Article
Biochemistry & Molecular Biology
Yingxin Cao, Laiyi Fu, Jie Wu, Qinke Peng, Qing Nie, Jing Zhang, Xiaohui Xie
Summary: In this study, we propose a deep learning framework called SAILERX for efficient, robust, and flexible analysis of multi-modal single-cell data. SAILERX utilizes invariant representation learning and multimodal data alignment mechanism to handle noise, integrate information, and provide various downstream analysis functions.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Alexander Munden, Mary Lauren Benton, John A. Capra, Jared T. Nordman
Summary: R-loops play important roles in various biological processes. This study reveals that R-loop abundance and genome localization change during Drosophila embryogenesis and that RNaseH1 activity is crucial for embryonic development. The findings also demonstrate the developmental plasticity of R-loops in gene formation and their relative positioning.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Genetics & Heredity
Federica Marasca, Shruti Sinha, Rebecca Vadala, Benedetto Polimeni, Valeria Ranzani, Elvezia Maria Paraboschi, Filippo Vittorio Burattin, Marco Ghilotti, Mariacristina Crosti, Maria Luce Negri, Susanna Campagnoli, Samuele Notarbartolo, Andrea Sartore-Bianchi, Salvatore Siena, Daniele Prati, Giovanni Montini, Giuseppe Viale, Olga Torre, Sergio Harari, Renata Grifantini, Giulia Solda, Stefano Biffo, Sergio Abrignani, Beatrice Bodega
Summary: This study reveals how non-canonical splicing variant LINE1 maintains T cell quiescence and interferes with gene expression, thus affecting cell function.
Article
Biochemistry & Molecular Biology
Seth A. Ament, Ricky S. Adkins, Robert Carter, Elena Chrysostomou, Carlo Colantuoni, Jonathan Crabtree, Heather H. Creasy, Kylee Degatano, Victor Felix, Peter Gandt, Gwenn A. Garden, Michelle Giglio, Brian R. Herb, Farzaneh Khajouei, Elizabeth Kiernan, Carrie McCracken, Kennedy McDaniel, Suvarna Nadendla, Lance Nickel, Dustin Olley, Joshua Orvis, Joseph P. Receveur, Mike Schor, Shreyash Sonthalia, Timothy L. Tickle, Jessica Way, Ronna Hertzano, Anup A. Mahurkar, Owen R. White
Summary: Scalable technologies for single-cell transcriptome and epigenome sequencing are revolutionizing our understanding of cell types and states. The BICCN, part of the BRAIN Initiative, is utilizing these technologies on an unprecedented scale to map cell types in the mammalian brain. To enhance data accessibility, the NIH has established the NeMO Archive as the primary repository for genomics data from the BRAIN Initiative, containing transcriptomic and epigenomic data from over 50 million brain cells.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Genetics & Heredity
Pia Rautenstrauch, Anna Hendrika Cornelia Vlot, Sepideh Saran, Uwe Ohler
Summary: A wealth of single-cell protocols enables the characterization of molecular layers at unprecedented resolution. Integrating multi-modal single-cell data to find cell-to-cell correspondences is challenging and requires considering biological abstraction and modal discrepancies.
TRENDS IN GENETICS
(2022)
Article
Biochemical Research Methods
Yang Xu, Priyojit Das, Rachel Patton McCord
Summary: SMILE is an unsupervised deep learning algorithm that successfully integrates multi-source single-cell omics data and removes batch effects. By maximizing mutual information, it can project cell types from different tissues into a shared space and integrate data from different modalities.
Article
Biochemical Research Methods
Pengcheng Zeng, Yuanyuan Ma, Zhixiang Lin
Summary: In this study, we propose an adaptively weighted multi-view learning method for the integrative analysis of parallel scRNA-seq and scATAC-seq data from the same cell. Application to four real datasets demonstrates the efficiency of our method in dissecting cellular heterogeneity for single-cell multi-omics data.
Article
Biotechnology & Applied Microbiology
Sitara Persad, Zi-Ning Choo, Christine Dien, Noor Sohail, Ignas Masilionis, Ronan Chaligne, Tal Nawy, Chrysothemis C. C. Brown, Roshan Sharma, Itsik Pe'er, Manu Setty, Dana Pe'er
Summary: Metacells are identified using an algorithm called SEACells, which overcomes the sparsity and retains heterogeneity of single-cell data. SEACells outperforms existing algorithms in identifying comprehensive, compact, and well-separated metacells in both RNA and ATAC modalities across datasets. This method is particularly well suited for patient cohorts and allows for improved gene-peak associations, ATAC gene scores computation, and inference of critical regulators' activities during differentiation. Our metacells reveal expression dynamics and chromatin landscape reconfiguration during hematopoietic differentiation and identify CD4 T cell differentiation and activation states associated with COVID-19 disease onset and severity.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Parashar Dhapola, Johan Rodhe, Rasmus Olofzon, Thomas Bonald, Eva Erlandsson, Shamit Soneji, Goran Karlsson
Summary: Scarf is a modularly designed Python package that enables memory-efficient single-cell analysis and can run on low-cost devices. It provides efficient implementations for memory and computation and supports accurate reference-anchored mapping and subsampling of large single-cell datasets.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Pia Fahme, Farah Ramadan, Diep Tien Le, Kieu-Oanh Nguyen Thi, Sandra E. Ghayad, Nader Hussein, Chantal Diaz, Martine Croset, Philippe Clezardin, Pascale A. Cohen
Summary: ZNF217 oncogene promotes cancer progression, pluripotency and resistance to therapy. High expression levels of ZNF217 are associated with poor prognosis in several cancers. ZNF217 shapes cancer growth through epigenetic mechanisms, including DNA methylation, interactions with noncoding RNAs, and epitranscriptome refining. Noncoding RNAs and DNA methylation status of ZNF217 locus can be potential biomarkers for poor prognosis and therapeutic response.
Article
Biotechnology & Applied Microbiology
Mariela Tenorio, Joanna Serwatowska, Selene L. Fernandez-Valverde, Katarzyna Oktaba, Diego Cortez
Summary: Researchers used Chromatin Associated RNA sequencing (ChAR-seq) to obtain a genome-wide map of RNA-chromatin interactions in Anolis carolinensis. They identified trans-acting long non-coding RNAs (lncRNAs) that are associated with chromatin and found three lncRNAs significantly associated with a specific chromatin modification, suggesting their potential role in gene regulation.
Article
Biochemistry & Molecular Biology
Emily Clough, Tanya Barrett, Stephen E. Wilhite, Pierre Ledoux, Carlos Evangelista, Irene F. Kim, Maxim Tomashevsky, Kimberly A. Marshall, Katherine H. Phillippy, Patti M. Sherman, Hyeseung Lee, Naigong Zhang, Nadezhda Serova, Lukas Wagner, Vadim Zalunin, Andrey Kochergin, Alexandra Soboleva
Summary: The Gene Expression Omnibus (GEO) is an international public repository that archives gene expression and epigenomics data sets. It handles raw data files, processed data files, and descriptive metadata, and also provides web-based tools for analyzing and visualizing differential gene expression.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Genetics & Heredity
Ruben Boon
Summary: Epigenetic modifications fine-tune gene expression profiles to meet the needs of cells, tissues, and organisms. The activity of chromatin modifiers depends on the concentration of metabolites, which act as substrates and co-factors, linking gene expression to metabolic states. Specific molecular mechanisms regulate epigenetic marker deposition in the nucleus, potentially influenced by subcellular metabolite production sites. Additionally, metabolic enzymes may operate in phase-separated nuclear microdomains within multienzyme and chromatin-bound protein complexes.
FRONTIERS IN GENETICS
(2021)
Review
Cell Biology
Benoit Palancade, Rodney Rothstein
Summary: RNA-containing structures play critical roles in maintaining genome integrity, with both detrimental and beneficial impacts. DNA polymerases and homologous recombination proteins contribute to the formation of such structures, while DNA repair enzymes are responsible for their removal. The diversity of pathways affected by RNA insertions likely reflects the ancestral function of RNA molecules in genome maintenance and transmission.
Article
Cell Biology
Alexandre Segelle, Yaiza Nunez-Alvarez, Andrew J. Oldfield, Kimberly M. Webb, Philipp Voigt, Reini F. Luco
Summary: Histone modifications play a role in final splicing decisions. In this study, researchers used CRISPR epigenome editing tools and found that a single change in H3K27ac or H3K27me3 levels at the alternatively spliced exon is sufficient to induce splicing changes associated with epithelial-to-mesenchymal transition (EMT). These findings suggest that the dynamic nature of chromatin and its histone marks can rapidly and reversibly regulate alternative splicing in response to cell-extrinsic cues like EMT induction.
Review
Biochemistry & Molecular Biology
Eliana Destefanis, Gulben Avsar, Paula Groza, Antonia Romitelli, Serena Torrini, Pinar Pir, Silvestro G. Conticello, Francesca Aguilo, Erik Dassi
Summary: RNA modifications play a crucial role in gene expression regulation, with over 170 distinct chemical modifications influencing RNA structure and function. These modifications affect the fate and activity of RNA in cells, ultimately impacting normal cellular and organismal functions.
Article
Multidisciplinary Sciences
Sebastien Relier, Julie Ripoll, Helene Guillorit, Amandine Amalric, Cyrinne Achour, Florence Boissiere, Jerome Vialaret, Aurore Attina, Francoise Debart, Armelle Choquet, Francoise Macari, Virginie Marchand, Yuri Motorin, Emmanuelle Samalin, Jean-Jacques Vasseur, Julie Pannequin, Francesca Aguilo, Evelyne Lopez-Crapez, Christophe Hirtz, Eric Rivals, Amandine Bastide, Alexandre David
Summary: The demethylase FTO was shown to remove N6-methyladenosine (m6A) and N6, 2'-O-dimethyladenosine (m6A(m)) modifications on RNAs. Here the authors show that FTO impedes cancer stem cell-like abilities in colorectal cancer cells through its m6A(m) demethylase activity, not through internal m6A demethylase activity.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sandhya Malla, Devi Prasad Bhattarai, Paula Groza, Dario Melguizo-Sanchis, Ionut Atanasoai, Carlos Martinez-Gamero, Angel-Carlos Roman, Dandan Zhu, Dung-Fang Lee, Claudia Kutter, Francesca Aguilo
Summary: This study reveals the role of ZFP207 in mouse embryonic stem cells through multiple functional analyses. Unlike human ESCs, mouse ZFP207 mainly exerts its effects by controlling AS networks and acting as RNA-binding proteins (RBPs) to maintain ESC identity and regulate neural fate commitment.
Article
Biochemistry & Molecular Biology
Pietro Boccaletto, Filip Stefaniak, Angana Ray, Andrea Cappannini, Sunandan Mukherjee, Elzbieta Purta, Malgorzata Kurkowska, Niloofar Shirvanizadeh, Eliana Destefanis, Paula Groza, Gulben Avsar, Antonia Romitelli, Pinar Pir, Erik Dassi, Silvestro G. Conticello, Francesca Aguilo, Janusz M. Bujnicki
Summary: MODOMICS database, established since 2006, has evolved from containing basic chemical structures of modified ribonucleosides to a comprehensive resource with new functionalities such as a catalog of RNA modifications linked to human diseases. The database, which is extensively linked to RCSB Protein Data Bank, provides users with an enhanced tool for research on RNA modification.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Cell Biology
Mo-Fan Huang, Lon Kai Pang, Yi-Hung Chen, Ruiying Zhao, Dung-Fang Lee
Summary: The field of cancer treatment has advanced, but the adverse effects of chemotherapy on the cardiovascular system require further research for mitigation strategies. The use of iPSC-CMs has emerged as a crucial platform for studying chemotherapy-induced cardiotoxicity.
Article
Multidisciplinary Sciences
Jian Tu, Zijun Huo, Yao Yu, Dandan Zhu, An Xu, Mo-Fan Huang, Ruifeng Hu, Ruoyu Wang, Julian A. Gingold, Yi-Hung Chen, Kuang-Lei Tsai, Nicolas R. Forcioli-Conti, Sarah X. L. Huang, Thomas R. Webb, Jie Su, Danielle A. Bazer, Peilin Jia, Jason T. Yustein, Lisa L. Wang, Mien-Chie Hung, Zhongming Zhao, Chad D. Huff, Jingnan Shen, Ruiying Zhao, Dung-Fang Lee
Summary: The study reveals that the spliceosome is an up-regulated target in RB1-mutant cells responding to oncogenic stress, and pRB and E2F3a coregulate spliceosomal gene expression, affecting cell proliferation and tumorigenesis. These findings suggest that the spliceosomal machinery could be a potential therapeutic vulnerability for pRB-deficient cancers.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell & Tissue Engineering
Yi-Hung Chen, Pei-San Huang, Meng-Hsuan Wen, Manhua Pan, Dung-Fang Lee, Tai-Yen Chen
Summary: A homozygous knock-in human embryonic stem cell clone expressing photoconvertible fluorescence protein tagged endogenous CTR1 has been successfully generated, allowing the study of CTR1 at an endogenous level in different cellular contexts.
STEM CELL RESEARCH
(2022)
Article
Medicine, General & Internal
Hong -Bo Li, Gang Huang, Jian Tu, Dong-Ming Lv, Qing-Lin Jin, Jun -Kai Chen, Yu -Tong Zou, Dung -Fang Lee, Jing-Nan Shen, Xian-Biao Xie
Summary: The study unveiled the abundance of m(6)A modifications in osteosarcoma (OS) and identified the oncogenic role of METTL14 in OS progression. MN1 was revealed as a downstream gene of METTL14, contributing to tumor progression and chemotherapy resistance. Mechanistically, MN1 is methylated by METTL14 in the coding sequence, recognized by IGF2BP2 to facilitate translation efficiency.
Editorial Material
Cell & Tissue Engineering
Dung-Fang Lee, Carlos-Filipe Pereira
CELLULAR REPROGRAMMING
(2023)
Editorial Material
Cell & Tissue Engineering
Mo-Fan Huang, Rachel Shoemaker, Dung-Fang Lee
Summary: By analyzing the transcriptional trajectories and epigenomic traits of reprogramming and transforming cells at the single-cell level, Huyghe et al identified two key transcription factors, Bcl11b and Atoh8, that control cell plasticity during pluripotent reprogramming and oncogenic transformation.
CELLULAR REPROGRAMMING
(2022)
Article
Biochemistry & Molecular Biology
Cyrinne Achour, Devi Prasad Bhattarai, Paula Groza, angel-Carlos Roman, Francesca Aguilo
Summary: This study identifies a specific alternative splicing (AS) signature associated with breast tumorigenesis and reveals the role of METTL3 in modulating breast cancer-associated AS programs. It also demonstrates that m(6)A deposition in splice site boundaries and in splicing and transcription factor transcripts can directly regulate AS switches of specific breast cancer-associated transcripts. Furthermore, the study suggests that five validated AS events in vitro are associated with a poor overall survival rate for patients with breast cancer, indicating their potential as novel prognostic biomarkers.
Article
Oncology
Dhruv Chachad, Lalit R. Patel, Carlos Vera Recio, Rasoul Pourebrahim, Elizabeth M. Whitley, Wenyi Wang, Xiaoping Su, An Xu, Dung-Fang Lee, Guillermina Lozano
Summary: Missense mutations in the DNA binding domain of p53 can be structural or contact mutations, affecting the protein's conformation. These mutations have gain-of-function activities and interact with transcription factors to promote increased metastatic potential. Mouse models expressing the p53 mutants specifically in osteoblasts show decreased survival and increased metastasis compared to p53-null mice. RNA sequencing reveals distinct gene expression profiles and interactions with different transcription factors for each mutant, and validation experiments demonstrate the role of p53R245W in driving migration and invasion in osteosarcoma. These findings identify unique mechanisms of action for the p53 mutants.
Article
Oncology
Joshua H. Choe, Tatsuya Kawase, An Xu, Asja Guzman, Aleksandar Z. Obradovic, Ana Maria Low-Calle, Bita Alaghebandan, Ananya Raghavan, Kaitlin Long, Paul M. Hwang, Joshua D. Schiffman, Yan Zhu, Ruiying Zhao, Dung -Fang Lee, Chen Katz, Carol Prives
Summary: This study investigates the pathogenic mechanism of cancer susceptibility genes and finds that the p53(A347D) mutation leads to the inability of p53 to form tetramers, resulting in a hyperstable dimeric state and the inability to bind and activate most canonical p53 target genes, but possessing neomorphic functions. Cells with the p53(A347D) mutation have similar tumorigenic capabilities compared to cells without p53, but the mutation can induce metabolic reprogramming and severe mitochondrial network abnormalities, and can drive apoptotic cell death via mitochondrial association in the absence of transcriptional activity upon topoisomerase II inhibition.
Article
Chemistry, Analytical
Jaskirat Singh Batra, Ting-Yen Chi, Mo-Fan Huang, Dandan Zhu, Zheyuan Chen, Dung-Fang Lee, Jun Kameoka
Summary: This study developed a wearable paper-based virus sensor based on molecular imprinting technique and conductive polyaniline, which can detect and monitor potential virus infections. This sensor can be integrated with a face mask, offering an alternative approach to virus monitoring in communities.
