ATARiS: Computational quantification of gene suppression phenotypes from multisample RNAi screens
What is ATARiS?
ATARiS is a computational method designed to analyze phenotypic readouts from multiple-sample RNAi screens in which each gene is targeted by multiple RNAi reagents. "ATARiS" stands for Analytic Technique for Assessment of RNAi by Similarity. ATARiS was developed by Aviad Tsherniak in the lab of Jill Mesirov.
What problem does ATARiS solve?
RNAi reagents designed to target the same gene often induce different degrees of on-target and off-target gene suppression, resulting in inconsistent phenotypes. This renders interpretation and downstream analysis of the gene-level phenotype challenging.
What does ATARiS do?
ATARiS generates two types of results:
Gene solutions – For each gene, ATARiS tries to identify subsets of its RNAi reagents that produce a significantly similar phenotypic pattern across the screened samples. If such a subset is found, the data from these reagents are summarized into a gene solution profile. The solution consists of one phenotype value for each sample, representing the phenotypic outcome of suppressing the target gene in that sample relative to the outcome in other screened samples.
Genes for which no such subset can be found will have no gene solutions associated with them. For some genes, more than one solution may exist (e.g., two pairs of reagents, each producing effects similar between the reagents but not between the pairs). In these cases, all gene solutions will be reported.
The resulting file, containing the gene solutions for all screened genes, can be used in downstream analyses using standard genomic tools (e.g. tools designed for gene expression analysis).
Reagent consistency scores – For each reagent, ATARiS computes a consistency score that represents the confidence that its observed phenotypic effects are the result of on-target gene suppression.
How can I run ATARiS on my own data?
ATARiS has been implemented as a module in the GenePattern computational genomics suite. To run ATARiS on GenePattern's public server click here (registration is required, quick and free). After signing in, you can find the ATARiS module on the left, under the category 'RNAi', or search for 'ATARiS' in the search box on the upper-left corner).
Please contact us if you have any questions or suggestions.
What is the input to ATARiS?
The main input for ATARiS is a file containing the phenotypic readouts for all RNAi reagents and samples screened. The file should be in a GCT file format – a tab-delimited text file originally used for gene expression data. It can be easily created using Excel or similar programs. See here for more details.
Each data row of the input GCT file contains readouts of screening data produced by one RNAi reagent. The first column of the file contains unique reagent IDs. The second column contains gene symbols/IDs (in any format) representing the genes targeted by each reagent. Each additional column holds the data for one screened sample with the column header being the sample (unique) name/ID. Note that the distributions of values for all samples are assumed to be similar (e.g., after sample-wise Z-score transformation).
ATARiS: Computational quantification of gene suppression phenotypes from multisample RNAi screens. [preprint] [supplementary info] [supplementary data]
Diane D Shao*, Aviad Tsherniak*, Shuba Gopal, Barbara A Weir, Pablo Tamayo, Nicolas Stransky, Steven E Schumacher, Travis I Zack, Rameen Beroukhim, Levi A Garraway, Adam A Margolin, David E Root, William C Hahn, and Jill P Mesirov. Genome Res. 2013 Apr;23(4):665-78. doi: 10.1101/gr.143586.112. Epub 2012 Dec 26.