TOPS: a versatile software tool for statistical analysis and visualization of combinatorial gene-gene and gene-drug interaction screens

BMC Bioinformatics

Markus K Muellner¹  Gerhard Duernberger²  Florian Ganglberger¹  Claudia Kerzendorfer¹  Iris Z Uras¹  Andreas Schoenegger¹  Klaudia Bagienski¹  Jacques Colinge¹  Sebastian MB Nijman¹ 

[1] Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM), Vienna, Austria

[2] Current address: The Research Institute of Molecular Pathology (IMP), Vienna, Austria

关键词: Epistasis;    Synergy;    Drug screens;    Luminex xMAP;    Massive parallel sequencing;    Functional genetics;    Synthetic lethality;    Double perturbation screens;   

Others  :  1087575
DOI  :  10.1186/1471-2105-15-98

 received in 2013-05-17, accepted in 2014-03-28,  发布年份 2014

【 摘 要 】

Background

Measuring the impact of combinations of genetic or chemical perturbations on cellular fitness, sometimes referred to as synthetic lethal screening, is a powerful method for obtaining novel insights into gene function and drug action. Especially when performed at large scales, gene-gene or gene-drug interaction screens can reveal complex genetic interactions or drug mechanism of action or even identify novel therapeutics for the treatment of diseases.

The result of such large-scale screen results can be represented as a matrix with a numeric score indicating the cellular fitness (e.g. viability or doubling time) for each double perturbation. In a typical screen, the majority of combinations do not impact the cellular fitness. Thus, it is critical to first discern true "hits" from noise. Subsequent data exploration and visualization methods can assist to extract meaningful biological information from the data. However, despite the increasing interest in combination perturbation screens, no user friendly open-source program exists that combines statistical analysis, data exploration tools and visualization.

Results

We developed TOPS (Tool for Combination Perturbation Screen Analysis), a Java and R-based software tool with a simple graphical user interface that allows the user to import, analyze, filter and plot data from double perturbation screens as well as other compatible data. TOPS was designed in a modular fashion to allow the user to add alternative importers for data formats or custom analysis scripts not covered by the original release.

We demonstrate the utility of TOPS on two datasets derived from functional genetic screens using different methods. Dataset 1 is a gene-drug interaction screen and is based on Luminex xMAP technology. Dataset 2 is a gene-gene short hairpin (sh)RNAi screen exploring the interactions between deubiquitinating enzymes and a number of prominent oncogenes using massive parallel sequencing (MPS).

Conclusions

TOPS provides the benchtop scientist with a free toolset to analyze, filter and visualize data from functional genomic gene-gene and gene-drug interaction screens with a flexible interface to accommodate different technologies and analysis algorithms in addition to those already provided here. TOPS is freely available for academic and non-academic users and is released as open source.

【 授权许可】

   
2014 Muellner et al.; licensee BioMed Central Ltd.

【 图 表 】

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