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Data Mining for Systems Biology Methods and Protocols
1st Edition Koji Tsuda Digital Instant Download
Author(s): Koji Tsuda, Elisabeth Georgii (auth.), Hiroshi Mamitsuka, Charles
DeLisi, Minoru Kanehisa (eds.)
ISBN(s): 9781627031066, 1627031065
Edition: 1
File Details: PDF, 8.01 MB
Year: 2013
Language: english
METHODS MOLECULAR BIOLOGY
TM
IN

Series Editor
John M. Walker
School of Life Sciences
University of Hertfordshire
Hatfield, Hertfordshire, AL10 9AB, UK

For further volumes:

http://www.springer.com/series/7651
Data Mining for Systems
Biology

Methods and Protocols

Edited by

Hiroshi Mamitsuka
Bioinformatics Center,
Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan

Charles DeLisi
Department of Biomedical Engineering, Boston University,
Boston, MA, USA

Minoru Kanehisa
Bioinformatics Center,
Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan
Editors
Hiroshi Mamitsuka Charles DeLisi, Ph.D.
Bioinformatics Center Department of Biomedical Engineering
Institute for Chemical Research Boston University
Kyoto University Boston, MA, USA
Uji, Kyoto, Japan

Minoru Kanehisa
Bioinformatics Center
Institute for Chemical Research
Kyoto University
Uji, Kyoto, Japan

ISSN 1064-3745 ISSN 1940-6029 (electronic)

ISBN 978-1-62703-106-6 ISBN 978-1-62703-107-3 (eBook)
DOI 10.1007/978-1-62703-107-3
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2012947383

ª Springer Science+Business Media New York 2013

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Preface

The post-genomic revolution is witnessing the generation of petabytes of information

annually, with deep implications ranging across evolutionary theory, developmental biol-
ogy, agriculture, and disease processes. The great challenge during the coming decades is
not so much in generating the data, for that will continue at an accelerating pace, but in
converting it into the information and knowledge that will improve the human condition
and deepen our understanding of the world around us. A first step in meeting that
challenge is to structure data so that it is easily accessed, integrated, and assimilated.
Data Mining in Systems Biology surveys and demonstrates the science and technology of
this important initial step in the data-to-knowledge conversion. The volume is organized
around two overlapping themes, network inference and functional inference.

Network Inference

Tsuda and Georgii (Dense Module Enumeration in Biological Networks) discuss a rigorous,
robust, and inclusive approach to inferring a particular type of network; viz, networks
defined by databases that record physical interactions between proteins. Willy, Sung, and
Ng (Discovering Interacting Domains and Motifs in Protein–Protein Interactions) discuss a
method for discovering interactions between protein domains and short linear sequences,
which are fundamental to multiple cellular processes. In particular, they discuss and
demonstrate how to exploit the surge in structural data to infer such interactions. Mon-
giovı̀ and Sharan (Global Alignment of Protein–Protein Interaction Networks) describe a
novel method for identifying proteins that are orthologous across species. Their method is
based on alignment of protein–protein interaction networks. This paper and that of Tsuda
and Georgii represent a good example of the knowledge amplification that can be achieved
by research on different but potentially complementary projects carried out by different
labs. These three papers illustrate important directions in the discovery and analysis of
protein–protein interactions.
While protein–protein interactions define the repertoire of cellular processes, pro-
tein–DNA interactions regulate those processes. In general, gene/protein networks
defined by such interactions can be inferred from experimental data by various multivariate
statistical methods. One of the widely used forms of inference is Bayesian probabilistic
modeling. Larjo, Shmulevich, and L€ahdesm€aki (Structure Learning for Bayesian Networks
as Models of Biological Networks) review recent progress in the development and application
of these methods. Mordelet and Vert (Supervised Inference of Gene Regulatory Networks
from Positive and Unlabeled Examples) discuss SIRENE, a machine learning method for
inferring networks of transcriptional regulators and their targets from expression data and
known regulatory relationships. Honkela, Rattray, and Lawrence (Mining Regulatory
Network Connections by Ranking Transcription Factor Target Genes Using Time Series
Expression Data) developed a reverse engineering approach to infer regulator target inter-
actions and applied it to candidate targets of the p53 tumor suppressor promoter.

v
vi Preface

Historically, molecular biology has focused on proteins and nucleic acids. One of
the major changes in the past decade has been a dramatic increase in understanding
metabolism; this, of course, is also stimulated by the availability of whole genome sequence
data. This constitutes the subject of Protein–Chemical Substance Interactions. Hancock,
Takigawa, and Mamitsuka (Identifying Pathways of Co-ordinated Gene Expression) present a
tutorial for the use of gene expression data to identify metabolic networks associated with
a given condition.
More direct approaches to metabolism include an increased emphasis on the structure
of complex carbohydrates. Aoki-Kinoshita (Mining Frequent Subtrees in Glycan Data
Using the RINGS Glycan Miner Tool) describes an algorithmic method for finding fre-
quently occurring tree structures with glycan databases, which are relevant to the binding
of particular proteins. This can be thought of as the metabolic analogue to approaches that
identify protein–protein and protein–DNA binding sites.
The chapter by Yamanishi (Chemogenomic Approaches to Infer Drug–Target Interaction
Networks) discusses another kind of network, those formed by drug–target interactions. In
this case, sequence and chemical structure databases provide the information that enable
statistical classification methods to identify plausible drug–target interactions.

Functional Inference

The ability to predicatively localize proteins to one or another cellular compartment can
generate important clues about their possible function. Imai, Hayat, Sakiyama, Fujita,
Tomii, Elofsson, and Horton (Localization Prediction and Structure-Based In Silico Anal-
ysis of Bacterial Proteins: With Emphasis on Outer Membrane Proteins) evaluate localization
prediction tools against a known dataset, and illustrate with an application to b-barrel outer
membrane proteins in E. coli. For biological interpretation of large-scale datasets, visuali-
zation tools play key roles. Hu (Analysis Strategy of Protein–Protein Interaction Networks)
explains how to use the multiple data sources and analytical tools in VisANT to identify and
analyze networks of various kinds. Karp, Paley, and Altman (Data Mining in the MetaCyc
Family of Pathway Databases) present an introduction to the contributions made by Karp
and his colleagues over many years. The chapter is a rich source of tools and methods for
mining this extensive, well-curated, and extremely important set of databases.
Approaches to genotype–phenotype correlations have evolved continuously over the
past several decades. With the advent of whole genome sequencing, the search for correla-
tions between genes and Mendelian traits accelerated enormously, but complex pheno-
types, whether normal traits or diseases, find their genetic basis in sets of genes, and in
particular combinations of alleles. Various procedures have been developed to infer such
sets from variations in transcriptional variation. Hung (Gene Set/Pathway Enrichment
Analysis) describes in detail how the so-called gene set enrichment analysis can be used
to draw functional inferences from such transcriptional datasets. The method has been
applied to identify processes that distinguish disease phenotypes from normal phenotypes.
This leads to the final four chapters of the volume, which are all disease related.
Linghu, Franzosa, and Xia (Construction of Functional Linkage Gene Networks by Data
Integration) discuss an approach to combining heterogeneous datasets in order to con-
struct full genome networks in which each gene is surrounded by functionally related
 Preface vii

neighbors, with the relationships specified by evidence-weighted links. Such functional

linkage networks (FLNs) of human genes can uncover surprising genetic associations
between phenotypically unrelated diseases and suggest that our current disease nosology
may need to be reformulated.
The chapter by Yang, Kon, and DeLisi (Genome-Wide Association Studies) presents an
overview of genome-wide association methods and explains how multiple data sources,
including databases generated by high-throughput genotyping technologies, can be used
to identify disease-associated chromosomal locations.
Kuiken, Yoon, Abfalterer, Gaschen, Lo, and Korber (Viral Genome Analysis and
Knowledge Management) discuss three of the major infectious disease sequence-function
databases—those for the human immunodeficiency, hepatitis C, and hemorrhagic fever
viruses. The challenge here again is combining information from different sources, but in
this case, integration and quality control are achieved by a continually upgraded
community-developed infrastructure.
Kanehisa (Molecular Network Analysis of Diseases and Drugs in KEGG) presents
another integrated approach where known disease genes and drug targets are integrated
into the KEGG molecular network database and explains how to make use of this resource
with the KEGG Mapper tool in large-scale data analysis.
We expect this book to be of interest to cell biologists and biotechnologists, as well as
to the scientists and engineers developing the databases and mining and visualization
systems that are central to the paradigm-altering discoveries being made with increasing
frequency.

Uji, Kyoto, Japan Hiroshi Mamitsuka

Boston, MA, USA Charles DeLisi
Uji, Kyoto, Japan Minoru Kanehisa
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 Politics - Solution Manual
Fall 2024 - Research Center

Prepared by: Lecturer Smith

Date: August 12, 2025

Background 1: Comparative analysis and synthesis

Learning Objective 1: Statistical analysis and interpretation
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Learning Objective 2: Learning outcomes and objectives
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Learning Objective 3: Research findings and conclusions
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 3: Diagram/Chart/Graph]
Learning Objective 4: Historical development and evolution
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 4: Diagram/Chart/Graph]
Learning Objective 5: Assessment criteria and rubrics
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 5: Diagram/Chart/Graph]
Key Concept: Fundamental concepts and principles
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 6: Diagram/Chart/Graph]
Practice Problem 6: Case studies and real-world applications
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Statistical analysis and interpretation
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Experimental procedures and results
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Problem-solving strategies and techniques
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Module 2: Ethical considerations and implications
Key Concept: Experimental procedures and results
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Important: Experimental procedures and results
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Ethical considerations and implications
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 13: Diagram/Chart/Graph]
Key Concept: Statistical analysis and interpretation
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Important: Literature review and discussion
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Definition: Best practices and recommendations
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Problem-solving strategies and techniques
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Practice Problem 17: Case studies and real-world applications
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Case studies and real-world applications
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 19: Diagram/Chart/Graph]
Key Concept: Learning outcomes and objectives
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Background 3: Interdisciplinary approaches
Important: Current trends and future directions
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 21: Diagram/Chart/Graph]
Note: Experimental procedures and results
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 22: Diagram/Chart/Graph]
Important: Key terms and definitions
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Theoretical framework and methodology
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Note: Research findings and conclusions
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 25: Comparative analysis and synthesis
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Critical analysis and evaluation
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Statistical analysis and interpretation
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Theoretical framework and methodology
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 29: Diagram/Chart/Graph]
Key Concept: Study tips and learning strategies
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Part 4: Statistical analysis and interpretation
Remember: Best practices and recommendations
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Historical development and evolution
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 32: Diagram/Chart/Graph]
Remember: Experimental procedures and results
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Practical applications and examples
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Historical development and evolution
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Current trends and future directions
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 36: Diagram/Chart/Graph]
Key Concept: Ethical considerations and implications
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Comparative analysis and synthesis
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Practical applications and examples
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Ethical considerations and implications
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 40: Diagram/Chart/Graph]
Chapter 5: Key terms and definitions
Important: Current trends and future directions
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Critical analysis and evaluation
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Ethical considerations and implications
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Assessment criteria and rubrics
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 44: Experimental procedures and results
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Assessment criteria and rubrics
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 46: Diagram/Chart/Graph]
Practice Problem 46: Best practices and recommendations
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Key Concept: Comparative analysis and synthesis
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 48: Diagram/Chart/Graph]
Important: Research findings and conclusions
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 49: Problem-solving strategies and techniques
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Introduction 6: Case studies and real-world applications
Practice Problem 50: Literature review and discussion
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 51: Diagram/Chart/Graph]
Note: Literature review and discussion
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 52: Diagram/Chart/Graph]
Note: Interdisciplinary approaches
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Note: Ethical considerations and implications
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 54: Diagram/Chart/Graph]
Important: Literature review and discussion
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Ethical considerations and implications
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Key terms and definitions
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 57: Diagram/Chart/Graph]
Definition: Literature review and discussion
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Problem-solving strategies and techniques
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Best practices and recommendations
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Background 7: Practical applications and examples
Definition: Experimental procedures and results
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 61: Diagram/Chart/Graph]
Definition: Statistical analysis and interpretation
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Statistical analysis and interpretation
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Critical analysis and evaluation
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Key terms and definitions
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 65: Problem-solving strategies and techniques
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 66: Ethical considerations and implications
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Best practices and recommendations
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 68: Diagram/Chart/Graph]
Example 68: Theoretical framework and methodology
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Experimental procedures and results
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Summary 8: Ethical considerations and implications
Example 70: Interdisciplinary approaches
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Experimental procedures and results
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Case studies and real-world applications
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Key Concept: Theoretical framework and methodology
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Statistical analysis and interpretation
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 75: Diagram/Chart/Graph]
Remember: Research findings and conclusions
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
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