Transcriptomics in Health and Disease

348 Pages·2014·9.431 MB·English

by  Geraldo A. Passos (eds.)

Transcriptomics in Health and Disease
Geraldo A. Passos
Editor
Transcriptomics in Health
and Disease
2123
Editor
Geraldo A. Passos
Department of Genetics
University of São Paulo
Ribeirão Preto
São Paulo
Brazil
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ISBN 978-3-319-11984-7 ISBN 978-3-319-11985-4 (eBook)
DOI 10.1007/978-3-319-11985-4
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This book is dedicated to the Department of
Genetics, Ribeirão Preto Medical School,
University of São Paulo, Brazil, which in
2015 celebrates its 50 years of research,
teaching and clinical activities.
Preface
The completion of the human genome, with its more than 3 billion base pairs (bp)
of sequenced DNA, has provided an unprecedented wealth of knowledge. With the
additional investigation of single nucleotide polymorphisms (SNPs), we have also
learned how little genetic variability there truly is in the human genome. More-
over, genome-wide association studies (GWAS) have revealed important genotype-
phenotype correlations. Nevertheless, our understanding of the functionality of the
genome is still lacking.
Dispersed among its 3 billion bp, the human genome features approximately
20–25,000 functional genes that encode various proteins and their isoforms. In re-
cent years, however, scientists realized that the functionality of the genome is not
restricted to only protein-encoding genes, which are transcribed into messenger
RNAs, but also to the transcription of non-coding RNAs [e.g., microRNAs (miR-
NAs)], which play important roles in the posttranscriptional control of gene expres-
sion and, consequently, influence the resulting phenotypes.
Broadly speaking, it is at this point—from studies investigating where the func-
tions of the genome first begin—that the science of transcriptomics emerged. For
example, how are RNA molecules transcribed, what are the different species of
RNA, what are the functions of each of these species and how are they differentially
expressed among cells, tissues and organs?
Transcriptomics can therefore be thought of as the molecular biology of gene
expression on a large scale. It is derived from functional genomics studies with a
focus on transcription. Since its inception, transcriptomics has benefitted from and
will continue to benefit from microarray technology. Sequencing is undoubtedly
the ultimate tool when the objective is to delve into the differences at the sequence
level or to confirm the specific RNA isoform involved. Even more so now, with the
emergence of new technologies for high-throughput RNA sequencing (RNA-Seq),
we can answer more questions about the structure of RNAs, such as those found in
alternative splicing. However, the bottleneck remains in the data analysis because
sequences are currently being obtained in quantities that have never been previously
achieved.
However, as microarray bioinformatics has reached a very advanced stage (with
more than 15 years to perfect the analysis pipeline) and as microarray slides them-
vii
viii Preface
selves have become increasingly “large”, currently encompassing sequences from
the entire functional genome plus the complete set of known non-coding RNAs,
researchers have not neglected the applications of this important technology.
Recent comparative analyses have indicated a strong concordance between exon
microarrays and RNA-Seq data. Therefore, the goal is now to use these two comple-
mentary strategies for in-depth transcriptomics studies.
This book was organized on the basis on these assumptions. It includes 17 chap-
ters and covers the fundamental concepts of transcriptomics, as well as the cur-
rent analytical methods. We provide examples in high-level technical and scientific
detail, using accessible language whenever possible, as each chapter is written by
experienced and productive researchers in the field.
Over the first six chapters (Part I), we introduce the concept of the transcriptome,
as well as how microarrays or RNA-Seq can be used to trace expression signatures,
measure transcriptional expression levels and establish connections between genes
based on their transcriptional activity in normal cells, differentiating cells and or-
gans.
Chapters 7–17 (Part II) then provide examples of the state of the transcriptome
associated with major human diseases, such as inflammatory diseases, autoimmune
diseases, metabolic diseases (such as type 2 diabetes mellitus), genetic diseases
(such as Down syndrome), cancer and infections caused by pathogenic microor-
ganisms, such as tuberculosis mycobacteria, fungi and the protozoan Trypanosoma
cruzi, which is the causative agent of Chagas disease.
Special attention is also given to Chap. 17, which was strategically placed at the
end of this book. The author of this chapter, who was one of the original develop-
ers of microarray technology in the mid-1990s, discusses the medical potential of
transcriptomics from an analytical point of view.
I hope this book will be useful to researchers who wish to gain a comprehensive
view of transcriptomics in health and human disease. I would like to thank all of the
authors for their dedication and time spent writing these chapters. Finally I thank
Springer for providing this opportunity and for its continued support during the
writing and organization of this work.
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978-3-319-11984-7.
Ribeirão Preto, Brazil Geraldo A. Passos
Contents
Part I Basic Principles of the Transcriptome and Its Analysis
1 What Is the Transcriptome and How it is Evaluated?............................ 3
Amanda F. Assis, Ernna H. Oliveira, Paula B. Donate,
Silvana Giuliatti, Catherine Nguyen and Geraldo A. Passos
2 Transcriptome Analysis Throughout RNA-seq ....................................... 49
Tainá Raiol, Daniel Paiva Agustinho, Kelly Cristina Rodrigues Simi,
Calliandra Maria de Souza Silva, Maria Emilia Walter,
Ildinete Silva-Pereira and Marcelo Macedo Brígido
3 Identification of Biomarkers and Expression Signatures ...................... 69
Patricia Severino, Elisa Napolitano Ferreira and Dirce Maria Carraro
4 M ethods for Gene Coexpression Network Visualization
and Analysis ................................................................................................ 79
Carlos Alberto Moreira-Filho, Silvia Yumi Bando, Fernanda Bernardi
Bertonha, Filipi Nascimento Silva and Luciano da Fontoura Costa
5 Posttranscriptional Control During Stem Cells Differentiation ............ 95
Bruno Dallagiovanna, Fabiola Holetz and Patricia Shigunov
6 T ranscriptome Analysis During Normal Human
Mesenchymal Stem Cell Differentiation .................................................. 109
Karina F. Bombonato-Prado, Adalberto L. Rosa, Paulo T. Oliveira,
Janaína A. Dernowsek, Vanessa Fontana, Adriane F. Evangelista
and Geraldo A. Passos
ix
x Contents
Part II Transcriptome in Disease
7 T hymus Gene Coexpression Networks: A Comparative
Study in Children with and Without Down Syndrome .......................... 123
Carlos Alberto Moreira-Filho, Silvia Yumi Bando, Fernanda Bernardi
Bertonha, Filipi Nascimento Silva, Luciano da Fontoura Costa
and Magda Carneiro-Sampaio
8 Transcriptome Profiling in Autoimmune Diseases.................................. 137
Cristhianna V. A. Collares and Eduardo A. Donadi
9 Expression of DNA Repair and Response to Oxidative Stress
Genes in Diabetes Mellitus ........................................................................ 161
Paula Takahashi, Danilo J. Xavier and Elza T. Sakamoto-Hojo
10 MicroRNAs in Cancer ............................................................................... 181
Adriane F. Evangelista and Marcia M. C. Marques
11 Transcriptome Profiling in Chronic Inflammatory Diseases
of the Musculoskeletal System .................................................................. 195
Renê Donizeti Ribeiro de Oliveira and Paulo Louzada-Júnior
12 Transcriptome Profiling in Experimental Inflammatory Arthritis ....... 211
Olga Martinez Ibañez, José Ricardo Jensen and Marcelo De Franco
13 Transcriptome in Human Mycoses ........................................................... 227
Nalu T. A. Peres, Gabriela F. Persinoti, Elza A. S. Lang,
Antonio Rossi and Nilce M. Martinez-Rossi
14 Transcriptomics of the Host–Pathogen Interaction in
Paracoccidioidomycosis ............................................................................. 265
Patrícia Albuquerque, Hugo Costa Paes, Aldo Henrique Tavares,
Larissa Fernandes, Anamélia Lorenzetti Bocca, Ildinete Silva-Pereira,
Maria Sueli Soares Felipe and André Moraes Nicola
15 Dissecting Tuberculosis Through Transcriptomic Studies ..................... 289
Rodrigo Ferracine Rodrigues, Rogério Silva Rosada, Thiago Malardo,
Wendy Martin Rios and Celio Lopes Silva
Contents xi
16 Understanding Chagas Disease by Genome
and Transcriptome Exploration ............................................................... 311
Ludmila Rodrigues P. Ferreira and Edecio Cunha-Neto
17 Expression Tests in Actual Clinical Practice: How Medically
Useful is the Transcriptome? .................................................................... 327
Bertrand R. Jordan
Concluding Remarks and Perspectives .......................................................... 341
Index .................................................................................................................. 343