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Old Data and Friends Improve with Age: Advancements with the Updated Tools of Genenetwork
bioRxiv preprint doi: https://doi.org/10.1101/2021.05.24.445383; this version posted May 25, 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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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 4.0 International license. Old data and friends improve with age: Advancements with the updated tools of GeneNetwork Alisha Chunduri1, David G. Ashbrook2 1Department of Biotechnology, Chaitanya Bharathi Institute of Technology, Hyderabad 500075, India 2Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA Abstract Understanding gene-by-environment interactions is important across biology, particularly behaviour. Families of isogenic strains are excellently placed, as the same genome can be tested in multiple environments. The BXD’s recent expansion to 140 strains makes them the largest family of murine isogenic genomes, and therefore give great power to detect QTL. Indefinite reproducible genometypes can be leveraged; old data can be reanalysed with emerging tools to produce novel biological insights. To highlight the importance of reanalyses, we obtained drug- and behavioural-phenotypes from Philip et al. 2010, and reanalysed their data with new genotypes from sequencing, and new models (GEMMA and R/qtl2). We discover QTL on chromosomes 3, 5, 9, 11, and 14, not found in the original study. We narrowed down the candidate genes based on their ability to alter gene expression and/or protein function, using cis-eQTL analysis, and variants predicted to be deleterious. Co-expression analysis (‘gene friends’) and human PheWAS were used to further narrow candidates. -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
Viewed Graphically with a Java Graphical User Interface (GUI), Allowing Users to Evaluate Contig Sequence Quality and Predict Snps
BMC Research Notes BioMed Central Short Report Open Access BEAP: The BLAST Extension and Alignment Program- a tool for contig construction and analysis of preliminary genome sequence James E Koltes†, Zhi-Liang Hu†, Eric Fritz and James M Reecy* Address: Department of Animal Science, Iowa State University, Ames, Iowa 50011-3150, USA Email: James E Koltes - [email protected]; Zhi-Liang Hu - [email protected]; Eric Fritz - [email protected]; James M Reecy* - [email protected] * Corresponding author †Equal contributors Published: 22 January 2009 Received: 29 October 2008 Accepted: 22 January 2009 BMC Research Notes 2009, 2:11 doi:10.1186/1756-0500-2-11 This article is available from: http://www.biomedcentral.com/1756-0500/2/11 © 2009 Reecy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Fine-mapping projects require a high density of SNP markers and positional candidate gene sequences. In species with incomplete genomic sequence, the DNA sequences needed to generate markers for fine-mapping within a linkage analysis confidence interval may be available but may not have been assembled. To manually piece these sequences together is laborious and costly. Moreover, annotation and assembly of short, incomplete DNA sequences is time consuming and not always straightforward. Findings: We have created a tool called BEAP that combines BLAST and CAP3 to retrieve sequences and construct contigs for localized genomic regions in species with unfinished sequence drafts. -
Gene Co-Expression Network Mining Using Graph Sparsification
Gene Co-expression Network Mining Using Graph Sparsification THESIS Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Jinchao Di Graduate Program in Electrical and Computer Engineering The Ohio State University 2013 Master’s Examination Committee: Dr. Kun Huang, Advisor Dr. Raghu Machiraju Dr. Yuejie Chi ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! Copyright by Jinchao Di 2013 ! ! Abstract Identifying and analyzing gene modules is important since it can help understand gene function globally and reveal the underlying molecular mechanism. In this thesis, we propose a method combining local graph sparsification and a gene similarity measurement method TOM. This method can detect gene modules from a weighted gene co-expression network more e↵ectively since we set a local threshold which can detect clusters with di↵erent densities. In our algorithm, we only retain one edge for each gene, which can generate more balanced gene clusters. To estimate the e↵ectiveness of our algorithm we use DAVID to functionally evaluate the gene list for each module we detect and compare our results with some well known algorithms. The result of our algorithm shows better biological relevance than the compared methods and the number of the meaningful biological clusters is much larger than other methods, implying we discover some previously missed gene clusters. Moreover, we carry out a robustness test by adding Gaussian noise with di↵erent variance to the expression data. We find that our algorithm is robust to noise. We also find that some hub genes considered as important genes could be artifacts. -
Exploring Autophagy with Gene Ontology
Autophagy ISSN: 1554-8627 (Print) 1554-8635 (Online) Journal homepage: https://www.tandfonline.com/loi/kaup20 Exploring autophagy with Gene Ontology Paul Denny, Marc Feuermann, David P. Hill, Ruth C. Lovering, Helene Plun- Favreau & Paola Roncaglia To cite this article: Paul Denny, Marc Feuermann, David P. Hill, Ruth C. Lovering, Helene Plun- Favreau & Paola Roncaglia (2018) Exploring autophagy with Gene Ontology, Autophagy, 14:3, 419-436, DOI: 10.1080/15548627.2017.1415189 To link to this article: https://doi.org/10.1080/15548627.2017.1415189 © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. View supplementary material Published online: 17 Feb 2018. Submit your article to this journal Article views: 1097 View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=kaup20 AUTOPHAGY, 2018 VOL. 14, NO. 3, 419–436 https://doi.org/10.1080/15548627.2017.1415189 RESEARCH PAPER - BASIC SCIENCE Exploring autophagy with Gene Ontology Paul Denny a,†,§, Marc Feuermann b,§, David P. Hill c,f,§, Ruth C. Lovering a,§, Helene Plun-Favreau d and Paola Roncaglia e,f,§ aFunctional Gene Annotation, Institute of Cardiovascular Science, University College London, London, UK; bSIB Swiss Institute of Bioinformatics, Geneva, Switzerland; cThe Jackson Laboratory, Bar Harbor, ME, USA; dDepartment of Molecular Neuroscience, UCL Institute of Neurology, London, UK; eEuropean Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Genome Campus, Hinxton, Cambridge, UK; fThe Gene Ontology Consortium ABSTRACT ARTICLE HISTORY Autophagy is a fundamental cellular process that is well conserved among eukaryotes. It is one of the Received 18 May 2017 strategies that cells use to catabolize substances in a controlled way. -
On ATG4B As Drug Target for Treatment of Solid Tumours—The Knowns and the Unknowns
cells Review On ATG4B as Drug Target for Treatment of Solid Tumours—The Knowns and the Unknowns Alexander Agrotis and Robin Ketteler * MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK; [email protected] * Correspondence: [email protected]; Tel.: +44-(0)20-7679-4063 Received: 3 December 2019; Accepted: 19 December 2019; Published: 24 December 2019 Abstract: Autophagy is an evolutionary conserved stress survival pathway that has been shown to play an important role in the initiation, progression, and metastasis of multiple cancers; however, little progress has been made to date in translation of basic research to clinical application. This is partially due to an incomplete understanding of the role of autophagy in the different stages of cancer, and also to an incomplete assessment of potential drug targets in the autophagy pathway. While drug discovery efforts are on-going to target enzymes involved in the initiation phase of the autophagosome, e.g., unc51-like autophagy activating kinase (ULK)1/2, vacuolar protein sorting 34 (Vps34), and autophagy-related (ATG)7, we propose that the cysteine protease ATG4B is a bona fide drug target for the development of anti-cancer treatments. In this review, we highlight some of the recent advances in our understanding of the role of ATG4B in autophagy and its relevance to cancer, and perform a critical evaluation of ATG4B as a druggable cancer target. Keywords: autophagy; ATG4; pancreatic ductal adenocarcinoma (PDAC); drug screening; small molecule compound; screening assay; biomarker 1. Introduction Autophagy is a cellular stress response that has been identified as a target pathway for intervention in various diseases such as neuro-degenerative disorders, pathogen infection, and various types of cancer [1]. -
Network Organization of the Human Autophagy System
Vol 466 | 1 July 2010 | doi:10.1038/nature09204 ARTICLES Network organization of the human autophagy system Christian Behrends1, Mathew E. Sowa1, Steven P. Gygi2 & J. Wade Harper1 Autophagy, the process by which proteins and organelles are sequestered in autophagosomal vesicles and delivered to the lysosome/vacuole for degradation, provides a primary route for turnover of stable and defective cellular proteins. Defects in this system are linked with numerous human diseases. Although conserved protein kinase, lipid kinase and ubiquitin-like protein conjugation subnetworks controlling autophagosome formation and cargo recruitment have been defined, our understanding of the global organization of this system is limited. Here we report a proteomic analysis of the autophagy interaction network in human cells under conditions of ongoing (basal) autophagy, revealing a network of 751 interactions among 409 candidate interacting proteins with extensive connectivity among subnetworks. Many new autophagy interaction network components have roles in vesicle trafficking, protein or lipid phosphorylation and protein ubiquitination, and affect autophagosome number or flux when depleted by RNA interference. The six ATG8 orthologues in humans (MAP1LC3/GABARAP proteins) interact with a cohort of 67 proteins, with extensive binding partner overlap between family members, and frequent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting regions in partner proteins. These studies provide a global view of the mammalian autophagy interaction landscape and a resource for mechanistic analysis of this critical protein homeostasis pathway. Protein homeostasis in eukaryotes is controlled by proteasomal turn- promote incorporation of Atg8p--PE into autophagosomes, allowing over of unstable proteins via the ubiquitin system and lysosomal turn- Atg8p to promote autophagosome closure and cargo recruitment. -
Ejhg2009157.Pdf
European Journal of Human Genetics (2010) 18, 342–347 & 2010 Macmillan Publishers Limited All rights reserved 1018-4813/10 $32.00 www.nature.com/ejhg ARTICLE Fine mapping and association studies of a high-density lipoprotein cholesterol linkage region on chromosome 16 in French-Canadian subjects Zari Dastani1,2,Pa¨ivi Pajukanta3, Michel Marcil1, Nicholas Rudzicz4, Isabelle Ruel1, Swneke D Bailey2, Jenny C Lee3, Mathieu Lemire5,9, Janet Faith5, Jill Platko6,10, John Rioux6,11, Thomas J Hudson2,5,7,9, Daniel Gaudet8, James C Engert*,2,7, Jacques Genest1,2,7 Low levels of high-density lipoprotein cholesterol (HDL-C) are an independent risk factor for cardiovascular disease. To identify novel genetic variants that contribute to HDL-C, we performed genome-wide scans and quantitative association studies in two study samples: a Quebec-wide study consisting of 11 multigenerational families and a study of 61 families from the Saguenay– Lac St-Jean (SLSJ) region of Quebec. The heritability of HDL-C in these study samples was 0.73 and 0.49, respectively. Variance components linkage methods identified a LOD score of 2.61 at 98 cM near the marker D16S515 in Quebec-wide families and an LOD score of 2.96 at 86 cM near the marker D16S2624 in SLSJ families. In the Quebec-wide sample, four families showed segregation over a 25.5-cM (18 Mb) region, which was further reduced to 6.6 Mb with additional markers. The coding regions of all genes within this region were sequenced. A missense variant in CHST6 segregated in four families and, with additional families, we observed a P value of 0.015 for this variant. -
Download Special Issue
BioMed Research International Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data Guest Editors: Julia Tzu-Ya Weng, Li-Ching Wu, Wen-Chi Chang, Tzu-Hao Chang, Tatsuya Akutsu, and Tzong-Yi Lee Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data BioMed Research International Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data Guest Editors: Julia Tzu-Ya Weng, Li-Ching Wu, Wen-Chi Chang, Tzu-Hao Chang, Tatsuya Akutsu, and Tzong-Yi Lee Copyright © 2014 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “BioMed Research International.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Contents Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data,JuliaTzu-YaWeng, Li-Ching Wu, Wen-Chi Chang, Tzu-Hao Chang, Tatsuya Akutsu, and Tzong-Yi Lee Volume2014,ArticleID814092,3pages Evolution of Network Biomarkers from Early to Late Stage Bladder Cancer Samples,Yung-HaoWong, Cheng-Wei Li, and Bor-Sen Chen Volume 2014, Article ID 159078, 23 pages MicroRNA Expression Profiling Altered by Variant Dosage of Radiation Exposure,Kuei-FangLee, Yi-Cheng Chen, Paul Wei-Che Hsu, Ingrid Y. Liu, and Lawrence Shih-Hsin Wu Volume2014,ArticleID456323,10pages EXIA2: Web Server of Accurate and Rapid Protein Catalytic Residue Prediction, Chih-Hao Lu, Chin-Sheng -
Human Leucine-Rich Repeat Proteins: a Genome-Wide Bioinformatic Categorization and Functional Analysis in Innate Immunity
Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity Aylwin C. Y. Nga,b,1, Jason M. Eisenberga,b,1, Robert J. W. Heatha, Alan Huetta, Cory M. Robinsonc, Gerard J. Nauc, and Ramnik J. Xaviera,b,2 aCenter for Computational and Integrative Biology, and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; bThe Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142; and cMicrobiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 Edited by Jeffrey I. Gordon, Washington University School of Medicine, St. Louis, MO, and approved June 11, 2010 (received for review February 17, 2010) In innate immune sensing, the detection of pathogen-associated proteins have been implicated in human diseases to date, notably molecular patterns by recognition receptors typically involve polymorphisms in NOD2 in Crohn disease (8, 9), CIITA in leucine-rich repeats (LRRs). We provide a categorization of 375 rheumatoid arthritis and multiple sclerosis (10), and TLR5 in human LRR-containing proteins, almost half of which lack other Legionnaire disease (11). identifiable functional domains. We clustered human LRR proteins Most LRR domains consist of a chain of between 2 and 45 by first assigning LRRs to LRR classes and then grouping the proteins LRRs (12). Each repeat in turn is typically 20 to 30 residues long based on these class assignments, revealing several of the resulting and can be divided into a highly conserved segment (HCS) fol- protein groups containing a large number of proteins with certain lowed by a variable segment (VS). -
Anti-ATG4B Antibody (ARG54818)
Product datasheet [email protected] ARG54818 Package: 100 μl anti-ATG4B antibody Store at: -20°C Summary Product Description Rabbit Polyclonal antibody recognizes ATG4B Tested Reactivity Hu Predict Reactivity Ms Tested Application ICC/IF, IHC-P, WB Host Rabbit Clonality Polyclonal Isotype IgG Target Name ATG4B Antigen Species Human Immunogen KLH-conjugated synthetic peptide corresponding to aa. 358-390 (C-terminus) of Human ATG4B. Conjugation Un-conjugated Alternate Names Cysteine protease ATG4B; hAPG4B; Autophagin-1; APG4B; Autophagy-related protein 4 homolog B; Autophagy-related cysteine endopeptidase 1; EC 3.4.22.-; AUT-like 1 cysteine endopeptidase; AUTL1 Application Instructions Application table Application Dilution ICC/IF 1:100 IHC-P Assay-dependent WB 1:1000 Application Note * The dilutions indicate recommended starting dilutions and the optimal dilutions or concentrations should be determined by the scientist. Positive Control HeLa Calculated Mw 44 kDa Properties Form Liquid Purification This antibody is prepared by Saturated Ammonium Sulfate (SAS) precipitation followed by dialysis against PBS. Buffer PBS and 0.09% (W/V) Sodium azide Preservative 0.09% (W/V) Sodium azide Storage instruction For continuous use, store undiluted antibody at 2-8°C for up to a week. For long-term storage, aliquot and store at -20°C or below. Storage in frost free freezers is not recommended. Avoid repeated freeze/thaw cycles. Suggest spin the vial prior to opening. The antibody solution should be gently mixed www.arigobio.com 1/3 before use. Note For laboratory research only, not for drug, diagnostic or other use. Bioinformation Database links GeneID: 23192 Human Swiss-port # Q9Y4P1 Human Gene Symbol ATG4B Gene Full Name autophagy related 4B, cysteine peptidase Background Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. -
Rabbit Anti-COPS3/FITC Conjugated Antibody-SL23085R-FITC
SunLong Biotech Co.,LTD Tel: 0086-571- 56623320 Fax:0086-571- 56623318 E-mail:[email protected] www.sunlongbiotech.com Rabbit Anti-COPS3/FITC Conjugated antibody SL23085R-FITC Product Name: Anti-COPS3/FITC Chinese Name: FITC标记的COP9信号复合体亚基3抗体 COP9 Signalosome Complex Subunit 3; CSN10; JAB1 Containing Signalosome Alias: Subunit 3; SGN3; Signalosome Subunit 3; CSN3_HUMAN. Organism Species: Rabbit Clonality: Polyclonal React Species: ICC=1:50-200IF=1:50-200 Applications: not yet tested in other applications. optimal dilutions/concentrations should be determined by the end user. Molecular weight: 48kDa Form: Lyophilized or Liquid Concentration: 2mg/1ml immunogen: KLH conjugated synthetic peptide derived from human COPS3 Lsotype: IgG Purification: affinity purified by Protein A Storage Buffer: 0.01M TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol. Storewww.sunlongbiotech.com at -20 °C for one year. Avoid repeated freeze/thaw cycles. The lyophilized antibody is stable at room temperature for at least one month and for greater than a year Storage: when kept at -20°C. When reconstituted in sterile pH 7.4 0.01M PBS or diluent of antibody the antibody is stable for at least two weeks at 2-4 °C. background: The protein encoded by this gene possesses kinase activity that phosphorylates regulators involved in signal transduction. It phosphorylates I kappa-Balpha, p105, and c-Jun. It acts as a docking site for complex-mediated phosphorylation. The gene is Product Detail: located within the Smith-Magenis syndrome region on chromosome 17. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010].