RNAseq technology provides unprecedented power in the assessment of the transcription abundance and can be used to perform a variety of downstream tasks such as inference of gene-correlation network and eQTL discovery. However, raw gene expression values have to be normalized for nuisance biological variation and technical covariates, and different normalization strategies can lead to dramatically different results in the downstream study. We describe a generalization of SVD-based reconstruction for which the common techniques of whitening, rank- k approximation, and removing the top k principle components are special cases. Our simple three-parameter transformation, DataRemix, can be tuned to reweight the contribution of hidden factors and reveal otherwise hidden biological signals. In particular, we demonstrate that the method can effectively prioritize biological signals over noise without leveraging external dataset-specific knowledge, and can outperform normalization methods that make explicit use of known technical factors. We also show that DataRemix can be efficiently optimized via Thompson Sampling approach, which makes it feasible for computationally expensive objectives such as eQTL analysis. Finally, we apply our method to the ROSMAP dataset and we report what to our knwoledge is the first replicable trans-eQTL effect in human brain.
- Downloaded 635 times
- Download rankings, all-time:
- Site-wide: 24,509 out of 94,912
- In genomics: 2,682 out of 5,955
- Year to date:
- Site-wide: 30,498 out of 94,912
- Since beginning of last month:
- Site-wide: 32,811 out of 94,912
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!