Detecting Phenotype-Specific Interactions Between Biological Processes from Microarray Data and Annotations
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Wo 2010/075007 A2
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 1 July 2010 (01.07.2010) WO 2010/075007 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C12Q 1/68 (2006.01) G06F 19/00 (2006.01) kind of national protection available): AE, AG, AL, AM, C12N 15/12 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US2009/067757 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 11 December 2009 ( 11.12.2009) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, (26) Publication Language: English TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 12/3 16,877 16 December 2008 (16.12.2008) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): DODDS, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, W., Jean [US/US]; 938 Stanford Street, Santa Monica, TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, CA 90403 (US). -
BMC Genomics Biomed Central
BMC Genomics BioMed Central Research article Open Access Differential gene expression in femoral bone from red junglefowl and domestic chicken, differing for bone phenotypic traits Carl-Johan Rubin1, Johan Lindberg2, Carolyn Fitzsimmons3, Peter Savolainen2, Per Jensen4, Joakim Lundeberg2, Leif Andersson3,5 and Andreas Kindmark*1 Address: 1Department of Medical Sciences, Uppsala University, Sweden, 2Department of Gene Technology, School of Biotechnology, Royal Institute of Technology, Stockholm, Sweden, 3Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden, 4IFM Biology, Linköping University, SE-585 83, Linköping, Sweden and 5Department of Medical Biochemistry and Microbiology, Uppsala University, Box 597, SE-75124 Uppsala, Sweden Email: Carl-Johan Rubin - [email protected]; Johan Lindberg - [email protected]; Carolyn Fitzsimmons - [email protected]; Peter Savolainen - [email protected]; Per Jensen - [email protected]; Joakim Lundeberg - [email protected]; Leif Andersson - [email protected]; Andreas Kindmark* - [email protected] * Corresponding author Published: 2 July 2007 Received: 2 April 2007 Accepted: 2 July 2007 BMC Genomics 2007, 8:208 doi:10.1186/1471-2164-8-208 This article is available from: http://www.biomedcentral.com/1471-2164/8/208 © 2007 Rubin 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: Osteoporosis is frequently observed among aging hens from egg-producing strains (layers) of domestic chicken. -
Knowledge Management Enviroments for High Throughput Biology
Knowledge Management Enviroments for High Throughput Biology Abhey Shah A Thesis submitted for the degree of MPhil Biology Department University of York September 2007 Abstract With the growing complexity and scale of data sets in computational biology and chemoin- formatics, there is a need for novel knowledge processing tools and platforms. This thesis describes a newly developed knowledge processing platform that is different in its emphasis on architecture, flexibility, builtin facilities for datamining and easy cross platform usage. There exist thousands of bioinformatics and chemoinformatics databases, that are stored in many different forms with different access methods, this is a reflection of the range of data structures that make up complex biological and chemical data. Starting from a theoretical ba- sis, FCA (Formal Concept Analysis) an applied branch of lattice theory, is used in this thesis to develop a file system that automatically structures itself by it’s contents. The procedure of extracting concepts from data sets is examined. The system also finds appropriate labels for the discovered concepts by extracting data from ontological databases. A novel method for scaling non-binary data for use with the system is developed. Finally the future of integrative systems biology is discussed in the context of efficiently closed causal systems. Contents 1 Motivations and goals of the thesis 11 1.1 Conceptual frameworks . 11 1.2 Biological foundations . 12 1.2.1 Gene expression data . 13 1.2.2 Ontology . 14 1.3 Knowledge based computational environments . 15 1.3.1 Interfaces . 16 1.3.2 Databases and the character of biological data . -
Screening for Subtle Chromosomal Rearrangements in an Egyptian Sample of Children with Unexplained Mental Retardation
The Egyptian Journal of Medical Human Genetics (2011) 12, 63–68 Ain Shams University The Egyptian Journal of Medical Human Genetics www.ejmhg.eg.net www.sciencedirect.com ORIGINAL ARTICLE Screening for subtle chromosomal rearrangements in an Egyptian sample of children with unexplained mental retardation Rabah M. Shawky *, Farida El-Baz, Ezzat S. Elsobky, Solaf M. Elsayed, Eman Zaky, Riham M. El-Hossiny Faculty of Medicine, Ain Shams University, Cairo, Egypt Received 16 October 2010; accepted 5 December 2010 KEYWORDS Abstract Mental retardation is present in about 1–3% of individuals in the general population, but Idiopathic mental retarda- it can be explained in about half of the cases. A descriptive study was carried out to screen for subtle tion (IMR); chromosomal rearrangements in a group of Egyptian children with idiopathic mental retardation High resolution banding (IMR) to estimate its frequency if detected. The study enrolled 30 patients with IMR, with the per- (HRB); quisite criteria of being <18 years at referral, their IQ <70, and manifesting at least one of the cri- Fluorescent in situ hybrid- teria for selection of patients with subtelomeric abnormalities. Males were 63.3% and females were ization (FISH); 36.7%, with a mean age of 7.08 ± 4.22 years. Full history taking, thorough clinical examination, Subtelomeric chromosomal IQ, visual, and audiological assessment, brain CT scan, plasma aminogram, pelvi-abdominal ultra- rearrangement sonography, echocardiography, and cytogenetic evaluation using routine conventional karyotyp- ing, high resolution banding (HRB), and fluorescent in situ hybridization (FISH) technique with appropriate probes were carried out for all studied patients. All enrolled patients had apparently normal karyotypes within 450 bands resolution, except for one patient who had 46, XY, [del (18) (p11.2)]. -
Supplemental Table 1: Genes That Show Altered Expression in Hepg2 Cells in the Presence of Exogenously Added Let-7
Supplemental Table 1: Genes that show altered expression in HepG2 cells in the presence of exogenously added let-7 Gene Title Gene Symbol RefSeq Transcriptp- IDvalue(TREAp-TMENTvalue(Let7bS) - negativLog2 Reatio control1) (Let7b - negativp-value(Let7be control1) - negativLog2 Reatio control2) (Let7b - negative control2) aldo-keto reductase family 1, member D1 (delta 4-3-ketosteroid-5-beta-reductase) AKR1D1 NM_005989 3.28E-12 2.52E-12 -3.85007 3.59E-12 -3.73727 lin-28 homolog B (C. elegans) LIN28B NM_001004317 6.13E-15 8.29E-15 -3.29879 1.55E-15 -3.79656 high mobility group AT-hook 2 /// high mobility group AT-hook 2 HMGA2 NM_001015886 /// NM_0034833.74E-14 /// NM_0034844.29E-14 -3.06085 4.56E-14 -3.04538 HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2 HECW2 NM_020760 1.27E-13 6.65E-13 -2.94724 4.47E-12 -2.50907 cell division cycle 25A CDC25A NM_001789 /// NM_2015672.01E-11 7.32E-11 -2.88831 1.99E-11 -3.22735 hypothetical protein FLJ21986 FLJ21986 NM_024913 1.05E-09 5.19E-10 -2.80277 1.18E-09 -2.61084 solute carrier family 2 (facilitated glucose transporter), member 3 SLC2A3 NM_006931 1.59E-13 3.49E-13 -2.78111 1.84E-12 -2.41734 Transcribed locus --- --- 2.58E-13 1.08E-13 -2.59794 1.69E-13 -2.50248 Hypothetical protein LOC145786 LOC145786 --- 4.23E-12 1.07E-11 -2.58849 3.00E-12 -2.88135 Dicer1, Dcr-1 homolog (Drosophila) DICER1 NM_030621 /// NM_1774381.06E-08 4.37E-09 -2.5442 4.49E-09 -2.53796 mannose-binding lectin (protein C) 2, soluble (opsonic defect) MBL2 NM_000242 9.73E-10 1.48E-09 -2.53211 9.84E-10 -2.62363 cell -
Integrating Protein Copy Numbers with Interaction Networks to Quantify Stoichiometry in Mammalian Endocytosis
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.29.361196; this version posted October 29, 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-ND 4.0 International license. Integrating protein copy numbers with interaction networks to quantify stoichiometry in mammalian endocytosis Daisy Duan1, Meretta Hanson1, David O. Holland2, Margaret E Johnson1* 1TC Jenkins Department of Biophysics, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218. 2NIH, Bethesda, MD, 20892. *Corresponding Author: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.10.29.361196; this version posted October 29, 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-ND 4.0 International license. Abstract Proteins that drive processes like clathrin-mediated endocytosis (CME) are expressed at various copy numbers within a cell, from hundreds (e.g. auxilin) to millions (e.g. clathrin). Between cell types with identical genomes, copy numbers further vary significantly both in absolute and relative abundance. These variations contain essential information about each protein’s function, but how significant are these variations and how can they be quantified to infer useful functional behavior? Here, we address this by quantifying the stoichiometry of proteins involved in the CME network. We find robust trends across three cell types in proteins that are sub- vs super-stoichiometric in terms of protein function, network topology (e.g. -
Stroke Genetics and Genomics
Faculdade de Medicina da Universidade de Lisboa Unidade Neurológica de Investigação Clínica PhD Thesis Stroke Genetics and Genomics Tiago Krug Coelho Host Institution: Instituto Gulbenkian de Ciência Supervisor at Instituto Gulbenkian de Ciência: Doctor Sofia Oliveira Supervisor at Faculdade de Medicina da Universidade de Lisboa: Professor José Ferro PhD in Biomedical Sciences Specialization in Neurosciences 2010 Stroke Genetics and Genomics A ciência tem, de facto, um único objectivo: a verdade. Não esgota perfeitamente a sua tarefa se não descobre a causa do todo. Chiara Lubich i Stroke Genetics and Genomics ii Stroke Genetics and Genomics A impressão desta dissertação foi aprovada pela Comissão Coordenadora do Conselho Científico da Faculdade de Medicina de Lisboa em reunião de 28 de Setembro de 2010. iii Stroke Genetics and Genomics iv Stroke Genetics and Genomics As opiniões expressas são da exclusiva responsabilidade do seu autor. v Stroke Genetics and Genomics vi Stroke Genetics and Genomics Abstract ABSTRACT This project presents a comprehensive approach to the identification of new genes that influence the risk for developing stroke. Stroke is the leading cause of death in Portugal and the third leading cause of death in the developed world. It is even more disabling than lethal, and the persistent neurological impairment and physical disability caused by stroke have a very high socioeconomic cost. Moreover, the number of affected individuals is expected to increase with the current aging of the population. Stroke is a “brain attack” cutting off vital blood and oxygen to the brain cells and it is a complex disease resulting from environmental and genetic factors. -
Supplementary Table 1 Genes Tested in Qrt-PCR in Nfpas
Supplementary Table 1 Genes tested in qRT-PCR in NFPAs Gene Bank accession Gene Description number ABI assay ID a disintegrin-like and metalloprotease with thrombospondin type 1 motif 7 ADAMTS7 NM_014272.3 Hs00276223_m1 Rho guanine nucleotide exchange factor (GEF) 3 ARHGEF3 NM_019555.1 Hs00219609_m1 BCL2-associated X protein BAX NM_004324 House design Bcl-2 binding component 3 BBC3 NM_014417.2 Hs00248075_m1 B-cell CLL/lymphoma 2 BCL2 NM_000633 House design Bone morphogenetic protein 7 BMP7 NM_001719.1 Hs00233476_m1 CCAAT/enhancer binding protein (C/EBP), alpha CEBPA NM_004364.2 Hs00269972_s1 coxsackie virus and adenovirus receptor CXADR NM_001338.3 Hs00154661_m1 Homo sapiens Dicer1, Dcr-1 homolog (Drosophila) (DICER1) DICER1 NM_177438.1 Hs00229023_m1 Homo sapiens dystonin DST NM_015548.2 Hs00156137_m1 fms-related tyrosine kinase 3 FLT3 NM_004119.1 Hs00174690_m1 glutamate receptor, ionotropic, N-methyl D-aspartate 1 GRIN1 NM_000832.4 Hs00609557_m1 high-mobility group box 1 HMGB1 NM_002128.3 Hs01923466_g1 heterogeneous nuclear ribonucleoprotein U HNRPU NM_004501.3 Hs00244919_m1 insulin-like growth factor binding protein 5 IGFBP5 NM_000599.2 Hs00181213_m1 latent transforming growth factor beta binding protein 4 LTBP4 NM_001042544.1 Hs00186025_m1 microtubule-associated protein 1 light chain 3 beta MAP1LC3B NM_022818.3 Hs00797944_s1 matrix metallopeptidase 17 MMP17 NM_016155.4 Hs01108847_m1 myosin VA MYO5A NM_000259.1 Hs00165309_m1 Homo sapiens nuclear factor (erythroid-derived 2)-like 1 NFE2L1 NM_003204.1 Hs00231457_m1 oxoglutarate (alpha-ketoglutarate) -
Microrna Regulation and Human Protein Kinase Genes
MICRORNA REGULATION AND HUMAN PROTEIN KINASE GENES REQUIRED FOR INFLUENZA VIRUS REPLICATION by LAUREN ELIZABETH ANDERSEN (Under the Direction of Ralph A. Tripp) ABSTRACT Human protein kinases (HPKs) have profound effects on cellular responses. To better understand the role of HPKs and the signaling networks that influence influenza replication, a siRNA screen of 720 HPKs was performed. From the screen, 17 “hit” HPKs (NPR2, MAP3K1, DYRK3, EPHA6, TPK1, PDK2, EXOSC10, NEK8, PLK4, SGK3, NEK3, PANK4, ITPKB, CDC2L5, CALM2, PKN3, and HK2) were validated as important for A/WSN/33 influenza virus replication, and 6 HPKs (CDC2L5, HK2, NEK3, PANK4, PLK4 and SGK3) identified as important for A/New Caledonia/20/99 influenza virus replication. Meta-analysis of the hit HPK genes identified important for influenza virus replication showed a level of overlap, most notably with the p53/DNA damage pathway. In addition, microRNAs (miRNAs) predicted to target the validated HPK genes were determined based on miRNA seed site predictions from computational analysis and then validated using a panel of miRNA agonists and antagonists. The results identify miRNA regulation of hit HPK genes identified, specifically miR-148a by targeting CDC2L5 and miR-181b by targeting SGK3, and suggest these miRNAs also have a role in regulating influenza virus replication. Together these data advance our understanding of miRNA regulation of genes critical for virus replication and are important for development novel influenza intervention strategies. INDEX WORDS: Influenza virus, -
Downregulation of Umbilical Cord Blood Levels of Mir-374A.Pdf
Downregulation of Umbilical Cord Blood Levels of miR-374a in Neonatal Hypoxic Ischemic Encephalopathy Ann-Marie Looney, MSc1, Brian H. Walsh, PhD1, Gerard Moloney, PhD2, Sue Grenham, PhD2, Ailis Fagan, PhD3, Gerard W. O’Keeffe, PhD1,2, Gerard Clarke, PhD3,4, John F. Cryan, PhD2,3, Ted G. Dinan, PhD3,4, Geraldine B. Boylan, PhD1, and Deirdre M. Murray, PhD1 Objective To investigate the expression profile of microRNA (miRNA) in umbilical cord blood from infants with hypoxic ischemic encephalopathy (HIE). Study design Full-term infants with perinatal asphyxia were identified under strict enrollment criteria. Degree of encephalopathy was defined using both continuous multichannel electroencephalogram in the first 24 hours of life and modified Sarnat score. Seventy infants (18 controls, 33 with perinatal asphyxia without HIE, and 19 infants with HIE [further graded as 13 mild, 2 moderate, and 4 severe]) were included in the study. MiRNA expression profiles were determined using a microarray assay and confirmed using quantitative real-time polymerase chain reaction. Results Seventy miRNAs were differentially expressed between case and control groups. Of these hsa-miR-374a was the most significantly downregulated in infants with HIE vs controls. Validation of hsa-miR-374a expression using quantitative real-time polymerase chain reaction confirmed a significant reduction in expression among infants with HIE compared with those with perinatal asphyxia and healthy controls (mean relative quantification [SD] = 0.52 [0.37] vs 1.10 [1.52] vs 1.76 [1.69], P < .02). Conclusions We have shown a significant step-wise downregulation of hsa-miR-374a expression in cord blood of infants with perinatal asphyxia and subsequent HIE. -
Homologs of Genes Expressed in Caenorhabditis Elegans Gabaergic
Hammock et al. Neural Development 2010, 5:32 http://www.neuraldevelopment.com/content/5/1/32 RESEARCH ARTICLE Open Access Homologs of genes expressed in Caenorhabditis elegans GABAergic neurons are also found in the developing mouse forebrain Elizabeth AD Hammock1,2*, Kathie L Eagleson3, Susan Barlow4,6, Laurie R Earls4,7, David M Miller III2,4,5, Pat Levitt3* Abstract Background: In an effort to identify genes that specify the mammalian forebrain, we used a comparative approach to identify mouse homologs of transcription factors expressed in developing Caenorhabditis elegans GABAergic neurons. A cell-specific microarray profiling study revealed a set of transcription factors that are highly expressed in embryonic C. elegans GABAergic neurons. Results: Bioinformatic analyses identified mouse protein homologs of these selected transcripts and their expression pattern was mapped in the mouse embryonic forebrain by in situ hybridization. A review of human homologs indicates several of these genes are potential candidates in neurodevelopmental disorders. Conclusions: Our comparative approach has revealed several novel candidates that may serve as future targets for studies of mammalian forebrain development. Background As with other cell types, the diversity of GABAergic Proper forebrain patterning and cell-fate specification neurons has its basis in different developmental origins, lay the foundation for complex behaviors. These neuro- with timing and location of birth playing key roles in developmental events in large part depend on a series of cell fate [1,6-8]. gene expression refinements (reviewed in [1]) that com- Despite the phenotypic variety of GABAergic neurons, mit cells to express certain phenotypic features that all use GABA as a neurotransmitter. -
Details About Three Fatty Acid Oxidation Pathways Occurring in Man
Supplement information Details about three fatty acid oxidation pathways occurring in man Alpha oxidation Definition: Oxidation of the alpha carbon of the fatty acid, chain shortened by 1 carbon atom. Localization: Peroxisomes1 Substrates: Phytanic acid, 3-methyl fatty acids and their alcohol and aldehyde derivatives, metabolites of farnesol, geranylgeraniol, and dolichols2, 3. Steps in the pathway: Activation requires ATP and CoA. Hydroxylation requires iron, ascorbate and alpha-keto-glutarate as cofactors and secondary substrates. Lysis requires thymine pyrophosphate and magnesium ions. Dehydrogenation requires NADP. End products are transported into mitochondria for further oxidation. Enzymes and genes involved: Very long-chain acyl-CoA synthetase (E.C. 6.2.1.-) (SLC27A2, GeneID: 11001)4, phytanoyl-CoA dioxygenase (E.C. 1.14.11.18, PHYH, GeneID: 5264), 2-hydrosyphytanoyl-coA lyase (E.C. 4.1.-.-, HACL1, GeneID: 26061), and aldehyde dehydrogenase (E.C. 1.2.1.3, ALDH3A2, GeneID: 224). Disorders associated: Zellweger syndrome including RCDP type 1, where PTS2 receptor is defective and PHYH is unable to enter peroxisomes, and Refsum’s disease. Special features/ purpose: At the sub cellular level, the activation step can occur in the mitochondrion, endoplasmic reticulum, and peroxisome. Formic acid is the main byproduct of this pathway as opposed to carbon dioxide. Phytanic acid usually undergoes alpha oxidation; however, under conditions of enzyme deficiency, it undergoes omega oxidation and 3- methyladipic acid is produced as the end product5. Omega oxidation Definition: Oxidation of omega carbon of the fatty acid for generation of mono- and di- carboxylic acids. No chain shortening occurs. Localization: Fatty acid shuttles between cytosol and microsomes before entering the peroxisomes6.