Information Exploration System for Sickle Cell Disease and Repurposing of Hydroxyfasudil

Background Sickle cell disease (SCD) is a fatal monogenic disorder with no effective cure and thus high rates of morbidity and sequelae. Efforts toward discovery of disease modifying drugs and curative strategies can be augmented by leveraging the plethora of information contained in available biomedical literature. To facilitate research in this direction we have developed a resource, Dragon Exploration System for Sickle Cell Disease (DESSCD) (http://cbrc.kaust.edu.sa/desscd/) that aims to promote the easy exploration of SCD-related data. Description The Dragon Exploration System (DES), developed based on text mining and complemented by data mining, processed 419,612 MEDLINE abstracts retrieved from a PubMed query using SCD-related keywords. The processed SCD-related data has been made available via the DESSCD web query interface that enables: a/information retrieval using specified concepts, keywords and phrases, and b/the generation of inferred association networks and hypotheses. The usefulness of the system is demonstrated by: a/reproducing a known scientific fact, the “Sickle_Cell_Anemia–Hydroxyurea” association, and b/generating novel and plausible “Sickle_Cell_Anemia–Hydroxyfasudil” hypothesis. A PCT patent (PCT/US12/55042) has been filed for the latter drug repurposing for SCD treatment. Conclusion We developed the DESSCD resource dedicated to exploration of text-mined and data-mined information about SCD. No similar SCD-related resource exists. Thus, we anticipate that DESSCD will serve as a valuable tool for physicians and researchers interested in SCD.

[1]  A. Fattori,et al.  Gene expression profiles of erythroid precursors characterise several mechanisms of the action of hydroxycarbamide in sickle cell anaemia , 2007, British journal of haematology.

[2]  O. Witt,et al.  Induction of fetal hemoglobin expression by the histone deacetylase inhibitor apicidin. , 2003, Blood.

[3]  J. Elion,et al.  Hydroxycarbamide stimulates the production of proinflammatory cytokines by endothelial cells: relevance to sickle cell disease , 2010, Pharmacogenetics and genomics.

[4]  Adam D. Schuyler,et al.  SciMiner: web-based literature mining tool for target identification and functional enrichment analysis , 2009, Bioinform..

[5]  Kazuhiro Takahashi,et al.  Fasudil-induced hypoxia-inducible factor-1α degradation disrupts a hypoxia-driven vascular endothelial growth factor autocrine mechanism in endothelial cells , 2008, Molecular Cancer Therapeutics.

[6]  E. Hatzimichael,et al.  Circulating endothelin-3 levels in patients with sickle cell disease during hydroxyurea treatment. , 2004, Haematologica.

[7]  K. Homma,et al.  Rho-kinase inhibition ameliorates peritoneal fibrosis and angiogenesis in a rat model of peritoneal sclerosis. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[8]  S. Saad,et al.  Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy , 2009, Journal of leukocyte biology.

[9]  A. Fischer,et al.  Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. , 2007, Blood.

[10]  P. Swerdlow,et al.  Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice. , 2011, Blood.

[11]  The UniProt Consortium,et al.  The Universal Protein Resource (UniProt) 2009 , 2008, Nucleic Acids Res..

[12]  Chuan-zhen Lu,et al.  Fasudil protects hippocampal neurons against hypoxia‐reoxygenation injury by suppressing microglial inflammatory responses in mice , 2010, Journal of neurochemistry.

[13]  Marc Weeber,et al.  Text-based discovery in biomedicine: the architecture of the DAD-system , 2000, AMIA.

[14]  S. Al Arrayed.  Campaign to Control Genetic Blood Diseases in Bahrain , 2005, Public Health Genomics.

[15]  Alan Christoffels,et al.  DDESC: Dragon database for exploration of sodium channels in human , 2008, BMC Genomics.

[16]  Vladimir B. Bajic,et al.  Database for exploration of functional context of genes implicated in ovarian cancer , 2008, Nucleic Acids Res..

[17]  M. Gladwin,et al.  Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase. , 2003, The Journal of clinical investigation.

[18]  M. Schuemie,et al.  Anni 2.0: a multipurpose text-mining tool for the life sciences , 2008, Genome Biology.

[19]  Nitin Patel,et al.  Placenta Growth Factor-induced Early Growth Response 1 (Egr-1) Regulates Hypoxia-inducible Factor-1α (HIF-1α) in Endothelial Cells* , 2010, The Journal of Biological Chemistry.

[20]  Jonathan D. Wren,et al.  Knowledge discovery by automated identification and ranking of implicit relationships , 2004, Bioinform..

[21]  Alan Christoffels,et al.  Dragon exploratory system on hepatitis C virus (DESHCV). , 2011, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[22]  Sebastian Schmeier,et al.  DDEC: Dragon database of genes implicated in esophageal cancer , 2009, BMC Cancer.

[23]  M. Sadelain.  Recent advances in globin gene transfer for the treatment of beta-thalassemia and sickle cell anemia , 2006, Current opinion in hematology.

[24]  David S. Wishart,et al.  Nucleic Acids Research Polysearch: a Web-based Text Mining System for Extracting Relationships between Human Diseases, Genes, Mutations, Drugs Polysearch: a Web-based Text Mining System for Extracting Relationships between Human Diseases, Genes, Mutations, Drugs and Metabolites , 2008 .

[25]  A. Hoffman,et al.  DP-155, a lecithin derivative of indomethacin, is a novel nonsteroidal antiinflammatory drug for analgesia and Alzheimer's disease therapy. , 2007, CNS drug reviews.

[26]  A. Duits,et al.  Levels of Endothelial, Neutrophil and Platelet-Specific Factors in Sickle Cell Anemia Patients during Hydroxyurea Therapy , 1999, Acta Haematologica.

[27]  R. Gambari,et al.  Effects of rapamycin on accumulation of alpha-, beta- and gamma-globin mRNAs in erythroid precursor cells from beta-thalassaemia patients. , 2006, European journal of haematology.

[28]  Vladimir B. Bajic,et al.  DDPC: Dragon Database of Genes associated with Prostate Cancer , 2010, Nucleic Acids Res..

[29]  P. Lane.  Sickle cell disease. , 1996, Pediatric clinics of North America.

[30]  Carlos Alberto Heuser,et al.  Integrating Biological Databases , 2003, SBBD.

[31]  Susumu Goto,et al.  The KEGG databases at GenomeNet , 2002, Nucleic Acids Res..

[32]  F. Costa,et al.  Increased soluble guanylate cyclase activity in the red blood cells of sickle cell patients , 2004, British journal of haematology.

[33]  Cathy H. Wu,et al.  The Universal Protein Resource (UniProt) , 2004, Nucleic Acids Res..

[34]  Barbara S. Paugh,et al.  Sphingosine-1-Phosphate and Interleukin-1 Independently Regulate Plasminogen Activator Inhibitor-1 and Urokinase-Type Plasminogen Activator Receptor Expression in Glioblastoma Cells: Implications for Invasiveness , 2008, Molecular Cancer Research.

[35]  G. Atweh,et al.  Induction of fetal hemoglobin in the treatment of sickle cell disease. , 2006, Hematology. American Society of Hematology. Education Program.

[36]  F. Costa,et al.  Leukocyte numbers correlate with plasma levels of granulocyte–macrophage colony-stimulating factor in sickle cell disease , 2007, Annals of Hematology.

[37]  A. Schechter,et al.  5-Azacytidine increases gamma-globin synthesis and reduces the proportion of dense cells in patients with sickle cell anemia , 1983 .

[38]  Tatiana A. Tatusova,et al.  Entrez Gene: gene-centered information at NCBI , 2004, Nucleic Acids Res..

[39]  I. Ikegaki,et al.  Amelioration of endothelial damage/dysfunction is a possible mechanism for the neuroprotective effects of Rho-kinase inhibitors against ischemic brain damage , 2010, Brain Research Bulletin.

[40]  J. Elion,et al.  Decreased plasma endothelin-1 levels in children with sickle cell disease treated with hydroxyurea. , 2005, Haematologica.

[41]  C. Chai,et al.  Attenuation of pulmonary hypertension secondary to left ventricular dysfunction in the rat by Rho‐kinase inhibitor fasudil , 2011, Pediatric pulmonology.

[42]  J. E. Thomson,et al.  Asymmetric synthesis of N,O,O,O-tetra-acetyl d-lyxo-phytosphingosine, jaspine B (pachastrissamine), 2-epi-jaspine B, and deoxoprosophylline via lithium amide conjugate addition. , 2008, Organic & biomolecular chemistry.

[43]  G. Serjeant,et al.  Improved survival in homozygous sickle cell disease: lessons from a cohort study , 1995, BMJ.

[44]  Wei Li,et al.  Identification of fetal hemoglobin-inducing agents using the human leukemia KU812 cell line , 2010, Experimental biology and medicine.

[45]  Jeyakumar Natarajan,et al.  Text mining of full-text journal articles combined with gene expression analysis reveals a relationship between sphingosine-1-phosphate and invasiveness of a glioblastoma cell line , 2006, BMC Bioinformatics.

[46]  R. Ware,et al.  Hydroxyurea for sickle cell anemia: what have we learned and what questions still remain? , 2011, Current opinion in hematology.

[47]  Roberto Gambari,et al.  Effects of rapamycin on accumulation of α‐, β‐ and γ‐globin mRNAs in erythroid precursor cells from β‐thalassaemia patients , 2006 .

[48]  S. Tsukamoto,et al.  Naamidines H and I, cytotoxic imidazole alkaloids from the Indonesian marine sponge Leucetta chagosensis. , 2007, Journal of natural products.

[49]  V. Bajic,et al.  HCVpro: hepatitis C virus protein interaction database. , 2011, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[50]  Alan Christoffels,et al.  DESTAF: a database of text-mined associations for reproductive toxins potentially affecting human fertility. , 2012, Reproductive toxicology.

[51]  S. Saad,et al.  Therapy with hydroxyurea is associated with reduced adhesion molecule gene and protein expression in sickle red cells with a concomitant reduction in adhesive properties , 2006, European journal of haematology.

[52]  D. Swanson,et al.  Indomethacin and Alzheimer's disease , 1996, Neurology.

[53]  B. Pace,et al.  Globin Gene Silencing in Primary Erythroid Cultures , 1997, The Journal of Biological Chemistry.

[54]  A. Hafezi-Moghadam,et al.  Rho Kinase Inhibition by Fasudil Ameliorates Diabetes-Induced Microvascular Damage , 2009, Diabetes.

[55]  M. Fung,et al.  Cucurbitacin D induces fetal hemoglobin synthesis in K562 cells and human hematopoietic progenitors through activation of p38 pathway and stabilization of the γ-globin mRNA. , 2010, Blood cells, molecules & diseases.

[56]  Martin H. Schaefer,et al.  MedlineRanker: flexible ranking of biomedical literature , 2009, Nucleic Acids Res..

[57]  Y. Maehara,et al.  Involvement of Rho-Kinase in Cold Ischemia-Reperfusion Injury after Liver Transplantation in Rats , 2004, Transplantation.

[58]  Carole A. Goble,et al.  State of the nation in data integration for bioinformatics , 2008, J. Biomed. Informatics.

[59]  G. Kato,et al.  Fetal haemoglobin response to hydroxycarbamide treatment and sar1a promoter polymorphisms in sickle cell anaemia , 2008, British journal of haematology.

[60]  M. Menger,et al.  Rho-kinase signalling regulates CXC chemokine formation and leukocyte recruitment in colonic ischemia–reperfusion , 2010, International Journal of Colorectal Disease.