Introduction to Bio-Ontologies

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ISBN: 9781439836651 | 1439836655
Cover: Hardcover
Copyright: 6/22/2011

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Ontologies have become the tool of choice for organizing and describing the meaning of biological and medical data. This book introduces the most important aspects of bio-ontologies, including statistical overrepresentation analysis, semantic similarity, and inference. Each chapter reviews the main goals of the methods discussed, explains the mathematical and computation methods used to achieve those goals, offers practical examples, and includes theoretical and practical exercises. A supporting website provides ontologies and files for the practical exercises and open-source software.

List of Figures	p. xxi
List of Tables	p. xxv
Symbol Description	p. xxvii
Basic Concepts	p. 1
Ontologies and Applications of Ontologies in Biomedicine	p. 3
What Is an Ontology?	p. 3
Ontologies and Bio-Ontologies	p. 5
Ontologies for Data Organization, Integration, and Searching	p. 6
Computer Reasoning with Ontologies	p. 9
Typical Applications of Bio-Ontologies	p. 10
Mathematical Logic and Inference	p. 11
Representation and Logic	p. 11
Propositional Logic	p. 13
First-Order Logic	p. 18
Sets	p. 25
Description Logic	p. 29
Description Language AL	p. 29
Description Language ALC	p. 31
Further Description Logic Constructors	p. 32
Exercises and Further Reading	p. 36
Probability Theory and Statistics for Bio-Ontologies	p. 41
Probability Theory	p. 41
Hypothesis Testing	p. 43
p-Values and Probability Distributions	p. 44
Multiple-Testing Correction	p. 51
Bayes' Theorem	p. 56
Introduction to Graphs	p. 58
Bayesian Networks	p. 62
Exercises and Further Reading	p. 64
Ontology Languages	p. 67
OBO	p. 67
OBO Stanzas	p. 68
Intersections: Computable Definitions	p. 70
OWL and the Semantic Web	p. 71
Resource Description Framework	p. 72
RDF Schema	p. 78
The Web Ontology Language OWL	p. 85
OBO, RDF, RDFS, and OWL	p. 95
Exercises and Further Reading	p. 99
Bio-Ontologies	p. 113
The Gene Ontology	p. 115
A Tool for the Unification of Biology	p. 115
Three Subontologies	p. 117
Molecular Function	p. 117
Biological Process	p. 117
Cellular Component	p. 118
Relations in GO	p. 120
GO Annotations	p. 121
Evidence for Gene Functions	p. 124
Inferred from Electronic Annotation	p. 127
The True Path Rule and Propagation of Annotations	p. 128
GO Slims	p. 133
Exercises and Further Reading	p. 134
Upper-Level Ontologies	p. 139
Basic Formal Ontology	p. 139
The Big Divide: Continuants and Occurrents	p. 140
Continuants	p. 141
Occurrents	p. 142
Universals and Particulars	p. 142
Relation Ontology	p. 143
Revisiting Gene Ontology	p. 147
Revisiting GO Annotations	p. 148
Exercises and Further Reading	p. 150
A Selective Survey of Bio-Ontologies	p. 153
OBO Foundry	p. 153
The National Center for Biomedical Ontology	p. 155
Bio-Ontologies	p. 155
Ontologies for Anatomy: The FMA and Model Organisms	p. 156
Cell Ontology	p. 159
Chemical Entities of Biological Interest	p. 160
OBI	p. 162
The Protein Ontology	p. 162
The Sequence Ontology	p. 165
Mammalian Phenotype Ontology (MPO)	p. 166
Human Phenotype Ontology (HPO)	p. 167
MPATH	p. 171
PATO	p. 172
What Makes a Good Ontology?	p. 175
Exercises and Further Reading	p. 177
Graph Algorithms for Bio-Ontologies	p. 179
Overrepresentation Analysis	p. 181
Definitions	p. 182
Term-for-Term	p. 183
Multiple Testing Problem	p. 185
Term-for-Term Analysis: An Extended Example	p. 188
Inferred Annotations Lead to Statistical Dependencies in Ontology DAGs	p. 192
Parent-Child Algorithms	p. 195
Parent-Child Analysis: An Extended Example	p. 198
Topology-Based Algorithms	p. 200
Elim	p. 200
Weight	p. 202
Topology-elim: An Extended Example	p. 205
Other Approaches	p. 207
Summary	p. 209
Exercises and Further Reading	p. 209
Model-Based Approaches to GO Analysis	p. 219
A Probabilistic Generative Model for GO Enrichment Analysis	p. 219
A Bayesian Network Model	p. 222
Maximum a posteriori	p. 226
Monte Carlo Markov Chain Algorithm	p. 227
MGSA Algorithm with Unknown Parameters	p. 230
MGSA: An Extended Example	p. 233
Summary	p. 234
Exercises and Further Reading	p. 235
Semantic Similarity	p. 237
Information Content in Ontologies	p. 237
Semantic Similarity of Genes and Other Items Annotated by Ontology Terms	p. 247
Graph-Based and Set-Based Measures of Semantic Similarity	p. 248
Applications of Semantic Similarity in Bioinformatics	p. 249
Applications of Semantic Similarity for Clinical Diagnostics	p. 251
Statistical Significance of Semantic Similarity Scores	p. 252
Exercises and Further Reading	p. 255
Frequency-Aware Bayesian Network Searches in Attribute Ontologies	p. 261
Modeling Queries	p. 262
High-Level Description of the Model	p. 262
Annotation Propagation Rule for Bayesian Networks	p. 264
LPDs of Hidden Term States	p. 266
LPDs of Observed Term States	p. 266
Probabilistic Inference for the Items	p. 270
Parameter-Augmented Network	p. 272
The Frequency-Aware Network	p. 273
Benchmark	p. 274
Inference in Ontologies	p. 279
Inference in the Gene Ontology	p. 281
Inference over GO Edges	p. 281
Cross-Products and Logical Definitions	p. 285
Intra-GO Cross-Product Definitions	p. 286
External Cross-Product Definitions	p. 288
Reasoning with Cross-Product Definitions	p. 288
Exercises and Further Reading	p. 289
RDFS Semantics and Inference	p. 293
Definitions	p. 293
Interpretations	p. 294
RDF Entailment	p. 303
RDFS Entailment	p. 305
Entailment Rules	p. 307
Summary	p. 314
Exercises and Further Reading	p. 314
Inference in OWL Ontologies	p. 317
The Semantics of Equality	p. 317
The Semantics of Properties	p. 320
The Semantics of Classes	p. 325
The Semantics of the Schema Vocabulary	p. 331
Conclusions	p. 333
Exercises and Further Reading	p. 333
Algorithmic Foundations of Computational Inference	p. 335
The Tableau Algorithm	p. 336
Negative Normal Form	p. 338
Algorithm for ABox	p. 339
Adding Support for the TBox	p. 344
Developer Libraries	p. 346
Exercises and Further Reading	p. 348
SPARQL	p. 357
SPARQL Queries	p. 357
Combining RDF Graphs	p. 365
Conclusions	p. 368
Exercises and Further Reading	p. 369
Appendices	p. 375
An Overview of R	p. 377
Information Content and Entropy	p. 395
W3C Standards: XML, URIs, and RDF	p. 399
W3C Standards: OWL	p. 427
Glossary	p. 457
Bibliography	p. 461
Index	p. 485
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