Jonathan Pevsner – Bioinformatics and Functional Genomics (3rd edition, 2015)

Автор: Jonathan Pevsner
Название книги: Bioinformatics and Functional Genomics (3rd edition)
Формат: PDF
Жанр: Биология
Страницы: 1161
Качество: Изначально компьютерное, E-book

The bestselling introduction to bioinformatics and genomics now in its third edition Widely received in its previous editions, Bioinformatics and Functional Genomics offers the most broad-based introduction to this explosive new discipline. Now in a thoroughly updated and expanded third edition, it continues to be the go-to source for students and professionals involved in biomedical research. This book provides up-to-the-minute coverage of the fields of bioinformatics and genomics. Features new to this edition include: * Extensive revisions and a slight reorder of chapters for a more effective organization * A brand new chapter on next-generation sequencing * An expanded companion website, also updated as and when new information becomes available * Greater emphasis on a computational approach, with clear guidance of how software tools work and introductions to the use of command-line tools such as software for next-generation sequence analysis, the R programming language, and NCBI search utilities The book is complemented by lavish illustrations and more than 500 figures and tables – many newly-created for the third edition to enhance clarity and understanding. Each chapter includes learning objectives, a problem set, pitfalls section, boxes explaining key techniques and mathematics/statistics principles, a summary, recommended reading, and a list of freely available software. Readers may visit a related Web page for supplemental information such as PowerPoints and audiovisual files of lectures, and videocasts of how to perform many basic operations: www.wiley.com/go/pevsnerbioinformatics. Bioinformatics and Functional Genomics, Third Edition serves as an excellent single-source textbook for advanced undergraduate and beginning graduate-level courses in the biological sciences and computer sciences. It is also an indispensable resource for biologists in a broad variety of disciplines who use the tools of bioinformatics and genomics to study particular research problems; bioinformaticists and computer scientists who develop computer algorithms and databases; and medical researchers and clinicians who want to understand the genomic basis of viral, bacterial, parasitic, or other diseases.
When the first edition of this textbook was published in 2003, the Human Genome Project
had just been completed at a cost of nearly US$ 3 billion. When the second edition
came into print in 2009, the first genome sequence of an individual (J. Craig Venter) had
recently been published at an estimated cost of US$ 80 million.
Let me tell you a remarkable story. It is now 2015 and it costs just several thousand
dollars to obtain the complete genome sequence of an individual. Sturge‐Weber syndrome
is a rare neurocutaneous disorder (affecting the brain and skin) that is sometimes
debilitating: some patients must have a hemispherectomy (removal of half the brain)
to alleviate the severe seizures. We obtained paired samples from just three individuals
with Sturge‐Weber syndrome: biopsies were from affected parts of the body (such as
port‐wine stains that occur on the face, neck, or shoulder) or from presumably unaffected
regions. We purified DNA and sequenced these six whole genomes, compared the
matched pairs, and identified a single base pair mutation in the GNAQ gene as responsible
for Sturge‐Weber syndrome. (The mutation is somatic, mosaic, and activating: somatic in
that it occurs during development but is not transmitted from the parents; mosaic in that
it affects just part of the body; and activating because GNAQ encodes a protein that in
the mutated form turns on a signaling cascade.) We found that mutations in this gene also
cause port‐wine stain birthmarks (which affect 1 in 300 people or about 23 million people
worldwide). Matt Shirley, then a graduate student in my lab, performed the bioinformatics
analyses that led to this discovery. He analyzed about 700 billion bases of DNA. After
finding the mutation he confirmed it by re‐sequencing dozens of samples, typically at over
10,000‐fold depth of coverage. We reported these findings in the New England Journal
of Medicine in 2013.
This story illustrates several aspects of the fields of bioinformatics and genomics.
First, we are in a time period when there is an explosive growth in the availability of DNA
sequence. This is enabling us to address biological questions in unprecedented ways. Second,
while it is inexpensive to acquire DNA sequences, it is essential to know how to analyze
them. One goal of this book is to introduce sequence analysis. Third, bioinformatics
serves biology: we can only interpret the significance of DNA sequence variation in the
context of some biological process (such as a disease state). In the case of the GNAQ
mutation, that gene encodes a protein (called Gαq) that we can study in tremendous detail
using the tools of bioinformatics; we can evaluate its three‐dimensional structure, the
proteins and chemical messengers it interacts with, and the cellular pathways it participates
in. Fourth, bioinformatics and genomics offer us hope. For Sturge‐Weber syndrome
patients and those with port‐wine stain birthmarks, we are hopeful that a molecular understanding
of these conditions will lead to treatments.
This book is written by a biologist who has used the tools of bioinformatics to help
understand biomedical research questions. I introduce concepts in the context of biological
problem‐solving. Compared to earlier editions, this new text emphasizes commandline
software on the Linux (or Mac) platform, complemented by web‐based approaches.
In an era of “Big Data” there is a great divide between those whose intellectual core is
centered in biomedical science and those whose focus involves computer science. I hope
this book helps to bridge the divide between these two cultures.
Writing a book like this is a wonderful and constant learning experience. I thank past
and present members of my lab who taught me including Shruthi Bandyadka (for advice
on R), Christopher Bouton, Carlo Colantuoni, Donald Freed (for extensive advice on
next‐generation sequencing or NGS), Laurence Frelin, Mari Kondo, Sarah McClymont,
Nathaniel Miller, Alicia Rizzo, Eli Roberson, Matt Shirley (who also provided extensive
NGS advice), Eric Stevens, and Jamie Wangen. For advice on specific chapters, I thank:
Ben Busby of the National Center for Biotechnology Information (NCBI) for advice
regarding Chapters 1, 2, and 5 and detailed comments on Chapters 9 and 10; Eric Sayers
and Jonathan Kans of NCBI for advice on EDirect in Chapter 2; Heiko Schmidt for advice
on TREE‐PUZZLE and MrBayes in Chapter 7; Joel Benington for detailed comments on
Chapters 8 and 15–19 and helpful discussions about teaching; Harold Lehmann for guidance
on various fields of informatics; and N. Varg for helpful comments on all chapters. I
thank many colleagues who participated in teaching bioinformatics and genomics courses
over the years. I've learned from all these teachers, including Dimitri Avramopoulos, Jef
Boeke, Kyle Cunningham, Garry Cutting, George Dimopoulos, Egert Hoiczyk, Rafael
Irizarry, Akhilesh Pandey, Sean Prigge, Ingo Ruczinski, Alan Scott, Alan F. Scott, Kirby
D. Smith, David Sullivan, David Valle, and Sarah Wheelan. I am grateful to faculty members
with whom I taught genomics workshops including Elana Fertig, Luigi Marchionni,
John McGready, Loris Mulroni, Frederick Tan, and Sarah Wheelan. This book includes
several thousand literature references, but I apologize to the many more colleagues whose
work I did not cite. I also cite 900 websites and again apologize to the developers of the
many I did not include.
I also acknowledge the support of Dr Gary W. Goldstein, President and CEO of the
Kennedy Krieger Institute where I work. Kennedy Krieger Institute sees 22,000 patients a
year, mostly children with neurodevelopmental disorders from common conditions (such
as autism spectrum disorder and intellectual disability) to rare genetic diseases. I am
motivated to try to apply the tools of bioinformatics and genomics to help these children.
This perspective has guided my writing of this book, which emphasizes the relevance of
all the topics in bioinformatics and genomics to human disease in general. We are hopeful
that genomics will lead to an understanding of the molecular bases of so many devastating
conditions, and this in turn may one day lead to better diagnosis, prevention, treatment,
and perhaps even cures.
It is my pleasure to thank my editors at Wiley‐Blackwell – Laura Bell, Celia Carden,
Beth Dufour, Elaine Rowan, Fiona Seymour, Audrie Tan, and Rachel Wade – for generous
support throughout this project. I appreciate all their dedication to the quality of the book.
On a personal note I thank my wife Barbara for her love and support throughout the
very long process of writing this textbook. Finally, to my girls Ava and Lillian: I hope
you'll always be inspired to be curious and full of wonder about the world around us.