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1دورية أكاديمية
المؤلفون: Julie Warin, Nicolas Vedrenne, Vivian Tam, Mengxia Zhu, Danqing Yin, Xinyi Lin, Bluwen Guidoux-D’halluin, Antoine Humeau, Luce Roseiro, Lily Paillat, Claire Chédeville, Caroline Chariau, Frank Riemers, Markus Templin, Jérôme Guicheux, Marianna A. Tryfonidou, Joshua W.K. Ho, Laurent David, Danny Chan, Anne Camus
المصدر: iScience, Vol 27, Iss 2, Pp 109018- (2024)
مصطلحات موضوعية: Biological sciences, Biology of human development, Developmental biology, Natural sciences, Omics, Transcriptomics, Science
الوصف: Summary: Understanding the emergence of human notochordal cells (NC) is essential for the development of regenerative approaches. We present a comprehensive investigation into the specification and generation of bona fide NC using a straightforward pluripotent stem cell (PSC)-based system benchmarked with human fetal notochord. By integrating in vitro and in vivo transcriptomic data at single-cell resolution, we establish an extended molecular signature and overcome the limitations associated with studying human notochordal lineage at early developmental stages. We show that TGF-β inhibition enhances the yield and homogeneity of notochordal lineage commitment in vitro. Furthermore, this study characterizes regulators of cell-fate decision and matrisome enriched in the notochordal niche. Importantly, we identify specific cell-surface markers opening avenues for differentiation refinement, NC purification, and functional studies. Altogether, this study provides a human notochord transcriptomic reference that will serve as a resource for notochord identification in human systems, diseased-tissues modeling, and facilitating future biomedical research.
وصف الملف: electronic resource
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2دورية أكاديمية
المؤلفون: Shichao Ma, Xiunan Fang, Yu Yao, Jianfu Li, Daniel C. Morgan, Yongyan Xia, Crystal S.M. Kwok, Michelle C.K. Lo, Dickson M.D. Siu, Kevin K. Tsia, Andrian Yang, Joshua W.K. Ho
المصدر: Computational and Structural Biotechnology Journal, Vol 21, Iss , Pp 1598-1605 (2023)
مصطلحات موضوعية: Web application, Single-cell data visualisation, Spatial-single cell integration, Narrative visualisation, Biotechnology, TP248.13-248.65
الوصف: Current single-cell visualisation techniques project high dimensional data into ‘map’ views to identify high-level structures such as cell clusters and trajectories. New tools are needed to allow the transversal through the high dimensionality of single-cell data to explore the single-cell local neighbourhood. StarmapVis is a convenient web application displaying an interactive downstream analysis of single-cell expression or spatial transcriptomic data. The concise user interface is powered by modern web browsers to explore the variety of viewing angles unavailable to 2D media. Interactive scatter plots display clustering information, while the trajectory and cross-comparison among different coordinates are displayed in connectivity networks. Automated animation of camera view is a unique feature of our tool. StarmapVis also offers a useful animated transition between two-dimensional spatial omic data to three-dimensional single cell coordinates. The usability of StarmapVis is demonstrated by four data sets, showcasing its practical usability. StarmapVis is available at: https://holab-hku.github.io/starmapVis.
وصف الملف: electronic resource
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3دورية أكاديمية
المؤلفون: Ian C.H. Lee, Sergey Tumanov, Jason W.H. Wong, Roland Stocker, Joshua W.K. Ho
المصدر: iScience, Vol 26, Iss 6, Pp 106881- (2023)
مصطلحات موضوعية: Lipidomics, Metabolomics, Biological sciences research methodologies, Biological sciences tools, Science
الوصف: Summary: Mass spectrometry (MS)-based untargeted metabolomic and lipidomic approaches are being used increasingly in biomedical research. The adoption and integration of these data are critical to the overall multi-omic toolkit. Recently, a sample extraction method called Multi-ABLE has been developed, which enables concurrent generation of proteomic and untargeted metabolomic and lipidomic data from a small amount of tissue. The proteomics field has a well-established set of software for processing of acquired data; however, there is a lack of a unified, off-the-shelf, ready-to-use bioinformatics pipeline that can take advantage of and prepare concurrently generated metabolomic and lipidomic data for joint downstream analyses. Here we present an R pipeline called MultiABLER as a unified and simple upstream processing and analysis pipeline for both metabolomics and lipidomics datasets acquired using liquid chromatography-tandem mass spectrometry. The code is available via an open-source license at https://github.com/holab-hku/MultiABLER.
وصف الملف: electronic resource
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4دورية أكاديمية
المؤلفون: Ralph Patrick, David T. Humphreys, Vaibhao Janbandhu, Alicia Oshlack, Joshua W.K. Ho, Richard P. Harvey, Kitty K. Lo
المصدر: Genome Biology, Vol 21, Iss 1, Pp 1-27 (2020)
مصطلحات موضوعية: scRNA-seq, Alternative polyadenylation, mRNA isoforms, Differential transcript use, Biology (General), QH301-705.5, Genetics, QH426-470
الوصف: Abstract High-throughput single-cell RNA-seq (scRNA-seq) is a powerful tool for studying gene expression in single cells. Most current scRNA-seq bioinformatics tools focus on analysing overall expression levels, largely ignoring alternative mRNA isoform expression. We present a computational pipeline, Sierra, that readily detects differential transcript usage from data generated by commonly used polyA-captured scRNA-seq technology. We validate Sierra by comparing cardiac scRNA-seq cell types to bulk RNA-seq of matched populations, finding significant overlap in differential transcripts. Sierra detects differential transcript usage across human peripheral blood mononuclear cells and the Tabula Muris, and 3 ′UTR shortening in cardiac fibroblasts. Sierra is available at https://github.com/VCCRI/Sierra .
وصف الملف: electronic resource
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5دورية أكاديمية
المؤلفون: Anita Ayer, Daniel J. Fazakerley, Cacang Suarna, Ghassan J. Maghzal, Diba Sheipouri, Kevin J. Lee, Michelle C. Bradley, Lucía Fernández-del-Rio, Sergey Tumanov, Stephanie MY. Kong, Jelske N. van der Veen, Andrian Yang, Joshua W.K. Ho, Steven G. Clarke, David E. James, Ian W. Dawes, Dennis E. Vance, Catherine F. Clarke, René L. Jacobs, Roland Stocker
المصدر: Redox Biology, Vol 46, Iss , Pp 102127- (2021)
مصطلحات موضوعية: Coenzyme Q, Mitochondria, PEMT, Insulin resistance, S-adenosylmethionine, S-adenosylhomocysteine, Medicine (General), R5-920, Biology (General), QH301-705.5
الوصف: Mitochondrial energy production and function rely on optimal concentrations of the essential redox-active lipid, coenzyme Q (CoQ). CoQ deficiency results in mitochondrial dysfunction associated with increased mitochondrial oxidative stress and a range of pathologies. What drives CoQ deficiency in many of these pathologies is unknown, just as there currently is no effective therapeutic strategy to overcome CoQ deficiency in humans. To date, large-scale studies aimed at systematically interrogating endogenous systems that control CoQ biosynthesis and their potential utility to treat disease have not been carried out. Therefore, we developed a quantitative high-throughput method to determine CoQ concentrations in yeast cells. Applying this method to the Yeast Deletion Collection as a genome-wide screen, 30 genes not known previously to regulate cellular concentrations of CoQ were discovered. In combination with untargeted lipidomics and metabolomics, phosphatidylethanolamine N-methyltransferase (PEMT) deficiency was confirmed as a positive regulator of CoQ synthesis, the first identified to date. Mechanistically, PEMT deficiency alters mitochondrial concentrations of one-carbon metabolites, characterized by an increase in the S-adenosylmethionine to S-adenosylhomocysteine (SAM-to-SAH) ratio that reflects mitochondrial methylation capacity, drives CoQ synthesis, and is associated with a decrease in mitochondrial oxidative stress. The newly described regulatory pathway appears evolutionary conserved, as ablation of PEMT using antisense oligonucleotides increases mitochondrial CoQ in mouse-derived adipocytes that translates to improved glucose utilization by these cells, and protection of mice from high-fat diet-induced insulin resistance. Our studies reveal a previously unrecognized relationship between two spatially distinct lipid pathways with potential implications for the treatment of CoQ deficiencies, mitochondrial oxidative stress/dysfunction, and associated diseases.
وصف الملف: electronic resource
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6دورية أكاديمية
المؤلفون: Chang Chen, Yonggang Zhu, Joshua W.K. Ho, Huaying Chen
المصدر: MethodsX, Vol 8, Iss , Pp 101190- (2021)
مصطلحات موضوعية: Dual pneumatic microvalves method for single cell screening, Science
الوصف: Printing single cells into individual chambers is of critical importance for single-cell analysis using traditional equipment, for instance, single-cell clonal expansion or sequencing. The size of cells can usually be a reflection of their types, functions, and even cell cycle phases. Therefore, printing individual cells within the desired size range is of essential application potential in single-cell analysis. This paper presents a method for the development of a microfluidic chip integrating pneumatic microvalves to print single cells with appropriate size into standard well plates. The reported method provided essential guidelines for the fabrication of multi-layer microfluidic chips, control of the membrane deflection to screen cell size, and printing of single cells. In brief, this paper reports: • the manufacturing of the chip using standard soft lithography; • the protocol to dynamically screen both the lower and the upper size limit of cells passing through the valves by deflection of the valve membrane; • the screening and dispensing of suspended human umbilical vein endothelial cells (HUVECs) into 384-well plates with high viability.
وصف الملف: electronic resource
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7دورية أكاديمية
المؤلفون: Andrian Yang, Michael Troup, Joshua W.K. Ho
المصدر: Computational and Structural Biotechnology Journal, Vol 15, Iss , Pp 379-386 (2017)
مصطلحات موضوعية: Biotechnology, TP248.13-248.65
الوصف: This review examines two important aspects that are central to modern big data bioinformatics analysis – software scalability and validity. We argue that not only are the issues of scalability and validation common to all big data bioinformatics analyses, they can be tackled by conceptually related methodological approaches, namely divide-and-conquer (scalability) and multiple executions (validation). Scalability is defined as the ability for a program to scale based on workload. It has always been an important consideration when developing bioinformatics algorithms and programs. Nonetheless the surge of volume and variety of biological and biomedical data has posed new challenges. We discuss how modern cloud computing and big data programming frameworks such as MapReduce and Spark are being used to effectively implement divide-and-conquer in a distributed computing environment. Validation of software is another important issue in big data bioinformatics that is often ignored. Software validation is the process of determining whether the program under test fulfils the task for which it was designed. Determining the correctness of the computational output of big data bioinformatics software is especially difficult due to the large input space and complex algorithms involved. We discuss how state-of-the-art software testing techniques that are based on the idea of multiple executions, such as metamorphic testing, can be used to implement an effective bioinformatics quality assurance strategy. We hope this review will raise awareness of these critical issues in bioinformatics.
وصف الملف: electronic resource
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8دورية أكاديمية
المؤلفون: Jennifer E. Cropley, Sally A. Eaton, Alastair Aiken, Paul E. Young, Eleni Giannoulatou, Joshua W.K. Ho, Michael E. Buckland, Simon P. Keam, Gyorgy Hutvagner, David T. Humphreys, Katherine G. Langley, Darren C. Henstridge, David I.K. Martin, Mark A. Febbraio, Catherine M. Suter
المصدر: Molecular Metabolism, Vol 5, Iss 8, Pp 699-708 (2016)
مصطلحات موضوعية: Internal medicine, RC31-1245
الوصف: Objective: Parental obesity can induce metabolic phenotypes in offspring independent of the inherited DNA sequence. Here we asked whether such non-genetic acquired metabolic traits can be passed on to a second generation that has never been exposed to obesity, even as germ cells. Methods: We examined the F1, F2, and F3 a/a offspring derived from F0 matings of obese prediabetic Avy/a sires and lean a/a dams. After F0, only lean a/a mice were used for breeding. Results: We found that F1 sons of obese founder males exhibited defects in glucose and lipid metabolism, but only upon a post-weaning dietary challenge. F1 males transmitted these defects to their own male progeny (F2) in the absence of the dietary challenge, but the phenotype was largely attenuated by F3. The sperm of F1 males exhibited changes in the abundance of several small RNA species, including the recently reported diet-responsive tRNA-derived fragments. Conclusions: These data indicate that induced metabolic phenotypes may be propagated for a generation beyond any direct exposure to an inducing factor. This non-genetic inheritance likely occurs via the actions of sperm noncoding RNA. Keywords: Paternal effects, Epigenetic inheritance, Noncoding RNA, Sperm RNA
وصف الملف: electronic resource
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المؤلفون: Andrian Yang, Dimuthu Alankarage, Hartmut Cuny, Eddie K.K. Ip, Moran Almog, Jessica Lu, Debjani Das, Annabelle Enriquez, Justin O. Szot, David T. Humphreys, Gillian M. Blue, Joshua W.K. Ho, David S. Winlaw, Sally L. Dunwoodie, Eleni Giannoulatou
المصدر: Circulation: Genomic and Precision Medicine. 15
مصطلحات موضوعية: Heart Defects, Congenital, Humans, Exome, General Medicine
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e5e7f54b93899b8913377970d78957fc
https://doi.org/10.1161/circgen.121.003539 -
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المؤلفون: Weizhong Zheng, John H.C. Fong, Yuk Kei Wan, Athena H.Y. Chu, Yuanhua Huang, Alan S.L. Wong, Joshua W.K. Ho
الوصف: Many studies have found that sequence in the 5’ untranslated regions (UTRs) impacts the translation rate of an mRNA, but the regulatory grammar that underpins this translation regulation remains elusive. Deep learning methods deployed to analyse massive sequencing datasets offer new solutions to motif discovery. However, existing works focused on extracting sequence motifs in individual datasets, which may not be generalisable to other datasets from the same cell type. We hypothesise that motifs that are genuinely involved in controlling translation rate are the ones that can be extracted from diverse datasets generated by different experimental techniques. In order to reveal more generalised cis-regulatory motifs for RNA translation, we develop a multi-task translation rate predictor,MTtrans, to integrate information from multiple datasets. Compared to single-task models,MTtransreaches a higher prediction accuracy in all the benchmarked datasets generated by various experimental techniques. We show that features learnt in human samples are directly transferable to another dataset in yeast systems, demonstrating its robustness in identifying evolutionarily conserved sequence motifs. Furthermore, our newly generated experimental data corroborated the effect of most of the identified motifs based onMTtranstrained using multiple public datasets, further demonstrating the utility ofMTtransfor discovering generalisable motifs.MTtranseffectively integrates biological insights from diverse experiments and allows robust extraction of translation-associated sequence motifs in 5’UTR.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::2f1b52aed0c38983b4e99481178ea78d
https://doi.org/10.1101/2022.05.03.490410
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