Mechanisms of tissue-specific genetic regulation revealed by latent factors across eQTLs
Surya B. Chhetri,
Alvaro N Barbeira,
Hae Kyung Im,
Christopher D. Brown,
Posted 06 Oct 2019
bioRxiv DOI: 10.1101/785584
Posted 06 Oct 2019
Background: Genetic regulation of gene expression, revealed by expression quantitative trait loci (eQTLs), varies across tissues in complex patterns ranging from highly tissue-specific effects to effects shared across many or all tissues. Improved characterization of these patterns may allow us to better understand the biological mechanisms that underlie tissue-specific gene regulation and disease etiology. Results: We develop a constrained matrix factorization model to learn patterns of tissue sharing and tissue specificity of eQTLs across 49 human tissues from the Genotype-Tissue Expression (GTEx) project. The learned factors include patterns reflecting tissues with known biological similarity or shared cell types, in addition to a dense factor representing a universal genetic effect across all tissues. To explore the regulatory mechanisms that generate tissue-specific patterns of expression, we evaluate chromatin state enrichment and identify specific transcription factors with binding sites enriched for eQTLs from each factor. Conclusions: Our results demonstrate that matrix factorization can be applied to learn the tissue specificity pattern of eQTLs and that it exhibits better biological interpretability than heuristic methods. We present a framework to characterize the tissue specificity of eQTLs, and we identify examples of tissue-specific eQTLs that may be driven by tissue-specific transcription factor (TF) binding, with relevance to interpretation of disease association. Keywords: Matrix factorization, Universal eQTLs, Tissue-specific eQTLs, Transcription factors
- Downloaded 1,117 times
- Download rankings, all-time:
- Site-wide: 9,540 out of 89,005
- In genomics: 1,403 out of 5,673
- Year to date:
- Site-wide: 4,323 out of 89,005
- Since beginning of last month:
- Site-wide: 5,727 out of 89,005
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!