Article
Biotechnology & Applied Microbiology
Feiyang Zhao, Yubin Yan, Yaxi Wang, Yuan Liu, Ruolin Yang
Summary: The study reveals the prevalence of highly splicing complex exons in mammals and their correlation with gene features. The splicing complexity of exons can be moderately predicted using machine learning and deep learning methods. Both developmentally regulated and non-developmentally regulated exons show dynamic splicing complexity during organ development.
Review
Multidisciplinary Sciences
Jiancheng Xue, Tie Ma, Xiaowen Zhang
Summary: The dysregulation of alternative splicing in cancer is commonly observed and serves as a crucial indicator for cancer progression and therapy. Transformer 2 (TRA2), a nuclear RNA binding protein, consisting of TRA2A and TRA2B, has been found to be dysregulated in various types of tumors. It modulates the proliferation, migration, invasion, and chemotherapy resistance of cancer cells by altering the alternative splicing of cancer-related genes. This review focuses on the role of TRA2 in tumorigenesis and metastasis, and discusses the potential molecular mechanisms by which TRA2 influences these processes through controlling alternative splicing. We propose that TRA2A is a novel biomarker and therapeutic target for cancer progression and therapy.
Review
Pharmacology & Pharmacy
Dianyang Li, Wenying Yu, Maode Lai
Summary: Serine-and arginine-rich splicing factors play important roles in regulating splicing by binding to cis-acting elements in precursor mRNAs and facilitating spliceosome assembly. SR proteins also have diverse functions in RNA metabolism as they shuttle between the nucleus and cytoplasm. Overexpression and/or hyperactivation of SR proteins have been associated with tumorigenesis, suggesting their potential as therapeutic targets. This review highlights the physiological and pathological roles of SR proteins and discusses small molecules and oligonucleotides that can modulate SR protein function for future studies.
DRUG DISCOVERY TODAY
(2023)
Article
Plant Sciences
Chang Du, Hai-Yan Bai, Jing-Jing Chen, Jia-Hui Wang, Zhi-Feng Wang, Zhong-Hui Zhang
Summary: In this study, the transcriptome changes in response to glucose stress in Arabidopsis seedlings were investigated using Oxford Nanopore sequencing technologies. The results showed that glucose stress affects alternative splicing (AS) of many genes, including the glycine-rich protein (GRP) family and arginine/serine-rich splicing factor 31 (RS31). The findings provide insights into the regulatory mechanism of AS in sugar signaling.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Genetics & Heredity
Jeru Manoj Manuel, Noe Guilloy, Ines Khatir, Xavier Roucou, Benoit Laurent
Summary: Alternative splicing (AS) is a mechanism that generates multiple mature transcripts from protein-coding genes and long non-coding RNA (lncRNA) genes, increasing transcriptome complexity and producing different protein isoforms. Despite the identification of numerous alternatively spliced transcripts, the low detection rate of protein isoforms has raised questions about the contribution of AS to proteomic diversity and the functional relevance of AS events.
FRONTIERS IN GENETICS
(2023)
Article
Oncology
Shijie Yao, Cheng Yuan, Yuying Shi, Yuwen Qi, Radhakrishnan Sridha, Mengyuan Dai, Hongbing Cai
Summary: This study explores the correlation between alternative splicing (AS) and prognosis in ovarian cancer (OV) and establishes a prognostic model and nomogram for OV. It provides potential biomarkers and targets for the treatment of OV and suggests the possibility of interfering with AS in the comprehensive treatment of OV.
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
(2022)
Review
Immunology
Pingping Ren, Luying Lu, Shasha Cai, Jianghua Chen, Weiqiang Lin, Fei Han
Summary: Alternative splicing is a complex regulatory mechanism that affects a large percentage of genes and organs, aberrant splicing can lead to various diseases, though its association with autoimmune diseases requires further examination.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Pablo Montanes-Agudo, Simona Aufiero, Eva N. Schepers, Ingeborg van der Made, Lucia Cocera-Ortega, Auriane C. Ernault, Stephane Richard, Diederik W. D. Kuster, Vincent M. Christoffels, Yigal M. Pinto, Esther E. Creemers
Summary: This study aims to investigate the function and relevance of QKI in the adult mouse heart. The results show that QKI regulates the alternative splicing of multiple genes and affects the functional properties of cardiomyocytes. Loss of QKI leads to severe disruption of sarcomeres and rapid development of heart failure.
CARDIOVASCULAR RESEARCH
(2023)
Article
Plant Sciences
Xiaohui Cheng, Chuanji Zhao, Lixia Gao, Lingyi Zeng, Yu Xu, Fan Liu, Junyan Huang, Lijiang Liu, Shengyi Liu, Xiong Zhang
Summary: This study systematically explored the genome-scale alternative splicing (AS) events of Sclerotinia sclerotiorum during infection and identified genes associated with successful infection and putative effectors. These findings are important for understanding the pathogenic mechanisms of S. sclerotiorum.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Geriatrics & Gerontology
Giuseppe Biamonti, Angela Amato, Elisa Belloni, Anna Di Matteo, Lucia Infantino, Davide Pradella, Claudia Ghigna
Summary: Alzheimer's disease is the most common neurodegenerative disorder in the elderly, with approximately 20% of people over 80 affected. Recent studies have shown that Alternative Splicing is involved in gene expression reprogramming and splicing abnormalities in AD tissues. While the molecular causes of AD are still poorly understood, therapeutic approaches targeting aberrant AS regulation offer potential new treatments.
AGING CLINICAL AND EXPERIMENTAL RESEARCH
(2021)
Article
Biology
Florian Becker, Simon Fuchs, Lukas Refisch, Friedel Drepper, Wolfgang Bildl, Uwe Schulte, Shuo Liang, Jonas Immanuel Heinicke, Sierra C. Hansen, Clemens Kreutz, Bettina Warscheid, Bernd Fakler, Evgeny Mymrikov, Carola Hunte
Summary: This study reveals that calcium binding and myristoylation independently affect the conformation and functions of human CHP3. Calcium binding increases the flexibility and hydrophobicity of CHP3, indicating an open conformation. Myristoylation enhances the flexibility of CHP3 and decreases its affinity to NHE1 independently of the bound ion.
Article
Biochemistry & Molecular Biology
Hiroki Ura, Sumihito Togi, Yo Niida
Summary: Alternative splicing is a regulated process that can lead to disease. The SMARTer method provides full-length double-strand cDNA synthesis, but faces non-specific genomic DNA amplification issue. The improved SMARTer Capture method, incorporating target-specific capture with exon probes, can accurately detect more alternative splicing events and reduce non-specific amplification.
Article
Immunology
Candelaria Ponce de Leon, Pedro Lorite, Miguel Angel Lopez-Casado, Francisco Barro, Teresa Palomeque, Maria Isabel Torres
Summary: Our study reveals an association between over-expression of sPD-1 protein and PD-1 Delta ex3 transcript in celiac disease. We also discovered three novel alternative spliced isoforms, one of which may encode a new soluble form of PD1 (sPD-1). Dietary gluten can modulate RNA splicing processes in response to different nutritional conditions, suggesting an adaptive mechanism for cell homeostasis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Seungjae Lee, Lu Wei, Binglong Zhang, Raeann Goering, Sonali Majumdar, Jiayu Wen, J. Matthew Taliaferro, Eric C. Lai
Summary: ELAV/Hu factors, a conserved family of RNA binding proteins, orchestrate multiple broad programs of neuronal mRNA processing and isoform diversification in both Drosophila and mammalian neurons. Their impacts on splicing, particularly in relation to 3' UTR extensions, play vital roles in regulating neural mRNA processing events.
Review
Oncology
Mengfei Sheng, Yuanyuan Zhang, Yaoyun Wang, Weiyi Liu, Xingyu Wang, Tiaoying Ke, Pingyang Liu, Sihan Wang, Wei Shao
Summary: Alternative splicing plays a critical role in gene expression by generating diverse transcript isoforms, which can affect protein function and regulation. Aberrant alternative splicing is an important factor in cancer development and impacts various activities of cancer cells.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Allergy
Lori Broderick, Gwendolyn M. Clay, Robert H. Blum, Yang Liu, Rachael McVicar, Fabio Papes, Laela M. Booshehri, Ian G. Cowell, Caroline A. Austin, Christopher D. Putnam, Dan S. Kaufman
Summary: The study examines the impact of Hoffman syndrome-associated mutations in TOP2B on the development and function of NK cells. Using a knockin murine model and patient-derived iPSCs, the researchers investigated NK-cell development in mouse bone marrow and spleen, and assessed the immunophenotype, gene expression, and cytotoxic activity of NK cells in both murine and human models.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Rebecca L. Swan, Ian G. Cowell, Caroline A. Austin
Summary: DNA topoisomerase II regulates DNA topology by introducing enzyme-bridged DNA double-strand breaks. Failure to complete repair of these breaks can be cytotoxic. Understanding the post-translational modifications involved in the repair process may improve the effectiveness of topoisomerase poison chemotherapy.
MOLECULAR PHARMACOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Katherine James, Anil Wipat, Simon J. Cockell
Summary: This article describes the application of computational interactome networks in diverse eukaryotic species, emphasizing on key interactome studies in non-model organisms.
BRIEFINGS IN FUNCTIONAL GENOMICS
(2022)
Article
Biochemistry & Molecular Biology
Elise M. Ling, Arnaud Basle, Ian G. Cowell, Bert van den Berg, Tim R. Blower, Caroline A. Austin
Summary: This study investigates the conformational changes and ATP hydrolysis mechanism of the ATPase domain of human topoisomerase II beta (TOP2B). It reveals that the GHKL domains are similar while the QTK loop can move for product release. Key drug-binding residues and the impact of the N-terminal strap and residue E103 on ATP hydrolysis are also identified.
Review
Microbiology
Katherine James, Jose Munoz-Munoz
Summary: This review describes the current techniques for network inference and analysis, and summarizes the applications of computationally-predicted microbial interactomes to date.
Article
Clinical Neurology
Marina Danilenko, Masood Zaka, Claire Keeling, Stephen Crosier, Stephanie Lyman, Martina Finetti, Daniel Williamson, Rafiqul Hussain, Jonathan Coxhead, Peixun Zhou, Rebecca M. Hill, Debbie Hicks, Vikki Rand, Abhijit Joshi, Edward C. Schwalbe, Simon Bailey, Steven C. Clifford
Summary: We used single-cell whole-genome sequencing to reconstruct the evolutionary trajectory of medulloblastoma, the most common childhood brain malignancy. The different molecular sub-classes and clinical risk groups showed varying levels of clonal diversity and evolutionary patterns. Early-stage chromosomal aberrations and gene mutations can be used as biomarkers for early disease detection. Novel events that occur later and/or sub-clonally may have clinical significance in disease evolution and require further investigation.
ACTA NEUROPATHOLOGICA
(2022)
Article
Biochemical Research Methods
Katherine James, Aoesha Alsobhe, Simon J. Cockell, Anil Wipat, Matthew Pocock
Summary: The ssNet integration technique allows for the construction of PFINs from a single database, eliminating the need for an external Gold Standard dataset while producing comparable network performance and reducing data loss. It scores and integrates high-throughput and low-throughput data in a consistent manner, overcoming challenges such as data redundancy and Gold Standard bias. The ssNet method provides a more efficient and complete approach to building functional integrated networks.
BMC BIOINFORMATICS
(2022)
Article
Neurosciences
Mushtaq M. Khazeem, John W. Casement, George Schlossmacher, Niall S. Kenneth, Nielda K. Sumbung, Janice Yuen Tung Chan, Jade F. McGow, Ian G. Cowell, Caroline A. Austin
Summary: The neuroblastoma cell line SH-SY5Y is a versatile tool for studying gene expression and differentiation. DNA topoisomerase IIB (TOP2B) plays an important role in regulating the phenotype of these cells, promoting the expression of neural-like characteristics and suppressing the mesenchymal transcription program.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biology
Bill Yang, Goksel Misirli, Anil Wipat, Jennifer Hallinan
Summary: The use of microorganisms for the production of industrially important compounds and enzymes is increasingly important. However, eukaryotes have been less widely used in biotechnology due to their complex genomic structure and biology. The Yeast2.0 project aims to engineer the yeast Saccharomyces cerevisiae to make it easier to manipulate and generate random variants. In this study, we developed a computer simulator for the SCRaMbLE system, which can be used to analyze and optimize the fitness landscape of any organism in which SCRaMbLE has been implemented.
Article
Parasitology
Marina Papaiakovou, Natalia Fraija-Fernandez, Katherine James, Andrew G. Briscoe, Andie Hall, Timothy P. Jenkins, Julia Dunn, Bruno Levecke, Zeleke Mekonnen, Piet Cools, Stephen R. Doyle, Cinzia Cantacessi, D. T. J. Littlewood
Summary: Currently, the identification of gastrointestinal helminth infections relies on traditional microscopy-based techniques, but molecular approaches using DNA detection and quantification offer increased sensitivity and specificity. In this study, low-depth whole genome sequencing (genome skimming) was used to detect and characterize helminth diversity in faecal samples. Three methods were evaluated to characterize metagenomic sequencing data, and the success of genome skimming was dependent on the availability of reference sequences and methods to detect parasite DNA in mixed samples.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ian G. Cowell, Caroline A. Austin
Summary: The MLL/KMT2A gene is frequently rearranged in childhood and adult acute leukaemia and in secondary leukaemias occurring after therapy with DNA topoisomerase targeting anti-cancer agents. Recent studies have shown that etoposide-induced DNA cleavage plays an important role in MLL/KMT2A translocations.
Article
Mathematics, Interdisciplinary Applications
Ajda Zagar, Tomaz Hocevar, Tomaz Curk
Summary: This study used computational analysis to answer questions about human mobility and translated the findings into anthropology based on a publicly available data set of road traffic counters in Slovenia. The analysis revealed insights about driving habits, tourism patterns, preferred locations, weekly and yearly variations, and outliers in road traffic. The study concluded that quantitative data analysis is a valuable tool for preliminary research in anthropology, but only partially answers anthropological questions.
Article
Computer Science, Information Systems
Amra Omanovic, Polona Oblak, Tomaz Curk
Summary: Tropical semiring has been widely used in various research fields and we propose a new algorithm called triFastSTMF, which performs tri-factorization over the tropical semiring. By applying triFastSTMF to analyze multipartite networks, we achieve better performance compared to previous methods.
Proceedings Paper
Computer Science, Artificial Intelligence
Christian Atallah, Katherine James, Zhen Ou, James Skelton, David Markham, James Finnigan, Simon Charnock, Anil Wipat
Summary: Enzymes are increasingly being utilized as biocatalysts in various industries. The reliable annotation of enzyme catalytic function is crucial for expanding the range of available and useful biocatalysts. However, experimental characterization in the laboratory is necessary to confidently guarantee the quality of such annotation. This study presents a novel approach for the automatic selection of subsets from enzyme families, which outperforms other methods and demonstrates its effectiveness through experiments on three diverse enzyme families.
2022 IEEE CONFERENCE ON COMPUTATIONAL INTELLIGENCE IN BIOINFORMATICS AND COMPUTATIONAL BIOLOGY (IEEE CIBCB 2022)
(2022)
