A network-based integrative approach to prioritize reliable hits from multiple genome-wide RNAi screens in DrosophilaReport as inadecuate




A network-based integrative approach to prioritize reliable hits from multiple genome-wide RNAi screens in Drosophila - Download this document for free, or read online. Document in PDF available to download.

BMC Genomics

, 10:220

First Online: 12 May 2009Received: 05 January 2009Accepted: 12 May 2009

Abstract

BackgroundThe recently developed RNA interference RNAi technology has created an unprecedented opportunity which allows the function of individual genes in whole organisms or cell lines to be interrogated at genome-wide scale. However, multiple issues, such as off-target effects or low efficacies in knocking down certain genes, have produced RNAi screening results that are often noisy and that potentially yield both high rates of false positives and false negatives. Therefore, integrating RNAi screening results with other information, such as protein-protein interaction PPI, may help to address these issues.

ResultsBy analyzing 24 genome-wide RNAi screens interrogating various biological processes in Drosophila, we found that RNAi positive hits were significantly more connected to each other when analyzed within a protein-protein interaction network, as opposed to random cases, for nearly all screens. Based on this finding, we developed a network-based approach to identify false positives FPs and false negatives FNs in these screening results. This approach relied on a scoring function, which we termed NePhe, to integrate information obtained from both PPI network and RNAi screening results. Using a novel rank-based test, we compared the performance of different NePhe scoring functions and found that diffusion kernel-based methods generally outperformed others, such as direct neighbor-based methods. Using two genome-wide RNAi screens as examples, we validated our approach extensively from multiple aspects. We prioritized hits in the original screens that were more likely to be reproduced by the validation screen and recovered potential FNs whose involvements in the biological process were suggested by previous knowledge and mutant phenotypes. Finally, we demonstrated that the NePhe scoring system helped to biologically interpret RNAi results at the module level.

ConclusionBy comprehensively analyzing multiple genome-wide RNAi screens, we conclude that network information can be effectively integrated with RNAi results to produce suggestive FPs and FNs, and to bring biological insight to the screening results.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-10-220 contains supplementary material, which is available to authorized users.

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Author: Li Wang - Zhidong Tu - Fengzhu Sun

Source: https://link.springer.com/article/10.1186/1471-2164-10-220



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