjee, J. William L. Brown, Andrew W. Michell, Declan T. Chard, Robin J. M. Franklin, Alasdair J. Coles, Nick G. Cunniffe
Summary: Remyelination efficiency decreases with age, particularly in patients with multiple sclerosis. Bexarotene, a retinoid-X receptor agonist, only shortens the visual evoked potential latency in patients under 42 years old and increases the magnetization transfer ratio of deep gray matter lesions in those under 43 years old.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Psychiatry
Hyojung Paik, Junehawk Lee, Chan-Seok Jeong, Jun Sung Park, Jeong Ho Lee, Nadav Rappoport, Younghoon Kim, Hee-Young Sohn, Chulman Jo, Jimin Kim, Seong Beom Cho
Summary: Observations have confirmed the comorbidity between heart diseases and cognitive impairment. Genetic variants in APOB and ADIPOQ genes were found to have a pleiotropic effect on both diseases. Integrating healthcare records and genetic evidence can help understand the molecular underpinnings of heart disease and associated cognitive impairment.
TRANSLATIONAL PSYCHIATRY
(2022)
Review
Cell Biology
Sonia Cabeza-Fernandez, Jessica A. White, Christopher E. McMurran, Jose A. Gomez-Sanchez, Alerie G. de la Fuente
Summary: The interaction between immune and stem cells is crucial for tissue homeostasis and regeneration. Recently, it has been discovered that oligodendrocyte progenitor cells (OPCs), a type of brain stem cell, engage in bidirectional interactions with the immune system. Understanding this interaction holds great potential for developing new therapeutic approaches to limit neuroinflammation and promote myelin repair, which are important features in neurodegenerative diseases.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Artem Lomakin, Jessica Svedlund, Carina Strell, Milana Gataric, Artem Shmatko, Gleb Rukhovich, Jun Sung Park, Young Seok Ju, Stefan Dentro, Vitalii Kleshchevnikov, Vasyl Vaskivskyi, Tong Li, Omer Ali Bayraktar, Sarah Pinder, Andrea L. Richardson, Sandro Santagata, Peter J. Campbell, Hege Russnes, Moritz Gerstung, Mats Nilsson, Lucy R. Yates
Summary: Genome sequencing of cancers often reveals mosaics of different subclones present in the same tumour. This study developed a workflow that generates detailed quantitative maps of genetic subclone composition to study clonal growth patterns, characteristics, and microenvironments. Applying this workflow to breast cancer tissue sections revealed intricate subclonal growth patterns validated by microdissection, providing examples of the benefits of spatial genomics in deciphering cancer evolution and microenvironmental ecology.
Article
Genetics & Heredity
Elo Madissoon, Amanda J. Oliver, Vitalii Kleshchevnikov, Anna Wilbrey-Clark, Krzysztof Polanski, Nathan Richoz, Ana Ribeiro Orsi, Lira Mamanova, Liam Bolt, Rasa Elmentaite, J. Patrick Pett, Ni Huang, Chuan Xu, Peng He, Monika Dabrowska, Sophie Pritchard, Liz Tuck, Elena Prigmore, Shani Perera, Andrew Knights, Agnes Oszlanczi, Adam Hunter, Sara F. Vieira, Minal Patel, Rik G. H. Lindeboom, Lia S. Campos, Kazuhiko Matsuo, Takashi Nakayama, Masahiro Yoshida, Kaylee B. Worlock, Marko Z. Nikolic, Nikitas Georgakopoulos, Krishnaa T. Mahbubani, Kourosh Saeb-Parsy, Omer Ali Bayraktar, Menna R. Clatworthy, Oliver Stegle, Natsuhiko Kumasaka, Sarah A. Teichmann, Kerstin B. Meyer
Summary: Single-cell transcriptomics provides detailed information on cell types in the human lung, but lacks spatial context. In this study, we used multi-omic single cell/nuclei and spatial transcriptomics to explore the tissue architecture of healthy human lungs. Through computational analysis, we identified previously unannotated cell types and discovered tissue compartments in different micro-environments. We also uncovered a survival niche for IgA plasma cells in the submucosal glands of the airways, which has implications for respiratory health.
Article
Oncology
Jonathan K. L. Mak, Christopher E. McMurran, Ralf Kuja-Halkola, Per Hall, Kamila Czene, Juulia Jylhaevae, Sara Haegg
Summary: By studying 308,156 UK Biobank participants, researchers found a link between biological age and cancer incidence. Using 18 age-related clinical biomarkers, three biological age measures were calculated and found to be associated with the incidence of any cancer, breast cancer, prostate cancer, lung cancer, colorectal cancer, and melanoma.
BRITISH JOURNAL OF CANCER
(2023)
Article
Clinical Neurology
Christopher E. Mcmurran, Yunzhang Wang, Jonathan K. L. Mak, Ida K. Karlsson, Bowen Tang, Alexander Ploner, Nancy L. Pedersen, Sara Hagg
Summary: Age is a major risk factor for neurological diseases, and the rate of biological aging may affect future disease diagnosis and clinical examination results. Measures of biological aging can predict the occurrence of neurological diseases, which helps explain the variability in disease risk among individuals of the same age, and emphasizes the importance of conducting anti-aging interventions for patients with neurological disorders.
Article
Clinical Neurology
Rafael Romero-Garcia, John Suckling, Mallory Owen, Moataz Assem, Rohitashwa Sinha, Pedro Coelho, Emma Woodberry, Stephen J. Price, Amos Burke, Thomas Santarius, Yaara Erez, Michael G. Hart
Summary: The objective of this study is to explore the interactions between brain tumors and brain networks, and identify protective features and risk factors for memory recovery after surgery. Using NODDI and resting-state networks, imaging biomarkers of cognitive recovery and decline can be identified. Brain tumors and their corresponding treatment can have a major impact on patients' memory recovery.
JOURNAL OF NEUROSURGERY
(2022)
