Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,655 bioRxiv papers from 298,484 authors.

IMPACT: Genomic annotation of cell-state-specific regulatory elements inferred from the epigenome of bound transcription factors

By Tiffany Amariuta, Yang Luo, Steven Gazal, Emma E Davenport, Bryce van de Geijn, Harm-Jan Westra, Nikola Teslovich, Yukinori Okada, Kazuhiko Yamamoto, RACI consortium, GARNET consortium, Alkes Price, Soumya Raychaudhuri

Posted 10 Jul 2018
bioRxiv DOI: 10.1101/366864 (published DOI: 10.1016/j.ajhg.2019.03.012)

Active regulatory elements within CD4+ T cells harbor disproportionate heritability (h2) for rheumatoid arthritis (RA). We hypothesized that regulatory elements specific to pathogenic CD4+ T cell-states better capture RA h2; however, defining these elements is challenging. To this end, we introduce IMPACT, a genome annotation strategy to identify cell-state-specific regulatory elements defined by key transcription factor binding profiles, learned from 398 chromatin and sequence annotations. Integrating IMPACT annotations of four CD4+ T cell-states with RA summary statistics of 38,242 Europeans and 22,515 East Asians, we observe that on average the top 5% of Treg predicted regulatory elements explain 85.7% (s.e. 19.4%, enrichment p<1.6e-05) of RA h2, and other cell-states explain a similar proportion. IMPACT captures RA h2 better than active CD4+ T cell regulatory elements, including super enhancers and specifically expressed genes (all p<0.05). IMPACT is generalizable to non-immune cell types and can identify other complex trait associated regulatory elements.

Download data

  • Downloaded 946 times
  • Download rankings, all-time:
    • Site-wide: 8,600 out of 67,655
    • In genetics: 648 out of 3,803
  • Year to date:
    • Site-wide: 14,536 out of 67,655
  • Since beginning of last month:
    • Site-wide: 26,775 out of 67,655

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News