Biomedical Informatics for Cancer Research 1st Edition

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Editors
Michael F. Ochs John T. Casagrande
Division of Oncology Biostatistics Cancer Research Informatics Core
and Bioinformatics University of Southern California Kenneth
Sidney Kimmel Comprehensive Norris Jr.
Cancer Center Comprehensive Cancer Center
John Hopkins University Los Angeles, CA 90089
Baltimore, MD 21205-2011 USA
USA [email protected]
[email protected]

Ramana V. Davuluri
The Wistar Institute
Philadelphia, PA 19104
USA
[email protected]

ISBN 978-1-4419-5712-2 e-ISBN 978-1-4419-5714-6

DOI 10.1007/978-1-4419-5714-6
Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2010924049

© Springer Science+Business Media, LLC 2010

All rights reserved. This work may not be translated or copied in whole or in part without the written
permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY
10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection
with any form of information storage and retrieval, electronic adaptation, computer software, or by similar
or dissimilar methodology now known or hereafter developed is forbidden.
The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are
not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject
to proprietary rights.

Cover Illustration: An image of matrix production by fibroblasts, showing the extracellular matrix
and cell adhesion structures that play a key role in cancer cell behavior and metastasis. Indirect
immunofluorescent images, of NIH-3T3 cells (murine fibroblasts), were acquired during the cellular
process of extracellular matrix deposition. Nuclei are shown in blue while extracellular fibronectin matrix
fibers (red) and cellular adhesion structures (integrin in green) can be seen co-localizing in yellow.
Image was acquired after 4 days of matrix production. Image kindly provided by Dr. Edna Cukierman
of the Fox Chase Cancer Center in Philadelphia.

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

 Michael F. Ochs
dedicates this volume to
Erica Golemis
Over half of our lives together so far, forget the asymptotic limit,
let’s go for all of our lives together.

John T. Casagrande
dedicates this volume to
Yolee Casagrande
Her continuous support and encouragement in all aspects of my life
are greatly appreciated. I would like to especially thank her for
encouraging me to pursue my “creative” side, which has resulted
in this volume.

Ramana V. Davuluri
dedicates this volume to
Adinarayana Davuluri
I owe a lot to my father, whose commitment encouraged me to
go to school. His loss to cancer inspired me to pursue medical
research in cancer.
Acknowledgments

Many people dedicated significant effort to making this volume possible. I would
like to thank Alisa Moore, who keeps my endless paperwork moving through
the impressive NIH and Hopkins bureaucracies. I would also like to thank my
coeditors, John and Ramana, for their efforts and especially for their patience –
emails from me tend to arrive in fits and starts, almost always proposing an imminent
deadline when at least a few weeks notice would have been more appropriate. They
(almost) always responded rapidly. Finally, my thanks to all the authors who produced
these chapters, despite the deluge of ARRA submissions and paperwork.
–Michael F. Ochs

I would like to thank Michael Ochs for inviting me to work on this project with him
and Ramana; although we collaborated cross-country via e-mail, it has been a very
gratifying and satisfying experience and a testament to the use of technology.
Finally, I would like to thank those of you who are reading this volume, I hope you
find it informative and helpful.
–John T. Casagrande

I would like to thank Michael Ochs for having me on this project, along with John.
I know that I tested the patience of Michael, who constantly had to send me
repeated emails to keep up with the deadlines. I am glad that the volume came out
so well, I hope many of the readers will find the information very useful.
–Ramana V. Davuluri

vii
Contents

Section 1 Concepts, Issues, and Approaches.............................................. 1

1 Biomedical Informatics for Cancer Research: Introduction............... 3

Michael F. Ochs, John T. Casagrande, and Ramana V. Davuluri

2 Clinical Research Systems and Integration

with Medical Systems.............................................................................. 17
Joyce C. Niland and Layla Rouse

3 Data Management, Databases, and Warehousing................................. 39

Waqas Amin, Hyunseok Peter Kang, and Michael J. Becich

4 Middleware Architecture Approaches for Collaborative

Cancer Research...................................................................................... 73
Tahsin Kurc, Ashish Sharma, Scott Oster, Tony Pan,
Shannon Hastings, Stephen Langella, David Ervin,
Justin Permar, Daniel Brat, T.J. Fitzgerald, James Purdy,
Walter Bosch, and Joel Saltz

5 Federated Authentication........................................................................ 91
Frank J. Manion, William Weems, and James McNamee

6 Genomics Data Analysis Pipelines.......................................................... 117

Michael F. Ochs

7 Mathematical Modeling in Cancer......................................................... 139

Robert A. Gatenby

8 Reproducible Research Concepts and Tools

for Cancer Bioinformatics....................................................................... 149
Vincent J. Carey and Victoria Stodden

ix
x Contents

9 The Cancer Biomedical Informatics Grid (caBIG‚):

An Evolving Community for Cancer Research..................................... 177
J. Robert Beck

Section 2 Tools and Applications................................................................. 201

10 The caBIG‚ Clinical Trials Suite............................................................ 203

John Speakman

11 The CAISIS Research Data System....................................................... 215

Paul Fearn and Frank Sculli

12 A Common Application Framework that is Extensible:

CAF-É....................................................................................................... 227
Richard Evans, Mark DeTomaso, Reed Comire, Vaibhav Bora,
Jeet Poonater, Aarti Vaishnav, Scott Catherall,
and John T. Casagrande

13 Shared Resource Management............................................................... 241

Matt Stine, Vicki Beal, Nilesh Dosooye, Yingliang Du,
Rama Gundapaneni, Andrew Pappas, Srinivas Raghavan,
Sundeep Shakya, Roshan Shrestha, Momodou Sanyang,
and Clayton Naeve

14 The caBIG® Life Sciences Distribution.................................................. 253

Juli Klemm, Anand Basu, Ian Fore, Aris Floratos,
and George Komatsoulis

15 MeV: MultiExperiment Viewer.............................................................. 267

Eleanor Howe, Kristina Holton, Sarita Nair, Daniel Schlauch,
Raktim Sinha, and John Quackenbush

16 Authentication and Authorization in Cancer

Research Systems..................................................................................... 279
Stephen Langella, Shannon Hastings, Scott Oster,
Philip Payne, and Frank Siebenlist

17 Caching and Visualizing Statistical Analyses........................................ 291

Roger D. Peng and Duncan Temple Lang

18 Familial Cancer Risk Assessment Using BayesMendel........................ 301

Amanda Blackford and Giovanni Parmigiani
Contents xi

19 Interpreting and Comparing Clustering Experiments

Through Graph Visualization and Ontology Statistical
Enrichment with the ClutrFree Package............................................... 315
Ghislain Bidaut

20 Enhanced Dynamic Documents for Reproducible Research............... 335

Deborah Nolan, Roger D. Peng, and Duncan Temple Lang

Index.................................................................................................................. 347
Contributors

Waqas Amin
Department of Biomedical Informatics, UPMC Cancer Pavilion, 5150 Centre
Avenue, Suite 301, Pittsburgh, PA 15232, USA
Anand Basu
Center for Biomedical Informatics and Information Technology, National Cancer
Institute, 2115 East Jefferson Street, Suite #5000, Rockville, MD 20852, USA
Vicki Beal
St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis,
TN 38105, USA
Michael J. Becich
Department of Biomedical Informatics, UPMC Cancer Pavilion,
5150 Centre Avenue, Suite 301, Pittsburgh, PA 15232, USA
J. Robert Beck
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
Ghislain Bidaut
Inserm, UMR891, CRCM, Integrative Bioinformatics, Marseille 13009, France
Institut Paoli-Calmettes, Marseille 13009, France
Université Méditerranée, Marseille 13007, France
Amanda Blackford
Division of Oncology Biostatistics and Bioinformatics, Johns Hopkins University,
550 North Broadway, Suite 1103, Baltimore, MD 21205, USA
Vaibhav Bora
Cancer Research Informatics Core, University of Southern California Kenneth
Norris Jr. Comprehensive Cancer Center, Harlyne Norris Cancer Research Tower
MC 9601, Los Angeles, CA 90089, USA
Walter Bosch
Department of Radiation Oncology at Washington University,
921 Parkview Place, Saint Louis, MO 63110, USA

xiii
xiv Contributors

Daniel Brat
Pathology and Laboratory Medicine, Emory University School of Medicine,
1648 Pierce Drive, Atlanta, GA 30322, USA
Vincent J Carey
Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School,
181 Longwood Avenue, Boston, MA 02115, USA
John T. Casagrande
Cancer Research Informatics Core, University of Southern California Kenneth
Norris Jr. Comprehensive Cancer Center, Harlyne Norris Cancer Research
Tower MC 9601, Los Angeles, CA 90089, USA
Scott Catherall
Financial and Business Services, University of Southern California,
University Gardens Building MC 8010, Los Angeles, CA 90089, USA
Reed Comire
Cancer Research Informatics Core, University of Southern California Kenneth
Norris Jr. Comprehensive Cancer Center, Harlyne Norris Cancer Research
Tower MC 9601, Los Angeles, CA 90089, USA
Ramana V. Davuluri
The Wistar Institute, 2601 Spruce Street, Philadelphia, PA 19104, USA
Mark DeTomaso
Cancer Research Informatics Core, University of Southern California Kenneth
Norris Jr. Comprehensive Cancer Center, Harlyne Norris Cancer Research
Tower MC 9601, Los Angeles, CA 90089, USA
Nilesh Dosooye
St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis,
TN 38105, USA
Yingliang Du
St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis,
TN 38105, USA
David Ervin
Department of Biomedical Informatics, Ohio State University,
333 W 10th Avenue, Columbus, OH 43210, USA
Richard Evans
University of California at Los Angeles, Transportation Services,
Los Angeles, CA 90095, USA
Paul Fearn
Division of Biomedical and Health Informatics, Department of Medical
Education and Biomedical Informatics, University of Washington,
1959 NE Pacific St #B509, Seattle, WA 98195, USA
Contributors xv

T.J. Fitzgerald
Quality Assurance Review Center, 272 West Exchange Street, Suite 101,
Providence, RI 02903, USA
Aris Floratos
Center for Computational Biology and Bioinformatics, Columbia University,
1130 St. Nicholas Avenue, New York, NY 10032, USA
Ian Fore
Center for Biomedical Informatics and Information Technology,
National Cancer Institute, 2115 East Jefferson Street, Suite #6000,
Rockville, MD 20852, USA
Robert A. Gatenby
Departments of Radiology and Integrative Mathematical Oncology,
Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA
Rama Gundapaneni
St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis,
TN 38105, USA
Shannon Hastings
Department of Biomedical Informatics, Ohio State University,
333 W 10th Avenue, Columbus, OH 43210, USA
Kristina Holton
Dana-Farber Cancer Institute, 44 Binney Street, Smith 822A,
Boston, MA 02115, USA
Eleanor Howe
Dana-Farber Cancer Institute, 44 Binney Street, Smith 822A,
Boston, MA 02115, USA
Hyunseok Peter Kang
Department of Pathology, Roswell Park Cancer Institute,
Elm and Carlton Streets, Buffalo, NY 14263, USA
Juli Klemm
Center for Biomedical Informatics and Information Technology,
National Cancer Institute, 2115 East Jefferson Street, Suite #6000,
Rockville, MD 20852, USA
George Komatsoulis
Center for Biomedical Informatics and Information Technology,
National Cancer Institute, 2115 East Jefferson Street, Suite #6000,
Rockville, MD 20852, USA
Tahsin Kurc
Center for Comprehensive Informatics, Emory University,
201 Dowman Drive, Atlanta, GA 30322, USA
xvi Contributors

Duncan Temple Lang

Department of Statistics, University of California at Davis, 4210 Mathematical
Sciences Building, One Shield Avenue, Davis, CA 95616, USA
Stephen Langella
Department of Biomedical Informatics, Ohio State University,
333 W 10th Avenue, Columbus, OH 43210, USA
Frank J. Manion
University of Michigan Comprehensive Cancer Center,
1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
James McNamee
School of Medicine, University of Maryland, 655 West Baltimore Street,
Baltimore, MD 21201, USA
Clayton Naeve
St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis,
TN 38105, USA
Sarita Nair
Dana-Farber Cancer Institute, 44 Binney Street, Smith 822A, Boston,
MA 02115, USA
Joyce C. Niland
City of Hope National Medical Center, 1500 East Duarte Road,
Duarte, CA 91010, USA
Deborah Nolan
Department of Statistics, University of California, 367 Evans Hall MC 3860,
Berkeley, CA 94720, USA
Michael F. Ochs
Division of Oncology Biostatistics and Bioinformatics, 550 North Broadway,
Suite 1103, Johns Hopkins University, Baltimore, MD 21205, USA
Scott Oster
Department of Biomedical Informatics, Ohio State University,
333 W 10th Avenue, Columbus, OH 43210, USA
Tony Pan
Center for Comprehensive Informatics, Emory University,
201 Dowman Drive, Atlanta, GA 30322, USA
Andrew Pappas
St. Jude Children’s Research Hospital, 262 Danny Thomas Place,
Memphis, TN 38105, USA
Giovanni Parmigiani
Department of Biostatistics and Computational Biology, Dana-Farber Cancer
Institute, 44 Binney Street, Boston, MA 02115, USA
Contributors xvii

Philip Payne
Department of Biomedical Informatics, Ohio State University,
333 W 10th Avenue, Columbus, OH 43210, USA
Roger D. Peng
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health,
615 North Wolfe Street, Baltimore, MD 21205, USA
Justin Permar
Department of Biomedical Informatics, Ohio State University,
333 W 10th Avenue, Columbus, OH 43210, USA
Jeet Poonater
Cancer Research Informatics Core, University of Southern California Kenneth
Norris Jr. Comprehensive Cancer Center, Harlyne Norris Cancer Research
Tower MC 9601, Los Angeles, CA 90089, USA
James Purdy
Department of Radiation Oncology, UC Davis Cancer Center,
4501 X Street, Sacramento, CA 95817, USA
John Quackenbush
Dana-Farber Cancer Institute, 44 Binney Street, Smith 822A, Boston,
MA 02115, USA
Srinivas Raghavan
St. Jude Children’s Research Hospital, 262 Danny Thomas Place,
Memphis, TN 38105, USA
Layla Rouse
City of Hope National Medical Center, 1500 East Duarte Road,
Duarte, CA 91010, USA
Joel Saltz
Center for Comprehensive Informatics, Emory University,
201 Dowman Drive, Atlanta, GA 30322, USA
Momodou Sanyang
St. Jude Children’s Research Hospital, 262 Danny Thomas Place,
Memphis, TN 38105, USA
Daniel Schlauch
Dana-Farber Cancer Institute, 44 Binney Street, Smith 822A, Boston,
MA 02115, USA
Frank Sculli
Biodigital Systems, 594 Broadway, New York, NY 10012, USA
Sundeep Shakya
St. Jude Children’s Research Hospital, 262 Danny Thomas Place,
Memphis, TN 38105, USA
xviii Contributors

Ashish Sharma
Center for Comprehensive Informatics, Emory University, 201 Dowman Drive,
Atlanta, GA 30322, USA
Roshan Shrestha
St. Jude Children’s Research Hospital, 262 Danny Thomas Place,
Memphis, TN 38105, USA
Frank Siebenlist
Mathematics and Computer Science Division, Argonne National Laboratory,
9700 South Cass Avenue, Argonne, IL 60439, USA
Raktim Sinha
Dana-Farber Cancer Institute, 44 Binney Street, Smith 822A, Boston,
MA 02115, USA
John Speakman
Center for Biomedical Informatics and Information Technology,
National Cancer Institute, 2115 East Jefferson Street, Suite #6000,
Rockville, MD 20852, USA
Matt Stine
St. Jude Children’s Research Hospital, 262 Danny Thomas Place,
Memphis, TN 38105, USA
Victoria Stodden
Yale Law School, 127 Wall St, New Haven, CT 06511, USA
Aarti Vaishnav
Cancer Research Informatics Core, University of Southern California Kenneth
Norris Jr. Comprehensive Cancer Center, Harlyne Norris Cancer Research
Tower MC 9601, Los Angeles, CA 90089, USA
William Weems
University of Texas Health Science Center at Houston, 7000 Fannin,
Suite 1200, Houston, TX 77030, USA
 Section 1
Concepts, Issues, and Approaches