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Screening and Identification of Key Biomarkers in Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Screening and identification of key biomarkers in clear cell renal cell carcinoma based on bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignancy of the urinary system. The pathogenesis and effective diagnosis of ccRCC have become popular topics for research in the previous decade. In the current study, an integrated bioinformatics analysis was performed to identify core genes associated in ccRCC. An expression dataset (GSE105261) was downloaded from the Gene Expression Omnibus database, and included 26 ccRCC and 9 normal kideny samples. Assessment of the microarray dataset led to the recognition of differentially expressed genes (DEGs), which was subsequently used for pathway and gene ontology (GO) enrichment analysis. -
Cow's Milk Allergy in Dutch Children
Petrus et al. Clin Transl Allergy (2016) 6:16 DOI 10.1186/s13601-016-0105-z Clinical and Translational Allergy RESEARCH Open Access Cow’s milk allergy in Dutch children: an epigenetic pilot survey Nicole C. M. Petrus1*†, Peter Henneman2†, Andrea Venema2, Adri Mul2, Femke van Sinderen2, Martin Haagmans2, Olaf Mook2, Raoul C. Hennekam1,2, Aline B. Sprikkelman1‡ and Marcel Mannens2‡ Abstract Background: Cow’s milk allergy (CMA) is a common disease in infancy. Early environmental factors are likely to con- tribute to CMA. It is known that epigenetic gene regulation can be altered by environmental factors. We have set up a proof of concept study, aiming to detect epigenetic associations specific with CMA. Methods: We studied children from the Dutch EuroPrevall birth cohort study (N 20 CMA, N 23 controls, N 10 tolerant boys), age and gender matched. CMA was challenge proven. Bisulfite converted= DNA =(blood) was analyzed= using the 450K infinium DNA-methylation array. Four groups (combined, girls, boys and tolerant boys) were analysed between CMA and controls. Statistical analysis and pathway-analysis were performed in “R” using IMA, Minfi and the global-test package. Differentially methylated regions in DHX58, ZNF281, EIF42A and HTRA2 genes were validated by quantitative amplicon sequencing (ROCHE 454®). Results: General hypermethylation was found in the CMA group compared to control children, while this effect was absent in the tolerant group. Methylation differences were, among others, found in regions of DHX58, ZNF281, EIF42A and HTRA2 genes. Several of these genes are known to be involved in immunological pathways and associated with other allergies. Conclusion: We show that epigenetic associations are involved in CMA. -
UCP1-Independent Thermogenesis in Brown/Beige Adipocytes: Classical Creatine Kinase/Phosphocreatine Shuttle Instead of “Futile Creatine Cycling”
UCP1-independent thermogenesis in brown/beige adipocytes: classical creatine kinase/phosphocreatine shuttle instead of “futile creatine cycling”. Theo Wallimann1*), Malgorzata Tokarska-Schlattner2) Laurence Kay2) and Uwe Schlattner2,3*) 1) Biology Dept. ETH-Zurich, Switzerland, emeritus, E-mail address: [email protected] 2) University Grenoble Alpes and Inserm U1055, Laboratory of Fundamental and Applied Bioenergetics & SFR Environmental and Systems Biology, Grenoble, France, E-mail address: [email protected] 3) Institut Universitaire de France (IUF), Paris, France *) joint corresponding authors Abstract Various studies have identified creatine kinase (CK) and creatine (Cr) as important players for thermogenesis. More recently, they have been specifically linked to UCP1-independent thermogenesis in beige/brown adipocytes, and a “Cr-driven futile cycle” within mitochondria was proposed as the mechanistic basis. Here, we provide a critical appraisal of such a mechanism, which would require a rather undefined phosphocreatine phosphatase. As alternative explanation, we suggest instead that the well-known functions of the CK system, that is ATP buffering and shuttling of high-energy phosphocreatine (PCr) from sites of ATP generation to sites of ATP utilization, are also working in brown/beige adipocytes. There, the CK/PCr system would be shunted between ATP generation, at the mitochondria and/or glycolysis, and ATP hydrolysis at the ER/SR. This would largely facilitate high-throughput calcium pumping by the ATP-dependent Ca2+ pump (SERCA) as described also in skeletal and cardiac muscle. This very CK/PCr system would then support adipocyte SERCA2b function and, in tandem with adipocyte ryanodine receptor (RyR2) and/or inositol 1,4,5- 2+ triphosphate receptor (IP3-R3), facilitate thermogenic futile Ca cycling that has been described to operate in UCP1-independent, but ATP-dependent non-shivering thermogenesis. -
GRIN3A and MAPT Stimulate Nerve Overgrowth in Macrodactyly
MOLECULAR MEDICINE REPORTS 14: 5637-5643, 2016 GRIN3A and MAPT stimulate nerve overgrowth in macrodactyly XU SHI1*, LU LU2*, XIU JIN3, BIN LIU4, XIGUANG SUN4, LAIJIN LU4 and YANFANG JIANG1,5 1Department of Genetic Diagnosis Center, Central Laboratory; Departments of 2Breast Surgery, 3Burn Surgery and 4Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, Jilin 130000; 5Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, Jilin 130000, P.R. China Received September 30, 2015; Accepted October 12, 2016 DOI: 10.3892/mmr.2016.5923 Abstract. As an uncommon and congenital condition, to abnormal nerve proliferation and underpin the pathogenesis macrodactyly is characterized by an increase in the size of all of macrodactyly, and provide potential application targets in the elements or structures of the digits or toes; however, the nerve tissue regeneration engineering. underlying pathogenesis remains to be fully elucidated. In the present study, the gene expression profiles of abnormal nerves Introduction were examined in three patients with macrodactyly using microarray analysis to identify potential genes contributing Macrodactyly is an uncommon congenital condition character- to nerve overgrowth. Gene expression profiling in the nerve ized by an increase in the size of all the elements or structures tissue samples were scanned using the microarray and the of the digits or toes, including phalanges, tendons, vessels, differentially expressed genes were verified at the transcrip- subcutaneous fat and finger nails. The malformation often tion level using reverse transcription-quantitative polymerase occurs unilaterally or asymmetrically and affects more than chain reaction analysis. Western blot analysis was used to one digit or toe. -
Structural Basis for Phosphorylation and Lysine Acetylation Cross-Talk In
THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 289, NO. 37, pp. 25890–25906, September 12, 2014 © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A. Structural Basis for Phosphorylation and Lysine Acetylation Cross-talk in a Kinase Motif Associated with Myocardial Ischemia and Cardioprotection*□S Received for publication, February 4, 2014, and in revised form, June 29, 2014 Published, JBC Papers in Press, July 9, 2014, DOI 10.1074/jbc.M114.556035 Benjamin L. Parker‡§¶1, Nicholas E. Shepherdʈ2, Sophie Trefely§, Nolan J. Hoffman§¶, Melanie Y. Whiteʈ**2, Kasper Engholm-Keller**, Brett D. Hambly‡**, Martin R. Larsen‡‡, David E. James§¶**, and Stuart J. Cordwell‡ʈ**3 From the ‡Discipline of Pathology, School of Medical Sciences, University of Sydney, Sydney 2006, Australia, the §Diabetes and Obesity Program, ¶Biological Mass Spectrometry Unit, Garvan Institute of Medical Research, 2010 Australia , the ʈSchool of Molecular Bioscience and the **Charles Perkins Centre, University of Sydney, Sydney 2006, Australia, and the ‡‡Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark Background: Myocardial ischemia and cardioprotection induce signal networks mediated by post-translational modification. Results: Phosphorylation sites altered by ischemia and/or cardioprotection were influenced by inhibition of lysine acetylation consistent with cross-talk. Conclusion: Lysine acetylation induces proximal dephosphorylation in a kinase motif by salt bridge inhibition. Significance: Cross-talk is likely to be an important aspect of signaling during ischemia and cardioprotection. Myocardial ischemia and cardioprotection by ischemic pre- Prolonged blockage of coronary blood flow (ischemia), even conditioning induce signal networks aimed at survival or cell with subsequent restoration (reperfusion), may result in death if the ischemic period is prolonged. -
Parallel High Throughput RNA Interference Screens Identify PINK1
Author Manuscript Published OnlineFirst on January 17, 2011; DOI: 10.1158/0008-5472.CAN-10-2836 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Parallel High Throughput RNA interference Screens Identify PINK1 as a Potential Therapeutic Target for the Treatment of DNA Mismatch Repair Deficient Cancers Sarah A. Martin1,2,3,4 Madeleine Hewish1,2,4, David Sims2, 2 1,2 Christopher J. Lord * and Alan Ashworth * 1Cancer Research UK Gene Function and Regulation Group 2The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London, SW3 6JB, UK 3Current address: Centre for Molecular Oncology and Imaging, Institute of Cancer, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, EC1M 6BQ 4Authors contributed equally to this work *Corresponding Authors: Christopher J. Lord & Alan Ashworth Email: [email protected], [email protected] Keywords: PINK1, oxidative damage, mitochondria, MLH1, MSH2, MSH6 Downloaded from cancerres.aacrjournals.org on October 1, 2021. © 2011 American Association for Cancer Research. Author Manuscript Published OnlineFirst on January 17, 2011; DOI: 10.1158/0008-5472.CAN-10-2836 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. MMR and PINK1 synthetic lethality 2 Abstract Synthetic lethal approaches to cancer treatment have the potential to deliver relatively large therapeutic windows and therefore significant patient benefit. To identify potential therapeutic approaches for cancers deficient in DNA mismatch repair (MMR), we have carried out parallel high throughput RNA interference screens using tumour cell models of MSH2 and MLH1-related MMR deficiency. -
Supplementary Data
Supplementary Fig. 1 A B Responder_Xenograft_ Responder_Xenograft_ NON- NON- Lu7336, Vehicle vs Lu7466, Vehicle vs Responder_Xenograft_ Responder_Xenograft_ Sagopilone, Welch- Sagopilone, Welch- Lu7187, Vehicle vs Lu7406, Vehicle vs Test: 638 Test: 600 Sagopilone, Welch- Sagopilone, Welch- Test: 468 Test: 482 Responder_Xenograft_ NON- Lu7860, Vehicle vs Responder_Xenograft_ Sagopilone, Welch - Lu7558, Vehicle vs Test: 605 Sagopilone, Welch- Test: 333 Supplementary Fig. 2 Supplementary Fig. 3 Supplementary Figure S1. Venn diagrams comparing probe sets regulated by Sagopilone treatment (10mg/kg for 24h) between individual models (Welsh Test ellipse p-value<0.001 or 5-fold change). A Sagopilone responder models, B Sagopilone non-responder models. Supplementary Figure S2. Pathway analysis of genes regulated by Sagopilone treatment in responder xenograft models 24h after Sagopilone treatment by GeneGo Metacore; the most significant pathway map representing cell cycle/spindle assembly and chromosome separation is shown, genes upregulated by Sagopilone treatment are marked with red thermometers. Supplementary Figure S3. GeneGo Metacore pathway analysis of genes differentially expressed between Sagopilone Responder and Non-Responder models displaying –log(p-Values) of most significant pathway maps. Supplementary Tables Supplementary Table 1. Response and activity in 22 non-small-cell lung cancer (NSCLC) xenograft models after treatment with Sagopilone and other cytotoxic agents commonly used in the management of NSCLC Tumor Model Response type -
Bioinformatics Analysis of Mitochondrial Disease
BIOINFORMATICS ANALYSIS OF MITOCHONDRIAL DISEASE By Kieren Lythgow Bsc (Hons), MRes Thesis submitted to the University of Newcastle upon Tyne in candidature for the degree of Doctor of Philosophy 2010 Abstract Several bioinformatic methods have been developed to aid the identification of novel nuclear-mitochondrial genes involved in disease. Previous research has aimed to increase the sensitivity and specificity of these predictions through a combination of available techniques. This investigation shows the optimum sensitivity and specificity can be achieved by carefully selecting seven specific classifiers in combination. The results also show that increasing the number of classifiers even further can paradoxically decrease the sensitivity and specificity of a prediction. Additionally, text mining applications are playing a huge role in disease candidate gene identification providing resources for interpreting the vast quantities of biomedical literature currently available. A work- flow resource was developed identifying a number of genes potentially associated with Lebers Hereditary Optic Neuropathy (LHON). This included specific orthologues in mouse displaying a potential association to LHON not annotated as such in humans. Mitochondrial DNA (mtDNA) fragments have been transferred to the human nu- clear genome over evolutionary time. These insertions were compared to an existing database of 263 mtDNA deletions to highlight any associated mechanisms governing DNA loss from mitochondria. Flanking regions were also screened within the nuclear genome that surrounded these insertions for transposable elements, GC content and mitochondrial genes. No obvious association was found relating NUMTs to mtDNA deletions. NUMTs do not appear to be distributed throughout the genome via trans- position and integrate predominantly in areas of low %GC with low gene content. -
Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva
UCSF UC San Francisco Previously Published Works Title Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva. Permalink https://escholarship.org/uc/item/95h5g8mq Journal Cell reports, 33(7) ISSN 2211-1247 Authors Saitou, Marie Gaylord, Eliza A Xu, Erica et al. Publication Date 2020-11-01 DOI 10.1016/j.celrep.2020.108402 Peer reviewed eScholarship.org Powered by the California Digital Library University of California HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Cell Rep Manuscript Author . Author manuscript; Manuscript Author available in PMC 2020 November 30. Published in final edited form as: Cell Rep. 2020 November 17; 33(7): 108402. doi:10.1016/j.celrep.2020.108402. Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva Marie Saitou1,2,3, Eliza A. Gaylord4, Erica Xu1,7, Alison J. May4, Lubov Neznanova5, Sara Nathan4, Anissa Grawe4, Jolie Chang6, William Ryan6, Stefan Ruhl5,*, Sarah M. Knox4,*, Omer Gokcumen1,8,* 1Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, NY, U.S.A 2Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, U.S.A 3Faculty of Biosciences, Norwegian University of Life Sciences, Ås, Viken, Norway 4Program in Craniofacial Biology, Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco, CA, U.S.A 5Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY, U.S.A 6Department of Otolaryngology, School of Medicine, University of California, San Francisco, CA, U.S.A 7Present address: Weill-Cornell Medical College, Physiology and Biophysics Department 8Lead Contact SUMMARY Salivary proteins are essential for maintaining health in the oral cavity and proximal digestive tract, and they serve as potential diagnostic markers for monitoring human health and disease. -
The Genome-Wide Landscape of Copy Number Variations in the MUSGEN Study Provides Evidence for a Founder Effect in the Isolated Finnish Population
European Journal of Human Genetics (2013) 21, 1411–1416 & 2013 Macmillan Publishers Limited All rights reserved 1018-4813/13 www.nature.com/ejhg ARTICLE The genome-wide landscape of copy number variations in the MUSGEN study provides evidence for a founder effect in the isolated Finnish population Chakravarthi Kanduri1, Liisa Ukkola-Vuoti1, Jaana Oikkonen1, Gemma Buck2, Christine Blancher2, Pirre Raijas3, Kai Karma4, Harri La¨hdesma¨ki5 and Irma Ja¨rvela¨*,1 Here we characterized the genome-wide architecture of copy number variations (CNVs) in 286 healthy, unrelated Finnish individuals belonging to the MUSGEN study, where molecular background underlying musical aptitude and related traits are studied. By using Illumina HumanOmniExpress-12v.1.0 beadchip, we identified 5493 CNVs that were spread across 467 different cytogenetic regions, spanning a total size of 287.83 Mb (B9.6% of the human genome). Merging the overlapping CNVs across samples resulted in 999 discrete copy number variable regions (CNVRs), of which B6.9% were putatively novel. The average number of CNVs per person was 20, whereas the average size of CNV per locus was 52.39 kb. Large CNVs (41 Mb) were present in 4% of the samples. The proportion of homozygous deletions in this data set (B12.4%) seemed to be higher when compared with three other populations. Interestingly, several CNVRs were significantly enriched in this sample set, whereas several others were totally depleted. For example, a CNVR at chr2p22.1 intersecting GALM was more common in this population (P ¼ 3.3706 Â 10 À44) than in African and other European populations. The enriched CNVRs, however, showed no significant association with music-related phenotypes. -
A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family
Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2018 A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family Linda Molla Follow this and additional works at: https://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Linda Molla June 2018 © Copyright by Linda Molla 2018 A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY Linda Molla, Ph.D. The Rockefeller University 2018 APOBEC2 is a member of the AID/APOBEC cytidine deaminase family of proteins. Unlike most of AID/APOBEC, however, APOBEC2’s function remains elusive. Previous research has implicated APOBEC2 in diverse organisms and cellular processes such as muscle biology (in Mus musculus), regeneration (in Danio rerio), and development (in Xenopus laevis). APOBEC2 has also been implicated in cancer. However the enzymatic activity, substrate or physiological target(s) of APOBEC2 are unknown. For this thesis, I have combined Next Generation Sequencing (NGS) techniques with state-of-the-art molecular biology to determine the physiological targets of APOBEC2. Using a cell culture muscle differentiation system, and RNA sequencing (RNA-Seq) by polyA capture, I demonstrated that unlike the AID/APOBEC family member APOBEC1, APOBEC2 is not an RNA editor. Using the same system combined with enhanced Reduced Representation Bisulfite Sequencing (eRRBS) analyses I showed that, unlike the AID/APOBEC family member AID, APOBEC2 does not act as a 5-methyl-C deaminase. -
(12) Patent Application Publication (10) Pub. No.: US 2003/0198970 A1 Roberts (43) Pub
US 2003O19897OA1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0198970 A1 Roberts (43) Pub. Date: Oct. 23, 2003 (54) GENOSTICS clinical trials on groups or cohorts of patients. This group data is used to derive a Standardised method of treatment (75) Inventor: Gareth Wyn Roberts, Cambs (GB) which is Subsequently applied on an individual basis. There is considerable evidence that a significant factor underlying Correspondence Address: the individual variability in response to disease, therapy and FINNEGAN, HENDERSON, FARABOW, prognosis lies in a person's genetic make-up. There have GARRETT & DUNNER been numerous examples relating that polymorphisms LLP within a given gene can alter the functionality of the protein 1300 ISTREET, NW encoded by that gene thus leading to a variable physiological WASHINGTON, DC 20005 (US) response. In order to bring about the integration of genomics into medical practice and enable design and building of a (73) Assignee: GENOSTIC PHARMA LIMITED technology platform which will enable the everyday practice (21) Appl. No.: 10/206,568 of molecular medicine a way must be invented for the DNA Sequence data to be aligned with the identification of genes (22) Filed: Jul. 29, 2002 central to the induction, development, progression and out come of disease or physiological States of interest. Accord Related U.S. Application Data ing to the invention, the number of genes and their configu rations (mutations and polymorphisms) needed to be (63) Continuation of application No. 09/325,123, filed on identified in order to provide critical clinical information Jun. 3, 1999, now abandoned. concerning individual prognosis is considerably less than the 100,000 thought to comprise the human genome.