Article
Biochemistry & Molecular Biology
Genevieve Hoopes, Xiaoxi Meng, John P. Hamilton, Sai Reddy Achakkagari, Fernanda de Alves Freitas Guesdes, Marie E. Bolger, Joseph J. Coombs, Danny Esselink, Natalie R. Kaiser, Linda Kodde, Maria Kyriakidou, Brian Lavrijssen, Natascha van Lieshout, Rachel Shereda, Heather K. Tuttle, Brieanne Vaillancourt, Joshua C. Wood, Jan M. de Boer, Nolan Bornowski, Peter Bourke, David Douches, Herman J. van Eck, Dave Ellis, Max J. Feldman, Kyle M. Gardner, Johannes C. P. Hopman, Jiming Jiang, Walter S. De Jong, Joseph C. Kuhl, Richard G. Novy, Stan Oome, Vidyasagar Sathuvalli, Ek Han Tan, Remco A. Ursum, M. Isabel Vales, Kelly Vining, Richard G. F. Visser, Jack Vossen, G. Craig Yencho, Noelle L. Anglin, Christian W. B. Bachem, Jeffrey B. Endelman, Laura M. Shannon, Martina Stromvik, Helen H. Tai, Bjorn Usadel, C. Robin Buell, Richard Finkers
Summary: Cultivated potato is a clonally propagated autotetraploid species with a highly heterogeneous genome. Phased assemblies of six cultivars revealed extensive allelic diversity and structural variation, resulting in a complex transcriptome and predicted proteome. Wild species contribute to the allelic diversity in tetraploid cultivars. Understanding the complexity of the potato genome is key for precision breeding and hybridization.
Article
Multidisciplinary Sciences
Sarah Grosche, Ingo Marenholz, Jorge Esparza-Gordillo, Aleix Arnau-Soler, Erola Pairo-Castineira, Franz Rueschendorf, Tarunveer S. Ahluwalia, Catarina Almqvist, Andreas Arnold, Hansjoerg Baurecht, Hans Bisgaard, Klaus Bonnelykke, Sara J. Brown, Mariona Bustamante, John A. Curtin, Adnan Custovic, Shyamali C. Dharmage, Ana Esplugues, Mario Falchi, Dietmar Fernandez-Orth, Manuel A. R. Ferreira, Andre Franke, Sascha Gerdes, Christian Gieger, Hakon Hakonarson, Patrick G. Holt, Georg Homuth, Norbert Hubner, Pirro G. Hysi, Marjo-Riitta Jarvelin, Robert Karlsson, Gerard H. Koppelman, Susanne Lau, Manuel Lutz, Patrik K. E. Magnusson, Guy B. Marks, Martina Mueller-Nurasyid, Markus M. Noethen, Lavinia Paternoster, Craig E. Pennell, Annette Peters, Konrad Rawlik, Colin F. Robertson, Elke Rodriguez, Sylvain Sebert, Angela Simpson, Patrick M. A. Sleiman, Marie Standl, Dora Stoelzl, Konstantin Strauch, Agnieszka Szwajda, Albert Tenesa, Philip J. Thompson, Vilhelmina Ullemar, Alessia Visconti, Judith M. Vonk, Carol A. Wang, Stephan Weidinger, Matthias Wielscher, Catherine L. Worth, Chen-Jian Xu, Young-Ae Lee
Summary: This study identified rare and common variants associated with eczema susceptibility through a meta-analysis, revealing promising therapeutic targets and genetic characteristics of the disease. Rare variants were linked to up-regulation of skin genes while common variants were related to immune cell function.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Guangsheng Pei, Ruifeng Hu, Peilin Jia, Zhongming Zhao
Summary: The Deep-Fun web server utilizes a convolutional neural network framework and chromatin profiles from ENCODE and Roadmap projects to assess the functional activity of non-coding genetic variants. It expands the functionality of existing non-coding variant prioritizing tools by providing specific functional assessments in a tissue- and cell type-specific manner. The server has been validated with datasets from various GWAS studies and is expected to be widely used in genetics, functional genomics, and disease studies.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biology
Manickam Gurusaran, Owen Richard Davies
Summary: The study proposes that the connecting structure formed by SUN-KASH is not a 3:3 complex, but a constitutive 6:6 complex composed of two 3:3 complexes, achieved through different mechanisms. The SUN-KASH 6:6 interface acts as nodes for force distribution and integration across the nuclear envelope, enabling the coordinated transduction of large forces within the cell.
Article
Multidisciplinary Sciences
Alexander S. Leonard, Danang Crysnanto, Zih-Hua Fang, Michael P. Heaton, Brian L. Vander Ley, Carolina Herrera, Heinrich Bollwein, Derek M. Bickhart, Kristen L. Kuhn, Timothy P. L. Smith, Benjamin D. Rosen, Hubert Pausch
Summary: This study demonstrates the consistency of structural variant-based pangenomes regardless of sequence platform, assembler, or coverage using bovine haplotype-resolved assemblies. The study also reveals numerous structural variants overlapping with coding sequences that have the potential to affect phenotype.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Eric Chen, Justin Chu, Jessica Zhang, Rene L. Warren, Inanc Birol
Summary: Short-read DNA sequencing instruments can generate high throughput sequencing data, but face difficulties in de novo assembly due to genome repetition and difficult-to-sequence regions. Scaffold assembly partially mitigates the issue, but unresolved sequences in the scaffolds remain as gaps.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2021)
Article
Multidisciplinary Sciences
You Li, Zhiqiang Li, Ruiling Chen, Min Lian, Hanxiao Wang, Yiran Wei, Zhengrui You, Jun Zhang, Bo Li, Yikang Li, Bingyuan Huang, Yong Chen, Qiaoyan Liu, Zhuwan Lyu, Xueying Liang, Qi Miao, Xiao Xiao, Qixia Wang, Jingyuan Fang, YongYong Shi, Xiangdong Liu, Michael F. Seldin, M. Eric Gershwin, Ruqi Tang, Xiong Ma
Summary: Genome-wide association studies have identified a genetic locus, 19p13.3, associated with primary biliary cholangitis (PBC). Through functional annotations and experimental validations, the study suggests that a specific variant, rs2238574, may regulate the expression of ARID3A and affect the severity of PBC.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Luke J. O'Connor
Summary: The genetic effect-size distribution of a disease, which includes the number of risk variants, their effect sizes, and sample sizes required to discover them, can be accurately estimated using Fourier Mixture Regression (FMR). FMR estimates that 100,000-1,000,000 cases will be needed to find genome-wide significant SNPs explaining 50% of SNP heritability. In large studies, genome-wide significance becomes more conservative and less stringent thresholds can achieve high true positive rates if confounding is controlled.
Article
Biotechnology & Applied Microbiology
Peng Jia, Lianhua Dong, Xiaofei Yang, Bo Wang, Stephen J. Bush, Tingjie Wang, Jiadong Lin, Songbo Wang, Xixi Zhao, Tun Xu, Yizhuo Che, Ningxin Dang, Luyao Ren, Yujing Zhang, Xia Wang, Fan Liang, Yang Wang, Jue Ruan, Han Xia, Yuanting Zheng, Leming Shi, Yi Lv, Jing Wang, Kai Ye
Summary: This study sequenced a Chinese Quartet using four short and long sequencing platforms, generating high-quality haplotype-resolved assemblies and a comprehensive dataset of various types of variants. The study provides expanded genomic coverage and insight into complex variant categories compared to existing benchmarks.
Article
Biochemistry & Molecular Biology
Marta Jorge-Oliva, Jan R. T. van Weering, Wiep Scheper
Summary: Tau aggregation plays a central role in the pathogenesis of tauopathies, but the response of neurons to tau pathology and the mechanisms leading to neurodegeneration are still unclear. This study investigated the accumulation of granulovacuolar degeneration bodies (GVBs), lysosomal structures that respond to tau pathology, in different tau aggregation models in primary neurons. The results showed that the structure and subcellular localization of tau aggregates may be important factors affecting GVB accumulation. The findings provide insights into the relationship between tau pathology and neurodegeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Astros Th. Skuladottir, Gyda Bjornsdottir, Gudmar Thorleifsson, G. Bragi Walters, Muhammad Sulaman Nawaz, Kristjan Helgi Swerford Moore, Pall I. Olason, Thorgeir E. Thorgeirsson, Brynja Sigurpalsdottir, Gardar Sveinbjornsson, Hannes P. Eggertsson, Sigurdur H. Magnusson, Asmundur Oddsson, Anna Bjornsdottir, Arnor Vikingsson, Olafur A. Sveinsson, Maria G. Hrafnsdottir, Gudrun R. Sigurdardottir, Bjarni V. Halldorsson, Thomas Folkmann Hansen, Helene Paarup, Christian Erikstrup, Kaspar Nielsen, Mads Klokker, Mie Topholm Bruun, Erik Sorensen, Karina Banasik, Kristoffer S. Burgdorf, Ole Birger Pedersen, Henrik Ullum, Ingileif Jonsdottir, Hreinn Stefansson, Kari Stefansson
Summary: Bell's palsy, the most common cause of unilateral facial paralysis, has been found to have a genetic component, with a newly discovered genetic variant linked to the condition. This variant also confers risk for intervertebral disc disorders, suggesting a potential common pathogenesis or true pleiotropy.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Ting Qi, Yang Wu, Hailing Fang, Futao Zhang, Shouye Liu, Jian Zeng, Jian Yang
Summary: Most genetic variants identified from GWAS in humans are noncoding and play a role in gene regulation. Previous studies have shown links between GWAS signals and eQTLs, but the links to other genetic regulatory mechanisms, such as sQTLs, have not been extensively explored. This study introduces a new sQTL mapping method and identifies distinct cis-sQTLs that are not associated with eQTLs in brain transcriptomic data. By integrating sQTL data into GWAS for brain-related complex traits, the study identifies genes associated with these traits that cannot be discovered using eQTL data alone.
Article
Biochemical Research Methods
Sumit Tarafder, Mazharul Islam, Swakkhar Shatabda, Atif Rahman
Summary: This paper presents a novel probabilistic method for filling gaps in draft genome assemblies using second-generation reads. The method takes into account information on insert sizes and sequencing errors and outperforms other state-of-the-art tools in terms of error and misassembly rate when filling gaps on real biological datasets.
Article
Genetics & Heredity
Paola Benaglio, Jacklyn Newsome, Jee Yun Han, Joshua Chiou, Anthony Aylward, Sierra Corban, Michael Miller, Mei-Lin Okino, Jaspreet Kaur, Sebastian Preissl, David U. Gorkin, Kyle J. Gaulton
Summary: This study used single nucleus ATAC-seq and genotyping to analyze peripheral blood mononuclear cells from 13 individuals, identifying 17 immune cell types and sub-types. They also annotated putative target genes of certain variants using single cell co-accessibility. Additionally, they fine-mapped loci associated with complex immune traits.
Article
Oncology
Matteo Giaccherini, Manuel Gentiluomo, Paolo Giorgio Arcidiacono, Massimo Falconi, Sabrina Gloria Giulia Testoni, Laura Apadula, Gaetano Lauri, Gregorio Di Franco, Lorenzo Maria Fatucchi, Maria Chiara Petrone, Chiara Corradi, Stefano Crippa, Luca Morelli, Gabriele Capurso, Daniele Campa
Summary: In this study, a polymorphic variant in the PXK gene was found to be associated with an increased risk of progression of intraductal papillary mucinous neoplasms (IPMNs). This novel finding highlights the importance of germline genetics in IPMN research.
Article
Biotechnology & Applied Microbiology
Hyobin Jeong, Karen Grimes, Kerstin K. Rauwolf, Peter-Martin Bruch, Tobias Rausch, Patrick Hasenfeld, Eva Benito, Tobias Roider, Radhakrishnan Sabarinathan, David Porubsky, Sophie A. Herbst, Busra Erarslan-Uysal, Johann-Christoph Jann, Tobias Marschall, Daniel Nowak, Jean-Pierre Bourquin, Andreas E. Kulozik, Sascha Dietrich, Beat Bornhauser, Ashley D. Sanders, Jan O. Korbel
Summary: This study introduces a computational method called scNOVA, which utilizes Strand-seq to analyze structural variations in single cells and infer gene expression. The research reveals the impact of structural variations on gene regulation and signaling pathways, and successfully applies the method to the study of chronic lymphocytic leukemia and T cell acute lymphoblastic leukemia.
NATURE BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Glenn Hickey, Jean Monlong, Jana Ebler, Adam M. Novak, Jordan M. Eizenga, Yan Gao, Tobias Marschall, Heng Li, Benedict Paten, Haley J. Abel, Lucinda L. Antonacci-Fulton, Mobin Asri, Gunjan Baid, Carl A. Baker, Anastasiya Belyaeva, Konstantinos Billis, Guillaume Bourque, Silvia Buonaiuto, Andrew Carroll, Mark J. P. Chaisson, Pi-Chuan Chang, Xian H. Chang, Haoyu Cheng, Justin Chu, Sarah Cody, Vincenza Colonna, Daniel E. Cook, Robert M. Cook-Deegan, Omar E. Cornejo, Mark Diekhans, Daniel Doerr, Peter Ebert, Jana Ebler, Evan E. Eichler, Jordan M. Eizenga, Susan Fairley, Olivier Fedrigo, Adam L. Felsenfeld, Xiaowen Feng, Christian Fischer, Paul Flicek, Giulio Formenti, Adam Frankish, Robert S. Fulton, Yan Gao, Shilpa Garg, Erik Garrison, Nanibaa' A. Garrison, Carlos Garcia Giron, Richard E. Green, Cristian Groza, Andrea Guarracino, Leanne Haggerty, Ira M. Hall, William T. Harvey, Marina Haukness, David Haussler, Simon Heumos, Glenn Hickey, Kendra Hoekzema, Thibaut Hourlier, Kerstin Howe, Miten Jain, Erich D. Jarvis, Hanlee P. Ji, Eimear E. Kenny, Barbara A. Koenig, Alexey Kolesnikov, Jan O. Korbel, Jennifer Kordosky, Sergey Koren, HoJoon Lee, Alexandra P. Lewis, Wen-Wei Liao, Shuangjia Lu, Tsung-Yu Lu, Julian K. Lucas, Magalhaes Hugo, Marco-Sola Santiago, Pierre Marijon, Charles Markello, Tobias Marschall, Fergal J. Martin, Ann McCartney, Jennifer McDaniel, Karen H. Miga, Matthew W. Mitchell, Jean Monlong, Jacquelyn Mountcastle, Katherine M. Munson, Moses Njagi Mwaniki, Maria Nattestad, Adam M. Novak, Sergey Nurk, Hugh E. Olsen, Nathan D. Olson, Trevor Pesout, Adam M. Phillippy, Alice B. Popejoy, David Porubsky, Pjotr Prins, Daniela Puiu, Mikko Rautiainen, Allison A. Regier, Arang Rhie, Samuel Sacco, Ashley D. Sanders, Valerie A. Schneider, Baergen Schultz, Kishwar Shafin, Jonas A. Sibbesen, Jouni Siren, Michael W. Smith, Heidi J. Sofia, Ahmad N. Abou Tayoun, Francoise Thibaud-Nissen, Chad Tomlinson, Francesca Floriana Tricomi, Flavia Villani, Mitchell R. Vollger, Justin Wagner, Brian Walenz, Ting Wang, Jonathan M. D. Wood, Aleksey Zimin, Justin M. Zook
Summary: Genome assemblies are used to directly construct genome graphs, which can represent various forms of genetic variation and improve analysis accuracy by overcoming single-reference bias.
NATURE BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Mikko Rautiainen, Sergey Nurk, Brian P. Walenz, Glennis A. Logsdon, David Porubsky, Arang Rhie, Evan E. Eichler, Adam M. Phillippy, Sergey Koren
Summary: The Telomere-to-Telomere consortium has achieved the first complete sequence of a human genome. They used a combination of long Nanopore sequencing reads and high-resolution assembly graph to resolve repeat sequences and automate the process in their Verkko pipeline. The result is a phased, diploid assembly with many chromosomes assembled from end to end. This advance is crucial for constructing comprehensive pangenome databases and chromosome-scale comparative genomics.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Annalisa Paparella, Alberto L'Abbate, Donato Palmisano, Gerardina Chirico, David Porubsky, Claudia R. Catacchio, Mario Ventura, Evan E. Eichler, Flavia A. M. Maggiolini, Francesca Antonacci
Summary: The impact of segmental duplications on human evolution and disease is significant and requires further research. Comparative analysis of duplication structures in human and nonhuman primates revealed potential genomic drivers for human-specific gene expansions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Pille Hallast, Peter Ebert, Mark Loftus, Feyza Yilmaz, Peter A. Audano, Glennis A. Logsdon, Marc Jan Bonder, Weichen Zhou, Wolfram Hoeps, Kwondo Kim, Chong Li, Savannah J. Hoyt, Philip C. Dishuck, David Porubsky, Fotios Tsetsos, Jee Young Kwon, Qihui Zhu, Katherine M. Munson, Patrick Hasenfeld, William T. Harvey, Alexandra P. Lewis, Jennifer Kordosky, Kendra Hoekzema, Rachel J. O'Neill, Jan O. Korbel, Chris Tyler-Smith, Evan E. Eichler, Xinghua Shi, Christine R. Beck, Tobias Marschall, Miriam K. Konkel, Charles Lee
Summary: De novo assemblies of 43 Y chromosomes spanning 182,900 years of human evolution reveal considerable diversity in the size and structure of the human Y chromosome. The male-specific euchromatic region is subject to large inversions with a higher recurrence rate compared to other chromosomes. Additionally, the study found extensive variation in the repeat arrays of the Y chromosome.
Article
Biotechnology & Applied Microbiology
David N. Porubsky, William Harvey, Allison Rozanski, Jana Ebler, Wolfram Hoeps, Hufsah Ashraf, Patrick Hasenfeld, Benedict Paten, Ashley D. Sanders, Tobias Marschall, Jan O. Korbel, Evan E. Eichler
Summary: The telomere-to-telomere (T2T) complete human reference has significantly improved our ability to characterize genome structural variation. Remapping data from 41 genomes against T2T reference genome showed a 21% increase in sensitivity for mapping inversions compared to the GRCh38 reference. The T2T reference also had a higher likelihood of representing the correct orientation of major human alleles, as shown by identifying 26 misorientations in GRCh38.
Article
Hematology
Cristina Lopez, Nikolai Schleussner, Stephan H. Bernhart, Kortine Kleinheinz, Stephanie Sungalee, Henrike L. Sczakiel, Helene Kretzmer, Umut H. Toprak, Selina Glaser, Rabea Wagener, Ole Ammerpohl, Susanne Bens, Maciej Giefing, Juan C. Gonzalez Sanchez, Gordana Apic, Daniel Huebschmann, Martin Janz, Markus Kreuz, Anja Mottok, Judith M. Mueller, Julian Seufert, Steve Hoffmann, Jan O. Korbel, Robert B. Russell, Roland Schuele, Lorenz Truemper, Wolfram Klapper, Bernhard Radlwimmer, Peter Lichter, Ralf Kueppers, Matthias Schlesner, Stephan Mathas, Reiner Siebert
Summary: Histone methylation-modifiers, including EZH2 and KMT2D, are frequently altered in B-cell lymphomas. In this study, we examined the whole genome and transcriptome data of 186 cases and identified recurrent alterations in KDM4C, a histone demethylase encoding gene on chromosome 9p24. We demonstrated that these structural variants in KDM4C result in loss-of-function and provide evidence that KDM4C can act as a tumor suppressor. Thus, our findings expand the mutational landscape of lymphomas and highlight the importance of KDM4C in B-cell derived lymphomas.