1 Inflammation Drives Alternative First Exon Usage to Regulate
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Recovery of Small Plasmid Sequences Via Oxford Nanopore Sequencing
bioRxiv preprint doi: https://doi.org/10.1101/2021.02.21.432182; this version posted February 22, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Recovery of small plasmid sequences via Oxford Nanopore sequencing Ryan R. Wick1*, Louise M. Judd1 , Kelly L. Wyres1 and Kathryn E. Holt1,2 1. Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia 2. Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK * [email protected] Abstract Oxford Nanopore Technologies (ONT) sequencing platforms currently offer two approaches to whole-genome native-DNA library preparation: ligation and rapid. In this study, we compared these two approaches for bacterial whole-genome sequencing, with a specific aim of assessing their ability to recover small plasmid sequences. To do so, we sequenced DNA from seven plasmid-rich bacterial isolates in three different ways: ONT ligation, ONT rapid and Illumina. Using the Illumina read depths to approximate true plasmid abundance, we found that small plasmids (<20 kbp) were underrepresented in ONT ligation read sets (by a mean factor of ~4) but were not underrepresented in ONT rapid read sets. This effect correlated with plasmid size, with the smallest plasmids being the most underrepresented in ONT ligation read sets. We also found lower rates of chimeric reads in the rapid read sets relative to ligation read sets. These results show that when small plasmid recovery is important, ONT rapid library preparations are preferable to ligation-based protocols. -
Regulation of Cdc42 and Its Effectors in Epithelial Morphogenesis Franck Pichaud1,2,*, Rhian F
© 2019. Published by The Company of Biologists Ltd | Journal of Cell Science (2019) 132, jcs217869. doi:10.1242/jcs.217869 REVIEW SUBJECT COLLECTION: ADHESION Regulation of Cdc42 and its effectors in epithelial morphogenesis Franck Pichaud1,2,*, Rhian F. Walther1 and Francisca Nunes de Almeida1 ABSTRACT An overview of Cdc42 Cdc42 – a member of the small Rho GTPase family – regulates cell Cdc42 was discovered in yeast and belongs to a large family of small – polarity across organisms from yeast to humans. It is an essential (20 30 kDa) GTP-binding proteins (Adams et al., 1990; Johnson regulator of polarized morphogenesis in epithelial cells, through and Pringle, 1990). It is part of the Ras-homologous Rho subfamily coordination of apical membrane morphogenesis, lumen formation and of GTPases, of which there are 20 members in humans, including junction maturation. In parallel, work in yeast and Caenorhabditis elegans the RhoA and Rac GTPases, (Hall, 2012). Rho, Rac and Cdc42 has provided important clues as to how this molecular switch can homologues are found in all eukaryotes, except for plants, which do generate and regulate polarity through localized activation or inhibition, not have a clear homologue for Cdc42. Together, the function of and cytoskeleton regulation. Recent studies have revealed how Rho GTPases influences most, if not all, cellular processes. important and complex these regulations can be during epithelial In the early 1990s, seminal work from Alan Hall and his morphogenesis. This complexity is mirrored by the fact that Cdc42 can collaborators identified Rho, Rac and Cdc42 as main regulators of exert its function through many effector proteins. -
Nanopore Sequencing of Long Ribosomal DNA Amplicons Enables
bioRxiv preprint first posted online Jun. 29, 2018; doi: http://dx.doi.org/10.1101/358572. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Nanopore sequencing of long ribosomal DNA amplicons enables portable and simple biodiversity assessments with high phylogenetic resolution across broad taxonomic scale Henrik Krehenwinkel1,4, Aaron Pomerantz2, James B. Henderson3,4, Susan R. Kennedy1, Jun Ying Lim1,2, Varun Swamy5, Juan Diego Shoobridge6, Nipam H. Patel2,7, Rosemary G. Gillespie1, Stefan Prost2,8 1 Department of Environmental Science, Policy and Management, University of California, Berkeley, USA 2 Department of Integrative Biology, University of California, Berkeley, USA 3 Institute for Biodiversity Science and Sustainability, California Academy of Sciences, San Francisco, USA 4 Center for Comparative Genomics, California Academy of Sciences, San Francisco, USA 5 San Diego Zoo Institute for Conservation Research, Escondido, USA 6 Applied Botany Laboratory, Research and development Laboratories, Cayetano Heredia University, Lima, Perú 7 Department of Molecular and Cell Biology, University of California, Berkeley, USA 8 Research Institute of Wildlife Ecology, Department of Integrative Biology and Evolution, University of Veterinary Medicine, Vienna, Austria Corresponding authors: Henrik Krehenwinkel ([email protected]) and Stefan Prost ([email protected]) Keywords Biodiversity, ribosomal, eukaryotes, long DNA barcodes, Oxford Nanopore Technologies, MinION Abstract Background In light of the current biodiversity crisis, DNA barcoding is developing into an essential tool to quantify state shifts in global ecosystems. -
ARHGEF7 (B-PIX) Is Required for the Maintenance of Podocyte Architecture and Glomerular Function
BASIC RESEARCH www.jasn.org ARHGEF7 (b-PIX) Is Required for the Maintenance of Podocyte Architecture and Glomerular Function Jun Matsuda, Mirela Maier, Lamine Aoudjit, Cindy Baldwin, and Tomoko Takano Division of Nephrology, McGill University Health Centre, Montreal, Quebec, Canada ABSTRACT Background Previous studies showed that Cdc42, a member of the prototypical Rho family of small GTPases and a regulator of the actin cytoskeleton, is critical for the normal development and health of podocytes. However, upstream regulatory mechanisms for Cdc42 activity in podocytes are largely unknown. Methods We used a proximity-based ligation assay, BioID, to identify guanine nucleotide exchange fac- tors that activate Cdc42 in immortalized human podocytes. We generated podocyte-specificARHGEF7 (commonly known as b-PIX) knockout mice by crossing b-PIX floxed mice with Podocin-Cre mice. Using shRNA, we established cultured mouse podocytes with b-PIX knockdown and their controls. Results We identified b-PIX as a predominant guanine nucleotide exchange factor that interacts with Cdc42 in human podocytes. Podocyte-specific b-PIX knockout mice developed progressive proteinuria and kidney failure with global or segmental glomerulosclerosis in adulthood. Glomerular podocyte density gradually decreased in podocyte-specific b-PIX knockout mice, indicating podocyte loss. Compared with controls, glomeruli from podocyte-specific b-PIX knockout mice and cultured mouse podocytes with b-PIX knockdown exhibited significant reduction in Cdc42 activity. Loss of b-PIX promoted podocyte apoptosis, which was mediated by the reduced activity of the prosurvival transcriptional regulator Yes-associated protein. Conclusions These findings indicate that b-PIX is required for the maintenance of podocyte architecture and glomerular function via Cdc42 and its downstream Yes-associated protein activities. -
Redefining the Specificity of Phosphoinositide-Binding by Human
bioRxiv preprint doi: https://doi.org/10.1101/2020.06.20.163253; this version posted June 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins Nilmani Singh1†, Adriana Reyes-Ordoñez1†, Michael A. Compagnone1, Jesus F. Moreno Castillo1, Benjamin J. Leslie2, Taekjip Ha2,3,4,5, Jie Chen1* 1Department of Cell & Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801; 2Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205; 3Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218; 4Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205; 5Howard Hughes Medical Institute, Baltimore, MD 21205, USA †These authors contributed equally to this work. *Correspondence: [email protected]. bioRxiv preprint doi: https://doi.org/10.1101/2020.06.20.163253; this version posted June 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. ABSTRACT Pleckstrin homology (PH) domains are presumed to bind phosphoinositides (PIPs), but specific interaction with and regulation by PIPs for most PH domain-containing proteins are unclear. Here we employed a single-molecule pulldown assay to study interactions of lipid vesicles with full-length proteins in mammalian whole cell lysates. -
Cdc42 Mediates Cancer Cell Chemotaxis in Perineural Invasion
Author Manuscript Published OnlineFirst on February 21, 2020; DOI: 10.1158/1541-7786.MCR-19-0726 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 1 Cdc42 mediates cancer cell chemotaxis in perineural invasion ______________________________________________________________________ Natalya Chernichenko1, Tatiana Omelchenko2, Sylvie Deborde1, Richard Bakst3, Shizhi He1, Chun-Hao Chen1, Laxmi Gusain1, Efsevia Vakiani4, Nora Katabi4, Alan Hall2*, Richard J Wong1 ______________________________________________________________________ 1Department of Surgery, 2Cell Biology Program, 4Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10021 3Department of Radiation Oncology Mount Sinai Hospital, New York, NY, 10029 * Deceased The authors declare that they each do not have any conflict of interest with the material in this manuscript. Correspondence: Richard J. Wong, MD Memorial Sloan-Kettering Cancer Center 1275 York Avenue, C-1069 New York, NY 10021 Office: (212) 639-7638 FAX: (212) 717-3302 Email: [email protected] Downloaded from mcr.aacrjournals.org on October 1, 2021. © 2020 American Association for Cancer Research. Author Manuscript Published OnlineFirst on February 21, 2020; DOI: 10.1158/1541-7786.MCR-19-0726 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 2 Abstract Perineural invasion (PNI) is an ominous form of cancer progression along nerves associated with poor clinical outcome. Glial derived neurotrophic factor (GDNF) interacts with cancer cell RET receptors to enable PNI, but downstream events remain undefined. We demonstrate that GDNF leads to early activation of the GTPase Cdc42 in pancreatic cancer cells, but only delayed activation of RhoA and does not affect Rac1. Depletion of Cdc42 impairs pancreatic cancer cell chemotaxis towards GDNF and nerves. -
Genomic Sequencing of SARS-Cov-2: a Guide to Implementation for Maximum Impact on Public Health
Genomic sequencing of SARS-CoV-2 A guide to implementation for maximum impact on public health 8 January 2021 Genomic sequencing of SARS-CoV-2 A guide to implementation for maximum impact on public health 8 January 2021 Genomic sequencing of SARS-CoV-2: a guide to implementation for maximum impact on public health ISBN 978-92-4-001844-0 (electronic version) ISBN 978-92-4-001845-7 (print version) © World Health Organization 2021 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization (http://www.wipo.int/amc/en/mediation/rules/). -
Using Long Nanopore Reads to Delineate Structural Variants (Svs)
Using long nanopore reads to delineate structural variants (SVs) in the human genome SVs, including large deletions, duplications, inversions, translocations and copy-number changes are abundant in large genomes, and require long reads for precise characterisation Contact: [email protected] More information at: www.nanoporetech.com and publications.nanoporetech.com Unique Repeat Unique Repeat Unique a) b) a) b) sequence 1 1 sequence 2 2 sequence 3 1,000 60 Short reads Insertions Long A B C D E Reference chromosome 1 40 reads 800 Deletions > 50 bp Short-read assembly 20 Collapsed repeat consensus Unique contig 1 Long-read Bases sequenced (Mb) assembly 600 0 Unique contig 1 Unique contig 3 0 10 20 30 40 V W X Y Z Reference chromosome 2 Single, fully-resolved contig Count Read length (kb) c) > 50 bp 400 chr7 (q33) 7p21.3 15.321.1 15.3 7p14.3 7p14.1 13 11.2 11.21 11.22 11.23 7q21.11 q21.3 7q22.1 7q31.1 7q33 7q34 7q35 36.1 36.3 Scale 50 kb hg38 chr7: 134,550,000 134,600,000 134,650,000 134,700,000 Inversion A D C B E GENCODE v24 comprehensive transcript set (only Basic displayed by default) 200 AKR1B10 AKR1B15 BGPM CALD1 AKR1B15 BGPM Deletion BGPM A B C E AC009276.4 Duplication A B C C C D E 0 1,000 10,000 20,000 30,000 Translocation V W C D E + A B X Y Z Event size (bp) Adapted from Huddleston, J. et al. Discovery and genotyping of structural variation from long-read haploid genome sequence data. -
The Tumor Suppressor SCRIB Is a Negative Modulator of the Wnt/-Catenin Signaling Pathway
The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β-Catenin Signaling Pathway Avais Daulat, Mônica Silveira Wagner, Alexandra Walton, Emilie Baudelet, Stéphane Audebert, Luc Camoin, Jean-Paul Borg To cite this version: Avais Daulat, Mônica Silveira Wagner, Alexandra Walton, Emilie Baudelet, Stéphane Audebert, et al.. The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β-Catenin Signaling Pathway. Pro- teomics, Wiley-VCH Verlag, 2019, 19 (21-22), pp.1800487. 10.1002/pmic.201800487. hal-02518664 HAL Id: hal-02518664 https://hal.archives-ouvertes.fr/hal-02518664 Submitted on 7 Apr 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. PROTEOMICS Page 2 of 35 1 2 3 1 The tumor suppressor SCRIB is a negative modulator of the Wnt/-catenin signaling 4 5 6 2 pathway 7 8 3 Avais M. Daulat1,§, Mônica Silveira Wagner1,§, Alexandra Walton1, Emilie Baudelet2, 9 10 4 Stéphane Audebert2, Luc Camoin2, #,*, Jean-Paul Borg1,2,#,* 11 12 13 5 14 15 6 16 17 7 18 19 8 20 21 For Peer Review 1 22 9 Centre de Recherche en Cancérologie de Marseille, Equipe -
Genome-Wide DNA Methylation Profiles in Community Members Exposed to the World Trade Center Disaster
International Journal of Environmental Research and Public Health Article Genome-Wide DNA Methylation Profiles in Community Members Exposed to the World Trade Center Disaster Alan A. Arslan 1,2,3,* , Stephanie Tuminello 2, Lei Yang 2, Yian Zhang 2, Nedim Durmus 4, Matija Snuderl 5, Adriana Heguy 5,6, Anne Zeleniuch-Jacquotte 2,3, Yongzhao Shao 2,3 and Joan Reibman 4 1 Department of Obstetrics and Gynecology, New York University Langone Health, New York, NY 10016, USA 2 Department of Population Health, New York University Langone Health, New York, NY 10016, USA; [email protected] (S.T.); [email protected] (L.Y.); [email protected] (Y.Z.); [email protected] (A.Z.-J.); [email protected] (Y.S.) 3 NYU Perlmutter Comprehensive Cancer Center, New York, NY 10016, USA 4 Department of Medicine, New York University Langone Health, New York, NY 10016, USA; [email protected] (N.D.); [email protected] (J.R.) 5 Department of Pathology, New York University Langone Health, New York, NY 10016, USA; [email protected] (M.S.); [email protected] (A.H.) 6 NYU Langone’s Genome Technology Center, New York, NY 10016, USA * Correspondence: [email protected] Received: 30 June 2020; Accepted: 25 July 2020; Published: 30 July 2020 Abstract: The primary goal of this pilot study was to assess feasibility of studies among local community members to address the hypothesis that complex exposures to the World Trade Center (WTC) dust and fumes resulted in long-term epigenetic changes. We enrolled 18 WTC-exposed cancer-free women from the WTC Environmental Health Center (WTC EHC) who agreed to donate blood samples during their standard clinical visits. -
Long Non-Coding RNA Landscape in Prostate Cancer Molecular Subtypes: a Feature Selection Approach
International Journal of Molecular Sciences Article Long Non-Coding RNA Landscape in Prostate Cancer Molecular Subtypes: A Feature Selection Approach Simona De Summa 1,* , Antonio Palazzo 2 , Mariapia Caputo 1, Rosa Maria Iacobazzi 3 , Brunella Pilato 1, Letizia Porcelli 3, Stefania Tommasi 1 , Angelo Virgilio Paradiso 4,† and Amalia Azzariti 3,† 1 Molecular Diagnostics and Pharmacogenetics Unit, IRCCS IstitutoTumori Giovanni Paolo II, 70124 Bari, Italy; [email protected] (M.C.); [email protected] (B.P.); [email protected] (S.T.) 2 Laboratory of Nanotechnology, IRCCS IstitutoTumori Giovanni Paolo II, 70124 Bari, Italy; [email protected] 3 Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy; [email protected] (R.M.I.); [email protected] (L.P.); [email protected] (A.A.) 4 Scientific Directorate, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy; [email protected] * Correspondence: [email protected] † Co-senior authors. Abstract: Prostate cancer is one of the most common malignancies in men. It is characterized by a high molecular genomic heterogeneity and, thus, molecular subtypes, that, to date, have not been used in clinical practice. In the present paper, we aimed to better stratify prostate cancer patients through the selection of robust long non-coding RNAs. To fulfill the purpose of the study, a bioinformatic approach focused on feature selection applied to a TCGA dataset was used. In such a way, LINC00668 and long non-coding(lnc)-SAYSD1-1, able to discriminate ERG/not-ERG subtypes, Citation: De Summa, S.; Palazzo, A.; were demonstrated to be positive prognostic biomarkers in ERG-positive patients. -
High-Fidelity Nanopore Sequencing of Ultra-Short DNA Sequences
bioRxiv preprint doi: https://doi.org/10.1101/552224; this version posted February 16, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Title: High-Fidelity Nanopore Sequencing of Ultra-Short DNA Sequences Authors: Brandon D. Wilson1, Michael Eisenstein2,3, H. Tom Soh2,3,4* Affiliations: 1Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA. 2Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA. 3Department of Radiology, Stanford University, Stanford, CA 94305, USA. 4Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. * Correspondence to [email protected] One Sentence Summary: We introduce a simple method of accurately sequencing ultra-short (<100bp) target DNA on a nanopore sequencing platform. Abstract Nanopore sequencing offers a portable and affordable alternative to sequencing-by-synthesis methods but suffers from lower accuracy and cannot sequence ultra-short DNA. This puts applications such as molecular diagnostics based on the analysis of cell-free DNA or single- nucleotide variants (SNV) out of reach. To overcome these limitations, We report a nanopore-based sequencing strategy in Which short target sequences are first circularized and then amplified via rolling-circle amplification to produce long stretches of concatemeric repeats. These can be sequenced on the Oxford Nanopore Technology’s (ONT) MinION platform, and the resulting repeat sequences aligned to produce a highly-accurate consensus that reduces the high error-rate present in the individual repeats.