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Systems biology of long non-coding RNAs

Abstract

It is estimated that thousands of long non-coding RNAs (lncRNAs) are transcribed in the genome of several organisms. Yet, only a small fraction of them have been functionally characterized. One of the main reasons for this lies in our poor understanding of their expression patterns under different biological conditions, and the difficulty in identifying their possible gene targets. Most of the high-throughput techniques, such as microarrays and next-generation sequencing (RNA-seq), aim to monitor the expression of protein-coding genes. Some of this data, although unexplored in the original publications, are derived from lncRNAs. In this project, we propose to utilize publicly-available high-throughput data to study the systems biology of lncRNAs under different perturbations and the implication of lncRNAs in the regulation of candidate target genes. For example, we re-annotated the most used Affymetrix chip, with which more than 2,300 studies have been published, and revealed the existence of 10,248 probe sets of putative lncRNAs. Studying the expression profile of lncRNAs and how their expression correlates with the expression of protein-coding genes in various tissues and conditions will reveal interesting mechanisms of gene regulation. These analyses will involve the identification of co-expression modules, the prediction of transcription factors responsible for lncRNA transcription, and the association of lncRNAs to diseases and infections. We also propose to validate the regulatory role of some of these lncRNAs. (AU)

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Scientific publications (18)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ZUCCOLI, GIULIANA S.; REIS-DE-OLIVEIRA, GUILHERME; GARBES, BRUNA; FALKAI, PETER; SCHMITT, ANDREA; NAKAYA, I, HELDER; MARTINS-DE-SOUZA, DANIEL. Linking proteomic alterations in schizophrenia hippocampus to NMDAr hypofunction in human neurons and oligodendrocytes. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 271, n. 8, p. 1579-1586, DEC 2021. Web of Science Citations: 0.
WANG, JAQUELINE YU TING; WHITTLE, MARTIN R.; PUGA, RENATO DAVID; YAMBARTSEV, ANATOLY; FUJITA, ANDRE; NAKAYA, HELDER I. Noninvasive prenatal paternity determination using microhaplotypes: a pilot study. BMC MEDICAL GENOMICS, v. 13, n. 1 OCT 23 2020. Web of Science Citations: 0.
PINTO, BRUNA G. G.; OLIVEIRA, ANTONIO E. R.; SINGH, YOUVIKA; JIMENEZ, LEANDRO; GONCALVES, ANDRE N. A.; OGAVA, RODRIGO L. T.; CREIGHTON, RACHEL; SCHATZMANN PERON, JEAN PIERRE; NAKAYA, I, HELDER. ACE2 Expression Is Increased in the Lungs of Patients With Comorbidities Associated With Severe COVID-19. Journal of Infectious Diseases, v. 222, n. 4, p. 556-563, AUG 15 2020. Web of Science Citations: 36.
BRANDAO, W. N.; DE OLIVEIRA, M. G.; ANDREONI, R. T.; NAKAYA, H.; FARIAS, A. S.; PERON, J. P. S. Neuroinflammation at single cell level: What is new?. Journal of Leukocyte Biology, AUG 2020. Web of Science Citations: 0.
AGUIAR, RENATO S.; POHL, FABIO; MORAIS, GUILHERME L.; NOGUEIRA, FABIO C. S.; DE CARVALHO, JOSEANE B.; GUIDA, LETICIA; ARGE, LUIS W. P.; MELO, ADRIANA; MOREIRA, MARIA E. L.; CUNHA, DANIELA P.; GOMES, LEONARDO; PORTARI, ELYZABETH A.; VELASQUEZ, ERIKA; MELANI, RAFAEL D.; PEZZUTO, PAULA; DE CASTRO, FERNANDA L.; GEDDES, VICTOR E. V.; GERBER, ALEXANDRA L.; AZEVEDO, GIRLENE S.; SCHAMBER-REIS, BRUNO L.; GONCALVES, ALESSANDRO L.; JUNQUEIRA-DE-AZEVEDO, INACIO; NISHIYAMA JR, MILTON Y.; HO, PAULO; SCHANOSKI, ALESSANDRA; SCHUCH, VIVIANE; TANURI, AMILCAR; CHIMELLI, LEILA; VASCONCELOS, ZILTON F. M.; DOMONT, GILBERTO B.; VASCONCELOS, ANA T. R.; NAKAYA, I, HELDER. Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome. Science Signaling, v. 13, n. 635 JUN 9 2020. Web of Science Citations: 0.
JEAN PIERRE SCHATZMANN PERON; HELDER NAKAYA. Susceptibility of the Elderly to SARS-CoV-2 Infection: ACE-2 Overexpression, Shedding, and Antibody-dependent Enhancement (ADE). Clinics, v. 75, p. -, 2020. Web of Science Citations: 1.
PERON, J. P. S.; NAKAYA, I, H.; SCHLINDWEIN, M. A. M.; GONCALVES, M. V. M. COVID-19 Pandemic and Dysbiosis: Can the Ivermectin Hysteria Lead to an Increase of Autoimmune Neuroinflammatory Diseases?. CRITICAL REVIEWS IN IMMUNOLOGY, v. 40, n. 6, SI, p. 537-542, 2020. Web of Science Citations: 0.
GONCALVES, ANDRE N. A.; LEVER, MELISSA; RUSSO, PEDRO S. T.; GOMES-CORREIA, BRUNO; URBANSKI, ALYSSON H.; POLLARA, GABRIELE; NOURSADEGHI, MAHDAD; MARACAJA-COUTINHO, VINICIUS; NAKAYA, I, HELDER. Assessing the Impact of Sample Heterogeneity on Transcriptome Analysis of Human Diseases Using MDP Webtool. FRONTIERS IN GENETICS, v. 10, OCT 24 2019. Web of Science Citations: 0.
DE LIMA, DIOGENES S.; CARDOZO, LUCAS E.; MARACAJA-COUTINHO, VINICIUS; SUHRBIER, ANDREAS; MANE, KARIM; JEFFRIES, DAVID; SILVEIRA, EDUARDO L. V.; AMARAL, PAULO P.; RAPPUOLI, RINO; DE SILVA, THUSHAN I.; NAKAYA, HELDER I. Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 116, n. 34, p. 17121-17126, AUG 20 2019. Web of Science Citations: 1.
MASTELIC-GAVILLET, BEATRIS; VONO, MARIA; GONZALEZ-DIAS, PATRICIA; FERREIRA, FREDERICO MORAES; CARDOZO, LUCAS; LAMBERT, PAUL-HENRI; NAKAYA, I, HELDER; SIEGRIST, CLAIRE-ANNE. Neonatal T Follicular Helper Cells Are Lodged in a Pre-T Follicular Helper Stage Favoring Innate Over Adaptive Germinal Center Responses. FRONTIERS IN IMMUNOLOGY, v. 10, AUG 13 2019. Web of Science Citations: 0.
SOARES-SCHANOSKI, ALESSANDRA; BAPTISTA CRUZ, NATALIA; DE CASTRO-JORGE, LUIZA ANTUNES; HOMEM DE CARVALHO, RENAN VILLANOVA; DOS SANTOS, CLIOMAR ALVES; DA ROS, NANCY; OLIVEIRA, URSULA; COSTA, DANUZA DUARTE; SIMOES DOS SANTOS, CECILIA LUIZA; CUNHA, MARIELTON DOS PASSOS; SARNO OLIVEIRA, MARIA LEONOR; ALVES, JULIANA CARDOSO; DE LUCENA COUTO OCEA, REGINA ADALVA; RIBEIRO, DANIELLE RODRIGUES; AQUIME GONCALVES, ANDRE NICOLAU; GONZALEZ-DIAS, PATRICIA; SUHRBIER, ANDREAS; DE ANDRADE ZANOTTO, PAOLO MARINHO; DE AZEVEDO, INACIO JUNQUEIRA; ZAMBONI, DARIO S.; ALMEIDA, ROQUE PACHECO; HO, PAULO LEE; KALIL, JORGE; NISHIYAMA, MILTON YUTAKA; NAKAYA, HELDER I. Systems analysis of subjects acutely infected with the Chikungunya virus. PLOS PATHOGENS, v. 15, n. 6 JUN 2019. Web of Science Citations: 4.
CARDOZO, LUCAS E.; RUSSO, PEDRO S. T.; GOMES-CORREIA, BRUNO; ARAUJO-PEREIRA, MARIANA; SEPULVEDA-HERMOSILLA, GONZALO; MARACAJA-COUTINHO, VINICIUS; NAKAYA, I, HELDER. webCEMiTool: Co-expression Modular Analysis Made Easy. FRONTIERS IN GENETICS, v. 10, MAR 6 2019. Web of Science Citations: 1.
JOCHEMS, SIMON P.; MARCON, FERNANDO; CARNIEL, BEATRIZ F.; HOLLOWAY, MARK; MITSI, ELENA; SMITH, EMMA; GRITZFELD, JENNA F.; SOLORZANO, CARLA; REINE, JESUS; POJAR, SHERIN; NIKOLAOU, ELISSAVET; GERMAN, ESTHER L.; HYDER-WRIGHT, ANGIE; HILL, HELEN; HALES, CAZ; PITERS, WOUTER A. A. DE STEENHUIJSEN; BOGAERT, DEBBY; ADLER, HUGH; ZAIDI, SEHER; CONNOR, VICTORIA; GORDON, STEPHEN B.; RYLANCE, JAMIE; NAKAYA, HELDER I.; FERREIRA, DANIELA M. Inflammation induced by influenza virus impairs human innate immune control of pneumococcus. NATURE IMMUNOLOGY, v. 19, n. 12, p. 1299+, DEC 2018. Web of Science Citations: 13.
FUKUTANI, KIYOSHI F.; NASCIMENTO-CARVALHO, CRISTIANA M.; BOUZAS, MAIARA L.; OLIVEIRA, JULIANA R.; BARRAL, ALDINA; DIERCKX, TIM; KHOURI, RICARDO; NAKAYA, HELDER I.; ANDRADE, BRUNO B.; VAN WEYENBERGH, JOHAN; DE OLIVEIRA, CAMILA I. In situ Immune Signatures and Microbial Load at the Nasopharyngeal Interface in Children With Acute Respiratory Infection. FRONTIERS IN MICROBIOLOGY, v. 9, NOV 9 2018. Web of Science Citations: 0.
FERREIRA, GUSTAVO RODRIGUES; NAKAYA, HELDER IMOTO; COSTA, LUCIANO DA FONTOURA. Gene regulatory and signaling networks exhibit distinct topological distributions of motifs. Physical Review E, v. 97, n. 4 APR 27 2018. Web of Science Citations: 0.
RUSSO, PEDRO S. T.; FERREIRA, GUSTAVO R.; CARDOZO, LUCAS E.; BUERGER, MATHEUS C.; ARIAS-CARRASCO, RAUL; MARUYAMA, SANDRA R.; HIRATA, THIAGO D. C.; LIMA, DIOGENES S.; PASSOS, FERNANDO M.; FUKUTANI, KIYOSHI F.; LEVER, MELISSA; SILVA, JOAO S.; MARACAJA-COUTINHO, VINICIUS; NAKAYA, HELDER I. CEMiTool: a Bioconductor package for performing comprehensive modular co-expression analyses. BMC Bioinformatics, v. 19, FEB 20 2018. Web of Science Citations: 15.
ARIAS-CARRASCO, RAUL; VASQUEZ-MORAN, YESSENIA; NAKAYA, HELDER I.; MARACAJA-COUTINHO, VINICIUS. StructRNAfinder: an automated pipeline and web server for RNA families prediction. BMC Bioinformatics, v. 19, FEB 17 2018. Web of Science Citations: 3.
BLOHMKE, CHRISTOPH J.; HILL, JENNIFER; DARTON, THOMAS C.; CARVALHO-BURGER, MATHEUS; EUSTACE, ANDREW; JONES, CLAIRE; SCHREIBER, FERNANDA; GOODIER, MARTIN R.; DOUGAN, GORDON; NAKAYA, HELDER I.; POLLARD, ANDREW J. Induction of Cell Cycle and NK Cell Responses by Live-Attenuated Oral Vaccines against Typhoid Fever. FRONTIERS IN IMMUNOLOGY, v. 8, OCT 12 2017. Web of Science Citations: 5.

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