Breaking Free from the Chains of Pathway Annotation: de Novo Pathway Discovery for the Analysis of Disease Processes

Abstract

Interpreting the biological implications of high-throughput experiments such as gene-expression studies, genome-wide association studies and large-scale sequencing studies is not trivial. Gene-set and pathway analyses are useful tools to support the interpretation of such experiments, but rely on curated pathways or gene sets. The recent development of de novo pathway discovery methods aims to overcome this limitation. This article provides an overview of the methods currently available and reviews the advantages and challenges of this approach. In detail, it highlights the particular issues of de novo pathway discovery based on genome-wide association studies data, for which multiple different strategies have been proposed.

KEYWORDS::

• disease gene identification
• gene function
• gene network
• genome-wide association studies
• pathway analysis
• protein network

Acknowledgements

The authors would like to thank N Barkas, N Dand, N Prescott, M Simpson, L Southgate and R Sutherland for critical discussions.

Financial & competing interests disclosure

Financial support from King‘s College London, the British Council (ARC 1297) and the Royal Society (RG100252) is gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Financial support from King‘s College London, the British Council (ARC 1297) and the Royal Society (RG100252) is gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.