Ten years of pathway analysis: current approaches and outstanding challenges

Pathway analysis has become the first choice for gaining insight into the underlying biology of differentially expressed genes and proteins, as it reduces complexity and has increased explanatory power. We discuss the evolution of knowledge base-driven pathway analysis over its first decade, distinc...

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Bibliographic Details
Published in:PLoS computational biology 2012-02, Vol.8 (2), p.e1002375-e1002375
Main Authors: Khatri, Purvesh, Sirota, Marina, Butte, Atul J
Format: Article
Language:English
Subjects:
Algorithms
Animals
Biology
Computational biology
Computational Biology - methods
Computational Biology - trends
Developmental biology
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Genomics
Humans
Industry analysis
Mathematics
Methods
Models, Biological
Models, Genetic
Models, Statistical
Multivariate Analysis
Ontology
Physiological aspects
Proteins
Reproducibility of Results
Review
Sensitivity and Specificity
Software
Studies
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Summary:Pathway analysis has become the first choice for gaining insight into the underlying biology of differentially expressed genes and proteins, as it reduces complexity and has increased explanatory power. We discuss the evolution of knowledge base-driven pathway analysis over its first decade, distinctly divided into three generations. We also discuss the limitations that are specific to each generation, and how they are addressed by successive generations of methods. We identify a number of annotation challenges that must be addressed to enable development of the next generation of pathway analysis methods. Furthermore, we identify a number of methodological challenges that the next generation of methods must tackle to take advantage of the technological advances in genomics and proteomics in order to improve specificity, sensitivity, and relevance of pathway analysis.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1002375