DOCSLIB.ORG

Bioinformatic Gene Analysis for Potential Biomarkers And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bioinformatic Gene Analysis for Potential Biomarkers And Zou et al. J Transl Med (2019) 17:45 https://doi.org/10.1186/s12967-019-1790-x Journal of Translational Medicine RESEARCH Open Access Bioinformatic gene analysis for potential biomarkers and therapeutic targets of atrial fbrillation-related stroke Rongjun Zou1†, Dingwen Zhang1†, Lei Lv1†, Wanting Shi2, Zijiao Song3, Bin Yi1, Bingjia Lai4, Qian Chen5, Songran Yang6,7* and Ping Hua1* Abstract Background: Atrial fbrillation (AF) is one of the most prevalent sustained arrhythmias, however, epidemiological data may understate its actual prevalence. Meanwhile, AF is considered to be a major cause of ischemic strokes due to irregular heart-rhythm, coexisting chronic vascular infammation, and renal insufciency, and blood stasis. We studied co-expressed genes to understand relationships between atrial fbrillation (AF) and stroke and reveal potential biomarkers and therapeutic targets of AF-related stroke. Methods: AF-and stroke-related diferentially expressed genes (DEGs) were identifed via bioinformatic analysis Gene Expression Omnibus (GEO) datasets GSE79768 and GSE58294, respectively. Subsequently, extensive target prediction and network analyses methods were used to assess protein–protein interaction (PPI) networks, Gene Ontology (GO) terms and pathway enrichment for DEGs, and co-expressed DEGs coupled with corresponding predicted miRNAs involved in AF and stroke were assessed as well. Results: We identifed 489, 265, 518, and 592 DEGs in left atrial specimens and cardioembolic stroke blood samples at < 3, 5, and 24 h, respectively. LRRK2, CALM1, CXCR4, TLR4, CTNNB1, and CXCR2 may be implicated in AF and the hub- genes of CD19, FGF9, SOX9, GNGT1, and NOG may be associated with stroke. Finally, co-expressed DEGs of ZNF566, PDZK1IP1, ZFHX3, and PITX2 coupled with corresponding predicted miRNAs, especially miR-27a-3p, miR-27b-3p, and miR-494-3p may be signifcantly associated with AF-related stroke. Conclusion: AF and stroke are related and ZNF566, PDZK1IP1, ZFHX3, and PITX2 genes are signifcantly associated with novel biomarkers involved in AF-related stroke. Keywords: Gene analysis, Biomarkers, Atrial fbrillation-related stroke Background 80-years-of-age [1, 2]. However, epidemiological data Atrial fbrillation (AF) is one of the most prevalent may understate its actual prevalence, because 40% of sustained arrhythmias, having an age-adjusted hospi- patients are asymptomatic and remain undiagnosed with talization incidence of 1–4% of the general population subclinical AF [3]. Tere is also evidence that patients and an prevalence rising of > 13% for those older than with AF have signifcantly increased cardiovascular- related morbidity, given its association with atrial and ventricular mechanical or electrical failure, structural *Correspondence: [email protected]; [email protected] †Rongjun Zou, Dingwen Zhang and Lei Lv contributed equally to this and hemodynamic alterations, and thromboembolic article events [3]. 1 Department of Cardio-Vascular Surgery, Sun Yat-sen Memorial Hospital, Stroke is the leading cause of disability and death and Sun Yat-sen University, Guangzhou 510120, China 6 The Biobank of Sun Yat-sen Memorial Hospital, Sun Yat-sen University, has an estimated incidence of 3.73 (95% CI 3.51–3.96) Guangzhou 510120, China per 1000 person-years among black- and white- adults in Full list of author information is available at the end of the article an atherosclerosis risk in communities (ARIC) cohort [4]. © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Zou et al. J Transl Med (2019) 17:45 Page 2 of 12 Furthermore, global increases in stroke prevalence plus Methods stroke-related disability and mortality associated with Materials and methods aging will increase [5, 6]. Tus, we may not now know the GSE79768 and GSE58294 datasets were downloaded actual true burden of stroke due to limits in brain imag- from GEO (http://www.ncbi.nlm.nih.gov/geo/) [13] and ing identifcation in < 10 mm small hypointense areas and expression profling arrays were generated using GPL570 silent infarctions for 28% of those patients older than (HG-U133_Plus_2) Afymetrix Human Genome U133 65-years-of-age [7]. AF is commonly classifed as parox- Plus 2.0 Array (Afymetrix, Santa Clara, CA). Addition- ysmal, persistent or permanent, or new onset arrhythmia ally, the GSE79768 dataset, including 26 specimens with basing on the present continuous time, which mainly paired left atrial (LA) and right atrial (RA) tissue obtained included that paroxysmal AF was self-terminates within from 13 patients was used to identify diferential LA- 7 days, while persistent AF was lasts longer than 7 days or to-RA gene expression and molecular mechanisms needs cardioversion, and usually has lasted for 3 months for patients with persistent AF or sinus rhythm (SR) [8]. As we all kwon, AF is considering to be a major cause abnormalities and we describe potential mechanisms of of ischemic strokes due to irregular heart-rhythm, coex- AF-related remodeling in the LA and the relationship isting chronic vascular infammation, and renal insuf- between LA arrhythmogenesis and thrombogenesis. In fciency, and blood stasis. According to Rivaroxaban this study, persistent AF patients has lasts continuously Once Daily Oral Direct Factor Xa Inhibition Compared for > 6 months, while the SR patients had no evidence of With Vitamin K Antagonism for Prevention of Stroke AF clinically and any anti-arrhythmic drug history. Blood and Embolism Trial in Atrial Fibrillation (ROCKET-AF) samples of GSE58294 were collected from cardioembolic trial study, Steinberg et al. [9] suggested that the par- stroke (N = 69) and control patents (N = 23) at < 3, 5, and oxysmal AF patients carrying a lower adjusted rate of 24 h. stroke or systemic embolism (adjusted HR: 0.78, 95% CI Data processing 0.61–0.99, P = 0.045), all-cause mortality (adjusted HR: 0.79, 95% CI 0.67–0.94, P = 0.006), and the composite of R packages of “afy”, “afyPLM”, and “limma” (http://www. stroke or systemic embolism or death (adjusted HR: 0.82, bioco nduct or.org/packa ges/relea se/bioc/html/afy.html), 95% CI 0.71–0.94, P = 0.005) than persistent AF patients provided by a bioconductor project [14], were applied after adjusted efcacy and safety outcomes. According to assess GSE79768 and GSE58294 RAW datasets. We to the Oxford vascular study (OXVASC), nearly 43.9% of used background correction, quantile normalization, ischemic strokes were associated with AF among patients probe summarization and log2-transformation, to create 80 years-of-age or older who had a threefold increase in a robust multi-array average (RMA), a log-transformed AF in the past 3 decades [10]. However, this assumption perfect match, and a mismatch probe (PM and MM) has been challenged by the atrial fbrillation reduction methods. Te Benjamini-Hochberg method was used atrial pacing trial (ASSERT) which identifed a tempo- to adjust original p-values, and the false discovery rate ral association between subclinical AF and stroke risk (FDR) procedure was used to calculate fold-changes (FC). among patients with implantable pacemakers and def- Genes expression values of the|log2 FC| > 1and adjusted brillators. Tey reported that only 8% and 16% of patients p < 0.05 were used for fltering AF-DEGs. However, the had an association between pre-detected and post- |log2 FC| > 1.5 and adjusted p < 0.05 were used to identify detected AF within months of stroke or systemic embo- stroke-DEGs, given that blood sample specifcity pointed lism, respectively [11]. Of note, AF is often intermittent to many genes. Additionally, we calculated and made and asymptomatic, and presents as an electromechani- Venn diagrams for co-DEGs for AF- and stroke-DEGs. cal disassociation of atrial fbrillation. Clinically, current Finally, we applied online prediction tools utilizing stroke risk scores and traditional diagnosis with an elec- microRNA Data Integration Portal (mirDIP) (http:// trocardiogram are practical, while the limitation of pre- ophid .utoro nto.ca/mirDI P) [15], miRDB (http://mirdb dict stroke risk accurately in individual AF patients was .org/) [16], TargetScan (v7.1; http://www.targe tscan .org/ signifcantly identifed, especially in persistent AF which vert_71/) [17], and DIANA Tools (http://diana .imis.athen carrying a higher risk of stroke or systemic embolism a-innov ation .gr/Diana Tools /) [18], to predict poten- and all-cause mortality [12]. In this study, we identifed tial microRNA targeting. Subsequently, we used the co-expressed diferentially expressed genes (co-DEGs) of mirDIP, miRDB, TargetScan, and Diana Tools software persistent AF and stroke and elucidated molecular mech- to predict which of the selected miRNAs could target co- anisms and pathology of AF-related DEGs (AF-DEGs) DEGs. We determined 5 top candidate miRNAs based on and stroke-related DEGs (stroke-DEGs). Finally, we higher predicted scores for ≥ 3 prediction tools for each provide a bioinformatic analysis of DEGs and predicted co-DEG. microRNAs (miRNAs) for AF patients prone to stroke. Zou et al. J Transl Med (2019) 17:45 Page 3 of 12 Identifcation of protein–protein interaction (PPI) networks AF- and stroke-DEGs were confrmed. We found 489 of DEGs DEGs in LA specimens of AF patients compared with PPI networks of AF- and stroke-DEGs were analyzed SR patients, including 428 down-regulated genes and using the search tool for the retrieval of interacting genes 61 up-regulated genes. However, total of 265, 518, and (STRING database, V10.5; http://strin g-db.org/) that 592 DEGs were identifed following the time points of predicted protein functional associations and protein– less than 3, 5, and 24 h after stroke, respectively.
Load more

Recommended publications
  • Genome-Wide Analysis of Allele-Specific Expression Patterns in Seventeen Tissues of Korean Cattle (Hanwoo)
    animals Article Genome-Wide Analysis of Allele-Specific Expression Patterns in Seventeen Tissues of Korean Cattle (Hanwoo) Kyu-Sang Lim 1 , Sun-Sik Chang 2, Bong-Hwan Choi 3, Seung-Hwan Lee 4, Kyung-Tai Lee 3 , Han-Ha Chai 3, Jong-Eun Park 3 , Woncheoul Park 3 and Dajeong Lim 3,* 1 Department of Animal Science, Iowa State University, Ames, IA 50011, USA; [email protected] 2 Hanwoo Research Institute, National Institute of Animal Science, Rural Development Administration, Pyeongchang 25340, Korea; [email protected] 3 Animal Genomics and Bioinformatics Division, National Institute of Animal Science, Rural Development Administration, Wanju 55365, Korea; [email protected] (B.-H.C.); [email protected] (K.-T.L.); [email protected] (H.-H.C.); [email protected] (J.-E.P.); [email protected] (W.P.) 4 Division of Animal and Dairy Science, Chungnam National University, Daejeon 34134, Korea; [email protected] * Correspondence: [email protected] Received: 26 July 2019; Accepted: 23 September 2019; Published: 26 September 2019 Simple Summary: Allele-specific expression (ASE) is the biased allelic expression of genetic variants within the gene. Recently, the next-generation sequencing (NGS) technologies allowed us to detect ASE genes at a transcriptome-wide level. It is essential for the understanding of animal development, cellular programming, and the effect on their complexity because ASE shows developmental, tissue, or species-specific patterns. However, these aspects of ASE still have not been annotated well in farm animals and most studies were conducted mainly at the fetal stages. Hence, the current study focuses on detecting ASE genes in 17 tissues in adult cattle.
    [Show full text]
  • Edinburgh Research Explorer
    Edinburgh Research Explorer International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list Citation for published version: Davenport, AP, Alexander, SPH, Sharman, JL, Pawson, AJ, Benson, HE, Monaghan, AE, Liew, WC, Mpamhanga, CP, Bonner, TI, Neubig, RR, Pin, JP, Spedding, M & Harmar, AJ 2013, 'International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands', Pharmacological reviews, vol. 65, no. 3, pp. 967-86. https://doi.org/10.1124/pr.112.007179 Digital Object Identifier (DOI): 10.1124/pr.112.007179 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: Pharmacological reviews Publisher Rights Statement: U.S. Government work not protected by U.S. copyright General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 02. Oct. 2021 1521-0081/65/3/967–986$25.00 http://dx.doi.org/10.1124/pr.112.007179 PHARMACOLOGICAL REVIEWS Pharmacol Rev 65:967–986, July 2013 U.S.
    [Show full text]
  • Potassium Channels in Epilepsy
    Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press Potassium Channels in Epilepsy Ru¨diger Ko¨hling and Jakob Wolfart Oscar Langendorff Institute of Physiology, University of Rostock, Rostock 18057, Germany Correspondence: [email protected] This review attempts to give a concise and up-to-date overview on the role of potassium channels in epilepsies. Their role can be defined from a genetic perspective, focusing on variants and de novo mutations identified in genetic studies or animal models with targeted, specific mutations in genes coding for a member of the large potassium channel family. In these genetic studies, a demonstrated functional link to hyperexcitability often remains elusive. However, their role can also be defined from a functional perspective, based on dy- namic, aggravating, or adaptive transcriptional and posttranslational alterations. In these cases, it often remains elusive whether the alteration is causal or merely incidental. With 80 potassium channel types, of which 10% are known to be associated with epilepsies (in humans) or a seizure phenotype (in animals), if genetically mutated, a comprehensive review is a challenging endeavor. This goal may seem all the more ambitious once the data on posttranslational alterations, found both in human tissue from epilepsy patients and in chronic or acute animal models, are included. We therefore summarize the literature, and expand only on key findings, particularly regarding functional alterations found in patient brain tissue and chronic animal models. INTRODUCTION TO POTASSIUM evolutionary appearance of voltage-gated so- CHANNELS dium (Nav)andcalcium (Cav)channels, Kchan- nels are further diversified in relation to their otassium (K) channels are related to epilepsy newer function, namely, keeping neuronal exci- Psyndromes on many different levels, ranging tation within limits (Anderson and Greenberg from direct control of neuronal excitability and 2001; Hille 2001).
    [Show full text]
  • Transcriptome Analyses of Rhesus Monkey Pre-Implantation Embryos Reveal A
    Downloaded from genome.cshlp.org on September 23, 2021 - Published by Cold Spring Harbor Laboratory Press Transcriptome analyses of rhesus monkey pre-implantation embryos reveal a reduced capacity for DNA double strand break (DSB) repair in primate oocytes and early embryos Xinyi Wang 1,3,4,5*, Denghui Liu 2,4*, Dajian He 1,3,4,5, Shengbao Suo 2,4, Xian Xia 2,4, Xiechao He1,3,6, Jing-Dong J. Han2#, Ping Zheng1,3,6# Running title: reduced DNA DSB repair in monkey early embryos Affiliations: 1 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 2 Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China 3 Yunnan Key Laboratory of Animal Reproduction, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 4 University of Chinese Academy of Sciences, Beijing, China 5 Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China 6 Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China * Xinyi Wang and Denghui Liu contributed equally to this work 1 Downloaded from genome.cshlp.org on September 23, 2021 - Published by Cold Spring Harbor Laboratory Press # Correspondence: Jing-Dong J. Han, Email: [email protected]; Ping Zheng, Email: [email protected] Key words: rhesus monkey, pre-implantation embryo, DNA damage 2 Downloaded from genome.cshlp.org on September 23, 2021 - Published by Cold Spring Harbor Laboratory Press ABSTRACT Pre-implantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA) and cell fate commitment.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Supplementary Table 3 Complete List of RNA-Sequencing Analysis of Gene Expression Changed by ≥ Tenfold Between Xenograft and Cells Cultured in 10%O2
    Supplementary Table 3 Complete list of RNA-Sequencing analysis of gene expression changed by ≥ tenfold between xenograft and cells cultured in 10%O2 Expr Log2 Ratio Symbol Entrez Gene Name (culture/xenograft) -7.182 PGM5 phosphoglucomutase 5 -6.883 GPBAR1 G protein-coupled bile acid receptor 1 -6.683 CPVL carboxypeptidase, vitellogenic like -6.398 MTMR9LP myotubularin related protein 9-like, pseudogene -6.131 SCN7A sodium voltage-gated channel alpha subunit 7 -6.115 POPDC2 popeye domain containing 2 -6.014 LGI1 leucine rich glioma inactivated 1 -5.86 SCN1A sodium voltage-gated channel alpha subunit 1 -5.713 C6 complement C6 -5.365 ANGPTL1 angiopoietin like 1 -5.327 TNN tenascin N -5.228 DHRS2 dehydrogenase/reductase 2 leucine rich repeat and fibronectin type III domain -5.115 LRFN2 containing 2 -5.076 FOXO6 forkhead box O6 -5.035 ETNPPL ethanolamine-phosphate phospho-lyase -4.993 MYO15A myosin XVA -4.972 IGF1 insulin like growth factor 1 -4.956 DLG2 discs large MAGUK scaffold protein 2 -4.86 SCML4 sex comb on midleg like 4 (Drosophila) Src homology 2 domain containing transforming -4.816 SHD protein D -4.764 PLP1 proteolipid protein 1 -4.764 TSPAN32 tetraspanin 32 -4.713 N4BP3 NEDD4 binding protein 3 -4.705 MYOC myocilin -4.646 CLEC3B C-type lectin domain family 3 member B -4.646 C7 complement C7 -4.62 TGM2 transglutaminase 2 -4.562 COL9A1 collagen type IX alpha 1 chain -4.55 SOSTDC1 sclerostin domain containing 1 -4.55 OGN osteoglycin -4.505 DAPL1 death associated protein like 1 -4.491 C10orf105 chromosome 10 open reading frame 105 -4.491
    [Show full text]
  • Molecular Mechanisms Involved in the Regulation of Agouti-Related Peptide and Neuropeptide Y by Endocrine Disrupting Chemical Bisphenol a in Hypothalamic Neurons
    Molecular mechanisms involved in the regulation of agouti-related peptide and neuropeptide Y by endocrine disrupting chemical bisphenol A in hypothalamic neurons by Neruja Loganathan A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Physiology University of Toronto © Copyright by Neruja Loganathan 2021 Molecular mechanisms involved in the regulation of agouti-related peptide and neuropeptide Y by endocrine disrupting chemical bisphenol A in hypothalamic neurons Neruja Loganathan Doctor of Philosophy Department of Physiology University of Toronto 2021 Abstract Bisphenol A (BPA), a ubiquitous endocrine disrupting chemical found in plastics and receipts, is a disruptor of reproductive function and is a known ‘obesogen’ as it is linked to increased body mass index in humans and leads to weight gain in animal models. The hypothalamus houses orexigenic NPY/AgRP neurons, which integrate peripheral hormones and nutritional signals, to increase food intake and decrease energy expenditure. NPY neurons are also afferent regulators of the hypothalamic-pituitary gonadal axis, and thus reproductive function. This thesis investigated whether the NPY/AgRP neurons, and particularly Npy and Agrp expression, are altered by BPA. We hypothesized that BPA increases Npy and Agrp gene expression in hypothalamic neurons and that this effect is mediated through nuclear receptor activation, induction of cellular stress and subsequent transcription factor activation or circadian dysregulation. We demonstrated that BPA increased Agrp mRNA expression in mHypoA-59 and mHypoE-41 cells. Inhibition of AMPK and knock-down of transcription factor ATF3 prevented the BPA-mediated increase in Agrp expression in the mHypoA-59 cells. ATF3 was also required for BPA-mediated increase in Npy in the mHypoE-41 cells.
    [Show full text]
  • A SARS-Cov-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
    A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing Supplementary Information Supplementary Discussion All SARS-CoV-2 protein and gene functions described in the subnetwork appendices, including the text below and the text found in the individual bait subnetworks, are based on the functions of homologous genes from other coronavirus species. These are mainly from SARS-CoV and MERS-CoV, but when available and applicable other related viruses were used to provide insight into function. The SARS-CoV-2 proteins and genes listed here were designed and researched based on the gene alignments provided by Chan et. al. 1 2020 .​ Though we are reasonably sure the genes here are well annotated, we want to note that not every ​ protein has been verified to be expressed or functional during SARS-CoV-2 infections, either in vitro or in vivo. ​ ​ In an effort to be as comprehensive and transparent as possible, we are reporting the sub-networks of these functionally unverified proteins along with the other SARS-CoV-2 proteins. In such cases, we have made notes within the text below, and on the corresponding subnetwork figures, and would advise that more caution be taken when examining these proteins and their molecular interactions. Due to practical limits in our sample preparation and data collection process, we were unable to generate data for proteins corresponding to Nsp3, Orf7b, and Nsp16. Therefore these three genes have been left out of the following literature review of the SARS-CoV-2 proteins and the protein-protein interactions (PPIs) identified in this study.
    [Show full text]
  • Supplemental Table 1. Complete Gene Lists and GO Terms from Figure 3C
    Supplemental Table 1. Complete gene lists and GO terms from Figure 3C. Path 1 Genes: RP11-34P13.15, RP4-758J18.10, VWA1, CHD5, AZIN2, FOXO6, RP11-403I13.8, ARHGAP30, RGS4, LRRN2, RASSF5, SERTAD4, GJC2, RHOU, REEP1, FOXI3, SH3RF3, COL4A4, ZDHHC23, FGFR3, PPP2R2C, CTD-2031P19.4, RNF182, GRM4, PRR15, DGKI, CHMP4C, CALB1, SPAG1, KLF4, ENG, RET, GDF10, ADAMTS14, SPOCK2, MBL1P, ADAM8, LRP4-AS1, CARNS1, DGAT2, CRYAB, AP000783.1, OPCML, PLEKHG6, GDF3, EMP1, RASSF9, FAM101A, STON2, GREM1, ACTC1, CORO2B, FURIN, WFIKKN1, BAIAP3, TMC5, HS3ST4, ZFHX3, NLRP1, RASD1, CACNG4, EMILIN2, L3MBTL4, KLHL14, HMSD, RP11-849I19.1, SALL3, GADD45B, KANK3, CTC- 526N19.1, ZNF888, MMP9, BMP7, PIK3IP1, MCHR1, SYTL5, CAMK2N1, PINK1, ID3, PTPRU, MANEAL, MCOLN3, LRRC8C, NTNG1, KCNC4, RP11, 430C7.5, C1orf95, ID2-AS1, ID2, GDF7, KCNG3, RGPD8, PSD4, CCDC74B, BMPR2, KAT2B, LINC00693, ZNF654, FILIP1L, SH3TC1, CPEB2, NPFFR2, TRPC3, RP11-752L20.3, FAM198B, TLL1, CDH9, PDZD2, CHSY3, GALNT10, FOXQ1, ATXN1, ID4, COL11A2, CNR1, GTF2IP4, FZD1, PAX5, RP11-35N6.1, UNC5B, NKX1-2, FAM196A, EBF3, PRRG4, LRP4, SYT7, PLBD1, GRASP, ALX1, HIP1R, LPAR6, SLITRK6, C16orf89, RP11-491F9.1, MMP2, B3GNT9, NXPH3, TNRC6C-AS1, LDLRAD4, NOL4, SMAD7, HCN2, PDE4A, KANK2, SAMD1, EXOC3L2, IL11, EMILIN3, KCNB1, DOK5, EEF1A2, A4GALT, ADGRG2, ELF4, ABCD1 Term Count % PValue Genes regulation of pathway-restricted GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, SMAD protein phosphorylation 9 6.34 1.31E-08 ENG pathway-restricted SMAD protein GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, phosphorylation
    [Show full text]
  • Role of the Wnt/ B-Catenin Pathway in Liver Development and Zonation
    University of Bath PHD Role of the Wnt/ -catenin Pathway in Liver Development and Zonation Shen Wen, Yeh Award date: 2012 Awarding institution: University of Bath Link to publication Alternative formats If you require this document in an alternative format, please contact: [email protected] General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 10. Oct. 2021 Role of the Wnt/ -catenin Pathway in Liver Development and Zonation YEH, SHENG-WEN A thesis submitted for the degree of Doctor of Philosophy University of Bath Department of Biology and Biochemistry September, 2012 COPYRIGHT Attention is drawn to the fact that copyright of this thesis rests with the author. A copy of this thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with the author and that they must not copy it or use material from it except as permitted by law or with the consent of the author.
    [Show full text]
  • Ck1δ Over-Expressing Mice Display ADHD-Like Behaviors, Frontostriatal Neuronal Abnormalities and Altered Expressions of ADHD-Candidate Genes
    Molecular Psychiatry (2020) 25:3322–3336 https://doi.org/10.1038/s41380-018-0233-z ARTICLE CK1δ over-expressing mice display ADHD-like behaviors, frontostriatal neuronal abnormalities and altered expressions of ADHD-candidate genes 1 1 1 2 1 1 1 Mingming Zhou ● Jodi Gresack ● Jia Cheng ● Kunihiro Uryu ● Lars Brichta ● Paul Greengard ● Marc Flajolet Received: 8 November 2017 / Revised: 4 July 2018 / Accepted: 18 July 2018 / Published online: 19 October 2018 © Springer Nature Limited 2018 Abstract The cognitive mechanisms underlying attention-deficit hyperactivity disorder (ADHD), a highly heritable disorder with an array of candidate genes and unclear genetic architecture, remain poorly understood. We previously demonstrated that mice overexpressing CK1δ (CK1δ OE) in the forebrain show hyperactivity and ADHD-like pharmacological responses to D- amphetamine. Here, we demonstrate that CK1δ OE mice exhibit impaired visual attention and a lack of D-amphetamine- induced place preference, indicating a disruption of the dopamine-dependent reward pathway. We also demonstrate the presence of abnormalities in the frontostriatal circuitry, differences in synaptic ultra-structures by electron microscopy, as 1234567890();,: 1234567890();,: well as electrophysiological perturbations of both glutamatergic and GABAergic transmission, as observed by altered frequency and amplitude of mEPSCs and mIPSCs. Furthermore, gene expression profiling by next-generation sequencing alone, or in combination with bacTRAP technology to study specifically Drd1a versus Drd2 medium spiny neurons, revealed that developmental CK1δ OE alters transcriptional homeostasis in the striatum, including specific alterations in Drd1a versus Drd2 neurons. These results led us to perform a fine molecular characterization of targeted gene networks and pathway analysis. Importantly, a large fraction of 92 genes identified by GWAS studies as associated with ADHD in humans are significantly altered in our mouse model.
    [Show full text]
  • Rabbit Anti-APLP2/FITC Conjugated Antibody
    SunLong Biotech Co.,LTD Tel: 0086-571- 56623320 Fax:0086-571- 56623318 E-mail:[email protected] www.sunlongbiotech.com Rabbit Anti-APLP2/FITC Conjugated antibody SL8462R-FITC Product Name: Anti-APLP2/FITC Chinese Name: FITC标记的淀粉样蛋白β前体样蛋白2抗体 amyloid beta (A4) precursor like protein 2; Amyloid like protein 2; amyloid precursor protein homolog HSD2; Amyloid protein homolog; Amyloid-like protein 2; APLP-2; Alias: Aplp2; APLP2_HUMAN; APPH; APPL2; CDEBP; CDEI box binding protein; CDEI box-binding protein. Organism Species: Rabbit Clonality: Polyclonal React Species: Human,Mouse,Rat,Chicken,Pig,Horse, IF=1:50-200 Applications: not yet tested in other applications. optimal dilutions/concentrations should be determined by the end user. Molecular weight: 80kDa Cellular localization: The cell membrane Form: Lyophilized or Liquid Concentration: 1mg/ml immunogen: KLH conjugated synthetic peptide derived from human APLP2 Lsotype: IgGwww.sunlongbiotech.com Purification: affinity purified by Protein A Storage Buffer: 0.01M TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol. Store 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: APLP2 is a human sperm membrane protein which contains a segment with high homology to the transmembrane-cytoplasmic domains of APP found in brain plaques of Product Detail: Alzheimer disease patients. The human amyloid precursor-like protein APLP2 is a highly conserved homolog of a sequence-specific DNA-binding mouse protein with an important function in the cell cycle.
    [Show full text]