---

This book is open access under a CC BY 4.0 license.

This book provides a practical and self-contained overview of the Gene Ontology (GO), the leading project to organize biological knowledge on genes and their products across genomic resources. Written for biologists and bioinformaticians, it covers the state-of-the-art of how GO annotations are made, how they are evaluated, and what sort of analyses can and cannot be done with the GO. In the spirit of the Methods in Molecular Biology book series, there is an emphasis throughout the chapters on providing practical guidance and troubleshooting advice. Authoritative and accessible, The Gene Ontology Handbook serves non-experts as well as seasoned GO users as a thorough guide to this powerful knowledge system.

---

Part I: Fundamentals

1. Primer on Ontologies

Janna Hastings

2. The Gene Ontology and the Meaning of Biological Function

Paul D. Thomas

3. Primer on the Gene Ontology

Pascale Gaudet, Nives Skunca, James C. Hu, and Christophe Dessimoz

Part II: Making Gene Ontology Annotations

4. Best Practices in Manual Annotation with the Gene Ontology

Sylvain Poux and Pascale Gaudet

5. Computational Methods for Annotation Transfers from Sequence

Domenico Cozzetto and David T. Jones

6. Text Mining to Support Gene Ontology Curation and Vice Versa

Patrick Ruch

7. How Does the Scientific Community Contribute to Gene Ontology?

Ruth C. Lovering

Part III: Evaluating Gene Ontology Annotations

8. Evaluating Computational Gene Ontology Annotations

Nives Skunca, Richard J. Roberts, and Martin Steffen

9. Evaluating Functional Annotations of Enzymes Using the Gene Ontology

Gemma L. Holliday, Rebecca Davidson, Eyal Akiva, and Patricia C. Babbitt

10. Community-Based Evaluation of Computational Function Prediction

Iddo Friedberg and Predrag Radivojac

Part IV: Using the Gene Ontology

11. Get GO!: Retrieving GO Data Using AmiGO, QuickGO, API, Files, and Tools

Monica Munoz-Torres and Seth Carbon

12. Semantic Similarity in the Gene Ontology

Catia Pesquita
13. Gene-Category Analysis

Sebastian Bauer

14. Gene Ontology: Pitfalls, Biases, and Remedies

Pascale Gaudet and Christophe Dessimoz

15. Visualizing GO Annotations

Fran Supek and Nives Skunca

16. A Gene Ontology Tutorial in Python

Alex Warwick Vesztrocy and Christophe Dessimoz

Part V: Advanced Gene Ontology Topics < 17. Annotation Extensions

Rachael P. Huntley and Ruth C. Lovering

18. The Evidence and Conclusion Ontology (ECO): Supporting GO Annotations

Marcus C. Chibucos, Deborah A. Siegele, James C. Hu, and Michelle Giglio

Part VI: Beyond the Gene Ontology

19. Complementary Sources of Protein Functional Information: The Far Side of GO

Nicholas Furnham

20. Integrating Bio-Ontologies and Controlled Clinical Terminologies: From Base Pairs to Bedside Phenotypes

Spiros C. Denaxas

Part VII: Conclusion

21. The Vision and Challenges of the Gene Ontology

Suzanna E. Lewis

---