Ballouz, S., Gillis, J. (April 2016) AuPairWise: A Method to Estimate RNA-Seq Replicability through Co-expression. PLoS Comput Biol, 12 (4). e1004868. ISSN 1553-7358 (Electronic)1553-734X (Linking)
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Abstract
In addition to detecting novel transcripts and higher dynamic range, a principal claim for RNA-sequencing has been greater replicability, typically measured in sample-sample correlations of gene expression levels. Through a re-analysis of ENCODE data, we show that replicability of transcript abundances will provide misleading estimates of the replicability of conditional variation in transcript abundances (i.e., most expression experiments). Heuristics which implicitly address this problem have emerged in quality control measures to obtain 'good' differential expression results. However, these methods involve strict filters such as discarding low expressing genes or using technical replicates to remove discordant transcripts, and are costly or simply ad hoc. As an alternative, we model gene-level replicability of differential activity using co-expressing genes. We find that sets of housekeeping interactions provide a sensitive means of estimating the replicability of expression changes, where the co-expressing pair can be regarded as pseudo-replicates of one another. We model the effects of noise that perturbs a gene's expression within its usual distribution of values and show that perturbing expression by only 5% within that range is readily detectable (AUROC~0.73). We have made our method available as a set of easily implemented R scripts.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression Investigative techniques and equipment > assays > RNA-seq |
| CSHL Authors: | |
| Communities: | CSHL labs > Gillis Lab |
| Depositing User: | Matt Covey |
| Date: | 15 April 2016 |
| Date Deposited: | 13 May 2016 16:56 |
| Last Modified: | 13 May 2016 16:56 |
| PMCID: | PMC4833304 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/32798 |
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