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  • Springer Science and Business Media LLC  (2)
  • Nelander, Sven  (2)
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  • Springer Science and Business Media LLC  (2)
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  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-10-03)
    Abstract: The gene regulatory network (GRN) of a cell executes genetic programs in response to environmental and internal cues. Two distinct classes of methods are used to infer regulatory interactions from gene expression: those that only use observed changes in gene expression, and those that use both the observed changes and the perturbation design, i.e. the targets used to cause the changes in gene expression. Considering that the GRN by definition converts input cues to changes in gene expression, it may be conjectured that the latter methods would yield more accurate inferences but this has not previously been investigated. To address this question, we evaluated a number of popular GRN inference methods that either use the perturbation design or not. For the evaluation we used targeted perturbation knockdown gene expression datasets with varying noise levels generated by two different packages, GeneNetWeaver and GeneSpider. The accuracy was evaluated on each dataset using a variety of measures. The results show that on all datasets, methods using the perturbation design matrix consistently and significantly outperform methods not using it. This was also found to be the case on a smaller experimental dataset from E. coli . Targeted gene perturbations combined with inference methods that use the perturbation design are indispensable for accurate GRN inference.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2020
    In:  npj Systems Biology and Applications Vol. 6, No. 1 ( 2020-11-09)
    In: npj Systems Biology and Applications, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2020-11-09)
    Abstract: The interactions among the components of a living cell that constitute the gene regulatory network (GRN) can be inferred from perturbation-based gene expression data. Such networks are useful for providing mechanistic insights of a biological system. In order to explore the feasibility and quality of GRN inference at a large scale, we used the L1000 data where ~1000 genes have been perturbed and their expression levels have been quantified in 9 cancer cell lines. We found that these datasets have a very low signal-to-noise ratio (SNR) level causing them to be too uninformative to infer accurate GRNs. We developed a gene reduction pipeline in which we eliminate uninformative genes from the system using a selection criterion based on SNR, until reaching an informative subset. The results show that our pipeline can identify an informative subset in an overall uninformative dataset, allowing inference of accurate subset GRNs. The accurate GRNs were functionally characterized and potential novel cancer-related regulatory interactions were identified.
    Type of Medium: Online Resource
    ISSN: 2056-7189
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2841868-2
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