metaModules identifies key functional subnetworks in microbiome-related disease.
The human microbiome plays a key role in health and disease. Thanks to comparative metatranscriptomics, the cellular functions that are deregulated by the microbiome in disease can now be computationally explored. Unlike gene-centric approaches, pathway-based methods provide a systemic view of such functions; however, they typically consider each pathway in isolation and in its entirety. They can therefore overlook the key differences that (i) span multiple pathways, (ii) contain bidirectionally deregulated components, (iii) are confined to a pathway region. To capture these properties, computational methods that reach beyond the scope of predefined pathways are needed.



By integrating an existing module discovery algorithm into comparative metatranscriptomic analysis, we developed metaModules, a novel computational framework for automated identification of the key functional differences between health- and disease-associated communities. Using this framework, we recovered significantly deregulated subnetworks that were indeed recognized to be involved in two well-studied, microbiome-mediated oral diseases, such as butanoate production in periodontal disease and metabolism of sugar alcohols in dental caries. More importantly, our results indicate that our method can be used for hypothesis generation based on automated discovery of novel, disease-related functional subnetworks, which would otherwise require extensive and laborious manual assessment.



metaModules is available at https://bitbucket.org/alimay/metamodules/



a.may@vu.nl or s.abeln@vu.nl



Supplementary data are available at Bioinformatics online.
Centre for Integrative Bioinformatics VU (IBIVU), VU University Amsterdam, Amsterdam, The Netherlands, Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), VU University Amsterdam, Amsterdam, The Netherlands.
Ali
A
May
Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
Bernd W
BW
Brandt
Centre for Integrative Bioinformatics VU (IBIVU), VU University Amsterdam, Amsterdam, The Netherlands, Department of Computer Science and Center for Computational Molecular Biology, Brown University, Providence, USA and Life Sciences, Centre for Mathematics and Computer Science (CWI), Amsterdam, The Netherlands.
Mohammed
M
El-Kebir
Centre for Integrative Bioinformatics VU (IBIVU), VU University Amsterdam, Amsterdam, The Netherlands, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), VU University Amsterdam, Amsterdam, The Netherlands, Life Sciences, Centre for Mathematics and Computer Science (CWI), Amsterdam, The Netherlands.
Gunnar W
GW
Klau
Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
Egija
E
Zaura
Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
Wim
W
Crielaard
Centre for Integrative Bioinformatics VU (IBIVU), VU University Amsterdam, Amsterdam, The Netherlands, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), VU University Amsterdam, Amsterdam, The Netherlands.
Jaap
J
Heringa
Centre for Integrative Bioinformatics VU (IBIVU), VU University Amsterdam, Amsterdam, The Netherlands, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), VU University Amsterdam, Amsterdam, The Netherlands.
Sanne
S
Abeln
D000465:Algorithms; D003731:Dental Caries; D006801:Humans; D064307:Microbiota