Article
Genetics & Heredity
Sofia Battaglia, Kevin Dong, Jingyi Wu, Zeyu Chen, Fadi J. Najm, Yuanyuan Zhang, Molly M. Moore, Vivian Hecht, Noam Shoresh, Bradley E. Bernstein
Summary: The use of targeted nanopore sequencing allowed researchers to analyze chromatin accessibility and DNA methylation on contiguous DNA molecules, leading to the identification of gene regulatory elements such as promoters, enhancers, insulators, and transcription factor binding sites. They also inferred relationships among dynamic elements within immune loci and determined the order of remodeling events during T cell stimulation. Additionally, they phased primary sequences and regulatory elements across the H19/IGF2 locus, revealing primate-specific features and a mechanism that overrides IGF2 imprinting in human cells.
Article
Biochemistry & Molecular Biology
Zeynep Kalender Atak, Ibrahim Ihsan Taskiran, Jonas Demeulemeester, Christopher Flerin, David Mauduit, Liesbeth Minnoye, Gert Hulselmans, Valerie Christiaens, Ghanem-Elias Ghanem, Jasper Wouters, Stein Aerts
Summary: This study introduces a deep learning model called DeepMEL2 that outperforms conventional motif-based scoring models in capturing regulatory programs in melanoma cells. It identifies hundreds to thousands of allele-specific chromatin accessibility variants in melanoma genomes, with some attributed to changes in transcription factor binding sites.
Article
Biochemistry & Molecular Biology
Can Yuan, Lijing Tang, Thomas Lopdell, Vyacheslav A. Petrov, Claire Oget-Ebrad, Gabriel Costa Monteiro Moreira, Jose Luis Gualdron Duarte, Arnaud Sartelet, Zhangrui Cheng, Mazdak Salavati, D. Claire Wathes, Mark A. Crowe, Wouter Coppieters, Mathew Littlejohn, Carole Charlier, Tom Druet, Michel Georges, Haruko Takeda
Summary: We have generated a catalog of cis-acting regulatory elements in the bovine using ATAC-seq and identified their potential regulatory roles. The analysis of variants mapping to these elements suggests purifying selection and their association with tissue-specific gene expression. The findings have implications for improving genomic selection accuracy.
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
Genetics & Heredity
Marc Jan Bonder, Craig Smail, Michael J. Gloudemans, Laure Fresard, David Jakubosky, Matteo D'Antonio, Xin Li, Nicole M. Ferraro, Ivan Carcamo-Orive, Bogdan Mirauta, Daniel D. Seaton, Na Cai, Dara Vakili, Danilo Horta, Chunli Zhao, Diane B. Zastrow, Devon E. Bonner, Matthew T. Wheeler, Helena Kilpinen, Joshua W. Knowles, Erin N. Smith, Kelly A. Frazer, Stephen B. Montgomery, Oliver Stegle
Summary: By integrating data from 1,367 human iPSC lines, researchers comprehensively mapped common and rare regulatory variants in human pluripotent cells, identified new colocalization events specific to iPSCs, and demonstrated the utility of iPSCs in identifying causal genes for rare diseases.
Article
Biochemistry & Molecular Biology
Qiangwei Zhou, Pengpeng Guan, Zhixian Zhu, Sheng Cheng, Cong Zhou, Huanhuan Wang, Qian Xu, Wing-kin Sung, Guoliang Li
Summary: DNA methylation is a stable epigenetic modification that plays crucial roles in cell differentiation, development, X chromosome inactivation, and disease. Allele-specific DNA methylation (ASM) is an established mechanism in genomic imprinting, closely related to tumorigenesis and plant development. The establishment of a comprehensive ASM database and in-depth analysis across multiple species revealed potential ASM-related genes in cancer and provided valuable insights into the functions of ASM in diseases and development.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemical Research Methods
Asia Mendelevich, Saumya Gupta, Aleksei Pakharev, Athanasios Teodosiadis, Andrey A. Mironov, Alexander A. Gimelbrant
Summary: A new spike-in approach is developed to correct technical noise in allele-specific expression analysis, which is highly accurate and cost-effective. This approach involves adding a distinct RNA as a spike-in before library preparation, allowing for efficient analysis of allele-specific expression in large studies.
Article
Multidisciplinary Sciences
Warren Winick-Ng, Alexander Kukalev, Izabela Harabula, Luna Zea-Redondo, Dominik Szabo, Mandy Meijer, Leonid Serebreni, Yingnan Zhang, Simona Bianco, Andrea M. Chiariello, Ibai Irastorza-Azcarate, Christoph J. Thieme, Thomas M. Sparks, Silvia Carvalho, Luca Fiorillo, Francesco Musella, Ehsan Irani, Elena Torlai Triglia, Aleksandra A. Kolodziejczyk, Andreas Abentung, Galina Apostolova, Eleanor J. Paul, Vedran Franke, Rieke Kempfer, Altuna Akalin, Sarah A. Teichmann, Georg Dechant, Mark A. Ungless, Mario Nicodemi, Lonnie Welch, Goncalo Castelo-Branco, Ana Pombo
Summary: The 3D structure of chromatin is crucial for gene regulation and cell function. A new method called immunoGAM has been developed to map 3D chromatin topology in specific brain cell types at a genome-wide scale. The results show that highly specific chromatin conformations in brain cells are closely related to gene regulation mechanisms and specialized functions.
Article
Multidisciplinary Sciences
Elizabeth D. Larson, Hideyuki Komori, Tyler J. Gibson, Cyrina M. Ostgaard, Danielle C. Hamm, Jack M. Schnell, Cheng-Yu Lee, Melissa M. Harrison
Summary: The pioneer transcription factor Zelda plays a crucial role in reprogramming germ cells during early Drosophila embryo development. Research further demonstrates that Zelda promotes undifferentiated stem-cell fate in the larval brain, and its ability to define cis-regulatory regions is influenced by cell-type-specific chromatin architecture. It is proposed that Zelda regulates essential transitions in neuroblasts and embryos through a shared gene-regulatory network driven by cell-type-specific enhancers.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Kevin W. Currin, Chael R. Erdos, Narisu Narisu, Vivek Rai, Swarooparani Vadlamudi, Hannah J. Perrin, Jacqueline R. Idol, Tingfen Yan, Ricardo D'Oliveira Albanus, K. Alaine Broadaway, Amy S. Etheridge, Lori L. Bonnycastle, Peter Orchard, John P. Didion, Amarjit S. Chaudhry, Federico Innocenti, Erin G. Schuetz, Laura J. Scott, Stephen C. J. Parker, Francis S. Collins, Karen L. Mohlke
Summary: This study mapped caQTLs in human liver tissue and identified thousands of caQTL variants enriched in liver tissue promoter and enhancer states. We predicted target genes for hundreds of caQTL peaks and identified dozens of colocalized caQTLs and GWAS signals. Validation at the LITAF LDL-cholesterol GWAS locus showed allelic differences in protein binding and transcriptional activity for a caQTL variant.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Tom Aharon Hait, Ran Elkon, Ron Shamir
Summary: In this study, we introduce the CT-FOCS method, which uses linear mixed effect models to infer enhancer-promoter links that are specifically active in certain cell types. The results show that CT-FOCS accurately predicts these links compared to other methods, and it reveals that strictly cell type-specific EP links are rare in the human genome.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Samuel Valentini, Francesco Gandolfi, Mattia Carolo, Davide Dalfovo, Lara Pozza, Alessandro Romanel
Summary: Many studies have found associations between common genetic variants and complex diseases, but the biological mechanisms explaining these associations are largely unknown. Common variants often have small effect sizes, suggesting that interactions among multiple variants may be a key genetic component of complex diseases. Polympact is a web-based resource that allows exploring functional relations among human common variants, characterizing over 18 million variants and identifying potential interactions.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Luqian Zheng, Jingjing Liu, Lijie Niu, Mohammad Kamran, Ally W. H. Yang, Arttu Jolma, Qi Dai, Timothy R. Hughes, Dinshaw J. Patel, Long Zhang, Supriya G. Prasanth, Yang Yu, Aiming Ren, Eric C. Lai
Summary: In this study, the researchers investigated how BEN factors identify their targets in humans by characterizing several mammalian BEN domain factors. They provided structural insights into sequence-specific DNA binding by these BEN proteins. The findings expand the understanding of BEN factors' DNA recognition activities and shed light on the mechanism of sequence-specific DNA binding by mammalian BEN proteins.
GENES & DEVELOPMENT
(2022)
Article
Chemistry, Multidisciplinary
Rohan Gupta, Pravir Kumar
Summary: Integrating omics data to decipher the biological regulatory network can reveal potential mechanisms of complex diseases like Alzheimer's and Parkinson's. The acetylation mechanism and HDAC enzymes play a crucial role in studying the shared phenomenon between AD and PD pathogenesis. The study highlights the importance of proteins, transcription factors, lysine residues, and HDAC enzymes shared between AD and PD, providing valuable insights for molecular studies on the AD-PD crosstalk.
Article
Genetics & Heredity
Maimuna S. Paul, Anna R. Duncan, Casie A. Genetti, Hongling Pan, Adam Jackson, Patricia E. Grant, Jiahai Shi, Michele Pinelli, Nicola Brunetti-Pierri, Alexandra Garza-Flores, Dave Shahani, Russell P. Saneto, Giuseppe Zampino, Chiara Leoni, Emanuele Agolini, Antonio Novelli, Ulrike Bluemlein, Tobias B. Haack, Wolfram Heinritz, Eva Matzker, Bader Alhaddad, Rami Abou Jamra, Tobias Bartolomaeus, Saber AlHamdan, Raphael Carapito, Bertrand Isidor, Seiamak Bahram, Alyssa Ritter, Kosuke Izumi, Ben Pode Shakked, Ortal Barel, Bruria Ben Zeev, Amber Begtrup, Deanna Alexis Carere, Sureni Mullegama, Timothy Blake Palculict, Daniel G. Calame, Katharina Schwan, Alicia R. P. Aycinena, Rasa Traberg, Sofia Douzgou, Harrison Pirt, Naila Ismayilova, Siddharth Banka, Hsiao-Tuan Chao, Pankaj B. Agrawal
Summary: Variants in the EIF4A2 gene cause a genetic neurodevelopmental syndrome characterized by global developmental delay, intellectual disability, hypotonia, epilepsy, and structural brain anomalies. These variants disrupt protein structure and result in both loss of function and gain of function mechanisms.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Eva Rye Rasmussen, Par Hallberg, Ekaterina V. Baranova, Niclas Eriksson, Malgorzata Karawajczyk, Caroline Johansson, Marco Cavalli, Cyrielle Maroteau, Abirami Veluchamy, Gunilla Islander, Svante Hugosson, Ingrid Terreehorst, Folkert W. Asselbergs, Pia Norling, Hans-Erik Johansson, Hugo Kohnke, Ann-Christine Syvanen, Moneeza K. Siddiqui, Chim C. Lang, Patrik K. E. Magnusson, Qun-Ying Yue, Claes Wadelius, Christian von Buchwald, Anette Bygum, Ana Alfirevic, Anke H. Maitland-van der Zee, Colin N. A. Palmer, Mia Wadelius
PHARMACOGENOMICS JOURNAL
(2020)
Article
Multidisciplinary Sciences
Klev Diamanti, Robin Visvanathar, Maria J. Pereira, Marco Cavalli, Gang Pan, Chanchal Kumar, Stanko Skrtic, Ulf Riserus, Jan W. Eriksson, Joel Kullberg, Jan Komorowski, Claes Wadelius, Hakan Ahlstrom
SCIENTIFIC REPORTS
(2020)
Article
Gastroenterology & Hepatology
Klev Diamanti, Juan Salvador Inda Diaz, Amanda Raine, Gang Pan, Claes Wadelius, Marco Cavalli
Summary: Integration of data from different platforms in single nucleus transcriptomics profiling allowed identification of major liver cell types and a small cluster of inactive hepatic stellate cells that were not characterized in either platform. This approach highlights the potential of single nucleus RNA sequencing integrative approaches and suggests the possibility of designing larger and cost-effective studies.
HEPATOLOGY RESEARCH
(2021)
Article
Genetics & Heredity
Mateusz Garbulowski, Karolina Smolinska, Klev Diamanti, Gang Pan, Khurram Maqbool, Lars Feuk, Jan Komorowski
Summary: This study utilized interpretable machine learning methods to analyze gene expression data of individuals with autism spectrum disorder (ASD), constructing a nonlinear model based on gene-gene co-predictive network. The findings revealed that autism is the most severe subtype of ASD, with other subtypes showing varying degrees of milder symptoms. Furthermore, the study identified several important gene co-predictors, such as EMC4 and TMEM30A, indicating potential co-regulation between these genes.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Gang Pan, Marco Cavalli, Claes Wadelius
Summary: The study showed that SCD1 is directly regulated by HNF4A through binding to key regulatory regions in the SCD1 gene. Knocking down HNF4A significantly decreased SCD1 expression, indicating a crucial role of HNF4A in regulating SCD1 activity and metabolic pathways associated with diseases.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2021)
Article
Pharmacology & Pharmacy
Johanna Karlsson Sundbaum, Eva Baecklund, Niclas Eriksson, Hugo Kohnke, Matilda Wallenberg, Marco Cavalli, Claes Wadelius, Mia Wadelius, Par Hallberg
Summary: The study identified novel genetic variants associated with elevation of Alanine aminotransferase (ALT) in rheumatoid arthritis (RA) patients after methotrexate (MTX) treatment, showing a potential link to the expression of JAK1 and RAVER2, genes involved in the pathogenesis of RA.
Article
Biology
Gang Pan, Klev Diamanti, Marco Cavalli, Ariadna Lara Gutierrez, Jan Komorowski, Claes Wadelius
Summary: YY1 plays a pivotal role in liver diseases by regulating genes involved in hepatic lipid metabolism in cooperation with key transcription factors. Knockdown of YY1 disrupts this cooperation, leading to dysregulated expression of key enzymes involved in lipogenesis.
LIFE SCIENCE ALLIANCE
(2021)
Article
Multidisciplinary Sciences
Amanda Raine, Anders Lundmark, Alva Annett, Ann-Christin Wiman, Marco Cavalli, Claes Wadelius, Claudia Bergin, Jessica Nordlund
Summary: DNA methylation is an important epigenetic mark that can be detected in single cells using bisulfite sequencing. Various strategies for single-cell DNA methylation studies have been described, but limitations in cost-efficiency and yield remain. A new method, scSPLAT, demonstrates higher scale and throughput in sample preparation compared to other scWGBS methods.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Marco Cavalli, Niclas Eriksson, Johanna Karlsson Sundbaum, Matilda Wallenberg, Hugo Kohnke, Eva Baecklund, Par Hallberg, Mia Wadelius
Summary: This study identified associations between single-nucleotide polymorphisms (SNPs) in genes related to male fertility and inflammatory processes and elevated alanine aminotransferase (ALT) levels through a genome-wide association study (GWAS).
Article
Biotechnology & Applied Microbiology
Marco Cavalli, Klev Diamanti, Yonglong Dang, Pengwei Xing, Gang Pan, Xingqi Chen, Claes Wadelius
Summary: The study integrated ATAC-seq data, multi-omics data, and CRE databases to identify candidate CREs associated with T2D, detecting differentially accessible regions in human liver samples from normal and T2D donors. A candidate enhancer for the ACOT1 gene was identified, linking its regulation to T2D. ACOTs are enzymes associated with regulation of triglyceride levels, fatty acid oxidation, mitochondrial function, and insulin signaling, with implications for T2D pathogenesis.
OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Gang Pan, Marco Cavalli, Bjrn Carlsson, Stanko Skrtic, Chanchal Kumar, Claes Wadelius
Article
Biotechnology & Applied Microbiology
Marco Cavalli, Klev Diamanti, Gang Pan, Rapolas Spalinskas, Chanchal Kumar, Atul Shahaji Deshmukh, Matthias Mann, Pelin Sahlen, Jan Komorowski, Claes Wadelius
OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
(2020)