The mammalian genome contains several million cis-regulatory elements, whose differential activity marked by open chromatin determines organogenesis and differentiation. This activity is itself embedded in the DNA sequence, decoded by sequence-specific transcription factors. Leveraging a granular ATAC-seq atlas of chromatin activity across 81 immune cell-types we show that a convolutional neural network (AI-TAC) can learn to infer cell-type-specific chromatin activity solely from the DNA sequence. AI-TAC does so by rediscovering, with astonishing precision, binding motifs for known regulators, and some unknown ones, mapping them with high concordance to positions validated by ChIP-seq data. AI-TAC also uncovers combinatorial influences, establishing a hierarchy of transcription factors (TFs) and their interactions involved in immunocyte specification, with intriguingly different strategies between lineages. Mouse-trained AI-TAC can parse human DNA, revealing a strikingly similar ranking of influential TFs. Thus, Deep Learning can reveal the regulatory syntax that drives the full differentiative complexity of the immune system.
- Downloaded 1,648 times
- Download rankings, all-time:
- Site-wide: 5,237 out of 93,037
- In genomics: 856 out of 5,863
- Year to date:
- Site-wide: 1,044 out of 93,037
- Since beginning of last month:
- Site-wide: 4,602 out of 93,037
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!